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@Cleveland Clinic – Serial measurements of high-sensitivity C-reactive protein (hsCRP) post acute coronary syndrome (ACS) may help identify patients at higher risk for morbidity and mortality

Posted in Acute coronary syndrome, Acute Myocardial Infarction, Atherogenic Processes & Pathology, Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, HTN, inflammation independent of lipid levels, Origins of Cardiovascular Disease, Pharmacotherapy of Cardiovascular Disease, Systemic Inflammatory Diseases as CVD Risk on May 5, 2019| Leave a Comment »

@Cleveland Clinic – Serial measurements of high-sensitivity C-reactive protein (hsCRP) post acute coronary syndrome (ACS) may help identify patients at higher risk for morbidity and mortality

Reporter: Aviva Lev-Ari, PhD, RN

Key Points

Question Are initial and serial increases in high-sensitivity C-reactive protein levels after acute coronary syndrome in medically optimized patients associated with increased risk of a major cardiac event, cardiovascular death, and all-cause death?

Findings In this secondary analysis of the VISTA-16 randomized clinical trial that included 5145 patients, baseline and longitudinal high-sensitivity C-reactive protein levels were independently associated with increased risk of a major adverse cardiac event, cardiovascular death, and all-cause death during the 16-week follow-up.

Meaning Monitoring high-sensitivity C-reactive protein levels in patients after acute coronary syndrome may help better identify patients at greater risk for recurrent cardiovascular events or death.

Abstract

Importance Higher baseline high-sensitivity C-reactive protein (hsCRP) levels after an acute coronary syndrome (ACS) are associated with adverse cardiovascular outcomes. The usefulness of serial hsCRP measurements for risk stratifying patients after ACS is not well characterized.

Objective To assess whether longitudinal increases in hsCRP measurements during the 16 weeks after ACS are independently associated with a greater risk of a major adverse cardiac event (MACE), all-cause death, and cardiovascular death.

Results Among 4257 patients in this study, 3141 (73.8%) were men and the mean age was 60.3 years (interquartile range [IQR], 53.5-67.8 years). The median 16-week low-density lipoprotein cholesterol level was 64.9 mg/dL (IQR, 50.3-82.3 mg/dL), and the median hsCRP level was 2.4 mg/L (IQR, 1.1-5.2 mg/L). On multivariable analysis, higher baseline hsCRP level (hazard ratio [HR], 1.36 [95% CI, 1.13-1.63]; P = .001) and higher longitudinal hsCRP level (HR, 1.15 [95% CI, 1.09-1.21]; P < .001) were independently associated with MACE. Similar significant and independent associations were shown between baseline and longitudinal hsCRP levels and cardiovascular death (baseline: HR, 1.61 per SD [95% CI, 1.07-2.41], P = .02; longitudinal: HR, 1.26 per SD [95% CI, 1.19-1.34], P < .001) and between baseline and longitudinal hsCRP levels and all-cause death (baseline: HR, 1.58 per SD [95% CI, 1.07-2.35], P = .02; longitudinal: HR, 1.25 per SD [95% CI, 1.18-1.32], P < .001).

Conclusions and Relevance Initial and subsequent increases in hsCRP levels during 16 weeks after ACS were associated with a greater risk of the combined MACE end point, cardiovascular death, and all-cause death despite established background therapies. Serial measurements of hsCRP during clinical follow-up after ACS may help to identify patients at higher risk for mortality and morbidity.

SOURCE

https://jamanetwork.com/journals/jamacardiology/fullarticle/2725734

Inflammation’s role in residual risk

Residual risk of cardiovascular events or death remains high following ACS, despite coronary revascularization and optimal guideline-directed treatment with antiplatelet and LDL cholesterol-lowering agents. Inflammation is thought to drive this risk, but no effective treatment for such inflammation is commercially available. The secretory phospholipase A2 inhibitor varespladib was developed to meet this need, and it was evaluated in VISTA-16.

VISTA-16 was an international, multicenter clinical trial that randomized 5,145 patients in a double-blind manner to varespladib or placebo on a background of atorvastatin treatment within 96 hours of presentation with ACS. The trial was terminated early due to futility and likely harm from the drug, which was subsequently pulled from development.

Implications for practice

The association of increasing CRP levels with residual cardiovascular risk may prompt more intensive treatment to lower this risk. In particular, a secondary analysis showed that use of antiplatelet agents (clopidogrel, ticlopidine and prasugrel) was associated with stable or decreasing hsCRP levels.

“Monitoring not only lipids but also hsCRP after ACS may help us better identify patients at increased risk for recurrent cardiovascular events or death,” notes Dr. Puri. “High or increasing CRP levels could be an indication to optimize dual antiplatelet therapy post-ACS, along with high-intensity statin therapy (and possibly PCSK9 inhibitors) and antihypertensive therapy, in addition to instituting measures that are globally beneficial, such as dietary modifications and cardiac rehabilitation/exercise.”

SOURCE

https://consultqd.clevelandclinic.org/increasing-inflammation-correlates-with-residual-risk-after-acute-coronary-syndrome/amp/?__twitter_impression=true

Lesson 8 Cell Signaling and Motility: Lesson and Supplemental Information on Cell Junctions and ECM: #TUBiol3373

Posted in Biological Networks, Bone Disease and Musculoskeletal Disease, Cancer - General, Cardiovascular Research, Cell Biology, Cell Biology, Signaling & Cell Circuits, Coagulation Therapy and Internal Bleeding, Cytoskeleton, Developmental biology, Disease Biology, Electrophysiology, Endoplasmic reticulum, tagged #TUBiol3373, adherens, basal membrane, cell junctions, collagen, connexin43 (Cx43), Extracellular matrix, fibrin, gap junctions, Integrins, αvβ5- integrin, proteoglycan, talin, tight junctions, trans-membrane gap junction protein on April 9, 2019| Leave a Comment »

Lesson 8 Cell Signaling and Motility: Lesson and Supplemental Information on Cell Junctions and ECM: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

Please click on the following link for the PowerPoint Presentation for Lecture 8 on Cell Junctions and the Extracellular Matrix: (this is same lesson from 2018 so don’t worry that file says 2018)

cell signaling 8 lesson 2018

Some other reading on this lesson on this Open Access Journal Include:

On Cell Junctions:

Translational Research on the Mechanism of Water and Electrolyte Movements into the Cell

(pay particular attention to article by Fischbarg on importance of tight junctions for proper water and electrolyte movement)

The Role of Tight Junction Proteins in Water and Electrolyte Transport

(pay attention to article of role of tight junction in kidney in the Loop of Henle and the collecting tubule)

EpCAM [7.4]

(a tight junction protein)

Signaling and Signaling Pathways

(for this lesson pay attention to the part that shows how Receptor Tyrosine Kinase activation (RTK) can lead to signaling to an integrin and also how the thrombin receptor leads to cellular signals both to GPCR (G-protein coupled receptors like the thrombin receptor, the ADP receptor; but also the signaling cascades that lead to integrin activation of integrins leading to adhesion to insoluble fibrin mesh of the newly formed clot and subsequent adhesion of platelets, forming the platelet plug during thrombosis.)

On the Extracellular Matrix

Three-Dimensional Fibroblast Matrix Improves Left Ventricular Function Post MI

Arteriogenesis and Cardiac Repair: Two Biomaterials – Injectable Thymosin beta4 and Myocardial Matrix Hydrogel

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Lesson 3 Cell Signaling And Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Posted in Calcium Signaling, Cancer - General, CANCER BIOLOGY & Innovations in Cancer Therapy, Cardiomyopathy, Cardiovascular Pharmacogenomics, Cardiovascular Research, Cell Biology, Signaling & Cell Circuits, Cerebrovascular and Neurodegenerative Diseases, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Disease Biology, Disease Biology, Small Molecules in Development of Therapeutic Drugs, Nitric Oxide in Health and Disease, Peripheral Arterial Disease & Peripheral Vascular Surgery, tagged #TUBiol3373, Antihypertensive drug, Cardiovascular and Metabolic Diseases, G protein, G protein-coupled receptor, nitric oxide, Nitric oxide synthase, nitric oxide synthase (NOS) isozymes, S-Nitrosylation Signaling, Vascular smooth muscle on February 4, 2019| Leave a Comment »

Lesson 3 Cell Signaling & Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Curator: Stephen J. Williams, Ph.D.

Lesson 3 Powerpoint (click link below):

cell signaling and motility 3 finalissima sjw

Four papers to choose from for your February 11 group presentation:

Structural studies of G protein Coupled receptor

Shapiro-2009-Annals_of_the_New_York_Academy_of_Sciences

G protein as target in neurodegerative disease

fish technique

Today’s lesson 3 explains how extracellular signals are transduced (transmitted) into the cell through receptors to produce an agonist-driven event (effect). This lesson focused on signal transduction from agonist through G proteins (GTPases), and eventually to the effectors of the signal transduction process. Agonists such as small molecules like neurotransmitters, hormones, nitric oxide were discussed however later lectures will discuss more in detail the large growth factor signalings which occur through receptor tyrosine kinases and the Ras family of G proteins as well as mechanosignaling through Rho and Rac family of G proteins.

Transducers: The Heterotrimeric G Proteins (GTPases)

An excellent review of heterotrimeric G Proteins found in the brain is given by

Heterotrimeric G Proteins by Eric J Nestler and Ronald S Duman.

from Seven-Transmembrane receptors – Scientific Figure on ResearchGate. Available from: https://www.researchgate.net/figure/Examples-of-heterotrimeric-G-protein-effectors_tbl1_11180073 [accessed 4 Feb, 2019] and see references within

See below for the G Protein Cycle

From Citation: Review: A. M. Preininger, H. E. Hamm, G protein signaling: Insights from new structures. Sci. STKE2004, re3 (2004)

For a tutorial on G Protein coupled receptors (GPCR) see

https://www.khanacademy.org/test-prep/mcat/organ-systems/biosignaling/v/g-protein-coupled-receptors

cyclic AMP (cAMP) signaling to the effector Protein Kinase A (PKA)

from https://courses.washington.edu/conj/gprotein/cyclicamp.htm

Cyclic AMP is an important second messenger. It forms, as shown, when the membrane enzyme adenylyl cyclase is activated (as indicated, by the alpha subunit of a G protein).

The cyclic AMP then goes on the activate specific proteins. Some ion channels, for example, are gated by cyclic AMP. But an especially important protein activated by cyclic AMP is protein kinase A, which goes on the phosphorylate certain cellular proteins. The scheme below shows how cyclic AMP activates protein kinase A.

Additional information on Nitric Oxide as a Cellular Signal

Nitric oxide is actually a free radical and can react with other free radicals, resulting in a very short half life (only a few seconds) and so in the body is produced locally to its site of action (i.e. in endothelial cells surrounding the vascular smooth muscle, in nerve cells). In the late 1970s, Dr. Robert Furchgott observed that acetylcholine released a substance that produced vascular relaxation, but only when the endothelium was intact. This observation opened this field of research and eventually led to his receiving a Nobel prize. Initially, Furchgott called this substance endothelium-derived relaxing factor (EDRF), but by the mid-1980s he and others identified this substance as being NO.

Nitric oxide is produced from metabolism of endogenous substances like L-arginine, catalyzed by one of three isoforms of nitric oxide synthase (for link to a good article see here) or release from exogenous compounds like drugs used to treat angina pectoris like amyl nitrate or drugs used for hypertension such as sodium nitroprusside.

The following articles are a great reference to the chemistry, and physiological and pathological Roles of Nitric Oxide:

46. The Molecular Biology of Renal Disorders: Nitric Oxide – Part III

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/11/26/the-molecular-biology-of-renal-disorders/

47. Nitric Oxide Function in Coagulation – Part II

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

https://pharmaceuticalintelligence.com/2012/11/26/nitric-oxide-function-in-coagulation/

48. Nitric Oxide, Platelets, Endothelium and Hemostasis

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/11/08/nitric-oxide-platelets-endothelium-and-hemostasis/

49. Interaction of Nitric Oxide and Prostacyclin in Vascular Endothelium

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/09/14/interaction-of-nitric-oxide-and-prostacyclin-in-vascular-endothelium/

50. Nitric Oxide and Immune Responses: Part 1

Curator and Author: Aviral Vatsa PhD, MBBS

https://pharmaceuticalintelligence.com/2012/10/18/nitric-oxide-and-immune-responses-part-1/

51. Nitric Oxide and Immune Responses: Part 2

Curator and Author: Aviral Vatsa PhD, MBBS

https://pharmaceuticalintelligence.com/2012/10/28/nitric-oxide-and-immune-responses-part-2/

56. Nitric Oxide and iNOS have Key Roles in Kidney Diseases – Part II

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/11/26/nitric-oxide-and-inos-have-key-roles-in-kidney-diseases/

57. New Insights on Nitric Oxide donors – Part IV

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/11/26/new-insights-on-no-donors/

59. Nitric Oxide has a ubiquitous role in the regulation of glycolysis -with a concomitant influence on mitochondrial function

Curator and Author: Larry H Bernstein, MD, FACP

https://pharmaceuticalintelligence.com/2012/09/16/nitric-oxide-has-a-ubiquitous-role-in-the-regulation-of-glycolysis-with- a-concomitant-influence-on-mitochondrial-function/

Biochemistry of the Coagulation Cascade and Platelet Aggregation: Nitric Oxide: Platelets, Circulatory Disorders, and Coagulation Effects

Nitric Oxide Function in Coagulation – Part II

Nitric oxide is implicated in many pathologic processes as well. Nitric oxide post translational modifications have been attributed to nitric oxide’s role in pathology however, although the general mechanism by which nitric oxide exerts its physiological effects is by stimulation of soluble guanylate cyclase to produce cGMP, these post translational modifications can act as a cellular signal as well. For more information of NO pathologic effects and how NO induced post translational modifications can act as a cellular signal see the following:

Nitric Oxide Covalent Modifications: A Putative Therapeutic Target?

58. Crucial role of Nitric Oxide in Cancer

Curator and Author: Ritu Saxena, Ph.D.

https://pharmaceuticalintelligence.com/2012/10/16/crucial-role-of-nitric-oxide-in-cancer/

Note: A more comprehensive ebook on Nitric Oxide and Disease Perspectives is found at

Cardiovascular Diseases, Volume One: Perspectives on Nitric Oxide in Disease Mechanisms

available on Kindle Store @ Amazon.com

http://www.amazon.com/dp/B00DINFFYC

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Hypertriglyceridemia: Evaluation and Treatment Guideline

Posted in Biomarkers & Medical Diagnostics, Biomedical Measurement Science, Cardiovascular Pharmacogenomics, Cardiovascular Research, Chemical Biology and its relations to Metabolic Disease, Chronic Thromboembolic Pulmonary Hypertension (CTEPH) and Pulmonary Arterial Hypertension (PAH), Clinical Diagnostics, Clinical Genomics, Diabetes Mellitus, Disease Biology, Endocrine Diseases, Epigenetics and Cardiovascular Risks, Frontiers in Cardiology and Cardiovascular Disorders, Lipid metabolism, Liver & Digestive Diseases Research, Metabolism, Myocardial Metabolism, Nutrition, Nutrition Disorders, Nutritional Supplements: Atherogenesis, lipid metabolism, Obesity, Origins of Cardiovascular Disease, Pancreatic adenocarcinoma classifier, Pancreatic cancer, Population Health Management, Population Health Management, Genetics & Pharmaceutical, tagged Cardiovascular disease, Cholesterol, diet, hypertriglyceridemia, life style, pancreatitis, triglycerides on January 22, 2019| 1 Comment »

Hypertriglyceridemia: Evaluation and Treatment Guideline

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Severe and very severe hypertriglyceridemia increase the risk for pancreatitis, whereas mild or moderate hypertriglyceridemia may be a risk factor for cardiovascular disease. Individuals found to have any elevation of fasting triglycerides should be evaluated for secondary causes of hyperlipidemia including endocrine conditions and medications. Patients with primary hypertriglyceridemia must be assessed for other cardiovascular risk factors, such as central obesity, hypertension, abnormalities of glucose metabolism, and liver dysfunction. The aim of this study was to develop clinical practice guidelines on hypertriglyceridemia.

The diagnosis of hypertriglyceridemia should be based on fasting levels, that mild and moderate hypertriglyceridemia (triglycerides of 150–999 mg/dl) be diagnosed to aid in the evaluation of cardiovascular risk, and that severe and very severe hypertriglyceridemia (triglycerides of >1000 mg/dl) be considered a risk for pancreatitis. The patients with hypertriglyceridemia must be evaluated for secondary causes of hyperlipidemia and that subjects with primary hypertriglyceridemia be evaluated for family history of dyslipidemia and cardiovascular disease.

The treatment goal in patients with moderate hypertriglyceridemia should be a non-high-density lipoprotein cholesterol level in agreement with National Cholesterol Education Program Adult Treatment Panel guidelines. The initial treatment should be lifestyle therapy; a combination of diet modification, physical activity and drug therapy may also be considered. In patients with severe or very severe hypertriglyceridemia, a fibrate can be used as a first-line agent for reduction of triglycerides in patients at risk for triglyceride-induced pancreatitis.

Three drug classes (fibrates, niacin, n-3 fatty acids) alone or in combination with statins may be considered as treatment options in patients with moderate to severe triglyceride levels. Statins are not be used as monotherapy for severe or very severe hypertriglyceridemia. However, statins may be useful for the treatment of moderate hypertriglyceridemia when indicated to modify cardiovascular risk.

References:

https://www.medpagetoday.com/clinical-connection/cardio-endo/77242?xid=NL_CardioEndoConnection_2019-01-21

https://www.ncbi.nlm.nih.gov/pubmed/19307519

https://www.ncbi.nlm.nih.gov/pubmed/23009776

https://www.ncbi.nlm.nih.gov/pubmed/6827992

https://www.ncbi.nlm.nih.gov/pubmed/22463676

https://www.ncbi.nlm.nih.gov/pubmed/17635890

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Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases

Posted in Acute Myocardial Infarction, Atrial Fibrilation (a-Fib), Cardiac Pacing and Arrhythmias, Biomarkers & Medical Diagnostics, Cardiovascular Research, Clinical Diagnostics, congestive heart failure, Disease Biology, Endocrine Diseases, Heart and Brain Disease in Women, Proteomics, Reproductive Andrology, Embryology, Genomic Endocrinology, Preimplantation Genetic Diagnosis and Reproductive Genomics, tagged androgen, Cardiovascular disease, Heart Failure, N-Terminal Pro–B-Type Natriuretic Peptide, sex hormones on January 13, 2019| Leave a Comment »

Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Considerable differences exist in the prevalence and manifestation of atherosclerotic cardiovascular disease (CVD) and heart failure (HF) between men and women. Premenopausal women have a lower risk of CVD and HF compared with men; however, this risk increases after menopause. Sex hormones, particularly androgens, are associated with CVD risk factors and events and have been postulated to mediate the observed sex differences in CVD.

B-type natriuretic peptides (BNPs) are secreted from cardiomyocytes in response to myocardial wall stress. BNP plays an important role in cardiovascular remodelling and volume homeostasis. It exerts numerous cardioprotective effects by promoting vasodilation, natriuresis, and ventricular relaxation and by antagonizing fibrosis and the effects of the renin-angiotensin-aldosterone system. Although the physiological role of BNP is cardioprotective, pathologically elevated N-terminal pro–BNP (NT-proBNP) levels are used clinically to indicate left ventricular hypertrophy, dysfunction, and myocardial ischemia. Higher NT-proBNP levels among individuals free of clinical CVD are associated with an increased risk of incident CVD, HF, and cardiovascular mortality.

BNP and NT-proBNP levels are higher in women than men in the general population. Several studies have proposed the use of sex- and age-specific reference ranges for BNP and NT-proBNP levels, in which reference limits are higher for women and older individuals. The etiology behind this sex difference has not been fully elucidated, but prior studies have demonstrated an association between sex hormones and NT-proBNP levels. Recent studies measuring endogenous sex hormones have suggested that androgens may play a larger role in BNP regulation by inhibiting its production.

Data were collected from a large, multiethnic community-based cohort of individuals free of CVD and HF at baseline to analyze both the cross-sectional and longitudinal associations between sex hormones [total testosterone (T), bioavailable T, freeT, dehydroepiandrosterone (DHEA), SHBG, and estradiol] and NT-proBNP, separately for women and men. It was found that a more androgenic pattern of sex hormones was independently associated with lower NT-proBNP levels in cross-sectional analyses in men and postmenopausal women.

This association may help explain sex differences in the distribution of NT-proBNP and may contribute to the NP deficiency in men relative to women. In longitudinal analyses, a more androgenic pattern of sex hormones was associated with a greater increase in NT-proBNP levels in both sexes, with a more robust association among women. This relationship may reflect a mechanism for the increased risk of CVD and HF seen in women after menopause.

Additional research is needed to further explore whether longitudinal changes in NT-proBNP levels seen in our study are correlated with longitudinal changes in sex hormones. The impact of menopause on changes in NT-proBNP levels over time should also be explored. Furthermore, future studies should aim to determine whether sex hormones directly play a role in biological pathways of BNP synthesis and clearance in a causal fashion. Lastly, the dual role of NTproBNP as both

a cardioprotective hormone and
a biomarker of CVD and HF, as well as
the role of sex hormones in delineating these processes,

should be further explored. This would provide a step toward improved clinical CVD risk stratification and prognostication based on

sex hormone and
NT-proBNP levels.

References:

https://www.medpagetoday.com/clinical-connection/cardio-endo/76480?xid=NL_CardioEndoConnection_2018-12-27

https://www.ncbi.nlm.nih.gov/pubmed/30137406

https://www.ncbi.nlm.nih.gov/pubmed/22064958

https://www.ncbi.nlm.nih.gov/pubmed/24036936

https://www.ncbi.nlm.nih.gov/pubmed/19854731

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Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality after cardiac catheterization

Posted in Atherogenic Processes & Pathology, Cardiovascular Research, Frontiers in Cardiology and Cardiovascular Disorders, Gene Regulation, Gene Regulation and Evolution, Genetic Mutations in Congenital Heart DIsease, Genetics & Innovations in Treatment, Genome Biology, Origins of Cardiovascular Disease on November 12, 2018| Leave a Comment »

Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality after cardiac catheterization

Reporter: Aviva Lev-Ari, PhD, RN

A genome-wide Polygenic risk scores (PRS) improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.

Genomic Risk Stratification Predicts All-Cause Mortality After Cardiac Catheterization

and Regeneron Genetics Center

Jinbo Chen

Daniel J. Rader

, and

Scott M. Damrauer

Originally published12 Nov 2018 Circulation: Genomic and Precision Medicine. 2018;11:e002352

Abstract

Background:

Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself.

Methods:

Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram.

Results:

Individuals with hiPRS were younger than controls (66 years versus 69 years; P=2.1×10^-5) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2–2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1–5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66–0.75 versus 0.66; 95% CI, 0.61–0.70; P=0.001).

Conclusions:

A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.

Footnotes

https://www.ahajournals.org/journal/circgen

*A list of all Regeneron Genetics Center members is given in the Data Supplement.

Guest Editor for this article was Christopher Semsarian, MBBS, PhD, MPH.

The Data Supplement is available at https://www.ahajournals.org/doi/suppl/10.1161/CIRCGEN.118.002352.

Scott M. Damrauer, MD, Department of Surgery, Hospital of the University of Pennsylvania, 3400 Spruce St, Silverstein 4, Philadelphia, PA 19104. Email Scott.Damrauer@uphs.upenn.edu

SOURCE

https://www.ahajournals.org/doi/10.1161/CIRCGEN.118.002352

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Live 11:00 AM- 12:00 Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : Opening Remarks October 19, 2018

Posted in Cancer - General, cancer metabolism, Cardiomyopathy, Cardiovascular and Vascular Systems, Cardiovascular Pharmacogenomics, Cardiovascular Research, Health Economics and Outcomes Research, Human aging, Human Immune System in Health and in Disease, interventional oncology, Metabolomics, Minerals in Medicine, Nutrition, Nutrition and Phytochemistry, Nutrition Disorders, Nutritional Supplements: Atherogenesis, Plant extract, Scientific & Biotech Conferences: Press Coverage, tagged application to nutrition, cancer prevention, cardiovascular and lung disease, Cardiovascular and Metabolic Diseases, essential micronutrients, healthcare, human health consequences, mediteranean diet, preventive healthcare on October 19, 2018| Leave a Comment »

Live 11:00 AM- 12:00 Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : Opening Remarks October 19, 2018

Reporter: Stephen J. Williams, Ph.D.

11:00 Welcome

Prof. Antonio Giordano, MD, PhD.

Director and President of the Sbarro Health Research Organization, College of Science and Technology, Temple University

Welcome to this symposium on Italian lifestyle and health. This is similar to a symposium we had organized in New York. A year ago Bloomberg came out with a study on higher longevity of the italian population and this study was concluded that this increased longevity was due to the italian lifestyle and diet especially in the southern part of Italy, a region which is older than Rome (actually founded by Greeks and Estonians). However this symposium will delve into the components of this healthy Italian lifestyle which contributes to this longevity effect. Some of this work was done in collaboration with Temple University and sponsored by the Italian Consulate General in Philadelphia ( which sponsors programs in this area called Ciao Philadelphia).

Greetings: Fucsia Nissoli Fitzgerald, Deputy elected in the Foreign Circumscription – North and Central America Division

Speaking for the Consulate General is Francesca Cardurani-Meloni. I would like to talk briefly about the Italian cuisine and its evolution, from the influence of the North and South Italy, economic factors, and influence by other cultures. Italian cooking is about simplicity, cooking with what is in season and freshest. The meal is not about the food but about comfort around the table, and comparible to a cullinary heaven, about sharing with family and friends, and bringing the freshest ingredients to the table.

Consul General, Honorable Pier Attinio Forlano, General Consul of Italy in Philadelphia

11:30 The Impact of Environment and Life Style in Human Disease

Prof. Antonio Giordano MD, PhD.

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

@ handles

# hashtags

#health

#nutrition

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LIVE 2018 The 21st Gabay Award to LORENZ STUDER, Memorial Sloan Kettering Cancer Center, contributions in stem cell biology and patient-specific, cell-based therapy

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Archive for the ‘Cardiovascular Research’ Category

@Cleveland Clinic – Serial measurements of high-sensitivity C-reactive protein (hsCRP) post acute coronary syndrome (ACS) may help identify patients at higher risk for morbidity and mortality

Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome, A Secondary Analysis of the VISTA-16 Trial

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

Lesson 8 Cell Signaling and Motility: Lesson and Supplemental Information on Cell Junctions and ECM: #TUBiol3373

Lesson 3 Cell Signaling & Motility: G Proteins, Signal Transduction: Curations and Articles of reference as supplemental information: #TUBiol3373

Transducers: The Heterotrimeric G Proteins (GTPases)

Heterotrimeric G Proteins by Eric J Nestler and Ronald S Duman.

cyclic AMP (cAMP) signaling to the effector Protein Kinase A (PKA)

Additional information on Nitric Oxide as a Cellular Signal

Hypertriglyceridemia: Evaluation and Treatment Guideline

Changes in Levels of Sex Hormones and N-Terminal Pro–B-Type Natriuretic Peptide as Biomarker for Cardiovascular Diseases

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality after cardiac catheterization

Abstract

Background:

Methods:

Results:

Conclusions:

Footnotes

Live 11:00 AM- 12:00 Mediterranean Diet and Lifestyle: A Symposium on Diet and Human Health : Opening Remarks October 19, 2018

To follow or Tweet on Twitter please use the following handles (@) and hashtags (#):

Please see related articles on Live Coverage of Previous Meetings on this Open Access Journal

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