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Acute Myocardial Infarction: Curations of Cardiovascular Original Research A Bibliography

Curators: Aviva Lev-Ari, PhD, RN and Larry H Bernstein, MD, FCAP

This article covers CURATIONS on one topic in Cardiology: Acute Myocardial Infarction. It represents a Bibliography on the subject matter using the Methodology of Curation.

The e-Reader is advised to read the article that describes what is this methodology and what makes it particularly appropriate for analysis, synthesis, interpretation and exposition of Medical Research Findings.

conceived: NEW Definition for Co-Curation in Medical Research

http://pharmaceuticalintelligence.com/2014/01/04/conceived-new-definition-for-co-curation-in-medical-research/

The e-Reader is advised to review the Curation methodology applied to case studies on Cardiovascular Diseases in the following volume:

Series A: e-Books on Cardiovascular Diseases

Series A Content Consultant: Justin D Pearlman, MD, PhD, FACC

VOLUME TWO 

Cardiovascular Original Research:

Cases in Methodology Design for Content Co-Curation

The Art of Scientific & Medical Curation

by

Justin D Pearlman, MD, PhD, FACC

Larry H Bernstein, MD, FCAP 

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/biomed-e-books/series-a-e-books-on-cardiovascular-diseases/volume-two-cardiovascular-original-research-cases-in-methodology-design-for-content-co-curation/

Acute Myocardial Infarction: Curations of Cardiovascular Original Research A Bibliography from the Open Access Online Scientific Journal

http://pharmaceuticalintelligence.com

  • A Software Agent for Diagnosis of ACUTE MYOCARDIAL INFARCTION

Isaac E. Mayzlin, Ph.D, David Mayzlin, Larry H. Bernstein, M.D

http://pharmaceuticalintelligence.com/2012/08/12/1815/

  • Response to Rosuvastatin in Patients With Acute Myocardial Infarction: Hepatic Metabolism and Transporter Gene Variants Effect

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/response-to-rosuvastatin-in-patients-with-acute-myocardial-infarction-hepatic-metabolism-and-transporter-gene-variants-effect/

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/12/microrna-in-serum-as-bimarker-for-cardiovascular-pathologies-acute-myocardial-infarction-viral-myocarditis-diastolic-dysfunction-and-acute-heart-failure/

  • Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

  • Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/21/genetic-polymorphisms-of-ion-channels-have-a-role-in-the-pathogenesis-of-coronary-microvascular-dysfunction-and-ischemic-heart-disease/

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/12/myocardial-damage-in-cardiovascular-disease-circulating-microrna-208b-and-microrna-499/

  • Intracoronary Transplantation of Progenitor Cells after Acute MI

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/11/02/progenitor-cells-coronary-graft-after-ami/

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/10/15/myocardial-infarction-the-new-definition-after-revascularization/

Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/08/25/coronary-circulation-combined-assessment-optical-coherence-tomography-oct-near-infrared-spectroscopy-nirs-and-intravascular-ultrasound-ivus-detection-of-lipid-rich-plaque-and-prevention-of-a/

  • Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/06/30/troponin-i-in-acute-decompensated-heart-failure/

  • Microchemistry Implant Device for Early Detection of Acute Coronary Syndrome

Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2013/03/26/microchemistry-implant-device/

  • Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/06/30/troponin-i-in-acute-decompensated-heart-failure/

  • Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI – Corus CAD, hs cTn, CCTA

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

  • Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

  • Amplifying Information Using S-Clustering and Relationship to Kullback-Liebler Distance: An Application to Myocardial Infarction

Reporter and curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/09/22/amplifying-information-using-s-clustering/

  • Human embryonic pluripotent stem cells and healing post-myocardial infarction

Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/08/07/human-embryonic-pluripotent-stem-cells-and-healing-post-myocardial-infarction/

  • Diagnostic Value of Cardiac Biomarkers

Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/01/04/diagnostic-value-of-cardiac-biomarkers/

  • On-Hours vs Off-Hours: Presentation to ER with Acute Myocardial Infarction – Lower Survival Rate if Off-Hours

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/22/on-hours-vs-off-hours-presentation-to-er-with-acute-myocardial-infarction-lower-survival-rate-if-off-hours/

On-Hours vs Off-Hours: Presentation to ER with Acute Myocardial Infarction – Lower Survival Rate if  Off-Hours

Reporter: Aviva Lev-Ari, PhD, RN

EDITORIAL

Acute myocardial infarction

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.f7696 (Published 21 January 2014)

Cite this as: BMJ 2014;348:f7696
Cite this as: BMJ 2014;348:f7696
  1. Lauren Lapointe-Shaw, fellow,
  2. Chaim M Bell, associate professor

Author Affiliations

  1. cbell@mtsinai.on.ca

Never a good time, but some times are better than others

Acute myocardial infarction has high mortality, but early medical and surgical intervention can be lifesaving.1 2 3 4 5 6 Previous studies have shown that the time of day or day of the week when patients seek care can affect outcomes.5 7 8In most of these studies, patients presenting to hospital with an acute myocardial infarction during off-hours (evenings and weekends) wait longer for interventional treatments than those presenting during regular office hours and have a higher mortality. In a linked paper (doi:10.1136/bmj.f7393), Sorita and colleagues report the first systematic review of the effect of off-hour presentation on outcomes after acute myocardial infarction.9

The authors evaluated the literature on acute myocardial infarction and off-hour care. Outcomes included in-hospital and 30 day mortality, as well as door to balloon time for the subset of patients with ST elevation myocardial infarction. Using a random effects model, they reported pooled odds ratios for each outcome measure. The pooled results confirmed the presence of a 5% relative increase in mortality (both in-hospital and 30 day) as well as a delay of nearly 15 minutes in door to balloon time for patients presenting during off-hours. Meta-regression based on year of data showed an increase in the risk posed by off-hours care over time.

This novel systematic review advances knowledge on quality of care for patients with myocardial infarction, although it is limited by the studies it contains. In the absence of randomization, differences in patient characteristics between compared groups can introduce substantial bias into study results. Because patients cannot be randomized to present during or outside working hours, a common method of adjusting for baseline risk is needed to facilitate meaningful comparison between studies. If the included studies use different methods to control bias, heterogeneity is increased, which limits the conclusions that can be drawn from pooled analyses.10These are important considerations when undertaking any systematic review of observational studies.

The authors were further challenged by clinical and statistical heterogeneity. The definition of the off-hour time period differed across studies, and varying geographical settings are likely to lead to differences in case mix, time to presentation, physician practices, and hospital characteristics. Such heterogeneity makes it difficult to pool study results and generate a single measure of relative risk. Publication bias, as demonstrated by the absence of small negative studies in the funnel plot, may complicate interpretation still further, although, as the authors point out, there was no significant change in the pooled effect of off-hours presentation after accounting for the missing studies.

Confounding is always a problem in syntheses of observational studies. In Sorita and colleagues analysis it is particularly important to consider whether patients presenting out of hours are systematically different from other patients in such a way that increases their risk of death. They might be sicker, for example, or they may delay calling for medical help for longer. If the last case were true, then delayed presentation would lead to delayed treatment and potentially worse outcomes, which would have little to do with the quality of off-hour care. As the authors point out, the results as to whether time to presentation (delay before reaching hospital) differs significantly between patients presenting during off-hours and working hours are conflicting. If delay in presentation differs between groups, this could bias the measured relative mortality associated with off-hour care.

Although differences in underlying patient characteristics, including time to presentation, can significantly affect mortality, it is less clear how they would affect door to balloon time. Prolongation of door to balloon time is arguably a more robust measure of altered care during off-hours, because it is more likely to be directly controlled by the hospital and care providers. In this case, a process measure (door to balloon time) truly enhances the interpretation of an outcome measure (mortality), albeit for a subgroup of patients. The nearly 15 minute delay in percutaneous coronary intervention experienced by patients presenting with ST elevation myocardial infarction during off-hours provides a potentially causal link between the quality of off-hour care and patient outcomes.

Patients presenting during off-hours experience delays in urgent care and worse outcomes, and the gap seems to be increasing over time. As healthcare managers in many countries move toward performance based remuneration, patient outcomes are increasingly being used to gauge the quality of hospital care. Managers seeking to boost their hospital’s performance for patients with acute myocardial infarction should focus on improving their off-hour care, with the goal of providing consistently high quality care 24 hours a day and seven days a week.

Studies of quality of care and patient outcomes highlight the challenges we face when trying to measure true hospital performance. Administrative data often do not capture all the factors that contribute to baseline patient risk. To properly evaluate the quality of healthcare delivered at all times, we must refine our methods of risk adjustment to include time to presentation and severity of illness. Future studies should try to identify specific deficits in the care pathway during off-hours, allowing differences in outcomes to be linked to differences in processes. We look forward to reading about innovative strategies to deal with this problem. Patients deserve the best possible outcome, at any given time, and on any given day.

Off-hour presentation and outcomes in patients with acute myocardial infarction: systematic review and meta-analysis

BMJ 2014; 348 doi: http://dx.doi.org/10.1136/bmj.f7393 (Published 21 January 2014)

Cite this as: BMJ 2014;348:f7393

http://www.bmj.com/content/348/bmj.f7393

  1. Atsushi Sorita, senior fellow in preventive medicine and public health1,
  2. Adil Ahmed, senior research fellow2,
  3. Stephanie R Starr, consultant physician3,
  4. Kristine M Thompson, consultant physician4,
  5. Darcy A Reed, consultant physician5,
  6. Larry Prokop, reference librarian6,
  7. Nilay D Shah, senior associate consultant7,
  8. M Hassan Murad, consultant physician1,
  9. Henry H Ting, consultant physician8

Author Affiliations

  1. Correspondence to: H H Ting Ting.Henry@mayo.edu
  • Accepted 28 November 2013

Abstract

Objective To assess the association between off-hour (weekends and nights) presentation, door to balloon times, and mortality in patients with acute myocardial infarction.

Data sources Medline in-process and other non-indexed citations, Medline, Embase, Cochrane Database of Systematic Reviews, and Scopus through April 2013.

Study selection Any study that evaluated the association between time of presentation to a healthcare facility and mortality or door to balloon times among patients with acute myocardial infarction was included.

Data extraction Studies’ characteristics and outcomes data were extracted. Quality of studies was assessed with the Newcastle-Ottawa scale. A random effect meta-analysis model was applied. Heterogeneity was assessed using the Q statistic and I2.

Results 48 studies with fair quality, enrolling 1 896 859 patients, were included in the meta-analysis. 36 studies reported mortality outcomes for 1 892 424 patients with acute myocardial infarction, and 30 studies reported door to balloon times for 70 534 patients with ST elevation myocardial infarction (STEMI). Off-hour presentation for patients with acute myocardial infarction was associated with higher short term mortality (odds ratio 1.06, 95% confidence interval 1.04 to 1.09). Patients with STEMI presenting during off-hours were less likely to receive percutaneous coronary intervention within 90 minutes (odds ratio 0.40, 0.35 to 0.45) and had longer door to balloon time by 14.8 (95% confidence interval 10.7 to 19.0) minutes. A diagnosis of STEMI and countries outside North America were associated with larger increase in mortality during off-hours. Differences in mortality between off-hours and regular hours have increased in recent years. Analyses were associated with statistical heterogeneity.

Conclusion This systematic review suggests that patients with acute myocardial infarction presenting during off-hours have higher mortality, and patients with STEMI have longer door to balloon times. Clinical performance measures may need to account for differences arising from time of presentation to a healthcare facility.

Conclusions and policy implications

In conclusion, this meta-analysis suggests that mortality is higher for patients with acute myocardial infarction who present during off-hours compared with regular hours. This finding may be partially attributed to longer door to balloon times during off-hours for patients with ST elevation myocardial infarction. Future studies should explore the variation in the quality of care by time of day, such as number of staff, expertise of staff, and other structural and process attributes in systems of care during off-hours. Performance measures used for value based purchasing, such as the 30 day risk standardized mortality rate, may need to account for differences by time of presentation to a healthcare facility to assess the quality of care.76 Efforts to improve systems of care should ensure that comparable outcomes are achieved for patients regardless of the time of day or day of the week that patients present to the healthcare system.

What is already known on this topic

  • Past studies suggest that patients with acute myocardial infarction may or may not have higher mortality when they present to hospital during off-hours (weekends and nights) compared with regular hours

  • No systematic reviews or meta-analyses of this topic have been done

What this study adds

  • Patients with acute myocardial infarction presenting during off-hours have higher mortality, and those with ST elevation myocardial infarction have longer door to balloon times

  • Efforts to improve systems of care should ensure comparable outcomes for patients regardless of time of presentation to hospital

Introduction

Acute myocardial infarction remains a leading cause of death worldwide.1 Every year, approximately one million people in the United States have an acute myocardial infarction and 400 000 die from coronary heart disease.2 Previous studies have suggested that patients with acute myocardial infarction who present to the hospital during off-hours (weekends and nights) may have higher mortality.3 45 6 Higher mortality during off-hours may be attributed to a lower likelihood of receiving evidence based treatment or timely reperfusion therapies.6 7Furthermore, the number of hospital staff and their level of expertise may contribute to gaps in the quality of care during off-hours.4 8 9 Because of the high incidence and case fatality of acute myocardial infarction, small increases in the relative risk of mortality during off-hours can translate to important effects in the population.

Using data from the National Registry of Myocardial Infarction database, Magid et al showed that patients with ST elevation myocardial infarction (STEMI) who presented during off-hours had higher in-hospital mortality and longer door to balloon times.6Kostis et al examined an administrative database in New Jersey and found that weekend admissions for patients with acute myocardial infarction were associated with higher in-hospital, 30 day, and one year mortality.4 Conversely, Jneid et al reported no significant difference in mortality between off-hours and regular hours for acute myocardial infarction patients in the Get With the Guidelines-Coronary Artery Disease (GWTG-CAD) national database, despite longer door to balloon times in off-hours for patients with STEMI.10 Other studies have also reported inconsistent results.11 12 13 14 15 16

To date, no systematic reviews or meta-analyses of this literature have been done. Therefore, we aimed to synthesize the available evidence on the effects of off-hour presentation of patients on outcomes of acute myocardial infarction. Our primary outcome was the difference in-hospital or 30 day mortality for patients with acute myocardial infarction who presented during off-hours compared with those who presented during regular hours. The secondary outcome was door to balloon time for patients with STEMI.

Outcome definition and subgroup analyses

Mortality outcomes

We used in-hospital or 30 day mortality as the main outcome. For studies without in-hospital mortality results, we used 30 day mortality when available. We did the main analysis for all studies combined. We also separately analyzed each mortality outcome (in-hospital versus 30 day). For the main outcome, we did subgroup analyses by diagnosis of patient cohort (STEMI versus non-STEMI), type of off-hours (weekend and night versus weekend versus night), measured time of presentation (arrival versus admission versus start of percutaneous coronary intervention), data source (clinical registry versus administrative data), region (North America versus Europe versus others), and outcome adjustment (adjusted versus unadjusted). To evaluate the possibility of a time trend effect of mortality across studies, we did meta-regression using the mid-year of enrollment of the cohort as the independent variable and the natural log of the effect size as the dependent variable. Owing to concern about potential overlapping patient sets, we did sensitivity analyses by excluding each single cohort and by including only one cohort from each study. We also did sensitivity analyses by excluding studies that expressed results as a hazard ratio.

Door to balloon time

We analyzed the proportion of patients with STEMI whose door to balloon time was less than 90 minutes and the mean or median door to balloon times. For mean or median door to balloon times, we did subgroup analyses by type of off-hours determination, measured time of presentation, and region, as well as meta-regression using the mid-year of enrollment of the cohort to evaluate time trends in door to balloon times. We also did sensitivity analyses limiting to studies that included only patients who were directly admitted to the hospital and excluding interventional studies.

Discussion

This systematic review and meta-analysis shows that patients with acute myocardial infarction who presented during off-hours had higher mortality than did those who presented during regular hours. Higher mortality during off-hours was seen for both in-hospital and 30 day mortality. The difference in mortality may be larger for patients with a diagnosis of STEMI and for a non-North American location of the study and may have worsened in recent years.

Comparison with other studies

This review showed that patients with STEMI were less likely to receive percutaneous coronary intervention within 90 minutes and had longer door to balloon times during off-hours. An approximate 30 minute delay in door to balloon time is associated with a 20-30% relative increase in in-hospital morality for STEMI patients, regardless of the baseline door to balloon time up to 180 minutes.62 63Therefore, the 15 minute increase in door to balloon time observed during off-hours could increase mortality by as much as 10-15%, assuming linearity between door to balloon time and mortality. This is consistent with our point estimate of 12% increase in odds of mortality for STEMI, which suggests that the mortality increase in off-hours may well be partially explained by prolonged door to balloon times. Magid et al reported that the difference in mortality became non-significant when adjusted for reperfusion treatment time.6 Additionally, a lower rate of urgent percutaneous coronary intervention for STEMI patients may also partially explain higher mortality during off-hours.4 64

Difference in door to balloon times and rate of percutaneous coronary intervention is likely associated with availability of cardiologists, support staff for the cardiac catheterization laboratory, or both. An around the clock on-site cardiology service is not uniformly available. During off-hours, many institutions need to assemble on-call staff and cardiologists to activate the cardiac catheterization laboratory. This is well illustrated in Magid’s study,6 in which the increase in the time interval from obtaining an electrocardiogram to arriving at the catheterization laboratory explained nearly all of the increases in door to balloon time during off-hours.

Other potential attributes to the increase in mortality during off-hours are availability of skilled staff in the cardiac care unit, availability of diagnostic tests, number of physicians or nursing staff, and human factors such as sleep deprivation and fatigue.65 66 67 68 A recent study found that patients with acute myocardial infarction in regions with a low density of cardiologists had higher 30 day mortality than did patients in regions with a high density, suggesting that the availability of cardiologists in the regional system of care may affect the outcomes of patients with acute myocardial infarction.69 Holmes et al reported that a successful regional care model can reduce the disparity of care between off-hours and regular hours for patients with STEMI.27 Therefore, establishing a local healthcare delivery system to provide consistent quality of care during weekends and nights may be the key to closing the mortality gap between off-hours and regular hours.

An alternative explanation for the increase in mortality during off-hours may be that the case mix differs between off-hours and regular hours. Some studies included in the meta-analysis show that patients who present during off-hours tend to be sicker when measured by the presence of cardiogenic shock or Killip class,6 36 44whereas others suggest no difference.12 15 41 52 53 61 In studies that measured time from onset of symptoms to presentation at hospital, the pre-hospital delay during off-hours was shorter,30 36 54 longer,5 or not different,12 16 3133 35 37 44 48 53 57 compared with regular hours. In fact, past studies showed that the pre-hospital delay was shorter during off-hours in both STEMI and non-STEMI patients.70 71 Furthermore, in studies in which mortality outcomes were adjusted (see table 1 for adjusted variables), the off-hours increase in mortality remained significant (table 2). Although residual confounding resulting from the difference in case mix cannot be excluded, these results suggest that increased mortality during off-hours is associated with factors that arise after presentation at hospital.

In meta-regression, we noted a significantly higher difference in mortality between off-hours and regular hours in the most recent years. We postulate that this may be due to the increase in shift work or hand-offs for off-hour coverage or to disproportionate improvement in the application of evidence based treatment during regular hours compared with off-hours; however, this could be also a chance finding and is certainly subject to ecological bias. In contrast, the difference in door to balloon time between off-hour and regular hour presentation did not significantly change over time. This discrepancy between trends in mortality and door to balloon time may be due to high heterogeneity or may suggest that factors other than door to balloon times contribute to the difference in mortality between off-hours and regular hours. These results should be viewed against secular trends showing decreases in both the absolute mortality rate and door to balloon times,72 73 and thus call attention to the opportunity to improve quality of care provided during off-hours.

REFERENCES 01 – 76
SOURCE

Other related articles published in this Open Access Online Scientific Journal, include the following:

A Software Agent for Diagnosis of ACUTE MYOCARDIAL INFARCTION

Isaac E. Mayzlin, Ph.D, David Mayzlin, Larry H. Bernstein, M.D

http://pharmaceuticalintelligence.com/2012/08/12/1815/

Response to Rosuvastatin in Patients With Acute Myocardial Infarction: Hepatic Metabolism and Transporter Gene Variants Effect

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2014/01/02/response-to-rosuvastatin-in-patients-with-acute-myocardial-infarction-hepatic-metabolism-and-transporter-gene-variants-effect/

MicroRNA in Serum as Bimarker for Cardiovascular Pathologies: acute myocardial infarction, viral myocarditis,  diastolic dysfunction, and acute heart failure

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/12/microrna-in-serum-as-bimarker-for-cardiovascular-pathologies-acute-myocardial-infarction-viral-myocarditis-diastolic-dysfunction-and-acute-heart-failure/

Acute and Chronic Myocardial Infarction: Quantification of Myocardial Perfusion Viability – FDG-PET/MRI vs. MRI or PET alone

Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/05/22/acute-and-chronic-myocardial-infarction-quantification-of-myocardial-viability-fdg-petmri-vs-mri-or-pet-alone/

Atherosclerosis Independence: Genetic Polymorphisms of Ion Channels Role in the Pathogenesis of Coronary Microvascular Dysfunction and Myocardial Ischemia (Coronary Artery Disease (CAD))

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/21/genetic-polymorphisms-of-ion-channels-have-a-role-in-the-pathogenesis-of-coronary-microvascular-dysfunction-and-ischemic-heart-disease/

Myocardial Damage in Cardiovascular Disease: Circulating MicroRNA-208b and MicroRNA-499

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/12/12/myocardial-damage-in-cardiovascular-disease-circulating-microrna-208b-and-microrna-499/

Intracoronary Transplantation of Progenitor Cells after Acute MI

Larry H. Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/11/02/progenitor-cells-coronary-graft-after-ami/

Myocardial Infarction: The New Definition After Revascularization

Reporter: Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/10/15/myocardial-infarction-the-new-definition-after-revascularization/

Coronary Circulation Combined Assessment: Optical Coherence Tomography (OCT), Near-Infrared Spectroscopy (NIRS) and Intravascular Ultrasound (IVUS) – Detection of Lipid-Rich Plaque and Prevention of Acute Coronary Syndrome (ACS)

Justin Pearlman, MD, PhD, FACC and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/08/25/coronary-circulation-combined-assessment-optical-coherence-tomography-oct-near-infrared-spectroscopy-nirs-and-intravascular-ultrasound-ivus-detection-of-lipid-rich-plaque-and-prevention-of-a/

Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/06/30/troponin-i-in-acute-decompensated-heart-failure/

Microchemistry Implant Device for Early Detection of Acute Coronary Syndrome

Larry H Bernstein, MD, FACP

http://pharmaceuticalintelligence.com/2013/03/26/microchemistry-implant-device/

Troponin I in acute decompensated heart failure: insights from the ASCEND-HF study

Larry H Bernstein, MD, FCAP and Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/06/30/troponin-i-in-acute-decompensated-heart-failure/

Acute Chest Pain/ER Admission: Three Emerging Alternatives to Angiography and PCI – Corus CAD, hs cTn, CCTA

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2013/03/10/acute-chest-painer-admission-three-emerging-alternatives-to-angiography-and-pci/

Clinical Trials Results for Endothelin System: Pathophysiological role in Chronic Heart Failure, Acute Coronary Syndromes and MI – Marker of Disease Severity or Genetic Determination?

Aviva Lev-Ari, PhD, RN

http://pharmaceuticalintelligence.com/2012/10/19/clinical-trials-results-for-endothelin-system-pathophysiological-role-in-chronic-heart-failure-acute-coronary-syndromes-and-mi-marker-of-disease-severity-or-genetic-determination/

Amplifying Information Using S-Clustering and Relationship to Kullback-Liebler Distance: An Application to Myocardial Infarction

Reporter and curator: Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/09/22/amplifying-information-using-s-clustering/

Human embryonic pluripotent stem cells and healing post-myocardial infarction

Larry H. Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2012/08/07/human-embryonic-pluripotent-stem-cells-and-healing-post-myocardial-infarction/

Diagnostic Value of Cardiac Biomarkers

Larry H Bernstein, MD, FCAP

http://pharmaceuticalintelligence.com/2014/01/04/diagnostic-value-of-cardiac-biomarkers/

 

 

2014 – Drug Patent Expirations – Top Ten moves to Generics

Reporter: Aviva Lev-Ari, PhD, RN

 

Teva appeals to Supreme Court for help thwarting Copaxone rivals

January 22, 2014 | By 

Teva Pharmaceutical Industries ($TEVA) is making one last desperate plea to the U.S. Supreme Court. The Israel-based drugmaker has asked SCOTUS to review a lower court’s decision to invalidate key patents on its top-selling drug, Copaxone.

The stakes for Teva are high: the U.S. Circuit Court’s ruling shortened Copaxone’s exclusive access to the market by 18 months. The blockbuster multiple sclerosis treatment accounts for about half of Teva’s sales, and the company already was scrambling to develop a successor drug and cut costs in anticipation of generic competition.

But even if the court takes up Teva’s case–even if the justices side with the company–Copaxone sales could suffer serious damage. Teva said today that it expects its case to get a hearing in April, a month before Copaxone faces generic competition, but a decision wouldn’t be forthcoming for months after that. Buyers would have plenty of time to stock up on a generic version before the Supreme Court speaks.

Read more: Teva appeals to Supreme Court for help thwarting Copaxone rivals – FiercePharma http://www.fiercepharma.com/story/teva-appeals-supreme-court-help-thwarting-copaxone-rivals/2014-01-22#ixzz2r9TZKeCa

2014 – Drug Patent Expirations – Top Ten moves to Generics

 

Top 10 Drug Patent Losses of 2014

October 28, 2013
In a way, the coming year isn’t a big one for patent expirations. The total amount of sales jeopardized by patent expirations is $34 billion. That’s more than the $28 billion this year, but far less than the $55 billion that hit in 2012. As for 2015? Forget about it. That year, products worth $66 billion will lose IP protection.

Plus, the drugs facing new competition won’t all take a big hit in 2014. In fact, EvaluatePharma figures that the products newly open to generic competition will only lose $13 billion off their previous totals.

But if you’re one of the companies looking at sudden exposure to would-be copycats, 2014 might be a very big year indeed. Consider Teva Pharmaceutical Industries ($TEVA), best known for its generic drugs. Its top seller is actually a branded medication: Copaxone, a blockbuster multiple sclerosis treatment. Teva has been scrambling to develop a longer-acting follow-up to Copaxone, hoping to woo patients to the new product before the old one loses exclusivity. A U.S. appeals court cut that timeframe short earlier this year, when it invalidated a key patent. Now, Copaxone looks to lose exclusivity in May 2014, rather than November 2015 as previously expected. That’s almost $3 billion in sales in the U.S. at risk.

And then there’s AstraZeneca ($AZN), which faces generic rivals for its famous “purple pill”: Nexium. The acid-reflux treatment goes off patent in May 2014. Of the drug’s $3.994 billion in global sales for 2012, almost $2.3 billion came from the U.S. Naturally, AstraZeneca has been dreading that day for years. In fact, the company has been making one deal after another, aiming to build up a strong enough pipeline to counter the Nexium losses with new sales. The company also loses another patent on Symbicort next year–a method-of-use patent–but the drugs included in the combination inhaler have both already lost exclusivity. So, the inhaled asthma and COPD treatment won’t be quickly copied.

In fact, several companies have more than one drug facing patent loss in 2014. Novartis ($NVS) loses exclusivity on Sandostatin LAR and Exforge, both in the top 10. Then there’s Allergan ($AGN), with Restasis and Lumigan, which didn’t make the top 10. A key patent on Lumigan expires in August, though the company is defending another that doesn’t run out ’til 2027. Finally, there’s Warner Chilcott ($WCRX), which has a trifecta, even if it’s not obvious from the list below. The company’s bone drug Actonel, colitis treatment Asacol HD and contraceptive Loestrin 24 Fe all lose exclusivity next year. Warner has already stopped selling the latter, however, aiming to convert patients to a newer version, and it’s steering Asacol patients toward its newer drug Delzicol.

We ranked these drugs by global sales in 2012; neither Boehringer Ingelheim, a private company, nor Allergan breaks out U.S. sales of its product listed below. We’ve included U.S. numbers for the rest. Sales figures are from the company’s earnings announcements and Securities and Exchange Commission filings. For companies reporting in foreign currencies–Boehringer and Sanofi ($SNY)–we converted sales figures according to the exchange rate on the last day of the relevant period.

Any questions or comments? Let us know directly, or start a discussion with FiercePharma‘s LinkedIn group. — Tracy Staton (email | Twitter)

Read more: Top 10 Drug Patent Losses of 2014 – FiercePharma http://www.fiercepharma.com/special-reports/top-10-drug-patent-losses-2014#ixzz2r9SlCV8S

 New Biomarker for Esophageal Cancer Reported in the Journal “Cancer Research”

Reporter: Aviva Lev-Ari, PhD, RN

January 21, 2014

New biomarker for esophageal squamous cell carcinoma

The leading cause of cancer death worldwide is esophageal squamous cell carcinoma (ESCC), the major histological form of esophageal cancer. A biomarker, adenosine deaminase acting on RNA-1 (ADAR1), has been discovered, and it has the potential to improve the diagnosis, prognosis, and treatment of this disease.

Led by Polly Chen, MD, PhD, of the Cancer Science Institute of the National University of Singapore, the research team also demonstrated that the editing of protein-making sequences promotes the development of ESCC. Their study was published in Cancer Research (2013; doi:10.1158/0008-5472.CAN-13-2545).

Currently, patients with ESCC have a poor prognosis, as overall survival ranges from 20% to 30%. These dismal numbers indicate the urgent need for biomarkers that can diagnose this disease as early as possible, estimate reactions to chemotherapy or radiotherapy in patients, and predict the overall survival rate of patients undergoing treatment.

In normal human cells, deoxyribonucleic acid (DNA), which comprises the genetic code, serves as a template for the precise production of ribonucleic acid (RNA) such that the DNA code and RNA code are identical. Editing is a process in which RNA is changed after it is made from DNA, resulting in an altered gene product. This RNA editing is likely to play a role in the formation of tumors by either inactivating a tumor suppressor or activating genes that promote tumor progression.

In this study, the researchers discovered that the RNA-editing enzyme ADAR1, which catalyzes the editing process, is significantly overexpressed in ESCC tumors. They observed that ADAR1 changes the product of the AZIN1 protein to a form which promotes the development of the disease. Clinically, the tumoral overexpression of ADAR1 was correlated with the shorter survival time of ESCC patients.

The findings suggest that ADAR1 can serve as a useful biomarker to detect disorders leading to ESCC and as a potential therapeutic target. The study may also provide the key to a biological process for drug development in the treatment of ESCC.

“Investigating the connection between ADAR1-mediated RNA editing and cancer progression is only the initial step in this research. The tumoral overexpression of ADAR1 can be used as an early warning sign of ESCC and halting or reversing the process may block the cells’ conversion from normal to malignant,” said Chen.

Moving forward, the researchers will further investigate the key RNA-editing events regulated by ADAR1 during ESCC development. They plan to develop a method to correct the RNA-editing process through restoring ADAR balance by silencing ADAR1 and reinstating a specific hyper-edited or hypo-edited transcript.

SOURCE

http://www.oncologynurseadvisor.com/new-biomarker-for-esophageal-squamous-cell-carcinoma/article/329964/

 

Adenosine-to-Inosine RNA Editing Mediated by ADARs in Esophageal Squamous Cell Carcinoma

 

  1. Yan-Ru Qin1,
  2. Jun-Jing Qiao1,6,
  3. Tim Hon Man Chan6,
  4. Ying-Hui Zhu2,
  5. Fang-Fang Li4,
  6. Haibo Liu3,
  7. Jing Fei6,
  8. Yan Li2,
  9. Xin-Yuan Guan2,5, and
  10. Leilei Chen6

+Author Affiliations


  1. Authors’ Affiliations: 1Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou; 2State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Centre; 3Key Laboratory for Major Obstetric Disease of Guangdong Province, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou; 4Department of Clinical Oncology, Nanyang city first people’s hospital, Henan; 5Department of Clinical Oncology, The University of Hong Kong, Hong Kong, China; and 6Cancer Science Institute of Singapore, National University of Singpaore, Singapore
  1. Corresponding Authors:
    Yan-Ru Qin, Department of Clinical Oncology, the First Affiliated Hospital, Zhengzhou University, Zhengzhou, China. Phone: 86-371-66295542; E-mail: yanruqin@zzu.edu.cn; Xin-Yuan Guan, State Key Laboratory of Oncology in Southern China, Sun Yat-Sen University Cancer Centre, Room 605, 651 East Dongfeng Road, Guangzhou 510050, China. Phone: 86-20-87343166; Fax: 86-852-28169126; E-mail: xyguan@hku.hk; and Leilei Chen, Cancer Science Institute of Singapore, National University of Singapore, 14 Medical Drive, Singapore 117599. Phone: 65-6516-8435; Fax: 65-6516-1873; E-mail:csicl@nus.edu.sg
  1. Y.-R. Qin and J.-J. Qiao contributed equally to this work.

Abstract 

Esophageal squamous cell carcinoma (ESCC), the major histologic form of esophageal cancer, is a heterogeneous tumor displaying a complex variety of genetic and epigenetic changes. Aberrant RNA editing of adenosine-to-inosine (A-to-I), as it is catalyzed by adenosine deaminases acting on RNA (ADAR), represents a common posttranscriptional modification in certain human diseases. In this study, we investigated the status and role of ADARs and altered A-to-I RNA editing in ESCC tumorigenesis. Among the three ADAR enzymes expressed in human cells, only ADAR1 was overexpressed in primary ESCC tumors. ADAR1 overexpression was due to gene amplification. Patients with ESCC with tumoral overexpression of ADAR1 displayed a poor prognosis. In vitro and in vivofunctional assays established that ADAR1 functions as an oncogene during ESCC progression. Differential expression of ADAR1 resulted in altered gene-specific editing activities, as reflected by hyperediting of FLNB and AZIN1 messages in primary ESCC. Notably, the edited form of AZIN1 conferred a gain-of-function phenotype associated with aggressive tumor behavior. Our findings reveal that altered gene-specific A-to-I editing events mediated by ADAR1 drive the development of ESCC, with potential implications in diagnosis, prognosis, and treatment of this disease. Cancer Res; 1–12. ©2013 AACR.

Note:  Supplementary data for this article are available at Cancer Research Online (http://cancerres.aacrjournals.org/).
  • Received September 4, 2013.
  • Revision received October 18, 2013.
  • Accepted November 6, 2013.

©2013 American Association for Cancer Research.

SOURCE
Published Online First December 3, 2013; doi:10.1158/0008-5472.CAN-13-2545

Voice from the Cleveland Clinic: On the New Lipid Guidelines and On the ACC/AHA Risk Calculator

Reporter: Aviva Lev-Ari, PhD, RN

Article ID #107: Voices from the Cleveland Clinic: On the New Lipid Guidelines and On the ACC/AHA Risk Calculator. Published on 1/21/2014

WordCloud Image Produced by Adam Tubman

This article covers the following related topics:

I. Voices from Cleveland Clinic: Love ‘Em or Leave ‘Em: Experts on Both Sides Debate the New Lipid Guidelines

http://www.medscape.com/viewarticle/819288?nlid=45683_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2

II.  JAMA Weighs In on CVD Guidance, Statins in Primary Prevention

http://www.medscape.com/viewarticle/814960

III.  How Good Is the New ACC/AHA Risk Calculator?

http://www.medscape.com/viewarticle/814579

IV.  New Cholesterol Guidelines Abandon LDL Targets

http://www.medscape.com/viewarticle/814152

V. New CV Risk-Assessment Guidance Counts Stroke With CHD Risk

http://www.medscape.com/viewarticle/814206

VI.  NIH Says ATP 4, JNC 8 Guidance Out ‘in a Matter of Months’ (With a Twist)

http://www.medscape.com/viewarticle/806563

VII.  New European Hypertension Guidelines Released: Goal Is Less Than 140 mm Hg for All

http://www.medscape.com/viewarticle/806367

VIII.  New guidelines on primary stroke prevention from AHA/ASA

http://www.medscape.com/viewarticle/790766

IX.  New ACC/AHA/NHLBI Guidance on Lifestyle for CVD Prevention

http://www.medscape.com/viewarticle/814139

X. New Obesity Guidelines: Authoritative ‘Roadmap’ to Treatment

http://www.medscape.com/viewarticle/814202

XI.  USPSTF Updates Adult Obesity-Overweight Screening Guidelines

http://www.medscape.com/viewarticle/766342

Voices from the Cleveland Clinic: On the New Lipid Guidelines and On the ACC/AHA Risk Calculator

Love ‘Em or Leave ‘Em: Experts on Both Sides Debate the New Lipid Guidelines

January 20, 2014

DALLAS, TX and WASHINGTON, DC — It has been two months since the new clinical guidelines for the treatment of cholesterol were published[1], and feedback is starting to slowly emerge as clinicians begin incorporating the recommendations into clinical practice.

The American College of Cardiology (ACC) and American Heart Association (AHA) guidelines, which were developed in conjunction with the National Heart, Lung, and Blood Institute (NHLBI), were a radical departure from previous iterations, most notably in their abandonment of LDL-cholesterol targets. In the past, clinicians were advised to treat patients with cardiovascular disease to less than 100 mg/dL or the optional goal of less than 70 mg/dL.

As reported by heartwire  at the time, the expert panel stated there was simply no evidence from randomized, controlled clinical trials to support treatment to a specific target. As a result, the new guidelines make no recommendations for specific LDL-cholesterol or non-HDL targets for the primary and secondary prevention of atherosclerotic cardiovascular disease.

Dr Stanley Hazen

For one clinician, Dr Stanley Hazen (Cleveland Clinic, OH), the strict adherence to only clinical-trial data is a limitation and not a strength of the new guidelines.

“First, it ignores a wealth of information on the pathophysiology of the disease process. Second, it presumes that the reason trials are designed is to answer guideline questions,” he told heartwire . “They aren’t. Trials are designed by pharmaceutical companies trying to get claims issued on their drugs. More important, the absence of randomized clinical-trial data does not justify inaction if LDL cholesterol remains elevated.”

Accelerating Vascular Age

In his commentary published January 8, 2014 in the Cleveland Clinic Journal of Medicine, Hazen, along with first author Dr Chad Raymond (Cleveland Clinic, OH), lay out their concerns with the clinical guidelines and highlight some of the shortcoming with the new recommendations[2].

For Hazen, there are multiple reasons that physicians should continue to treat to specific LDL-cholesterol targets, the first and foremost being that patients are different and no single treatment fits such a large and heterogeneous patient population at risk for cardiovascular disease and stroke. The guidelines simply call for a moderate- or high-dose statin in high-risk patients depending on the clinical scenario and no subsequent assessment of LDL cholesterol.

“In the very highest-risk patients, the ones with extraordinarily high levels of cholesterol, those who get maximally tolerated statins, if there is still a substantial LDL-cholesterol burden, they are going to have substantial residual risk,” he said. “The preponderance of data in aggregate shows that there is higher residual risk proportionate to the LDL level that’s remaining. The new guidelines completely ignore the pathophysiology of the disease process—a disease that takes decades to develop.”

The clinical guidelines are unique among documents past in that the emphasis is strictly on statin therapy rather than LDL-cholesterol-lowering medications more generally. In individuals with atherosclerotic cardiovascular disease, high-intensity statin therapy—such as rosuvastatin (Crestor, AstraZeneca) 20 to 40 mg or atorvastatin 40 to 80 mg—should be used to achieve at least a 50% reduction in LDL cholesterol unless otherwise contraindicated or when statin-associated adverse events are present. In that case, doctors should use a moderate-intensity statin. Similarly, for those with LDL-cholesterol levels >190 mg/dL, a high-intensity statin should be used with the goal of achieving at least a 50% reduction in LDL-cholesterol levels.

For Hazen, the new clinical guidelines “turn back the clock on cardiovascular disease prevention” and have the potential to both overtreat older low-risk patients and undertreat those who are young yet are at higher lifetime risk.

For example, he cites a 25-year-old man who presents because his 45-year-old father just died from a heart attack. He has a fasting total cholesterol level of 310 mg/dL, HDL cholesterol of 50 mg/dL, triglyceride level of 400 mg/dL, and LDL cholesterol of 180 mg/dL. Even with the strong family history of premature coronary disease, because of his young age, the current guidelines do not suggest treatment because they do not apply to those less than 40 years old. However, even if his age were 40, his calculated 10-year risk would be <7.5% based on a new and controversial risk calculator published alongside the guidelines.

“I can’t imagine there is a lipidology expert or cardiologist out there who would think that this patient does not deserve aggressive preventive efforts and intervention,” said Hazen. “It is lifetime risk and lifetime exposure to higher LDL cholesterol that contributes to the disease process. Ignoring that scientific fact in a document whose focus is on treating cholesterol to prevent cardiovascular disease is simply illogical.”

A Massive Paradigm Shift

Speaking with heartwire Dr James de Lemos (University of Texas Southwestern Medical Center, Dallas) suspects there remains some hesitancy on the part of practicing primary-care physicians to adopt the guidelines, mainly because they are a “massive paradigm shift that dramatically changes the approach to disease.” He said while there are always early adopters, there have been some questions as to which major journals and cardiology organizations would line up behind them (and nearly all have, with the exception of the American Association of Clinical Endocrinologists ).

For cardiologists, on the other hand, the shift to focus on four specific types of patients is not so dramatic, because these are patients they routinely see in clinical practice. For de Lemos, it is reasonable to focus on at-risk patients and treat according to that level of risk. He still incorporates measuring LDL-cholesterol levels, however, noting that the measurement can provide some reassurance or concern depending on the threshold achieved with treatment, dietary changes, and exercise.

Dr Mariel Jessup

To heartwire Dr Mariel Jessup (University of Pennsylvania, Philadelphia), the president of the AHA, said that immediately following their publication many of her colleagues began implementing the guidelines and using the new calculator for risk assessment. In doing so, they identified patients on statins who did not require the lipid-lowering drugs as well as patients who weren’t on them but should be.

“In the first week, we were all coming to terms with what contributes to risk,” said Jessup. She added that she hasn’t heard a great deal of criticism about the guidelines and believes most physicians are getting on board with the new changes.

She noted that a member of the Penn faculty recently delivered medical grand rounds on the new lipid guidelines and while it was mostly positive, one criticism that arose was the emphasis on randomized, controlled clinical-trial data. Jessup said that even though the new guidelines focus on clinical-trial data, this does not negate findings from observational or epidemiological studies.

Dr Roger Blumenthal

Dr Roger Blumenthal (Johns Hopkins Ciccarone Preventive Cardiology Center, Baltimore, MD), on the other hand, predicts a return to LDL treatment goals in the not-so-distant future.

“I think the guidelines will revert back to the way they were once we get a positive study showing that adding another agent to a statin reduces risk,” Blumenthal said. He predicts positive results with anacetrapib (Merck, Whitehouse Station, NJ), the novel cholesteryl ester transfer protein (CETP) inhibitor, or one of the investigational proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, when given on top of statins. “When that happens, the new randomized controlled trial data would support going lower than what would be achieved with giving just 40 mg or 80 mg of atorvastatin.”

In very selected patients, Blumenthal still aggressively targets to low LDL levels, even if this requires adding a second agent. For example, in patients treated with a statin, LDL cholesterol might be reduced to 80 mg or so, but triglyceride levels remain high or HDL cholesterol is low. He notes that the ACCORD study with fenofibrate was borderline nonsignificant in patients with low HDL cholesterol and high triglyceride levels. Beyond fibrates, he notes there have been angiographic studies published in support of the “lower-is-better” hypothesis.

Jessup said that most physicians understand why the LDL targets were eliminated, but many institutions used the thresholds as a performance measure. Penn Health, for example, used the number of patients treated to the old LDL-cholesterol targets as an internal marker of performance for physicians in internal medicine and general practice. “As you struggle to come up with an easily defined target that you can use to talk about quality in a large practice, and not just among cardiologists, that’s one less target you can use,” said Jessup.

Concerns Among Clinicians as Well

Dr Rita Redberg

Dr Rita Redberg (University of California, San Francisco) also has significantconcerns about the new guidelines, albeit for entirely different reasons. An outspoken critic when the guidelines were presented, her views have not changed, telling heartwire that she is already looking forward to the next version of the cholesterol guidelines. When they were first published and presented, Redberg, along with Dr John Abramson (Harvard Medical School, Boston, MA), argued that statins were beneficial for individuals with heart disease but do not reduce the risk of death in individuals with a 10-year risk of cardiovascular disease of less than 20%.

“I have not been implementing these guidelines because I don’t think they’re in the best interests of my patients, and I really do look forward to the revisions,” she said. “I’m all for looking at risk, and I’m all for targeting prevention strategies on the basis of risk, so I think this is a strong point of the new guidelines. However, that is really undermined by the risk calculator, in which anybody over age 65 basically needs to be on a statin. I don’t think the data support this.”

The new cholesterol guidelines weathered a rough roll-out their first week when Drs Paul Ridker and Nancy Cook (Brigham and Women’s Hospital, Boston, MA) calculated the 10-year risk of cardiovascular events in three large-scale primary prevention cohorts—the Women’s Health Study(WHS), the Physicians’ Health Study (PHS), and the Women’s Health Initiative Observational Study (WHI-OS)—and found the new algorithm overestimated the risk by 75% to 150%.

Dr James de Lemos

To de Lemos, the controversial aspect of the new guidelines remains in the primary-prevention population. For those without cardiovascular disease but who have LDL-cholesterol levels ranging from 70 mg/dL to 189 mg/dL and a 10-year risk of cardiovascular disease >7.5%, physicians can initiate treatment with a statin. Given the controversy surrounding the risk calculator, there have been suggestions that people who don’t need statins will receive treatment.

“It doesn’t mean the concept is flawed,” de Lemos told heartwire , “but it just might not be ready to implement widely.” As a result, he suspects that physicians might be keeping the risk calculator at arm’s length until it is studied and debated further. As for his own use, de Lemos said he doesn’t calculate 10-year risk in every patient, even though he is fairly aggressive with initiating statin therapy, and that his decisions are more intuitive and empirical, something which he doesn’t see changing.

Jessup said the risk calculator, as well as the clinical guidelines, will be updated as new information emerges. While she was not able to speak to specifics, Jessup is aware of researchers testing the predictive strength of the risk calculator in different cohorts to see how well it performs. In general, she said the calculator performs reasonably well.

Some Docs Finding the Calculator Helpful

Dr Sekar Kathiresan

Dr Sekar Kathiresan (Brigham and Women’s Hospital, Boston, MA), who runs a primary-prevention clinic, does use the new clinical guidelines and the new risk calculator to inform his decisions about whether or not to start patients with a moderate- or high-dose statin. He said Ridker and Cook raise a valid scientific point in terms of how well it is calibrated, but this should be put in perspective, given that physicians for the past 20 years or so have used the Framingham Risk Score, a score derived from a few thousand white individuals from one town in the US. The new risk equation increases the population sampled, includes different ethnicities, and is derived from more than one geographic area.

“Is the pooled-cohort equation perfect?” he asked. “No, it won’t be perfect, because it’s an attempt to estimate risk on a sample of 25 000 people.”

Blumenthal made similar comments, telling heartwire that the risk calculator is a better way to estimate risk in women and African Americans, for example. Given that the risk calculator might overestimate risk, he expands his definition of intermediate risk to include patients with a 5% to 15% 10-year risk of cardiovascular disease. In doing so, even if the risk calculator overestimates by a factor of two, they have some wiggle room in discussing care with the patient.

In addition, Blumenthal said the guidelines emphasize a discussion with the patient about care in those with a 10-year risk exceeding 7.5%, just as would be done with an intermediate-risk patient. The discussion can lead to further refinement of risk by taking family history into account or by performing a computed tomography (CT) scan to assess coronary artery calcium (CAC).

To Kathiresan, moving away from LDL-cholesterol targets will require some time before they become readily accepted, mainly because physicians have gotten used to the targets. For the most part, though, he views the changes to the guidelines as more of a “tweak.”

“I don’t find them as radical as some people do,” Kathiresan told heartwire . “I actually think the major thing that was accomplished was taking the focus away from using medications to change lab tests and to now focus on medication proven to reduce the risk of disease. This is a huge plus for the new guidelines.”

In cardiology, the evidence base is very rich, with many trials and millions of dollars spent to evaluate whether specific medicines work to reduce disease risk in specific clinical situations, he added. This is the evidence that should be used to inform clinical practice. For this reason, he entirely agrees with the new focus on statins and not simply lipid-lowering agents.

“There is an incredible amount of inappropriate use of both niacin and fibrates in the US, all based on the fact that they change lab tests,” said Kathiresan. “The clinical-trial evidence for those two medicines is disappointingly poor.”

Hazen is a coinventor on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics. He is a paid consultant to the Cleveland Heart Lab, Esperion, Liposciences, Merck, Pfizer, and Procter & Gamble. He has received research funds from Abbott, Astra Zeneca, Cleveland Heart Lab, Esperion, Liposciences, Procter & Gamble, and Takeda. In addition, he is entitled to royalty payments for inventions/discoveries related to cardiovascular diagnostics and therapeutics from Abbott Laboratories, Cleveland Heart Lab, Esperion, Frantz Biomarkers, and Liposciences 

de Lemos acknowledges grant support from Roche Diagnostics and Abbott Diagnostics and has consulted for Diadexus. 

Kathiresan reports serving as a consultant to Merck, Pfizer, Celera, and Alnylam.

Jessup, Blumenthal, and Redberg report no conflicts of interest.

REFERENCES

  1. Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: A report of the American College of Cardiology/American Heart Association. J Am Coll Cardiol 2013. ArticleCirculation 2013. Article.
  2. Raymond C, Cho L, Rocco M, Hazen SL. New cholesterol guidelines: Worth the wait? Cleve Clin J Med 2014; DOI: 10.3949/ccjm.81a.13161. Article

SOURCE

http://www.medscape.com/viewarticle/819288#1

Diet Strategies for Prevention of Hypertension in Japanese vs. Americans: Alcohol Consumption vs. Weight Management

Reporter: Aviva Lev-Ari, PhD, RN

In a new article on a study supported by the Ministry of Health, Labor, and Welfare of Japan; Intramural Research Fund, National Cerebral and Cardiovascular Center; and Ministry of Education, Science, and Culture of Japan, Dr. Kokubo explains the different strategies needed for Prevention of Hypertension in Japanese by decrease of Alcohol Consumption and in Americans by applying Weight Management methods to reduce weight.

Kokubo Y. Prevention of hypertension and cardiovascular diseases: A comparison of lifestyle factors in Westerners and East Asians. Hypertension 2014; DOI:10.1161/HYPERTENSIONAHA.113.00543. Text

http://hyper.ahajournals.org/content/early/2014/01/13/HYPERTENSIONAHA.113.00543.citation

Best Ways to Cut Hypertension Differ for Westerners, Asians

Fran Lowry

January 17, 2014

OSAKA, Japan — A new review should serve as a reminder to physicians that lifestyle modifications are the cornerstone of hypertension prevention, but not all changes work for all populations. Because of differences in genes, diet, and lifestyle, the contributions of blood pressure to stroke are different for Westerners and East Asians, writes Dr Yoshihiro Kokubo (National Cerebral and Cardiovascular Center, Osaka, Japan).

“The guidelines put out by the United States, Europe, China, and Japan for lifestyle modifications for prevention of hypertension are similar,” Yoshihiro writes. “Namely, salt restriction, high consumption of vegetables and fruits, increased intake of fish and reduced content of saturated/total fat, appropriate weight control, regular physical exercise, moderate alcohol consumption, and quitting smoking.”

These factors are also considered important for stroke prevention, Kokubo adds in his review published online January 13, 2014 in Hypertension.

Given how different these populations are, Kokubo decided to compare findings from lifestyle status in Westerners vs East Asians with regard to these hypertension guidelines.

“Even in East Asians, for example, fish consumption is different between Chinese and Japanese,” he told heartwire . “I wanted to review lifestyles according to the lifestyle modifications that appear in different guidelines, because I thought that this would lead to a beginning of improvement of both lifestyle changes and effects on blood pressure.”

Salt Restriction

Many studies have shown that reduced salt intake is directly related to decreased blood pressure, including the Dietary Approaches to Stop Hypertension (DASH), International Study of Salt and Blood Pressure (INTERSALT), and International Study of Macro-Micronutrients and Blood Pressure (INTERMAP).

However, salt intake of Northern Japanese is among the highest in East Asia due to a high consumption of tsukemono (pickled vegetables), soy sauce, and miso soup. Consumption of carbohydrate in the form of rice and lower intakes of saturated fat and animal protein are believed to be the link with an increased risk of intracerebral hemorrhage in this population, Kokubo notes.

Also, Asians have a genetically higher salt sensitivity, and salt sensitivity in general is different among different populations, which indicates that the blood pressure response to sodium varies among ethnic groups.

Because of these factors, East Asians need to have more counseling about salt consumption, Kokubo says.

More of This, Less of That

Other findings of Kokubo’s review include:

  • Westerners consume more meat and saturated fat, and therefore diets that restrict these foods will result in greater benefit regarding blood pressure control and atherosclerotic disease in this population.
  • Japanese, on the other hand, have high fish and soy intake, which may contribute to their having the lowest coronary heart disease mortality in the world.
  • Obesity and overweight are increasing worldwide, but men and women from East Asia are generally less heavy, potentially reducing their risk. However, increased body-mass index in male Japanese office workers has been shown to be a strong risk factor for hypertension.
  • Regular physical exercise is important for reducing hypertension in both Westerners and East Asians.
  • Japanese men have the highest consumption of alcohol, higher than American and British men. On the other hand, Western women consume more alcohol than Asian women. A campaign to reduce alcohol intake among Japanese men may be particularly beneficial in reducing their blood pressure.
  • East Asian men continue to smoke more than Westerners. Smoking rates of 40% to 60% among East Asian men are among the highest in the world. Smoking cessation efforts would have a greater impact in East Asian than Western countries.

Different Strokes for Different Folks

In his conclusion, Kokubo writes that a high consumption of fruits and vegetables, regular physical exercise, and maintaining appropriate body weight are all beneficial for blood pressure control in both Western and East Asian populations.

East Asians have the benefit of diets higher in fruits, vegetables, and fish, and a lower incidence of obesity, but they have a genetically higher salt sensitivity and greater salt intake than Westerners.

Also, excessive alcohol intake contributes to increased blood pressure in Japanese men, which is especially dangerous given their high rate of aldehyde dehydrogenase deficiency, a risk factor for hypertension, Kokubo writes.

By contrast, “Westerners need to pay attention to weight control, including regular exercise, and consider replacing dietary meat high in saturated fat with fish,” he said.

“Further comprehensive prospective studies are anticipated to show how each factor contributes to blood pressure control and a reduced risk of CVD in Westerners and East Asians,” Kokubo concludes.

Kokubo reports no relevant financial relationships. The study was supported by the Ministry of Health, Labor, and Welfare of Japan; Intramural Research Fund, National Cerebral and Cardiovascular Center; and Ministry of Education, Science, and Culture of Japan.

SOURCE

http://www.medscape.com/viewarticle/819392?nlid=45683_2562&src=wnl_edit_medp_card&uac=93761AJ&spon=2

Other related articles published in this Open Access Online Scientific Journal, include the following:

Increased Consumption of Dietary Fiber is associated with a significantly Lower Risk of CVD and CHD
Aviva Lev-Ari, PhD, RN
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2014 Winter in New England: The Effect of Record Cold Temperatures on Cardiovascular Diseases

Curator: Aviva Lev-Ari, PhD, RN

Int J Circumpolar Health. 2002 Nov;61(4):373-80.

Cold and the risk of cardiovascular diseases. A review – Global perspective

Näyhä S.

The higher occurrence of cardiovascular diseases in winter is well known, and several explanatory mechanisms have been suggested based on
  • increased blood pressure,
  • haematological changes and
  • respiratory infections.

Most investigations have used ecological data such as daily temperatures recorded at weather stations and mortality in the general population. Cause-specific mortality is the outcome measure most commonly used. Local myocardial infarction community registers would offer an ideal database, but may suffer from inadequate statistical power. Hospital discharge records, linked with out-of-hospital deaths, provide a powerful tool for detecting even weak effects of temperature. The association of coronary heart disease and temperature is usually U-shaped, mortality being lowest within the range 15-20 degrees C and higher on both sides of this. The increase in mortality on the colder side is in the region of 1% per 1 degree C fall in temperature, but the increase on the warmer side may be very steep. The exact location of the minimum temperature and the magnitude of the effect can vary between countries. In Finland the winter excess mortality from coronary heart disease has been levelling off during recent decades, but it still represents approximately 6% of annual deaths due to this condition.

SOURCE

http://www.ncbi.nlm.nih.gov/pubmed/12546195

Cold Weather and Cardiovascular Disease – Heart.org Perspective

Updated:Dec 4,2013

Heart-shaped Winter Leaf in Ice

This winter season will bring cooler temperatures and ice and snow for some. It’s important to know how cold weather can affect your heart, especially if you have cardiovascular disease.  People who are outdoors in cold weather should avoid sudden exertion, like lifting a heavy shovel full of snow. Even walking through heavy, wet snow or snow drifts can strain a person’s heart.

How does cold weather affect the heart?
Many people aren’t conditioned to the physical stress of outdoor activities and don’t know the dangers of being outdoors in cold weather. Winter sports enthusiasts who don’t take certain precautions can suffer accidental hypothermia.

Hypothermia means the body temperature has fallen below 95 degrees Fahrenheit. It occurs when your body can’t produce enough energy to keep the internal body temperature warm enough. It can kill you. Heart failure causes most deaths in hypothermia. Symptoms include lack of coordination, mental confusion, slowed reactions, shivering and sleepiness.

Children, the elderly and those with heart disease are at special risk. As people age, their ability to maintain a normal internal body temperature often decreases. Because elderly people seem to be relatively insensitive to moderately cold conditions, they can suffer hypothermia without knowing they’re in danger.

People with coronary heart disease often suffer angina pectoris (chest pain or discomfort) when they’re in cold weather. Some studies suggest that harsh winter weather may increase a person’s risk of heart attack due to overexertion.

Besides cold temperatures, high winds, snow and rain also can steal body heat. Wind is especially dangerous, because it removes the layer of heated air from around your body.  At 30 degrees Fahrenheit in a 30-mile wind, the cooling effect is equal to 15 degrees Fahrenheit. Similarly, dampness causes the body to lose heat faster than it would at the same temperature in drier conditions.

To keep warm, wear layers of clothing. This traps air between layers, forming a protective insulation. Also, wear a hat or head scarf. Heat can be lost through your head. And ears are especially prone to frostbite. Keep your hands and feet warm, too, as they tend to lose heat rapidly.

Don’t drink alcoholic beverages before going outdoors or when outside. Alcohol gives an initial feeling of warmth, because blood vessels in the skin expand. Heat is then drawn away from the body’s vital organs.

Learn more:

SOURCE

Patient and Public Education on Cardiovascular Hazards of Winter from Beth Israel Deaconess Medical Center (BIDMC) in Boston

The chill. Can it kill?

Baby, it’s cold outside. If you’re a New Englander, you can handle what Mother Nature throws your way – but did you know that winter poses a wide range of risks to your heart and blood vessels?

Shoveling snow can trigger heart attacks and other cardiac conditions. Staying out in the cold too long without protection can cause life-threatening hypothermia. Winter’s frigid temperatures can narrow blood vessels through a mechanism known as cold-induced spasm, bringing on vascular conditions such as Raynaud’s Phenomenon, chilblains, and skin ulcerations.

Brrr — it’s tempting to stay inside! But even that won’t necessarily protect you from the risks of the winter wallop. Exposure to viruses, whether indoors or out, can lead to flu which has been shown to be associated with heart attacks. Even the common cold can bring cardiovascular challenges, since widely used over-the-counter cold remedies can cause your blood pressure to soar. The cold season also coincides with the holidays and the stressors they bring.

Nanooks of the North should know the risks associated with the winter and how to recognize the signs of seasonal diseases and conditions when they occur. The good news is that by taking precautions, you can muffle yourself against many of these dangers. Most winter-related health problems can be prevented by taking common sense precautions.

The heart in winter

“We prefer to talk about the cold weather season, not just cold weather,” says Dr. Amjad AlMahameed, right, director of the Vascular Medicine Program of the CardioVascular Institute at Beth Israel Deaconess Medical Center. “Cold weather can lead to health issues, but there are other problems that might arise not from the cold itself but from our responses to the weather, such as when a sedentary person or a person with a heart condition goes out and shovels snow.”

Cardiovascular death rates are an average of 26 to 34 percent higher from January through March, according to a four-year study of 1.7 million death certificates in a variety of warm and cold U.S. locations. These included Massachusetts, Southern California, Texas, Arizona, Georgia, Washington and Pennsylvania. The causes of death were heart attack, heart failure, stroke and a general “cardiovascular disease” category.

Additional research revealed a 33 percent increase in coronary-related deaths during the months of December and January compared to the June-September period.  The study focused on coronary deaths in Los Angeles County during a 12-year time period. The authors concluded that, “Although cooler temperatures may play a role, other factors such as overindulgence or the stress of the holidays might also contribute to excess deaths during these peak times.”

“These studies and others leave little doubt that death rates due to cardiovascular and other diseases are higher in winter than in summer,” says AlMahameed. “The question is why. Research has not nailed this down yet, although it has identified potential culprits.”

Other studies have suggested that residents of areas with cold-weather winters do appear to face higher risks.  Researchers in Switzerland found that heart-attack risk factors — such as high blood pressure, cholesterol levels and extra weight in the midsection — appear to increase during winter months, especially in January and February.  A second study discovered a direct connection between chillier temperatures and increased heart attack risk, finding that the chance of a heart attack rose by 7 percent for every 10 degree Celsius drop in temperature.

“Whether cold temperatures are the key factor in cardiovascular deaths, or just one factor among many,” AlMahameed said, “they pose risks that should be taken seriously.”

Beware the snow shovel

Perhaps the most notorious cold-weather cardiovascular risk is heart attack after shoveling snow. Research has shown that heavy activity increases the likelihood of a heart attack – sometimes called “snow-shoveler’s infarction” by researchers – shortly after the intense exertion. This is especially true for people with known existing cardiovascular disease and those with cardiovascular risk factors such as high blood pressure, high cholesterol or a sedentary life style who may have as yet undiagnosed (so-called subclinical) cardiovascular disease.

Some researchers have suggested a link between deaths related to shoveling snow – often a morning task – and a well-documented pattern of more heart attacks and sudden cardiac deaths taking place in the morning.

The dangers of snow-shoveling go beyond heart attacks. One study in the aftermath of a series of snowstorms in New Jersey in 1996 profiled 19 patients who arrived at the hospital with acute chest pains, breathlessness or both. Of these, nine had heart attacks, six had unstable angina (chest discomfort caused by poor blood flow in the heart), two had aortic dissection (a tear in the body’s largest artery) and two experienced ventricular fibrillation a severely abnormal heart rhythm) that killed them.

Thirteen of the cardiac events were precipitated by the rupture of coronary plaque due to a surge in blood pressure and other factors. A huge study of US veterans has shown that blood pressures tend to be higher in the winter months, anyway. The sudden exertion of shoveling snow may cause blood pressure to spike, resulting in heart attack and stroke.

People who are outdoors in cold weather should avoid sudden exertion, like lifting heavy shovels full of snow. Even walking through heavy snow can strain the heart, according to the American Heart Association. Those with coronary artery disease may suffer chest pains (such as angina) simply by being out in cold weather.

“For people with known heart disease, those who have had heart attacks, stents or bypass surgery, cold weather makes the heart do extra work to generate the same amount of heat the body needs to function,” says AlMahameed. “It is like undergoing a stress test. They can suffer angina pains that can lead to a heart attack.”

Avoid the risks of snow shoveling:

  • If you have a heart condition or have been sedentary for a long time, do not shovel snow. Consider using a snow blower or having someone help you.
  • If you do shovel, use a small shovel so the load isn’t too heavy, work slowly and take frequent breaks.
  • Don’t eat a heavy meal or drink alcoholic beverages before or immediately after shoveling.
  • Be aware of the heart attack warning signs, including discomfort in the chest or other parts of the upper body, shortness of breath and nausea.

If you suspect you or someone else is having a heart attack, immediately call 911.

Fight flu and colds (with care)

hands clutching heart-shaped pillowFlu is caused by viruses, not cold weather. However, there is a higher incidence of heart attack during flu season, which typically starts in October and runs until mid-March. The holidays are an especially great time for getting sick, since people come together in crowds to share good cheer, food and germs.

This may be due to the inflammatory process — a complex immune response — that the flu can bring to the body, says AlMahameed. Having the flu can cause the heart to work harder to pump blood to the lungs. Inflammation may also cause plaques to rupture, blocking blood vessels and causing a heart attack. Plaques are deposits of a fatty, sticky substance found in the blood that may build up on artery walls.

That’s why it is so important to get an annual flu shot, AlMahameed says. This is especially true for people who already have cardiovascular disease or are getting older.

While it’s advisable to be inoculated in September since the vaccine kicks in after two weeks, a flu shot at any time during the season will help keep you healthy. The good news is that getting a flu vaccine may protect you from more than just the flu. A recent study conducted in Australia found that a flu vaccination can reduce the risk of a heart attack by 45 percent. It is particularly important for those with a history of heart disease to get a flu shot.

Colds, too, are caused by viruses and not cold temperatures. The issue here is that many over-the-counter cold medications can cause blood pressure to rise, whether you already have hypertension or not. This can be dangerous because high blood pressure is one of the risk factors for heart attack and stroke. Anyone with blood pressure greater than 120/80 should read the small print on medications carefully and monitor his or her blood pressure response to the over the counter cold medication.

“Decongestants can interfere with blood pressure medications,” AlMahameed says. “In addition, some over-the-counter cold medications are high in sodium, which can also raise blood pressure. If blood pressure is an issue, consult with your doctor or a pharmacist before using cold medicines.”

Avoid the risks of flus and colds:

  • Get a flu shot
  • If you get the flu, see your doctor right away as an oral antiviral treatment may help reduce the duration of your illness
  • Wash your hands frequently, especially before eating and after using the bathroom
  • Avoid large crowds during the flu season

If you have high blood pressure, be aware of the decongestants and sodium in cold medications. More information

Keep warm

People who spend a lot of time outdoors in the extreme cold can suffer from hypothermia, in which the core body temperature falls below 95 degrees Fahrenheit. This can cause complete heart failure, organ damage, brain damage and even death.

“Hypothermia can sneak up on you,” says AlMahameed, “especially where the elderly and children are concerned. They can get it and not notice it. They don’t even have to be outside. They can get hypothermia in a poorly heated apartment.”

In hypothermia, the balance between the body’s heat production and heat loss – thermoregulation — edges toward heat loss for a prolonged period of time. This can happen accidentally if a person is out in cold weather for an extended period without enough warm, dry clothing. Rain, snow and especially wind contribute to even riskier situations.

People who are experienced being outside in cold weather for long periods, such as mountain climbers, don’t typically get hypothermia because they wear specialized gear designed for the conditions. Alcohol consumption is often implicated in hypothermia, because it increases the flow of blood toward the extremities while making the person feel warmer.

“What happens is the overall blood flow to vital organs is compromised,” he says. “The brain could potentially shut down. It can lead to mental confusion, damage to the nervous system, falls and sleepiness. If you fall asleep because you are hypothermic, you can freeze to death.”

Those most at risk for hypothermia, according to information from the American Heart Association, include the elderly, children, the mentally ill, people who already have heart disease, those who are out in the cold while intoxicated and anyone who is outside in frigid weather for prolonged periods of time. Many elderly people do not feel the cold and can therefore experience hypothermia without being aware of a problem.

Signs of mild-to-moderate hypothermia include shivering, mental confusion, stumbling and blue lips. Extreme hypothermia can trigger amnesia, faltering heart rate and other physiological signs and bizarre behavior, including “paradoxical undressing,” in which the person feels warm despite the heat loss and throws off his or her clothes.

Avoid the risk of hypothermia:

  • Stay indoors in frigid weather.
  • Keep warm by layering clothing. The layers trap warm air, providing protective insulation.
  • Wear a hat to prevent heat from escaping through the head.
  • Do not drink alcohol outdoors or before going outdoors in very cold weather.

Raynaud’s Phenomenon

Raynaud’s Phenomenon is a vascular condition in which blood flow is sharply reduced in response to cold or emotional stress. People who live in colder climates are more likely to get it, as well as women, people over 30 and those with a family history.

“Cold leads to the narrowing of blood vessels, particularly the small ones in the hands, toes, face nose and ears,” says AlMahameed. “When they are narrowed, the body wants to shunt blood away from the skin to the internal organs so they can continue their vital functions. Therefore, your skin loses heat. The skin of the affected area, typically the fingers or toes, turns colors to reflect the extent of blood flow. First it becomes pale or whitish, then blue, and eventually pinkish discoloration is seen. Raynaud’s Phenomenon can be very painful.”

Raynaud’s afflicts an estimated 5 percent of the population, according to the Vascular Disease Foundation. Sufferers are unusually sensitive to cold or stress. Even reaching into the refrigerator to grab a cold drink can set it off. The hands are the body part most commonly affected.

The episodes — reversible blood vessel spasms — are usually brief and come and go. They leave no lasting harm in most cases. A rarer form, called Secondary Raynaud’s Phenomenon, can result in ulcers and tissue death (gangrene) and is linked to connective tissue disease. It can be treated with a variety of medications such as calcium channel blockers. Researchers are studying techniques to better diagnose and understand Raynaud’s and are evaluating new treatments to improve blood flow for those who suffer from the condition.

The cause of Raynaud’s is unknown. However, those who already have it can lessen its effects:

  • Avoid exposure to cold, stress and certain medications
  • Wear warm clothing when outdoors in winter weather with special attention to hands and feet
  • Always wear shoes
  • When an attack occurs, resort to a warm environment, and soak your hands in warm water
  • If you have Secondary Raynaud’s, seek treatment for the underlying disease

Chilblains

Chilblains (also known as pernio) is another vascular condition that is characterized by painful swelling in the small blood vessels of the toes, fingers, nose and ears. Typically symptoms appear after exposure to damp, cold weather to a heated environment. Chilblains may result in blue or purplish discoloration of the fingers and toes, accompanied by burning pain, itching, red patches, swelling and/or blisters and ulcers.

“As in Raynaud’s Phenomenon, spasms occur in the tiny blood vessels of the skin , but they last longer and are not as readily reversible,” says AlMahameed.

The condition may affect people who are shoveling snow without gloves or who get icy water in their boots. Also at risk are elderly persons living in damp residences, especially in basements, and outdoor workers who wear inadequate foot and hand gear. Symptoms can persist for days or weeks. In some cases, however, chilblains can result in long lasting sores or ulcers that can become infected and even lead to significant tissue loss, AlMahameed says.

Sometimes, symptoms appear a day after the exposure. In the future, people who have suffered chilblains must be very careful to protect themselves when they go out in cold damp weather by wearing gloves and layers of clothing. They also may need to avoid damp places for a while after suffering the condition.

“Medications called vasodilators are sometimes given to dilate the blood vessels,” says AlMahameed. “Studies suggest they work quite well to reduce pain, facilitate healing and prevent recurrences as long as the affected individuals abide by the above recommendations and stay warm and dry.”

If you are susceptible to chilblains:

  • Avoid exposure to cold
  • Dress warmly when outdoors
  • When you have been exposed to extreme cold, warm up gradually
  • Do not smoke
  • Improve circulation through exercise

Let it snow …

While it’s true that we can’t control the weather, we can control our response to it. Be cautious in extremely cold weather, especially during unusual exertions like snow shoveling. Boost your overall health with a healthy diet, regular exercise and an annual flu shot. Then, when the weather outside is frightful, let it snow, let it snow, let it snow!

– See more at: http://www.bidmc.org/Centers-and-Departments/Departments/Medicine/Divisions/Cardiovascular-Medicine/Programs-and-Services/Vascular-Medicine/Cardiovascular-Hazards-of-Winter.aspx#sthash.IzKTBgXD.dpuf

SOURCE

http://www.bidmc.org/Centers-and-Departments/Departments/Medicine/Divisions/Cardiovascular-Medicine/Programs-and-Services/Vascular-Medicine/Cardiovascular-Hazards-of-Winter.aspx

MODERATING EFFECTS OF THE CLIMATIC ENVIRONMENT

[Reproduced from Rushall, B. S., & Pyke, F. S. (1990). Training for sports and fitness (pp. 126-135). Melbourne, Australia: Macmillan Educational.]

The Olympic Games have drawn attention to a number of environmental influences on sports performance. During the time of the Summer Olympics it is usually hot and/or humid. On the other hand, the Winter Olympics invariably call for protection against the cold. The 1968 Mexico City Games, sited at 2,350 meters above sea-level, presented the situation of lowered barometric pressure and reduced air density. World records were set in the men’s 100, 200, and 400 meter races and the long jump. Distance races were appreciably slower than in previous Games. In Los Angeles in 1984, concern was expressed for athletes possibly experiencing high levels of both heat and air pollution. While some athletes certainly suffered as a result of the climate, British middle-distance runner, Steve Ovett, and Swiss woman marathoner, Gabriela Anderson-Schiess, being the most obvious examples, the weather in Los Angeles during the Games was generally comfortable.

It is the purpose of this section to describe the physiological responses to a number of environmental conditions and to offer considerations that could be given during the performance of sporting activities.

Heat

During exercise the body produces a great deal of heat. In extreme circumstances this can elevate its core temperature from 37° C to beyond 40° C. When the surrounding air is cool heat can be lost from the body by the process of radiation (transfer of heat by electromagnetic waves), convection (by air movement), conduction (by contact), and evaporation (by sweating). As the surrounding temperature increases it becomes more and more difficult to lose heat by radiation, convection, and conduction. Hence, the predominant source of heat loss in warm to hot conditions is from the evaporation of sweat on the skin surface.

Sweat losses exceeding 6 liters have been recorded in marathon runners. These deficits constitute a body weight reduction of 8-10 percent and a body water loss of 13-14 percent (Costill, 1979). Team-game players performing in warm to hot conditions can sweat at a rate of 2 liters per hour. During a game this can amount to a loss in body weight of 5 percent and a reduction in body water of more than 10 percent (Pyke & Hahn, 1981). Losses in body weight of 2 percent have been shown to result in reductions in endurance performance as well as increase heart rate by 5 bpm.

The requirement for copious sweating places a heavy load on the circulation to provide blood flow to both the muscles to maintain work rate and to the skin for cooling. As the body progressively dehydrates the circulation is further compromised and heat storage exceeds heat removal. The resultant strain is indicated by increased heart rate, sweat rate, and core and skin temperatures. Collapse can occur if work is continued.

There are a number of factors that must be considered before individuals are exposed to work in hot conditions.

The Climate

Other than air temperature, both humidity and radiant heat should be assessed before athletes engage in hard training or competition in hot weather conditions. The most commonly used heat index in sport is the WBGT index which includes measurements of air temperature (dry bulb), humidity (wet bulb), and radiant temperature. These temperatures can be easily measured with a whirling hygrometer and a black bulb thermometer placed in a black sphere.

When this climatic index exceeds 25° C and the work rate is reasonably high, coaches should be aware of the potential negative effects on athletes. When it exceeds 28° C the coach should abandon vigorous activities for poorly conditioned and unacclimatized individuals and be wary of signs of heat intolerance in others. In hotter months, training should be scheduled in the early morning or evening rather than at noon or mid-afternoon.

The impact that a hot, humid climate has on the physiological responses of a runner was well exemplified during performances in Darwin, Australia. Throughout a 30-minute run in cool conditions at a speed of 230 meters per minute, a man increased his rectal temperature from 37.7 to 39.3° C and incurred a weight loss of 750 grams. This contrasted with an increase in rectal temperature from 37.2 to 40.6° C, accompanied by a weight loss of 1,000 grams, when the run was repeated in the hot, humid conditions of Darwin. The skin temperature rose to nearly 38° C in the heat whereas in the cool it fell to 31° C. The reduced temperature gradient between the body core and skin experienced in the hot conditions meant that a large blood flow was required to transport heat from the core of the body to the periphery. This resulted in heart rates measured during the last 15 minutes of the run in the heat (190-200 bpm) being much higher than those measured in the cool (152-154 bpm). Hot, humid climates reduce endurance capacity in long-duration events.

Characteristics of the Individual

There are certain individuals who have a low tolerance to heat and need careful supervision by coaches. Those with heavier builds possess a lower ratio between skin surface area and body mass than those with more linear builds. This is a disadvantage for heat removal. High levels of body fat also encourage heat storage. Fat tissue has a lower specific heat than lean tissue and therefore, absorbs heat more readily. Individuals with a high level of endurance fitness tolerate hot conditions much better than those who are unfit. The average male has a higher level of endurance fitness than the average female and endurance fitness decreases substantially with age. This explains why males usually are more heat tolerant than females and younger adults more heat tolerant than older ones. However, when males and females and older and younger adults of equivalent levels of aerobic fitness are compared, these differences in heat tolerance disappear. One group that requires special attention in the heat is pre-pubertal children. They have poorly developed sweating mechanisms and overheat rapidly. Coaches should monitor them carefully for signs of heat intolerance during practice sessions. Risks should not be taken with them in hot, humid conditions.

Heat Acclimatization

It has been shown that physical training in cool conditions improves tolerance to hot conditions. However, full adaptation to heat can only be achieved by actually working in hot conditions. The adjustment is very rapid and is achievable in about 7 to 10 days if regular daily exercise for 90 minutes is undertaken. Heat acclimatization expands the blood volume, which supports an increased capacity and precision of sweating. At a given relative workload a fit, acclimatized person commences sweating sooner, sweats more evenly over the skin surface and thereby loses less salt. An acclimatized person performs in a heat tolerance test with greater circulatory stability (lower heart rate) and lower core and skin temperatures than someone who is not acclimatized. However, the acclimatization process is retarded by dehydration. For optimal adaptation to occur, fluid balance should be maintained during the recovery periods between daily bouts of work in the heat.

It might also be noted that pre-pubertal children acclimatize more slowly than do adults. Elevations in the sweating response take longer in children despite their perceiving that they are adjusting. This makes it particularly hazardous to rely on the subjective response of children as to their reaction to hot conditions. Recovery breaks for cooling and fluid replacement should be regularly scheduled to counteract young athletes’ inabilities to accurately discern fluid replacement needs.

The procedure of adding extra layers of clothing (tracksuit, windcheater, and head covering) while training during the winter months has been tested as a means of promoting heat acclimatization. Despite producing elevated thermoregulatory responses during each training session, the practice has been only partially successful in improving heat tolerance of well-conditioned team-game players (i.e., field hockey). If this procedure is used, particular care needs to be taken to ensure that players do not overheat during training, since heat will produce levels of fatigue that substantially erode the capacity to perform substantial volumes of skill trials (Dawson & Pyke, 1988).

Clothing

During exercise in hot conditions, it is recommended that participants wear light-colored clothing made from open-weave natural fibers (e.g., cotton, wool). As much of the skin as possible should be exposed to the air to maximize the evaporation of sweat. Clothing made from synthetic fibers, such as nylon and polyesters, offers more resistance to heat removal and, in time, becomes uncomfortable.

Fluid Replacement

When fluid losses exceed 2 percent of body weight prior to exercising, significant endurance performance deterioration occurs. It is wise to drink (hydrate) before exercising so that no dehydration occurs. However, during some high energy sporting contests, despite experiencing sweat losses of 4-6 kg, it is neither necessary nor advisable to attempt to entirely replace the amount of fluid lost. The body actually produces water during exercise. Most athletes only drink enough fluid to recover between 40 and 50 percent of the sweat lost. Partial fluid replacement has been shown to reduce the risk of overheating. During a series of 2-hour runs, marathoners who ingested 100mL of fluid every 5 minutes for the first 100 minutes maintained a lower rectal temperature than those who abstained. This occurred despite only absorbing 1,660 ml of fluid while losing 4,000 ml of sweat during the run (Costill, Kammer, & Fisher, 1970). The sensation of thirst lags behind the state of negative water balance, and should not be used as the signal to drink. Drink breaks must be regularly scheduled and made compulsory during training and competitions.

Since the body loses more water than electrolytes during exercise, the body fluids become concentrated. Hence there is a greater need to replace water than electrolytes during periods of heavy sweating. The answers to questions concerning the frequency, quantity, and qualities of replacement fluids depend, to some extent, on the individual concerned, the intensity of effort, and the environmental conditions. The major concern is to replace water. Flavored drinks, commercial preparations, and other solutions are not necessarily the best forms of fluid replacement.

On hot days, fluid should be consumed before, during, and after training. This maintains the stability of circulation that is so important for endurance efforts. Water is the primary requirement and, in most circumstances, is the ideal replacement fluid. Fluids with high sugar and electrolyte concentrations empty slowly from the stomach for absorption into the blood via the small intestine. That slow emptying will actually delay the replacement of needed water. It is only when excessive sweat losses occur on successive days that small amounts of salt and sugar may be necessary in a replacement fluid. On cooler days, when fluid losses are less, a higher concentration of carbohydrate in the fluid assists in maintaining the blood glucose level. Whether the amount of carbohydrate ingested is large or small is not a critical factor in `feeding’ during events or training. It has been shown that more frequent feeds maintain more stable blood glucose levels. Therefore, if carbohydrate supplementation occurs during exercise, the frequency of feeding should be considered to be of the utmost importance.

In sports such as wrestling, body-building, weight-lifting, and rowing, where weight limits have to be achieved to perform in competition categories, the loss of weight at the right time is important. Such weight loss is best achieved through gradual dietary accomplishments. Attempts to `crash diet’ a short time before a contest can have debilitating effects on athletes by causing disruptions to internal well-being, feelings of distress, and reduced performance states through anti-carboloading. The even more harmful procedure of trying to lose `water weight’ through taking diuretics or dehydrating should also be avoided. The maximum safe value to lose, as has been pointed out above, is 2 percent of body weight. Values that exceed that will reduce the efficiency of the body’s physiology, cause the circulatory system to work harder for a stated amount of work, and will reduce endurance performance. More often than not, unsound weight loss programs cause performances to decrease. Their value and benefit to the athlete should be seriously questioned.

The following are sensible fluid replacement guidelines for exercise:

  1. The temperature of the fluid should be cool (8-10° C).
  2. The fluid should be low in or lack sugar (carbohydrate) to enhance absorption of the water. The highest concentration of sugar should be 2-5 g per 100 ml of water.
  3. During exercise, the volume taken should be no more than 0.5 liters per hour in doses of 100-200 ml every 15 minutes.
  4. At least 0.5 liters of water should be consumed prior to exercise.
  5. The loss of electrolytes in most activities is minimal in sweat and can be adequately replaced in the diet after exercise. The need for replacement during exercise is generally non-existent.
  6. Keeping a record of body weight after waking in the morning is an easy method of monitoring hydration.
  7. Forced regular fluid intakes are required. Do not rely on the feeling of thirst to determine when ingestion should occur.

Cold

In cold climates the athlete continually tries to prevent heat loss and a fall in the core body temperature. A cooled state is referred to as `hypothermia’ or `exposure’. In a fatigued person its symptoms are poor control of movement, disorientation, and poor judgment and reasoning. The two ways to cope with this problem are to produce more heat or reduce the amount being lost.

Increased Heat Production

Extra heat can be produced either by shivering or by exercising. Shivering raises the resting metabolism about fourfold but in the process interferes with the expression of skill. Nadel, Holmer, Bergh, Astrand, and Stolzijk (1974) studied breaststroke swimming in water temperatures of 18, 26, and 33° C and attributed the extra oxygen cost of performing in the cold water to the shivering response. Depending on the endurance fitness level of the individual, metabolism can be elevated twelve- or fifteenfold during intensive exercise. Fitness is necessary to maintain a high work rate and heat production during endurance sports. If a marathoner slows down towards the end of an event held on a cold day it is possible that heat loss will exceed heat production and that hyperthermic problems will arise. This is a particular threat in endurance winter sports (e.g., biathlon, cross-country skiing). Fatigue is the nemesis of the endurance athlete competing in cold conditions.

Decreased Heat Loss

There are several physical avenues for heat loss which must be considered if an athlete is to remain warm.

Radiation is the physical action whereby heat is radiated from the body to nearby cooler objects. Curling the body into a tuck and reducing the exposed surface area can minimize heat lost. Such a response is common when resting in cold conditions. Limiting the blood flow through the skin also can reduce heat loss by radiation. This is the first line of defense against cold and is managed by reflex constriction of the blood vessels supplying the skin. This mechanism is capable of improving the insulative capacity of the skin sixfold. Cooling the skin in this way reduces the temperature gradient between it and the environment and effectively reduces heat loss. However, this means of heat conservation results in the fingers and toes, with their large surface area to mass ratio, becoming particularly cold and losing their speed and dexterity. This is a problem in target and touch sports such as fishing, shooting, and golf. In extreme conditions, frostbite injuries can be sustained. Acclimatization to cold conditions promotes some improvements in local blood flow and enhances the capabilities of the extremities to perform with skill and precision.

The shutdown of blood flow to the skin of the head is much less than that in the hands and feet. If the head is exposed to the cold, substantial heat loss can occur. This has resulted in strong recommendations to wear headgear during sports played in the cold and to wear life jackets to prevent immersion of the head during aquatic rescues.

Another means of conserving heat by reducing radiation is to increase the insulative properties of the shell of the body by depositing fat under the skin. This has been observed in successful Channel swimmers (Pugh & Edholm, 1955).

Thin pre-pubertal children with a high surface area:mass ratio are particularly susceptible to cooling while swimming in cold water. Central body temperatures below 35° C have been commonly observed in children after swimming in 20° C water temperatures (Keatinge & Sloan, 1972). This is of some concern to swimming coaches who rely on the child’s perception of cold to provide necessary protection. A lean and ambitious young athlete could easily become hypothermic while training enthusiastically in cool conditions (particularly when swimming) and should be watched carefully.

Convection occurs when heat is transferred from the body to free air. As cold air comes into contact with the body it is warmed, becomes less dense through expansion, and rises. The role of clothing is to trap warmed air close to the skin and develop a microclimate that is comfortable and heat retaining. Forced air convection occurs when the body is either fanned by or creates its own breeze in the process of movement. In external circumstances the `wind chill factor’ is such that a temperature of -1° C in still air effectively becomes -18° C if a 40 km/h wind is blowing or if a skier or cyclist is moving at that speed. Windproof overgarments should be worn to avoid excessive heat loss in such conditions.

Conduction is the means by which heat is lost by direct contact with other surfaces that are cooler than the skin. Handling of ice axes, metal pitons, and ski poles with bare hands should be avoided since the temperature gradient between those pieces of equipment and the skin is usually very severe. Gloves and insulated boots are used to reduce the amount of conducted heat loss. The conductivity of water is 25 times greater than that of air. Much more heat is lost in water than in air at the same temperature. In one sense, the increased conductivity of water allows swimmers to perform greater volumes of work than runners since they are not inhibited by the build-up of heat.

Evaporation is the means by which heat is lost through sweating. Becoming inactive immediately after heavy sweating can invite rapid cooling and a dramatic fall in body temperature. This can occur on the bench after an intensive period of play in a team game or perhaps as a result of an enforced rest during an endurance event. It is important to have warm, dry clothing available to arrest the decrease in body temperature in such situations. The hiker or skier should try to avoid the situation arising where layers of clothing close to the skin become saturated with sweat. This destroys the insulatory value of the clothing and accelerates heat removal. Rain has the same effect. Clothing should be suited to the energy requirements of the sport, remembering that less insulation is needed as heat production increases. A doubling of the work rate from 3 to 6 Mets performed in 5° C air temperatures requires only one-third of the original insulation (Burton & Edholm, 1969). This is why it is appropriate to have layers of clothing in vigorous winter sports. The appropriate number of layers can be removed to maintain the proper level of heat loss while maintaining dry clothing. Clothing which permits insulation to be added or subtracted in accordance with the intensity of exercise is the most useful. Jackets that open down the front are more convenient than pullovers. Hoods that can be drawn back are ideal during intermittent activity. Drawstrings that allow clothes to be tightened or loosened at the collar, waist, and arm and leg cuffs conveniently vary the insulative value of garments.

It is important not to overprotect the hands and feet against the cold as the body will perceive itself to be very warm and not invoke the physiological temperature regulation processes that prevent a fall in core body temperature. It is better to insulate the trunk rather than the extremities. Three units for the torso, two units for the limbs, and one unit for the hands and feet has been recommended by Kaufman (1982) as the appropriate proportions of clothing distribution.

Should an athlete not follow these recommendations and develop hypothermia during a sporting contest it is critical to immediately start the rewarming process. After providing shelter, wet clothes should be removed and replaced with dry, warm ones. The individual should be warmed gradually under blankets or in a sleeping bag, administered warm, sugared drinks and kept awake until normal body temperature has been restored.

References

  1. Burton, A. C., & Edholm, O. G. (1969). Man in a Cold Environment. New York, NY: Hafner.
  2. Costill, D. L. (1979). A Scientific Approach to Distance Running. Los Altos, CA: Track and Field News.
  3. Costill, D. L., Kammer, W. F., & Fisher, A. (1970). Fluid ingestion during distance running. Archives of Environmental Health, 21, 520-525.
  4. Dawson, B., & Pyke, F. S. (1988). I: Responses to wearing sweat clothing during exercise in cool conditions. II: Training in sweat clothing in cool conditions to improve heat tolerance. Journal of Human Movement Studies, 15, 171-183.
  5. Kaufman, W. C. (1982). Cold weather comfort or heat conservation. The Physician and Sportsmedicine, 10, 70-75.
  6. Keatinge, W. R., & Sloan, R. E. (1972). Effect of swimming in cold water on body temperatures in children. Journal of Physiology, 226, 55-56.
  7. Nadel, E. R., Holmer, I., Bergh, U., Astrand, P-O., & Stolzijk, J. A. (1974). Energy exchanges of swimming man. Journal of Applied Physiology, 36, 465-471.
  8. Pyke, F. S., & Hahn, A. G. (1981). Body temperature regulation in summer football. Sports Coach, 4 (3), 41-3.
  9. Pugh, L. G., & Edholm, O. G. (1955). The physiology of channel swimmers. Lancet, 2, 761-768.

SOURCE

http://coachsci.sdsu.edu/csa/vol36/rushall1.htm

Daily Sugar Intake: Diet Soft Drinks – Weight Gain and Diabetes

Reporter: Aviva Lev-Ari, PhD, RN

Diet soda is no healthier than regular soda: report

A recent study from Purdue University said that, even though they lack the high calorie and sugar content of regular soda, diet soft drinks can still contribute to weight gain and diabetes.

THE ASSOCIATED PRESS

FRIDAY, JULY 12, 2013, 12:44 PM
Instead of asking whether regular or diet soft drinks are healthier, people should question their daily sugar intake, a Purdue University professor said.

DARRON CUMMINGS/ASSOCIATED PRESS

Instead of asking whether regular or diet soft drinks are healthier, people should question their daily sugar intake, a Purdue University professor said.

WEST LAFAYETTE, Ind. — Walking back to work after a trip to Chauncey Hill for fountain soft drinks, the two women had their health in mind.

Suzanne Payne had a regular soft drink, but knew it was a rare, sugary treat that she probably wouldn’t finish. Susan Corwin chose a diet, caffeine-free drink.

Which soft drink — regular or diet — is the healthier choice?

That’s the wrong question to ask, said Susie Swithers, a professor of psychological sciences and a behavioral neuroscientist at Purdue University. She said the real question is: What is our daily sugar intake?

“It’s about the overall sweetening of our diets,” she told the Journal & Courier.

RELATED: DIET SODA AS BAD AS METH FOR YOUR TEETH: STUDY

A cultural shift has made having daily soft drinks acceptable, she said.

“It’s really candy in a can. If people think of it as candy, they would say that they wouldn’t have candy at every meal.”

The message has been that diet soda is healthier since it has artificial sweetener and no calories, but Swithers said tracking sugar intake means limiting real and artificial sugars.

She reviewed recent scientific studies about the long-term link between artificial sweeteners and health outcomes.

“Findings from a variety of studies show that routine consumption of diet sodas, even one per day, can be connected to higher likelihood of heart disease, stroke, diabetes, metabolic syndrome and high blood pressure, in addition to contributing to weight gain,” she said.

RELATED: EVEN ONE CAN OF SODA PER DAY RAISES RISK OF DIABETES: STUDY

“Although it seems like common sense that diet sodas would not be problematic, that doesn’t appear to be the case.”

Her findings were published Wednesday in “Trends in Endocrinology & Metabolism.”

The study triggered an immediate reaction from the American Beverage Association, the trade association for the non-alcoholic drinks industry.

In an emailed statement the organization called Swithers’ study “an opinion piece, not a scientific study.”

“Low-calorie sweeteners are some of the most studied and reviewed ingredients in the food supply today. They are safe and an effective tool in weight loss and weight management, according to decades of scientific research and regulatory agencies around the globe.”

RELATED: JUST ONE SODA A DAY UPS KIDNEY STONE RISK: STUDY

Swithers said there could be several causes for the link between negative health outcomes and artificial sweeteners.

When the body tastes something sweet, it reacts to prepare for calories and sugar intake, she said. But when that doesn’t happen — because the sweetener is artificial — the body reacts again, learning that sweet doesn’t mean calories.

Then, when a diet soda drinker eats something sugary, the body doesn’t react properly, Swithers said. She said that may be why people who drink a mix of diet and regular soda have the largest chance of negative health outcomes.

Another possibility is that people who drink diet soft drinks think they are being health conscious, so they splurge with a piece of cake — replacing the calories they just avoided, Swithers said. Or it may be a combination of factors, she said. She said some possibilities have been proven in animals but not humans.

Since there isn’t a large body of research to discourage artificial sweeteners, Patty Denton, a dietitian at IU Health Arnett, said she doesn’t discourage them. However, she said, sugars should be consumed in moderation. Even some flavored waters and energy drinks contain sugar. A can of regular soda can have 150 calories.

For Payne, a regular soft drink is a special treat. Corwin said caffeine-free and diet drinks have helped her cut down on calories.

“At the end of the day,” Denton said about gaining and losing weight, “it’s calories in and it’s calories out.”

SOURCE

http://www.nydailynews.com/life-style/health/diet-soda-healthier-regular-report-article-1.1397209

 

2014 Surgeon General’s Report: Smoking implicated in Diabetes, Liver Cancer, Colorectal Cancer and Chronic Diseases

Reporter: Aviva Lev-Ari, PhD, RN

Tobacco

Logo for 50th Anniversary of the first Surgeon General's Report on Smoking and Health: 1964-2014January 11, 2014 marked the 50th anniversary of the first Surgeon General’s Report on Smoking and Health. The 1964 landmark report, released by Surgeon General Dr. Luther Terry, was the first federal government report linking smoking and ill health, including lung cancer and heart disease. This scientifically rigorous report laid the foundation for tobacco control efforts in the United States.

In the last 50 years, 31 Surgeon General’s Reports have been released, increasing our understanding of the devastating health and financial burdens caused by tobacco use. We now know that smoking causes a host of cancers and other illnesses and is still the leading preventable cause of death in the United States, killing 443,000 people each year.

In 2014, we highlight half a century of progress in tobacco control and prevention, present new data on the health consequences of tobacco use, and introduce initiatives that can potentially end the tobacco use epidemic in the United States in the 32rd Surgeon General’s Report on smoking and health, The Health Consequences of Smoking—50 Years of Progress.

Get Involved

As part of the commemoration of the 50th Anniversary of the Surgeon General’s Report on Smoking and Health, the Office of the Surgeon General developed several resources to promote and share highlights from the last 50 years of tobacco control efforts. You can be a part of the effort to share information on the dangers of tobacco use. Find resources to help promote the anniversary.

The Office of the Surgeon will continue to highlight this historic anniversary throughout 2014. We also invite you to contact us at INFO2014SGR50@CDC.GOV if you want to share your plans for promoting this historic anniversary or have general questions. If you would like to receive updates related to the 2014 Surgeon Generals’ Report on Smoking and Health, send a message to the above address and put “subscribe” in the subject line

Reflecting on 50 Years of Progress

The landmark report released by the ninth Surgeon General, Dr. Luther Terry, laid the foundation for tobacco control efforts in the U.S. Through the efforts of tobacco control professionals, advocates and researchers the work has continued to move forward. Learn about the progress of tobacco control in the 50th Anniversary on Smoking and Health Video and Podcast Series, featuring interviews from key leaders in the fight against tobacco.

Past Reports

2010-present

2000-2009

1990-1999

1980-1989

1970-1979

1960-1969

SOURCE

http://www.surgeongeneral.gov/initiatives/tobacco/

The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General, 2014

Executive Summary

This Executive Summary provides an overview of the full report of the Surgeon General and highlights the conclusions and findings.

Premature deaths caused by smoking and exposure to secondhand smoke, 1965–2014

Cause of death Total
Smoking-related cancers 6,587,000
Cardiovascular and metabolic diseases 7,787,000
Pulmonary diseases 3,804,000
Conditions related to pregnancy and birth 108,000
Residential fires 86,000
Lung cancers caused by exposure to secondhand smoke 263,000
Coronary heart disease caused by exposure to secondhand smoke 2,194,000
Total 20,830,000

Source:Source: Centers for Disease Control and Prevention, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, unpublished data.

The Health Consequences of Smoking—50 Years of Progress: A Report of the Surgeon General

This is the 32nd tobacco-related Surgeon General’s report issued since 1964.  It highlights 50 years of progress in tobacco control and prevention, presents new data on the health consequences of smoking, and discusses opportunities that can potentially end the smoking epidemic in the United States. Scientific evidence contained in this report supports the following facts:

The century-long epidemic of cigarette smoking has caused an enormous, avoidable public health catastrophe in the United States. 

  • Since the first Surgeon General’s report on smoking and health was published 50 years ago, more than 20 million Americans have died because of smoking.
  • If current rates continue, 5.6 million Americans younger than 18 years of age who are alive today are projected to die prematurely from smoking-related disease.
  • Most of the 20 million smoking-related deaths since 1964 have been adults with a history of smoking; however, 2.5 million of those deaths have been among nonsmokers who died from diseases caused by exposure to secondhand smoke.
  • More than 100,000 babies have died in the last 50 years from Sudden Infant Death Syndrome, complications from prematurity, complications from low birth weight, and other pregnancy problems resulting from parental smoking.
  • The tobacco epidemic was initiated and has been sustained by the tobacco industry, which deliberately misled the public about the risks of smoking cigarettes.

Despite significant progress since the first Surgeon General’s report, issued 50 years ago, smoking remains the single largest cause of preventable disease and death in the United States.

  • Smoking rates among adults and teens are less than half what they were in 1964; however, 42 million American adults and about 3 million middle and high school students continue to smoke.
  • Nearly half a million Americans die prematurely from smoking each year.
  • More than 16 million Americans suffer from a disease caused by smoking.
  • On average, compared to people who have never smoked, smokers suffer more health problems and disability due to their smoking and ultimately lose more than a decade of life.
  • The estimated economic costs attributable to smok­ing and exposure to tobacco smoke continue to increase and now approach $300 billion annually, with direct medical costs of at least $130 billion and productivity losses of more than $150 billion a year.

The scientific evidence is incontrovertible: inhaling tobacco smoke, particularly from cigarettes, is deadly. Since the first Surgeon General’s Report in 1964, evidence has linked smoking to diseases of nearly all organs of the body.

  • In the United States, smoking causes 87 percent of lung cancer deaths, 32 percent of coronary heart disease deaths, and 79 percent of all cases of chronic obstructive pulmonary disease (COPD).
  • One out of three cancer deaths is caused by smoking.
  • This report concludes that smoking causes colorectal and liver cancer and increases the failure rate of treatment for all cancers.
  • The report also concludes that smoking causes diabetes mellitus, rheumatoid arthritis and immune system weakness, increased risk for tuberculosis disease and death, ectopic (tubal) pregnancy and impaired fertility, cleft lip and cleft palates in babies of women who smoke during early pregnancy, erectile dysfunction, and age-related macular degeneration.
  • Secondhand smoke exposure is now known to cause strokes in nonsmokers.
  • This report finds that in addition to causing multiple serious diseases, cigarette smoking diminishes overall health status, impairs immune function, and reduces quality of life.

Smokers today have a greater risk of developing lung cancer than did smokers in 1964.

  • Even though today’s smokers smoke fewer cigarettes than those 50 years ago, they are at higher risk of developing lung cancer.
  • Changes in the design and composition of cigarettes since the 1950s have increased the risk of adenocarcinoma of the lung, the most common type of lung cancer.
  • Evidence suggests that ventilated filters may have contributed to higher risks of lung cancer by enabling smokers to inhale more vigorously, thereby drawing carcinogens contained in cigarette smoke more deeply into lung tissue.
  • At least 70 of the chemicals in cigarette smoke are known carcinogens. Levels of some of these chemicals have increased as manufacturing processes have changed.

For the first time, women are as likely to die as men from many diseases caused by smoking.

  • Women’s disease risks from smoking have risen sharply over the last 50 years and are now equal to men’s for lung cancer, COPD, and cardiovascular diseases. The number of women dying from COPD now exceeds the number of men.
  • Evidence also suggests that women are more susceptible to develop severe COPD at younger ages.
  • Between 1959 and 2010, lung cancer risks for smokers rose dramatically. Among female smokers, risk increased 10-fold. Among male smokers, risk doubled.

Proven tobacco control strategies and programs, in combination with enhanced strategies to rapidly eliminate the use of cigarettes and other combustible, or burned, tobacco products, will help us achieve a society free of tobacco-related death and disease. 

  • The goal of ending tobacco-related death and disease requires additional action.
  • Evidence-based tobacco control interventions that are effective continue to be underused. What we know works to prevent smoking initiation and promote quitting includes hard-hitting media campaigns, tobacco excise taxes at sufficiently high rates to deter youth smoking and promote quitting, easy-to-access cessation treatment and promotion of cessation treatment in clinical settings, smoke-free policies, and comprehensive statewide tobacco control programs funded at CDC-recommended levels.
  • Death and disease from tobacco use in the United States is overwhelmingly caused by cigarettes and other burned tobacco products. Rapid elimination of their use will dramatically reduce this public health burden.
  • New “end-game” strategies have been proposed with the goal of eliminating tobacco smoking. Some of these strategies may prove useful for the United States, particularly reduction of the nicotine yield of tobacco products to non-addictive levels.

http://www.surgeongeneral.gov/library/reports/50-years-of-progress/fact-sheet.html

Full Report

This comprehensive report chronicles the devastating consequences of 50 years of tobacco use in the United States.

The above PDFs are currently undergoing remediation for compliance with Section 508. The anticipated completion date for the remediation is the end of February. In the interim, if you need accessibility assistance with any of the content on the below file, please call 240-276-8853.

Consumer Booklet

This easy-to-read, illustrated booklet summarizes the Surgeon General’s Report released in January, 2014. It is designed to give concerned adults information to help them make choices that will improve their own health and the health of their children, their families, and their communities.

Order Documents

To order 2014 Surgeon General’s Report documents, go to CDC’s Smoking & Tobacco Use Publications Catalog.  In the Publications Catalog, type in 2014 SGRin the search box, choose all of these words, and hit the search button.

Fact Sheets

Video and Podcast Series
Public Servide Announcement – 5.6 Milllion Children

A public service announcement (PSA) designed to educate adults about the long-term impact of tobacco use on this nation’s future – its youth. The PSA points out that 5.6 million children alive today will ultimately die early from smoking if we do not do more to reduce current smoking rates.

Learn more about the progress of tobacco control in the 50th Anniversary on Smoking and Health Video and Podcast Series, featuring interviews from key leaders in the fight against tobacco.

Partner Resources

Find resources to help you promote the 50th  Anniversary of the Surgeon General’s Report  on Smoking and Health.

SOURCE

http://www.surgeongeneral.gov/library/reports/50-years-of-progress/index.html

In the Press – The version sent by American Nursing Association to its Members, Registered Nurses in the US

The latest Surgeon General’s report links smoking to a myriad of diseases that include diabetes, liver cancer and colorectal cancer. In addition to deadly cancers, smoking is tied to scores of other chronic diseases in the new report.

http://www.usatoday.com/story/news/nation/2014/01/17/surgeon-general-report-smoking/4476323/

Source: Sources: surgeongeneral.gov; USA TODAY Research
Kevin A. Kepple, Denny Gainer and Liz Szabo, USA TODAY

More on the Performance of High Sensitivity Troponin T and with Amino Terminal Pro BNP in Diabetes

Writer and Curator: Larry H. Bernstein, MD, FCAP

 

UPDATED on 9/1/2019

Risk-Based Thresholds for hs-Troponin I Safely Speed MI Rule-Out

HISTORIC suggests benefit to patients, clinicians

PARIS — Using different cutoffs for high-sensitivity cardiac troponin I (hs-cTnI) testing based on risk accurately ruled out MI and sent patients home from the emergency department sooner without missing adverse cardiac events, the HISTORIC trial found.

In the stepped-wedge trial of over 30,000 consecutive patients, introduction of the risk-based approach reduced length of stay at the emergency department by over 3 hours compared with standard care (6.8 vs 10.1 hours, P<0.001), reported Nicholas Mills, MD, PhD, of the University of Edinburgh in Scotland.

And 74% of patients under the new pathway were discharged without requiring hospital admission versus 53% under standard protocols (adjusted risk ratio 1.57, 95% CI 1.34-1.83, P<0.001).

For the primary safety endpoint, 2.5% of patients in the standard group died from cardiac causes or had an MI at 12 months post-discharge versus 1.8% of those in the early rule-out group (adjusted OR 1.02, 95% CI 0.74-1.40).

“Adoption of this approach will have major benefit for both patients and healthcare providers,” said Mills during a late-breaking press briefing at the 2019 European Society of Cardiology (ESC) congress.

For example, many patients will need only a single troponin test under the algorithm to lead to a decision on admission, he noted, which could have “absolutely enormous” cost savings.

SOURCE

https://www.medpagetoday.com/meetingcoverage/esc/81926?xid=nl_mpt_ACC_Reporter_2019-09-01&eun=g5099207d2r

 

UPDATED on 8/7/2018

Siemens’ high-sensitivity Troponin I (TnIH) assays got FDA clearance for use in diagnosing acute myocardial infarction. (Cardiovascular Business) The first high-sensitivity Troponin T test was cleared last year, as MedPage Today reported.

SOURCE

https://www.medpagetoday.com/cardiology/prevention/74423?xid=nl_mpt_cardiobreak2018-08-06&eun=g99985d0r&utm_source=Sailthru&utm_medium=email&utm_campaign=Ca

 

This is the final up to date review of the status of hs troponin T (or I) with or without the combined use of the Brain Type Natriuretic Peptide or its Amino Terminal peptide precursor.  In addition, a new identification of the role of the Atrial Natriuretic Peptide has been reported with respect to arrythmogenic activity.  On the one hand, the diagnostic value of the NT-proBNP has been seen as disappointing, in part because of the question of what information is gained by the test in overt known congestive heart failure, and in part because of uncertainty about following the test during a short hospital stay.  At least, this is the view of this reviewer.  However, in the last several years there has been an emphasis on the value this test adds to prediction of adverse outcomes.   In addition, there has been a hidden nvariable that has much to do with the original reference values that were established for age ranges, without any consideration of pathophysiology that might affect the values within those ranges, leading one to consider values in an aging population as normal, that might well be high.  Why is this?  Aging patients are more likely to have hypertension, and also the onset of type-2 diabetes mellitus, with cardiovascular disease consequences.  Type-2 diabetes mellitus (T2DM), for instance, is associated with insulin resistance and also fat gain with generation of adipokines, but the is also a hyalinization of insulin forming beta-cells of the pancreas, and there is hyalinization of glomeruli (glomerulosclerosis) and afferent arteriolonephrosclerosis with expected decline in glomerular filtrattion rate and hypertension as well.   Of course, this is also associated with hepatosteatosis.   Nevertheless, a reference range is established that takes none of this pathophysiology into account.   While a more reasonable approach has been pointed out, there has been no followup in the literature.

On the other hand, there has been much confusion over the restandardization of a high sensitivity troponin I or T test (hs-Tn(I or T).  The reference range declines precipitously, and there is a good identification of patients who are for the most part disease free, but there is no delineation of patients who are at high risk of acute coronary syndrome with plaque rupture, vs a  host of other cardiovascular conditions.  These have no relationship to plaque rupture, but may be serious and require further evaluation.  The question then becomes whether to admit for a hospital stay, to refer to clinic after an evaluation in the ICU without admission, or to do an extensive evaluation in the emergency department overnight before release for followup.  There is still another dimension of this that has to do with prediction of outcomes using hs-Tn(s) with or without the natriuretic peptides.  Another matter that is not for discussion in this article is the underutilization of hs-CRP.  Originally used for a marker of sepsis in the 1970s, it has come to be tied in with identification of an ongoing inflammatory condition.  Therefore, the existence of a known inflammatory condition in the family of autoimmune diseases, with one exception, might make it unnecessary.

The discussion is broken into three parts:

Part 1.   New findings on the troponins.
Part 2.  The use of combined hs-Tn with a natriuretic peptide (NT-proBNP)
Part 3.  Atrial natriuretic peptide

Part 1.    New findings on the troponins.

Troponin: more lessons to learn

C Liebetrau,HM Nef,andCW.Hamm*
KerckhoffHeartandThoraxCenter;DepartmentofCardiology,BadNauheim,
Germany; (GermanCentreforCardiovascularResearch),partnersite
RheinMain,BadNauheim, Germany; and UniversityofGiessen,Medizinische
KlinikI,KardiologieundAngiologie,Giessen,Germany
European Hear tJournal
http://dx.doi.org/10.1093/eurheartj/eht357This editorial refers to ‘Risk stratification in patients with acute chest pain
using three high-sensitivity cardiac troponin assays’,
by P. Haafetal. http://dx.doi.org/10.1093/eurheartj/eht218Cardiac troponin entered our diagnostic armamentarium 20 years ago and –
unlike any other biomarker –

  • is going through constant expansion in its application.

Troponin started out as a marker of risk in unstable angina’, then was used

  • as gold standard for risk stratification and therapy guiding in acute coronary syndrome
  •  served further to redefine myocardial infarction, and
  • has also become a risk factor in apparently healthy subjects.

The recently introduced high-sensitivity cardiac troponin (hs-cTn) assays

  • have not only expanded the potential of troponins, but
  • have also resulted in a certain amount of confusion
    • among unprepared users.

After many years troponins were accepted as the gold standard in

  • patients with chest pain by
  • classifying them into troponin-positive and
    • troponin-negative patients.

The new generation of hs-cTn assays has

  • improved the accuracy at the lower limit of detection and
  • provided incremental diagnostic information especially
    • in the early phase of myocardial infarction.

Moreover, low levels of measurable troponins

  • unrelated to ACS have been associated with
    • an adverse long-term outcome.

Several studies demonstrated that

  • these low levels of cardiac troponin measureable 
    • only by hs-Tn assays
  • are able to predict mortality in patients with ACS
  • as well as patients with assumed
    • stable coronary artery disease.

Furthermore, hs-cTn has the potential

  • to play a role in the care of patients
    • undergoing non-cardiac surgery.

The additional determination of hs-cTn

  • improves risk stratification despite
  • established risk scores providing both diagnosis and
  • for prognosis prediction in chest pain patients.

The daily clinical challenge in using the highly sensitive assays is to 

  • interpret the troponin concentrations, especially
  • in patients with concomitant diseases
    • independently from myocardial ischaemia
  • influencing cardiac troponin concentrations
    (e.g. chronic kidney disease, or stroke). 

The troponin test lost its ‘pregnancy test’ quality with the different users.
Different opinions exist on

  • the change of hs-cTn levels compared to simple ‘positive–negative’ interpretation
  • and thereby makes diagnosis finding more complex than before.

This uncertainty probably has the paradigm that

  • serial measurements of troponins are necessary, and also
    • boosted the number of diagnoses of ACS and
    • invasive diagnostic procedures in some locations.

This is more than understandable, with acute chest pain using

  • three high-sensitivity cardiac troponins with their respective baseline value
    • before the diagnosis of acute myocardial infarction (AMI) can be made.

What is a relevant change in concentrations compatible with acute myocardial necrosis and

  • what is only biological variation for the specific biomarker and assay?

Changes in serial measurements between 20% and 200% have been debated, and
the discussion is ongoing. Furthermore, it has been proposed that

  • absolute changes in cardiac troponin concentrations 
    • have a higher diagnostic accuracy for AMI
  • compared with relative changes, and

it might be helpful in distinguishing AMI from other causes of cardiac troponin elevation.

Do we obtain any helpful directives from experts and guidelines for our daily practice?
Foreseeing this dilemma, the 2011 European Society of Cardiology (ESC) Guidelines

  • on non ST-elevation ACS acted.
  • Minor elevations of  troponins were accepted as hs-cTn values in the ‘grey zone’.

This was and still is the rule, but

  • the ESC provided a general algorithm on how to manage patients with limited data.

The ‘Study Group on Biomarkers in Cardiology’ suggested

  • a rise of 50% from the baseline value at low concentrations.

However, this group of experts could also not find a substitute for the missing data

  • needed to validate the proposed recommendation.

The story is just too complex:

  • different troponin assays with
  • different epitope targets,
  • different patient populations,
  • different sampling protocols,
  • different follow-up lengths, and much more.

Therefore, any study that helps us to see better through the fog is welcome here.

Haaf et al. have now presented the results of their study of

  • different hs-cTn assays
    (hs-cTnT, Roche Diagnostics; hs-cTnI, Beckman-Coulter; and  hs-cTnI, Siemens)

    • with respect to the -outcome of patients with acute chest pain.

The authors examine 1117 consecutive patients presenting with acute chest pain.
[340 patients with ACS (30.5%)] from the Advantageous Predictors of Acute Coronary Syndrome
Evaluation (APACE) study. Blood was collected

  • directly on admission and
  • serially thereafter at 2, 3, and 6h.

Eighty-two patients (7.3%) died during the 2-year follow-up. The main finding of the study is that

  1. hs-cTnT predicts mortality more accurately than the hs-cTnI assays, 
  2. -that a single measurement is sufficient
  3. challenges causes of cardiac troponin elevation.

These results of APACE remain in contrast to recent findings from a GUSTO IV cohortof 1335 patients with ACS (Table1).

Table1 Studies investigating high sensitivity troponins for long-term prognosis

Variable                                                       APACE (n 5 1117)              GUSTO IV (n 5 1335)              PEACE (n 5 3567)

………………………………………………………………………………………………………………………………………………………….

Patient cohort                                                   Unstable                            Unstable                               Stable

Blood sampling                                     On admission,1,2,3,6h                    48h after
study randomization           Before randomization

No. of patients with detection limit             883 (79.1%)                                 UKN                                      UKN

No. of patients with hs-cTnT.
99thpercentile                                        401 (35.9%)                              1015 (76%)                          395 (10.9%)

No. of patients with hs-cTnI (Abbott).
detection limit                                           UKN                                             UKN                              3567 (98.5%)

No.of patients with hs-cTnI (Abbott).
99th percentile                                          UKN                                         988(74%)                           105 (2.9%)

No. of patients with NSTEMI                     170 (15.2%)                              100 (100%)                             0 (0%)

Follow-up                                               24 months                                  12 months                            5.2 years

Non-fatal AMI                                           UKN                                              UKN                               209 (5.9%)

Mortality or primary endpoint                    82 (7.3%)                                 119(8.9%)                           203 (5.7%)

………………………………………………………………………………………………………………………………………………………….

Key findings                                    cTnT better than cTnI                      cTnI ¼cTnT                   cTnI better than cTnT

Single cTn sample sufficient

AMI, acute mycordial infaction; cTn, cardiac tropononin; NSTEMI ,non-ST-elevation myocardial infarction; UKN, unknown

NSTEMI defined in the GUSTO IV trial:
  1. one or more episodes of angina lasting ≥ 5min,
  2. within 24h of admission and
  3. either a positive cardiac TnT or I test
    (above the upper limit of a normal for the local assay; during the years 1999 and 2000)
  4. or ≥ 0.5 mm of transient or persistent ST-segment depression.

the prognostic capacity of four different sensitive cardiac troponin assays were compared

  1. hs-cTnT; Roche Diagnostics,
  2. cTnI and hs-cTnI;
  3. Abbott Diagnostics, and
  4. Acc-cTnI; Beckman-Coulter.

In total, 119 patients (8.9%) died during the 1-year follow-up. Looking at their

  • receiver operating characteristic curve (ROC) analyses,
  • there were only negligible diffferences
    • in the area under the curves between the assays.

Contrasting results have also been reported in patients(n 1/4 3.623)

  • with stable coronary artery disease and preserved systolic left ventricular function

from the PEACE trial (Table1).

During a median follow-up period of 5.2 years,

  • there were 203 (5.6%) cardiovascular deaths or
  • first hospitalization for heart failure.

Concentrations of hs-cTnI (Abbott Diagnostics) at or above

  • the limit of detection of the assay were measured in 3567 patients (98.5%), but
  • concentrations of hs-cTnI at or above the gender-specific 99th percentile
    • were found in only 105 patients (2.9%).

This study revealed that

  • there was a strong and graded association
  • between increasing quartiles of hs-cTnI concentrations and
  • the risk for cardiovascular death or heart failure.

Hs-cTnI provided incremental prognostication information

  • over conventional risk markers and
  • other established cardiovascular biomarkers,
  • including hs-cTnT.

In contrast to the APACE results, only hs-cTnI, but

  • no ths-cTnT, was significantly
  • associated with the risk for AMI.

Is there a real difference between cardiac troponin T and cardiac troponin I

  • in predicting long term prognosis?

The question arises of whether there is a true clinically relevant

  • difference between cTnT and cTnI.

Given the biochemical and analytical differences,the two

  • troponins display rather similar serum profiles during AMI.

While minor biological differences between cTnT and cTnI are

  • apparently not relevant for diagnosis
  • and clinical management in the acute setting of ACS.

This is a provocative theory, but appears premature in our opinion.
Above all, the results of the current study appear

  • too inconsistent to allow such conclusions.

In the present study, hs-cTnT (Roche Diagnostics) outperformed

  • hs-cTnI (Siemens and Beckman-Coulter) in terms of
  • very long term prediction of cardiovascular death and
    • heart failure in stable patients.

We don’t know how hs-cTnI from Abbott Diagnostics

  • performs in the APACE consort.

The number of patients and endpoints provided

  • by the APACE registry are rather low.
  • The results could, therefore, be a chance finding.

It is far too early to favour one high sensitivity assay over the other. The findings need confirmation.

Implications for clinical practice

There is no doubt that high-sensitivity assays

  • are the analytical method of choice
    • in terms of risk stratification in patients with ACS.

What is new?
A single measurement of hs-cTn seems to be adequate

  • for long-term risk stratification in patients without AMI.

However, the question of which troponin might be preferable

  • for long-term risk stratification remains unanswered.

Part 2. ability of high-sensitivity cTnT and NT pro-BNP to predict cardiovascular events and death in patients with T2DM

Hillis GS; Welsh P; Chalmers J; Perkovic V; Chow CK; Li Q; Jun M; Neal B; Zoungas S; Poulter N; Mancia G; Williams B; Sattar N; Woodward M
Diabetes Care.  2014; 37(1):295-303 (ISSN: 1935-5548)

OBJECTIVE

Current methods of risk stratification in patients with

  • type 2 diabetes are suboptimal.

The current study assesses the ability of

  • N-terminal pro-B-type natriuretic peptide (NT-proBNP) and
  • high-sensitivity cardiac troponin T (hs-cTnT)

to improve the prediction of cardiovascular events and death in patients with type 2 diabetes.

RESEARCH DESIGN AND METHODS

A nested case-cohort study was performed in 3,862 patients who participated in the Action in Diabetes and Vascular Disease:

Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

RESULTS

Seven hundred nine (18%) patients experienced a

  • major cardiovascular event

(composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke) and

  • 706 (18%) died during a median of 5 years of follow-up.

In Cox regression models, adjusting for all established risk predictors,

  • the hazard ratio for cardiovascular events for NT-proBNP was 1.95 per 1 SD increase (95% CI 1.72, 2.20) and
  • the hazard ratio for hs-cTnT was 1.50 per 1 SD increase (95% CI 1.36, 1.65). The hazard ratios for death were
    • 1.97 (95% CI 1.73, 2.24) and
    • 1.52 (95% CI 1.37, 1.67), respectively.

The addition of either marker improved 5-year risk classification for cardiovascular events
(net reclassification index in continuous model,

  • 39% for NT-proBNP and 46% for hs-cTnT).

Likewise, both markers greatly improved the accuracy with which the 5-year risk of death was predicted.
The combination of both markers provided optimal risk discrimination.

CONCLUSIONS

NT-proBNP and hs-cTnT appear to greatly improve the accuracy with which the

  • risk of cardiovascular events or death can be estimated in patients with type 2 diabetes.

PreMedline Identifier: 24089534


Part 3. M-Atrial Natriuretic Peptide

M-Atrial Natriuretic Peptide and Nitroglycerin in a Canine Model of Experimental Acute Hypertensive Heart Failure:
Differential Actions of 2 cGMP Activating Therapeutics.

Paul M McKie, Alessandro Cataliotti, Tomoko Ichiki, S Jeson Sangaralingham, Horng H Chen, John C Burnett
Journal of the American Heart Association 01/2014; 3(1):e000206. http://dx.doi.org/10.1161/JAHA.113.000206
Source: PubMed

ABSTRACT

Systemic hypertension is a common characteristic in

  • acute heart failure (HF).

This increasingly recognized phenotype

  • is commonly associated with renal dysfunction and
  • there is an unmet need for renal enhancing therapies.

In a canine model of HF and acute vasoconstrictive hypertension

  • we characterized and compared the cardiorenal actions of M-atrial natriuretic peptide (M-ANP),
    a novel particulate guanylyl cyclase (pGC) activator, and
  • nitroglycerin, a soluble guanylyl cyclase (sGC) activator.

HF was induced by rapid RV pacing (180 beats per minute) for 10 days. On day 11, hypertension was induced by continuous angiotensin II
infusion. We characterized the cardiorenal and humoral actions

  • prior to,
  • during, and
  • following intravenous infusions of
  1. M-ANP (n=7),
  2. nitroglycerin (n=7),
  3. and vehicle (n=7) infusion.

Mean arterial pressure (MAP) was reduced by

  1. M-ANP (139±4 to 118±3 mm Hg, P<0.05) and
  2. nitroglycerin (137±3 to 116±4 mm Hg, P<0.05);

similar findings were recorded for

  1. pulmonary wedge pressure (PCWP) with M-ANP (12±2 to 6±2 mm Hg, P<0.05)
  2. and nitroglycerin (12±1 to 6±1 mm Hg, P<0.05).

M-ANP enhanced renal function with significant increases (P<0.05) in

  • glomerular filtration rate (38±4 to 53±5 mL/min),
  • renal blood flow (132±18 to 236±23 mL/min), and
  • natriuresis (11±4 to 689±37 mEq/min) and
  • also inhibited aldosterone activation (32±3 to 23±2 ng/dL, P<0.05), whereas

nitroglycerin had no significant (P>0.05) effects on these renal parameters or aldosterone activation.

Our results advance

the differential cardiorenal actions of

  • pGC (M-ANP) and sGC (nitroglycerin) mediated cGMP activation.

These distinct renal and aldosterone modulating actions make

M-ANP an attractive therapeutic for HF with concomitant hypertension, where

  • renal protection is a key therapeutic goal.