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Posts Tagged ‘National Heart Lung and Blood Institute’


American Association of Clinical Endocrinologists (AACE) can’t support the new cardiovascular risk guidelines issued by the American Heart Association (AHA) and the American College of Cardiology (ACC)

Reporter: Aviva Lev-Ari,PhD, RN

Endocrinology Group Rejects New AHA/ACC CVD Guidelines

Miriam E. Tucker

December 13, 2013

The American Association of Clinical Endocrinologists (AACE) says it can’t support the new cardiovascular risk guidelines issued by the American Heart Association (AHA) and the American College of Cardiology (ACC), saying the set of 4 guideline documents is out of step with its own recommendations.

“AACE was asked to review and endorse the obesity and cholesterol guidelines. After careful consideration by the appropriate scientific committees of our organization, AACE declined to endorse these new cholesterol and obesity guidelines,” the organization said in a statement that was sent to its members in November and forwarded to the media today. “There are multiple reasons for this decision, including, principally, the incompatibility of these new guidelines with our existing guidelines.”

The 4 guidelines are:

All of the guidelines were issued with the support of the National Heart, Lung and Blood Institute, which had last updated its Adult Treatment Panel 3 (ATP3) National Cholesterol Education Panel (NCEP) guidelines for cholesterol and lipid management in 2004. AACE had “generally agreed” with those guidelines.

AACE welcomes the intent of the AHA and ACC in the creation of these new guidelines but cannot endorse them.

The endocrinology group faults the new AHA/ACC guidelines for focusing exclusively on randomized clinical trials and for not including studies published since 2011. “They are highly restrictive regarding the database considered and omit much new information… Taken together, these actions have resulted in a considerable number of at-risk patients being omitted from consideration.”

And, AACE says that the new cardiovascular disease calculator that was published along with the guidelines—and generated the most controversy—is already outdated. “It is based upon outmoded data, does not model the totality of the US population, has not been validated, and therefore has only limited applicability.”

As for new lipid guidelines, AACE disagrees with removal of the LDL targets and the idea that statin therapy alone is sufficient for all at-risk patients, noting that many who have multiple risk factors, including diabetes and established heart disease, will need additional therapies.

Finally, the new obesity guidelines, AACE says, “fail to classify obesity as a disease and continue the paradigm of [body-mass-index] BMI-centric risk stratification, both of which are contrary to recently stated AACE positions.” In addition, newly FDA-approved weight-loss medications are not included.

The statement concludes, “AACE welcomes the intent of the AHA and ACC in the creation of these new guidelines but does not agree with the complete content and therefore cannot endorse them.”

SOURCE

http://www.medscape.com/viewarticle/817810?nlid=42483_2105&src=wnl_edit_medp_card&uac=93761AJ&spon=2

 

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Atherosclerosis Risk and Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks: Genome-Wide Variation Association Study

Reporter: Aviva Lev-Ari, PhD, RN

Association of Genome-Wide Variation With Highly Sensitive Cardiac Troponin-T Levels in European Americans and Blacks

A Meta-Analysis From Atherosclerosis Risk in Communities and Cardiovascular Health Studies

Bing Yu, MD, MSc, Maja Barbalic, PhD, Ariel Brautbar, MD, Vijay Nambi, MD, Ron C. Hoogeveen, PhD, Weihong Tang, PhD, Thomas H. Mosley, PhD, Jerome I. Rotter, MD,Christopher R. deFilippi, MD, Christopher J. O’Donnell, MD, Sekar Kathiresan, MD,Ken Rice, PhD, Susan R. Heckbert, MD, PhD, Christie M. Ballantyne, MD, Bruce M. Psaty, MD, PhD and Eric Boerwinkle, PhD on behalf of the CARDIoGRAM Consortium

Author Affiliations

From the Human Genetic Center, University of Texas Health Science Center at Houston, Houston, TX (B.Y., M.B., E.B.); Deptartment of Medicine (A.B., V.N., R.C.H., C.M.B.), and Human Genome Sequencing Center (E.B.), Baylor College of Medicine, Houston, TX; Department of Epidemiology, University of Minnesota, Minneapolis, MN (W.T.); Division of Geriatrics, University of Mississippi Medical Center, Jackson, MS (T.H.M.); Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, CA (J.I.R.); School of Medicine, University of Maryland, Baltimore, MD (C.R.D.); National Heart, Lung, and Blood Institute and Framingham Heart Study, National Institutes of Health, Bethesda, MD (C.J.O.D.); Center for Human Genetic Research & Cardiovascular Research Center, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, MA (S.K.); Department of Biostatistics (K.R.), and Cardiovascular Health Research Unit & Department of Epidemiology (S.R.H.), University of Washington, Seattle, WA; and Cardiovascular Health Research Unit, Departments of Medicine, Epidemiology, and Health Services, University of Washington & Group Health Research Institute, Group Health Cooperative, Seattle, WA (B.M.P.).

Correspondence to Eric Boerwinkle, PhD, Human Genetic Center, University of Texas School of Public Health, 1200 Herman Pressler E-447, Houston, TX 77030. E-mailEric.Boerwinkle@uth.tmc.edu

Abstract

Background—High levels of cardiac troponin T, measured by a highly sensitive assay (hs-cTnT), are strongly associated with incident coronary heart disease and heart failure. To date, no large-scale genome-wide association study of hs-cTnT has been reported. We sought to identify novel genetic variants that are associated with hs-cTnT levels.

Methods and Results—We performed a genome-wide association in 9491 European Americans and 2053 blacks free of coronary heart disease and heart failure from 2 prospective cohorts: the Atherosclerosis Risk in Communities Study and the Cardiovascular Health Study. Genome-wide association studies were conducted in each study and race stratum. Fixed-effect meta-analyses combined the results of linear regression from 2 cohorts within each race stratum and then across race strata to produce overall estimates and probability values. The meta-analysis identified a significant association at chromosome 8q13 (rs10091374;P=9.06×10−9) near the nuclear receptor coactivator 2 (NCOA2) gene. Overexpression of NCOA2 can be detected in myoblasts. An additional analysis using logistic regression and the clinically motivated 99th percentile cut point detected a significant association at 1q32 (rs12564445; P=4.73×10−8) in the gene TNNT2, which encodes the cardiac troponin T protein itself. The hs-cTnT-associated single-nucleotide polymorphisms were not associated with coronary heart disease in a large case-control study, but rs12564445 was significantly associated with incident heart failure in Atherosclerosis Risk in Communities Study European Americans (hazard ratio=1.16; P=0.004).

Conclusions—We identified 2 loci, near NCOA2 and in the TNNT2 gene, at which variation was significantly associated with hs-cTnT levels. Further use of the new assay should enable replication of these results.

SOURCE:

Circulation: Cardiovascular Genetics.2013; 6: 82-88

Published online before print December 16, 2012,

doi: 10.1161/ CIRCGENETICS.112.963058

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Resistance Hypertension: Renal Artery Intervention using Stenting

Reporter: Aviva Lev-Ari, PhD, RN

UPDATED 2/4/2014

Stenting and Medical Therapy for Atherosclerotic Renal-Artery Stenosis

Christopher J. Cooper, M.D., Timothy P. Murphy, M.D., Donald E. Cutlip, M.D., Kenneth Jamerson, M.D., William Henrich, M.D., Diane M. Reid, M.D., David J. Cohen, M.D., Alan H. Matsumoto, M.D., Michael Steffes, M.D., Michael R. Jaff, D.O., Martin R. Prince, M.D., Ph.D., Eldrin F. Lewis, M.D., Katherine R. Tuttle, M.D., Joseph I. Shapiro, M.D., M.P.H., John H. Rundback, M.D., Joseph M. Massaro, Ph.D., Ralph B. D’Agostino, Sr., Ph.D., and Lance D. Dworkin, M.D. for the CORAL Investigators

N Engl J Med 2014; 370:13-22 January 2, 2014DOI: 10.1056/NEJMoa1310753

BACKGROUND

Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain.

METHODS

We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy).

RESULTS

Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval [CI], 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (−2.3 mm Hg; 95% CI, −4.4 to −0.2; P=0.03).

CONCLUSIONS

Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.)

SOURCE

http://www.nejm.org/doi/full/10.1056/NEJMoa1310753

based on

What Do CORAL and ERASE Mean for Peripheral Intervention?

Seth Bilazarian, MD, Mark A. Creager, MD

November 27, 2013

Seth Bilazarian, MD: Hi. I’m Seth Bilazarian from the heart.org on Medscape. I’m here at the American Heart Association Scientific Sessions in Dallas with Dr. Mark Creager, Director of Vascular Medicine at Brigham and Women’s Hospital in Boston. Dr. Creager was the moderator of a session enriched with peripheral vascular disease topics yesterday. And I’m fortunate to be with him to unpack 2 of those studies: the ERASE study,[1] a study of peripheral artery disease in the lower extremities and exercise; and the CORAL study,[2] a study of renal artery intervention using stenting.

As a practicing endovascular medicine physician, I’m excited to get Dr. Creager’s take on this. The CORAL study, to start with, was a study that was sponsored by the NHLBI (National Heart, Lung, and Blood Institute), -looking at patients who had greater than 60% stenosis who had resistant hypertension or renal insufficiency and were optimally treated with medical therapy. The patients were given free antihypertensive therapies and statin therapy. And that alone was compared with medical therapy plus renal artery intervention with stenting.

Dr. Creager, can you summarize the take-home message and the results for our audience?

Mark A. Creager, MD: Thank you, Seth. This was an important study. The CORAL study compared these 2 groups, and the primary endpoints were cardiovascular and renal death, hospitalization for congestive heart failure, stroke, myocardial infarction, progressive renal insufficiency, and renal replacement therapy. The trial found that there was no significant difference in this primary composite endpoint between the 2 groups.

That’s an important message: that if we treat our patients with hypertension and renal insufficiency who have concomitant renal artery stenosis with appropriate medical therapy, they will do as well — in terms of cardiovascular and renal endpoints — as those who undergo renal artery stenting.

Dr. Bilazarian: A very strong message that stenting adds nothing, if we take home the short answer that renal stenting adds nothing on top of optimal medical therapy. Previously, enthusiasts for renal stenting criticized studies such as ASTRAL[3] and STAR[4] that the patients may not have been optimally chosen and may not have had significant enough renal artery stenosis.

In the CORAL study, we saw yesterday that in a subgroup analysis looking at patients who had greater or less than 80% stenosis, the average was 72% in the whole trial. But those at greater than 80% did not seem to fare any better from this study. They were the same as those at less than 80%. So does this largely close the door to renal stenting for atherosclerotic disease?

Dr. Creager: As implied by your question, one might have anticipated that those individuals with the most severe renal artery stenosis would have been those most likely to benefit. But as you stated, there was no difference between the patients who had a greater than 80% stenosis and those who did not. That really continues to raise questions about the efficacy of renal artery stenting in this population in general.

But it doesn’t entirely close the door. I think it still is very important for all physicians to deal with their patients individually and inform their decisions by the evidence that’s available. But there will be patients who have hypertension and remain refractory despite aggressive and appropriate medical therapy. And in those individuals, one might consider looking for the presence of renal artery stenosis, and if found, treat them.

But keep in mind that in this trial, the group randomized to medical therapy did demonstrate benefit. In fact, they demonstrated a 15-mm Hg (on average) decrease in systolic blood pressure, indicating that before enrollment in the trial they probably were being treated as aggressively as they should be.

My take-home message is: If you have a patient with significant hypertension, make sure you’re implementing guideline-based therapies to bring their blood pressure into appropriate control. And if one is not successful in that case, then consider other options.

Dr. Bilazarian: One of the findings in the study was that at the end of the trial, there was a 2.5-mm Hg blood pressure difference between those with renal stenting and those without renal stenting (both on optimal medical therapy). Did that result surprise you?

Dr. Creager: It did surprise me for the very reason I just alluded to. I think that prior to enrollment in the trial, many of these patients who were treated with 2 or more antihypertensive drugs still might not have been treated aggressively enough with the right doses of these drugs or the right number of drugs to bring their blood pressure down.

In fact, I was pleased to see that an intensive medical regimen could be effective in these patients. And it sends another important message to our medical community that we can do more for these patients.

Dr. Bilazarian: You mentioned in this last answer that there may still be a role for identifying patients with renal artery stenosis. Can you help clarify that for me as a director of the vascular lab at Brigham and Women’s Hospital? As a teacher of postgraduate physicians, help me understand in what situation patients should be evaluated.

Currently, patients who may not have frank resistant hypertension get referrals to duplex ultrasound for assessment. Should that bar be moved up? Or is it only the most refractory patients who should be investigated? Or is it still valuable to know whether a patient has renal artery stenosis with noninvasive testing?

Dr. Creager: The bar does need to be moved without question. But there are several situations. I’ll give you 2 examples. One I mentioned: The patient who continues to have resistant hypertension despite aggressive medical therapy will be one such patient where I’ll be looking for secondary causes. And one of those secondary causes could be renal artery stenosis. So in that individual, duplex ultrasound would be appropriate, and if renal artery stenosis is found, continue the evaluation and treat that patient as the renal artery stenosis is confirmed.

Another example might be an individual who has recurrent acute pulmonary edema that cannot be explained by coronary artery disease or severe left ventricular dysfunction. That’s a patient I would consider working up for bilateral renal artery stenosis. And if found, I would treat. That patient population was really not the type that was included in the CORAL trial. So those are 2 examples.

Dr. Bilazarian: Our current guidelines say that there is a role for renal artery intervention for resistant hypertension, acute pulmonary edema, and declining renal function. It seems like the first of those has been taken off the table. Is there a role in the patient with declining renal function?

Dr. Creager: Well, that’s an important subset of patients, indeed. And I would be evaluating them for the potential causes of declining renal function. If they have renal artery stenosis, I would then initiate aggressive risk factor modification, antiplatelet therapy, and if they’re hypertensive, treat that as well.

But if in spite of that there still is evidence of declining renal function, then there’s a situation of someone who has failed medical therapy, and I would consider evaluating them for a renal artery stenosis. If one were to find, for example, bilateral renal artery stenosis in that patient or a severe stenosis to a single functioning kidney, then, yes, I would consider renal artery stenting in that individual.

Dr. Bilazarian: Great. Thank you for that summary on the trial called CORAL. Let’s move on to the second trial that you moderated. That trial is called ERASE, a study looking at supervised exercise therapy — an abbreviation I wasn’t familiar with: SET — supervised exercise therapy alone or supervised exercise therapy plus intervention of lower-extremity peripheral arterial disease. And that study was called ERASE. It built on an earlier study called CLEVER.[5] Please summarize the take-home message for the audience in that trial.

Dr. Creager: These were patients with peripheral artery disease and intermittent claudication, and the peripheral artery disease could have affected the aortoiliac system or the femoropopliteal system. The bottom line is that those patients who were randomized to both endovascular intervention and supervised exercise training had a much greater improvement in their walking time as assessed by treadmill testing, and also in quality of life as assessed by a number of instruments, compared with those patients who were just treated with supervised exercise training.

It adds incrementally to what we’ve previously understood. We know that supervised exercise training is extremely effective in improving walking time in patients with intermittent claudication. And as was shown with CLEVER, compared with medical therapy, endovascular intervention — at least in the aortoiliac area — is also associated with improvement in walking time.

So perhaps it’s no surprise that if you put the two together, they’re going to do better. And that’s what the ERASE trial showed.

Dr. Bilazarian: I agree with you. Many times, studies compare one or the other. And, of course, both is better than one or the other. I was happy to see that this trial looked at both.

There is one part of the trial that I had difficulty getting a take-home message from, and I’d love your input. As endovascular medicine physicians, we think in terms of the 3 zones of lower-extremity vascular disease: above the inguinal ligament, the fem-pop system, and then below the knee. Each becomes increasingly difficult, both for acute result as well as for durability. In this trial, half the patients had aortoiliac disease and half had fem-pop disease. Am I right to say that that might make it somewhat difficult to interpret whether the effects of supervised exercise therapy might be different for fem-pop disease or, say, aortoiliac disease, and that the bar for intervention might be lower for aortoiliac disease?

Dr. Creager: That’s a very important question. We don’t know yet what the subset analysis will be between those patients who had aortoiliac disease and underwent randomization and those who had femoropopliteal artery disease. And I’m sure we all await that analysis when it’s available.

Having said that, however, the studies show several things. It underscores the fact that no matter where the lesion is, patients still do better when exercise training is included in their therapeutic interventions. I think those of us who practice vascular medicine recognize the fact that endovascular intervention in the iliac arteries has been extremely successful and durable. And those patients really do benefit. d Our practice pattern and standard of care is to do endovascular intervention in patients with disabling claudication who have aortoiliac disease.

Superficial femoral artery disease, as you implied, is a little bit of a different situation. Those lesions are sometimes more difficult to treat and the durability is not as great. Within the context of this study, durability was pretty good in terms of restenosis. But I still think we need to see the subset analysis to make sure that those patients benefited as much as the entire group.

Dr. Bilazarian: Help us with a take-home message for US-based physicians. This was supervised exercise therapy in-home. We don’t have that available in the United States. Other than adding to our knowledge base, which is, of course, valuable, and being able to impart this knowledge to our patients and show them that this is of value, what other things can we do as a change in our practice to integrate this?

Dr. Creager: Currently we do need changes in healthcare policy, at least as it applies to supervised exercise training. We need reimbursement from CMS (Centers for Medicare & Medicaid Services). We need reimbursement from other third-party payers to provide additional incentive for physicians to recommend supervised exercise training for their patients. Unfortunately, that’s not available. And that’s one reason why patients in this country are not being referred for supervised exercise training. It’s an extremely effective intervention in patients with intermittent claudication.

Dr. Bilazarian: Great. Mark, thanks for joining me and for helping unpack these 2 trials for our audience: the ERASE trial of lower-extremity exercise in PAD patients, and the CORAL trial of renal artery stenting. I think they will add to our knowledge base and hopefully make practice changes in both areas. Thank you again for joining. And thank you for joining us for this program.

SOURCE

http://www.medscape.com/viewarticle/815029?src=emailthis#1

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Myocardial Strain and Segmental Synchrony: Age and Gender in Speckle-tracking-based Echocardiographic Study

Reporter: Aviva Lev-Ari, PhD, RN

  • Original Article

Age- and Sex-based Reference Limits and Clinical Correlates of Myocardial Strain and Synchrony: The Framingham Heart Study

  1. Susan Cheng1*,
  2. Martin G. Larson2,
  3. Elizabeth L. McCabe3,
  4. Ewa Osypiuk4,
  5. Birgitta T. Lehman4,
  6. Plamen Stanchev4,
  7. Jayashri Aragam5,
  8. Emelia J. Benjamin6,
  9. Scott D. Solomon7 and
  10. Ramachandran S. Vasan8

+Author Affiliations


  1. 1Framingham Heart Study, Framingham, MA; Brigham and Women’s Hospital, Boston, MA

  2. 2Framingham Heart Study, Framingham, MA; Boston University, Boston, MA

  3. 3Boston University, Boston, MA

  4. 4Framingham Heart Study, Framingham, MA

  5. 5Veterans Administration Hospital, West Roxbury, MA

  6. 6Framingham Heart Study, Framingham, MA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA; Boston University School of Public Health, Boston, MA

  7. 7Brigham and Women’s Hospital, Boston, MA

  8. 8Framingham Heart Study, Framingham, MA; Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA
  1. * Brigham and Women’s Hospital, 75 Francis Street, PBB-119 Boston, MA 02115scheng3@partners.org

Abstract

Background—There is rapidly growing interest in applying measures of myocardial strain and segmental synchrony in clinical investigations and in practice, but data are limited regarding their reference ranges in healthy individuals.

Methods and Results—We performed speckle-tracking-based echocardiographic measures of left ventricular (LV) myocardial strain and segmental synchrony in healthy Framingham Heart Study participants (n=738, mean age 63 years, 64% women) who were free of cardiovascular disease. Reference values (2.5th, 50th, 97.5th quantiles) were estimated using quantile regression. Age- and sex-based upper (97.5th quantile) limits were as follows:

  • 15.5% to -16.9% (women) and -14.5 to -15.4% (men) for longitudinal strain;
  • -21.9% to -24.3% (women) and -18.9% to -25.0% (men) for circumferential strain;
  • 114-158 msec (women) and 133-206 msec (men) for longitudinal segmental synchrony (SD of regional time-to-peak strains); and,
  • 204-224 msec (women) and 201-288 msec (men) for transverse segmental synchrony.

In multivariable analyses, women compared to men had

  • ~1.7% greater longitudinal strain,
  • ~2.2% greater transverse strain, and
  • ~3.2% greater circumferential strain (P<0.0001 for all).

Older age and higher diastolic blood pressure, even within the normal range, was associated with worse transverse segmental synchrony (P<0.001). Overall, clinical covariates contributed ≤12% of the variation in myocardial strain or synchrony in this healthy sample.

Conclusions—We estimated age- and sex-specific reference limits for echocardiographic measures of LV strain and synchrony in a healthy community-based sample, wherein clinical covariates contributed only a modest proportion of the variation. These data may facilitate interpretation of LV strain-based measures obtained in future clinical research and practice.

Key Words:

  • Received November 19, 2012.
  • Accepted July 18, 2013.

SOURCE

CIRCIMAGING.112.000627Published online before print August 5, 2013,doi: 10.1161/​CIRCIMAGING.112.000627

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Reporter: Aviva Lev-Ari, PhD, RN

CT Scanner Delivers Less Radiation

Faster, more sensitive scans and better image processing may reduce the risk of x-ray-related cancers.

 WHY IT MATTERS

A new CT scanner exposes patients to less radiation while providing doctors with clearer images to help with diagnoses, according to researchers at the National Institutes of Health.

“CT” stands for Computerized Tomography, which involves combining lots of x-ray images taken from different angles into a three-dimensional view of what’s inside the body. The technology can be especially useful for diagnoses in emergency situations, and the number of CT scans in recent years has increased dramatically, says Marcus Chen, a cardiovascular imager at the National Heart, Lung and Blood Institute, in Bethesda, Maryland.  But the increase in the use of CT scans raises concerns about the amount of radiation to which patients are exposed, says Chen.

The risk of developing cancer from the radiation delivered by one CT scan is low, but the large number of scans performed each year—more than 70 million—translates to a significant risk. Researchers at the National Cancer Institute estimated that the 72 million CT scans performed in the U.S. in 2007 could lead to 29,000 new cancers. On average, the organ studied in a CT scan of an adult receives around 15 millisieverts of radiation, compared with roughly 3.1 millisieverts of radiation exposurefrom natural sources each year.

This concern has led researchers to seek ways to reduce the amount of radiation exposure a patient receives in a scan. They are working to improve both hardware, to make the scans go faster and need less repetition, and software, to process the x-ray data better (see “Clear CT Scans with Less Radiation”).

The new CT scanning system, from Toshiba Medical, combines several improvements to reduce radiation exposure. The overall body of a CT scanner is shaped like a large ring. An x-ray tube and a detector spin separately in the ring, opposite one another, and a patient lies in the center.  X-rays travel through the patient as they are delivered by the tube and captured by the detectors. The new Toshiba machine has five times as many detectors as most machines, which means that more of an organ can be captured at a time, decreasing the number of passes of the scanner required.

The x-ray components in the new system also spin faster—it takes only 275 milliseconds for them to complete a rotation, instead of 350 millisesconds—which means a patient gets irradiated for less time. In cases where doctors are looking at a moving organ such as the heart, the faster spinning also reduces the number of times a doctor may need to try to get a good image. “It’s like having faster film in your camera,” says Chen.  Changes to the way the system generates x-rays and computes the images also mean patients spend less time getting hit with radiation.

Chen and colleagues at the National Heart Lung and Blood Institute used the Toshiba system to examine 107 adult patients of different ages and sizes for plaque buildup and cardiovascular problems. Patient size matters because more x-rays are required to image a larger person. “A lot of imaging centers will use one setting for all patients,” says Chen. “You get beautiful image quality on everybody, but the downside is that some patients get more radiation than they probably should.” In his study, the system takes a quick preliminary scan that uses low-dose x-rays to figure out how big a patient is and how much radiation will be needed for the diagnostic image.

Most patients who got a scan in the new Toshiba machine received 0.93 millisieverts of radiation, and almost every patient received less than 4 millisieverts. Radiation exposure was decreased by as much as 95 percent relative to other CT scanners currently in use.

http://www.linkedin.com/profile/view?id=87597&trk=tab_pro

The reader is advised to review Alternative #3 in the following article, published on 3/10/2013, including the Editorial in NEJM by Dr. Redberg, UCSF, included in the article, prior to reading the content, below — as background on this important topic having the potential to change best practice and standard of care in the ER/ED.

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

CCTA for Chest Pain Cuts Costs, Admissions

By Eric Barnes, AuntMinnie.com staff writer

May 14, 2013 — One of the largest studies yet comparing medical resource use and outcomes among chest pain patients found that coronary CT angiography (CCTA) reduced medical resource utilization compared to standard care, generating fewer hospital admissions and shorter emergency room stays, researchers reported in the Journal of the American College of Cardiology.

The retrospective study compared matched cohorts of nearly 1,000 patients presenting with chest pain before and after implementation of routine CCTA evaluation. The study team from Stony Brook, NY, and two other institutions found that patients receiving the standard workup for chest pain — which is to say, mostly observation — were admitted to the hospital almost five times as frequently as patients receiving CT. The standard workup patients also had significantly longer stays when admitted.

The rates of invasive angiography without revascularization and recidivism were also much higher for patients receiving standard care (JACC, May 14, 2013).

“I think the take-home message is that CT done correctly by experts with the resources to do it correctly on a routine basis is not only safe and feasible, but reduces healthcare resource utilization,” said lead author Dr. Michael Poon, from Stony Brook Medical Center, in an interview with AuntMinnie.com.

More than $10 billion in costs

Caring for chest pain is an expensive proposition in the U.S., costing upward of $10 billion a year for some 6 million emergency department (ED) visits. To reduce the problem of overcrowded emergency rooms, some hospitals have implemented chest pain evaluation units, but the care isn’t comprehensive or necessarily all that helpful, Poon said.

“It has been a problem and a major dilemma for emergency rooms because for most patients, it’s a false alarm,” he said. “I would say nine out of 10 are false alarms, but how to pick out that one is very tricky and costly. So what most hospitals tend to do is a one-size-fits-all policy where everybody gets blood tests and an electrocardiogram, and they keep patients in the ED for an extended period of time. So if you come in Friday, you may stay until Monday.”

Coronary CTA has been shown to be safe and cost-effective for acute chest pain evaluation in several smaller studies and in three smaller multicenter trials, but those studies have been limited by a lack of CT availability outside of weekdays and office hours, while EDs must operate 24/7, Poon said.

“All of those studies were done in a randomized, controlled fashion and in an artificial environment,” where each patient was randomized to either a stress test or CT during weekday office hours, Poon said. “But in real life, there is no such thing; it cannot be done.”

More often, chest pain patients get a couple of tests and several hours of observation before they are sent home.

Poon and colleagues from Stony Brook, William Beaumont Hospital, and the University of Toronto wanted to do a “real-world” observational study to show that CT remained cost-effective and efficient for triaging chest pain patients.

The study sought to compare the overall impact of CT on clinical outcomes and efficacy, when comparing CCTA and the hospital’s standard evaluation for the triage of chest pain patients, with CCTA available 12 hours a day, seven days a week.

From a total of 9,308 patients with a chest pain diagnosis upon admission, the study used a matched sample of 894 patients without a history of coronary artery disease and without positive troponin or ischemic changes on an electrocardiogram.

Patients undergoing CT were scanned on a 64-detector-row scanner (LightSpeed VCT, GE Healthcare) following administration of iodinated contrast and metoprolol as a beta-blocker for those with heart rates faster than 65 beats per minute (bpm).

Those with a body mass index (BMI) less than 30 were scanned at 100 kV, while those with a BMI between 30 and 50 were scanned at 120 kV. Retrospective gating was reserved for patients whose heart rates remained above 65 bpm. Obstructive stenosis was defined as 50% or greater lumen narrowing.

CT choice faster, more efficient

The results showed a lower overall admission rate of 14% for CCTA, compared with 40% for the standard of care (p < 0.001). In fact, patients undergoing standard evaluation were 5.5 times more likely to be admitted (p < 0.001) than CCTA patients.

The length of stay in the ED was 1.6 times longer for standard care (p < 0.001) than for CCTA. For patients undergoing CCTA, the median radiation dose was 5.88 mSv.

“We also showed that the recidivism rate is higher for standard of care, meaning that they come back within one month with recurrent chest pain,” Poon said. The odds of returning to the ED within 30 days were five times greater for patients in the standard evaluation group (odds ratio, 5.06; p = 0.022).

“In the era of Obamacare, this is a penalty to the hospital; you don’t want the patient returning within one month with the same diagnosis,” he said. When that happens, “you’re not only not getting paid, you have to pay a penalty. It’s a double whammy. We also show that downstream invasive coronary angiography is significantly less in the CCTA arm.”

More invasive angiography

Patients receiving standard care were seven times more likely to undergo invasive coronary angiography without revascularization (odds ratio, 7.17; p ≤ 0.001), while neither patient group was significantly more likely to undergo revascularization.

“Many physicians use [catheterization] as a way of getting patients in and out of the hospital,” Poon said. However, the cost is more than $10,000 per procedure.

The high rate of angiography without revascularization in the standard care group was not seen in the Rule Out Myocardial Infarction/Ischemia Using Computer Assisted Tomography (ROMICAT) I and II trials, where all patients in the standard care group underwent stress testing before angiography was considered, he said.

Poon credited the ROMICAT trials’ routine use of stress tests with diminishing CT’s relative advantage in resource use. “In the real world, that is not available,” he said. The present study, in which only about 20% of the standard care patients underwent stress tests, is more realistic.

Finally, Poon and colleagues showed no difference in rates of myocardial infarction between CT and the standard of care within the first 30 days of follow up. However, that is changing as patients are followed for longer time periods, he noted.

“We see a trend starting to diverge in our next report, which follows [patients] for six months,” he said. “You see a lot more acute myocardial infarction in the standard care arm, and we’re going to extend it for a year.”

The authors concluded that using CCTA to rule out acute coronary syndromes in low-risk chest pain patients is likely to improve doctors’ ability to triage patients with the common presentation of chest pain. The result of this approach appears to be fewer hospital admissions, shorter stays, less recidivism, less invasive angiography, and better patient outcomes.

In any case, Poon said, the study method is permanent at Stony Brook University, where the standard of care now incorporates CCTA.

“We didn’t stop doing it after the study,” he said. “If you look at some of the randomized, controlled studies, they actually went back to the standard of care.” They had to because those kinds of protocols are only practical with a grant.

Related Reading

CORE 320 study evaluates CCTA and SPECT for CAD diagnosis, March 25, 2013

Study affirms CCTA’s value to rule out myocardial infarction, March 19, 2013

CCTA predicts heart attack in people without risk factors, February 19, 2013

Study: Use CCTA 1st for lower-risk chest pain patients, February 4, 2013

2010 CCTA appropriateness criteria yield mixed results, January 31, 2013
Copyright © 2013 AuntMinnie.com

http://www.auntminnie.com/index.aspx?sec=sup&sub=cto&pag=dis&ItemID=103419&wf=5447

Other related articles on this Open Access Online Scientific Journal include the following:

Economic Toll of Heart Failure in the US: Forecasting the Impact of Heart Failure in the United States – A Policy Statement From the American Heart Association

Aviva Lev-Ari, PhD, RN, 4/25/2013

https://pharmaceuticalintelligence.com/2013/04/25/economic-toll-of-heart-failure-in-the-us-forecasting-the-impact-of-heart-failure-in-the-united-states-a-policy-statement-from-the-american-heart-association/

Diagnosis of Cardiovascular Disease, Treatment and Prevention: Current & Predicted Cost of Care and the Promise of Individualized Medicine Using Clinical Decision Support Systems

Larry H Bernstein, MD, FACP and Aviva Lev-Ari, PhD, RN, Curator, 5/15/2013

https://pharmaceuticalintelligence.com/2013/05/15/diagnosis-of-cardiovascular-disease-treatment-and-prevention-current-predicted-cost-of-care-and-the-promise-of-individualized-medicine-using-clinical-decision-support-systems-2/

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Artherogenesis: Predictor of CVD – the Smaller and Denser LDL Particles

Reporter: Aviva Lev-Ari, PhD, RN

Updated 3/5/2013

Genetic Associations with Valvular Calcification and Aortic Stenosis

N Engl J Med 2013; 368:503-512

February 7, 2013DOI: 10.1056/NEJMoa1109034

METHODS

We determined genomewide associations with the presence of aortic-valve calcification (among 6942 participants) and mitral annular calcification (among 3795 participants), as detected by computed tomographic (CT) scanning; the study population for this analysis included persons of white European ancestry from three cohorts participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (discovery population). Findings were replicated in independent cohorts of persons with either CT-detected valvular calcification or clinical aortic stenosis.

CONCLUSIONS

Genetic variation in the LPA locus, mediated by Lp(a) levels, is associated with aortic-valve calcification across multiple ethnic groups and with incident clinical aortic stenosis. (Funded by the National Heart, Lung, and Blood Institute and others.)

SOURCE:

N Engl J Med 2013; 368:503-512

HDL is more than an eNOS Agonist

 In addition to the modulation of NO production by signaling events that rapidly dictate the level of enzymatic activity, important control of eNOS involves changes in the abundance of the enzyme. In a clinical trial by the Karas laboratory of niacin therapy in patients with low HDL levels (nine males and two females), flow-mediated dilation of the brachial artery was improved in association with a rise in HDL of 33% over 3 months (Kuvin et al., 2002).

Am. Heart J., 144:165–172.

They also demonstrated that eNOS expression in cultured human endothelial cells is increased by HDL exposure for 24 hours. They further showed that the increase in eNOS is related to an increase in the half-life of the protein, and that this is mediated by PI3K–Akt kinase and MAPK (Ramet et al., 2003).

J. Am. Coll. Cardiol., 41:2288–2297.

Thus, the same mechanisms that underlie the acute activation of eNOS by HDL appear to be operative in upregulating the expression of the enzyme.

The current understanding of the mechanism by which HDL enhances endothelial NO production is summarized in Shaul & Mineo (2004), Figure 1.

J Clin Invest., 15; 113(4): 509–513.

It describes the mechanism of action for HDL enhancement of NO production by eNOS in vascular endothelium.

(a)   HDL causes membrane-initiated signaling, which stimulates eNOS activity. The eNOS protein is localized in cholesterol-enriched (orange circles) plasma membrane caveolae as a result of the myristoylation and palmitoylation of the protein. Binding of HDL to SR-BI via apoAI causes rapid activation of the nonreceptor tyrosine kinase src, leading to PI3K activation and downstream activation of Akt kinase and MAPK. Akt enhances eNOS activity by phosphorylation, and independent MAPK-mediated processes are additionally required (Duarte, et al., 1997). Eur J Pharmacol, 338:25–33.

HDL also causes an increase in intracellular Ca2+ concentration (intracellular Ca2+ store shown in blue; Ca2+ channel shown in pink), which enhances binding of calmodulin (CM) to eNOS. HDL-induced signaling is mediated at least partially by the HDL-associated lysophospholipids SPC, S1P, and LSF acting through the G protein–coupled lysophospholipid receptor S1P3. HDL-associated estradiol (E2) may also activate signaling by binding to plasma membrane–associated estrogen receptors (ERs), which are also G protein coupled. It remains to be determined if signaling events are also directly mediated by SR-BI (Yuhanna et al., 2001), (Nofer et al., 2004), (Gong et al., 2003), (Mineo et al., 2003).

Nat. Med., 7:853–857.

J. Clin. Invest.,113:569–581.

J. Clin. Invest., 111:1579–1587.

J. Biol. Chem., 278:9142–9149.

(b)   HDL regulates eNOS abundance and subcellular distribution. In addition to modulating the acute response, the activation of the PI3K–Akt kinase pathway and MAPK by HDL upregulates eNOS expression (open arrows). HDL also regulates the lipid environment in caveolae (dashed arrows). Oxidized LDL (OxLDL) can serve as a cholesterol acceptor (orange circles), thereby disrupting caveolae and eNOS function. However, in the presence of OxLDL, HDL maintains the total cholesterol content of caveolae by the provision of cholesterol ester (blue circles), resulting in preservation of the eNOS signaling module (Ramet et al., 2003), (Blair et al., 1999), (Uittenbogaard et al., 2000).

J. Am. Coll. Cardiol., 41:2288–2297.

J. Biol. Chem., 274:32512–32519.

J. Biol. Chem., 275:11278–11283.

SOURCE:

Shaul, PW and Mineo, C, (2004). HDL action on the vascular wall: is the answer NO? J Clin Invest., 15; 113(4): 509–513.

Are Additional Lipid Measures Useful?

Ryan D. Bradley, ND; and Erica B. Oberg, ND, MPH

http://www.imjournal.com/resources/web_pdfs/recent/1208_bradley.pdf

Total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) are the well-established standards by which clinicians identify individuals at risk for coronary artery disease (CAD), yet nearly 50% of people who have a myocardial infarction have normal cholesterol levels. Measurement of additional biomarkers may be useful to more fully stratify patients according to disease risk. The typical lipid panel includes TC, LDL-C, high-density lipoprotein cholesterol  (HDL-C), and triglycerides (TGs). Emerging biomarkers for cardiovascular risk include measures of LDL-C pattern, size,  and density; LDL particle number; lipoprotein(a); apolipoproteins  (apoA1 and apoB100 being the most useful);  C-reactive protein; and lipoprotein-associated phospholipase

Some of these emerging biomarkers have been proven to add to, or be more accurate than, traditional risk factors in predicting coronary artery disease and, thus, may be useful for clinical decision-making in high-risk patients and in patients with borderline traditional risk factors.  However, we still believe that until treatment strategies can uniquely address these added risk factors—ie, until protocols to rectify unhealthy findings are shown to improve cardiovascular outcomes—healthcare providers should continue to focus primarily on helping patients reach optimal LDL-C, HDL-C, and TG levels

Table 1. Traditional Lipid Panel and Recommended Treatment

Goals for Cardiovascular Disease Prevention34

  • Total Cholesterol Desirable (low) < 200 mg/dL
  • Borderline high 200-239 mg/dL
  • High 240 mg/dL or greater
  • HDL Cholesterol Desirable (high) > 60 mg/dL
  • Acceptable 40-60 mg/dL
  • Low < 40 mg/dL
  • LDL Cholesterol Desirable (low) < 100 mg/dL
  • Acceptable 100-129 mg/dL
  • Borderline high 130-159 mg/dL
  • High 160-189 mg/dL
  • Very high 190 mg/dL or greater
  • Triglycerides Desirable (low) < 150 mg/dL
  • Borderline high 150-199 mg/dL
  • High 200-499 mg/dL
  • Very high 500 mg/dL or greater

LDL-C and HDL-C: Pattern, Size, and Density

Two patterns predominate and are used to describe the average size of LDL particles. Pattern A refers to a preponderance of large LDL particles, while Pattern B refers to a preponderance of small LDL particles; a minority of individuals displays an intermediate or mixed pattern. Some commercially available assays further subdivide LDL-C into 7 distinct designations based on particle size.9,10

LDL Lipoprotein Particle Number

LDL particle number (LDL-P) is a measure of the number of lipoprotein particles independent of the quantity of lipid within the cholesterol particle; ie, LDL-P measures the number of individual particles, not a concentration like LDL-C. It is measured using nuclear magnetic resonance technology and is unaffected by fasting status.21 Higher LDL-P measures have been associated with a higher risk of CAD. This might simply be because there are more particles susceptible to oxidation in circulation.

There are suggestions, but not definitive proof, that reducing LDL-P increases intra-LDL antioxidant capacity.  The European Prospective Investigation of Cancer (EPIC)-Norfolk cohort, a study that has followed 25 663 participants  (men and women aged 45-79 years) over 6 years, evaluated associations between LDL-P and risk of CAD. Compared to controls,  cases of CAD had a higher number of LDL particles (LDL-P P<.0001), smaller average LDL-particle size (P=.002), and higher concentrations of small LDL particles (P<.0001).22

Once again,  small, dense LDL-C were positively associated with TG and negatively associated with HDL.  In another study investigating incident angina and MI with LDL-P, females, but not males, had a significantly increased odds ratio for incident MI and angina for higher LDL-P—but not for LDL size—after adjustment for LDL, age, and race.  Males had increased (but not significant) point estimates showing the same relationship.23 Of note, LDL-P and non-HDL-C (ie,  TC minus HDL-C, or, specifically, LDL-C plus VLDLs), added equivalently to Framingham-predicted CAD risk stratification, thus reducing our enthusiasm for this additional measurement when TC and HDL-C are routinely available.22 Based on these results, LDL-P is becoming recognized as a more-precise measure of LDL-related risk and, as it becomes more available, is likely to replace LDL-C in risk-stratification tools. Clinical availability is currently limited; however, Medicare recently began reimbursing for regular testing of LDL-P in highrisk patients, so we should see availability increase soon. There are no novel treatments based on LDL-P at this time, and data shows therapies that lower LDL-C lower LDL-P as well.

 Apolipoproteins

Apolipoproteins are the protein components of plasma lipoproteins. Several different apolipoproteins have been identified and numbered; however, apoB48, apoB100, and apoA are the most commonly referenced.  ApoB48 is associated with LDL particles that transport dietary cholesterol to the liver for processing. ApoB100 is found in lipoproteins originating from the liver (eg, LDL and VLDL); it transports these lipoproteins and, also, TGs to the periphery. In addition, ApoB100 is involved with the binding of LDL particles to the vascular wall, implicating itself as a key player in the development of atherogenic plaques. Importantly, there is one apoB100 molecule per hepatic-derived lipoprotein. Hence, it is possible to quantify the number of LDL/VLDL particles by noting the total apoB100 concentration.

Measurement of apoB100 has been shown in nearly all studies to outperform LDL-C and non-HDL-C as a predictor of CAD events and as an index of residual CAD risk, perhaps due to differences in measurement sensitivity between measurement methodologies. Direct measurement of apolipoproteins is superior to calculated lipid measurements. Yet, currently, apoB100 measurement is more costly than routine measurements and,  because apoB100 is so closely associated with non-HDL-C (which,  as mentioned previously, can be estimated by TC minus HDL-C),  our enthusiasm for the clinical use of this test is limited.24 For its part, apoA is associated with HDL particles; the 2 major proteins in HDL are apoAI and apoAII. Of these, apoAI has more frequently been used to estimate HDL-C, but, in contrast to apoB100, apoAI is not unique to HDL and so the ratio of apoAI to HDL is not 1 to 1.24

Lipoprotein(a)

Lipoprotein(a)—Lp(a)—is attached to apoB. The association of Lp(a) with CAD and its ability to act as a biomarker of risk appears to be strongest in patients with hypercholesterolemia and, in particular, in young patients with premature atherosclerosis (males younger than 55 and females younger than 65). Part of the reason for this is the observation that there seem to be important threshold effects such that only very high Lp(a) levels (> 30 mg/dL) are associated with elevated vascular risk; in this regard, these increased plasma levels of Lp(a) independently predict the presence of CAD, particularly in patients with elevated LDL-C levels.28

In the Cardiovascular Health Study, a relative risk of approximately 3-fold for death from vascular events and stroke was seen in the highest quintile compared to the lowest quintile of Lp(a) but for males only, whereas no such relation existed for women.29 Lp(a) is commonly considered a marker for familial hypercholesterolemia. Lp(a) may best be used in assessing the risk of younger males with strong family histories of CVD but  should not be used more generally.

Risk Factors for Cardiovascular Disease

(Exclusive of LDL Cholesterol)34

  • Cigarette smoking
  • Hypertension (BP > 140/90 mmHg or on antihypertensive medication)
  • Low HDL cholesterol (< 40 mg/dL)
  • Family history of premature CHD (CHD in first-degree male relative <
  • 55 years; CHD in first-degree female relative < 65 years)
  • Age (men > 44 years; women > 54 years

In addition,

  • Clinical coronary heart disease,
  • symptomatic carotid artery disease,
  • peripheral arterial disease, or
  • abdominal aortic aneurysm

Conclusion

In the United States, treatment guidelines for high CVD risk factors are set by the National Cholesterol Education Program (NCEP) Expert Panel, which developed the third report of the Adult Treatment Panel (ATPIII).34 Treatment goals are determined according to risk stratification by LDL-C and by known additional risk factors such as smoking, low HDL, hypertension,  family history, and age. Yet, clinically, decision-making is always more complex than this. Additional risk stratification can be accomplished by measuring the biomarkers discussed above, and this may potentially provide additive benefit beyond NCEP guidelines. However, we always encourage clinicians to treat known risks to goal levels before adding additional goals for treatment. In a future article we will provide further detail on treatment options for novel biomarkers.

REFERENCES

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2. Tsimikas S, Willerson JT, Ridker PM. C-reactive protein and other emerging blood

biomarkers to optimize risk stratification of vulnerable patients. J Am Coll Cardiol.

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3. Nicholls SJ, Tuzcu EM, Sipahi I, et al. Statins, high-density lipoprotein cholesterol,

and regression of coronary atherosclerosis. JAMA. 2007;297(5):499-508.

4. Hausenloy DJ, Yellon DM. Targeting residual cardiovascular risk: raising high-density

lipoprotein cholesterol levels. JAMA. 2007;297(5):499-508.

5. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with

nonfasting triglycerides and risk of cardiovascular events in women. JAMA.

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6. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides

and risk of myocardial infarction, ischemic heart disease, and death in men and

women. JAMA. 2007;298(3):299-308.

7. Stampfer MJ, Krauss RM, Ma J, et al. A prospective study of triglyceride level, lowdensity

lipoprotein particle diameter, and risk of myocardial infarction. JAMA.

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8. Ceriello A. The post-prandial state and cardiovascular disease: relevance to diabetes

mellitus. Diabetes Metab Res Rev. 2000;16(2):125-132.

9. Carmena R, Duriez P, Fruchart JC. Atherogenic lipoprotein particles in artherosclerosis.

Circulation. 2004;109(23 Suppl 1):III2-III7.

10. Dormans TP, Swinkels DW, de Graaf J, Hendriks JC, Stalenhoef AF, Demacker PN.

Single-spin density-gradient ultracentrifugation vs gradient gel electrophoresis: two

methods for detecting low-density-lipoprotein heterogeneity compared. Clin Chem.

1991;37(6):853-858.

11. Roheim PS, Asztalos BF. Clinical significance of lipoprotein size and risk for coronary

atherosclerosis. Clin Chem. 1995;41(1):147-152.

12. Swinkels DW, Demacker PN, Hendriks JC, van ‘t Laar A. Low density lipoprotein

subfractions and relationship to other risk factors for coronary artery disease in

healthy individuals. Arteriosclerosis. 1989;9(5):604-613.

13. Tan CE, Chew LS, Chio LF, et al. Cardiovascular risk factors and LDL subfraction

profile in Type 2 diabetes mellitus subjects with good glycaemic control. Diabetes Res

Clin Pract. 2001;51(2):107-114.

14. Lamarche B, Tchernof A, Mauriège P, et al. Fasting insulin and apolipoprotein B levels

and low-density lipoprotein particle size as risk factors for ischemic heart disease.

JAMA. 1998;279(24):1955-1961.

15. St-Pierre AC, Ruel IL, Cantin B, et al. Comparison of various electrophoretic characteristics

of LDL particles and their relationship to the risk of ischemic heart disease.

Circulation. 2001;104(19):2295-2299.

16. Mora S, Szklo M, Otvos JD, et al. LDL particle subclasses, LDL particle size, and

carotid atherosclerosis in the Multi-Ethnic Study of Atherosclerosis (MESA).

Atherosclerosis. 2007;192(1):211-217.

17. Singh IM, Shishehbor MH, Ansell BJ. High-density lipoprotein as a therapeutic target:

a systematic review. JAMA. 2007;298(7):786-798.

18. Lewis GF. Determinants of plasma HDL concentrations and reverse cholesterol

transport. Curr Opin Cardiol. 2006;21(4):345-352.

19. Kontush A, de Faria EC, Chantepie S, Chapman MJ. A normotriglyceridemic, low

HDL-cholesterol phenotype is characterised by elevated oxidative stress and HDL

particles with attenuated antioxidative activity. Atherosclerosis. 2005;182(2):277-285.

20. Nobécourt E, Jacqueminet S, Hansel B, et al. Defective antioxidative activity of small

dense HDL3 particles in type 2 diabetes: relationship to elevated oxidative stress and

hyperglycaemia. Diabetologia. 2005;48(3):529-538.

21. Dungan KM, Guster T, DeWalt DA, Buse JB. A comparison of lipid and lipoprotein

measurements in the fasting and nonfasting states in patients with type 2 diabetes.

Curr Med Res Opin. 2007;23(11):2689-2695.

22. El Harchaoui K, van der Steeg WA, Stroes ES, et al. Value of low-density lipoprotein

particle number and size as predictors of coronary artery disease in apparently

healthy men and women: the EPIC-Norfolk Prospective Population Study. J Am Coll

Cardiol. 2007;49(5):547-553.

23. Kuller L, Arnold A, Tracy R, et al. Nuclear magnetic resonance spectroscopy of lipoproteins

and risk of coronary heart disease in the cardiovascular health study.

Arterioscler Thromb Vasc Biol. 2002;22(7):1175-1180.

24. Olofsson SO, Wiklund O, Borén J. Apolipoproteins A-I and B: biosynthesis, role in

the development of atherosclerosis and targets for intervention against cardiovascular

disease. Vasc Health Risk Manag. 2007;3(4):491-502.

25. Walldius G, Jungner I. Is there a better marker of cardiovascular risk than LDL cholesterol?

Apolipoproteins B and A-I—new risk factors and targets for therapy. Nutr

Metab Cardiovasc Dis. 2007;17(8):565-571.

26. Anand SS, Islam S, Rosengren A, et al. Risk factors for myocardial infarction in

women and men: insights from the INTERHEART study. Eur Heart J.

2008;29(7):932-940.

27. McQueen MJ, Hawken S, Wang X, et al. Lipids, lipoproteins, and apolipoproteins as

risk markers of myocardial infarction in 52 countries (the INTERHEART study): a

case-control study. Lancet. 2008;372(9634):224-233.

28. Danesh J, Collins R, Peto R. Lipoprotein(a) and coronary heart disease. Metaanalysis

of prospective studies. Circulation. 2000;102(10):1082-1085.

29. Ariyo AA, Thach C, Tracy R; Cardiovascular Health Study Investigators. Lp(a) lipoprotein,

vascular disease, and mortality in the elderly. N Engl J Med.

2003;349(22):2108-2115.

30. Retterstol L, Eikvar L, Bohn M, Bakken A, Erikssen J, Berg K. C-reactive protein predicts

death in patients with previous premature myocardial infarction—a 10 year

follow-up study. Atherosclerosis. 2002;160(2):433-440.

31. Kiechl S, Willeit J, Mayr M, et al. Oxidized phospholipids, lipoprotein(a), lipoprotein-

associated phospholipase A2 activity, and 10-year cardiovascular outcomes:

prospective results from the Bruneck study. Arterioscler Thromb Vasc Biol.

2007;27(8):1788-1795.

32. Kolko M, Rodriguez de Turco EB, Diemer NH, Bazan NG. Neuronal damage by

secretory phospholipase A2: modulation by cytosolic phospholipase A2, plateletactivating

factor, and cyclooxygenase-2 in neuronal cells in culture. Neurosci Lett.

2003;338(2):164-168.

33. Robins SJ, Collins D, Nelson JJ, Bloomfield HE, Asztalos BF. Cardiovascular events

with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-

cholesterol: the Veterans Affairs HDL Intervention Trial. Arterioscler Thromb

Vasc Biol. 2008;28(6):1172-1178.

34. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in

Adults. Executive Summary of The Third Report of The National Cholesterol

Education Program (NCEP) Expert Panel on Detection, Evaluation, And Treatment

of High Blood Cholesterol In Adults (Adult Treatment Panel III). JAMA.

2001;285(19):2486-2497.

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Hypertriglyceridemia concurrent Hyperlipidemia: Vertical Density Gradient Ultracentrifugation a Better Test to Prevent Undertreatment of High-Risk Cardiac Patients

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High-Density Lipoprotein (HDL): An Independent Predictor of Endothelial Function & Atherosclerosis, A Modulator, An Agonist, A Biomarker for Cardiovascular Risk

Aviva Lev-Ari, PhD, RN

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CABG or PCI: Patients with Diabetes – CABG Rein Supreme

Reporter: Aviva Lev-Ari, PhD, RN

 

VIEW VIDEO

105

Compelling Evidence for Coronary-Bypass Surgery in Patients with Diabetes

Mark A. Hlatky, M.D.

November 4, 2012DOI: 10.1056/NEJMe1212278

Seventeen years ago, the National Heart, Lung, and Blood Institute issued a clinical alert1 that coronary-artery bypass grafting (CABG) had better rates of survival than percutaneous coronary intervention (PCI) in patients with diabetes. The alert was based on the results of the Bypass Angioplasty Revascularization Investigation (BARI) trial,2 in which patients with multivessel coronary artery disease were randomly assigned to undergo either CABG or PCI.

This recommendation has been controversial ever since, largely because subsequent trials comparing CABG and PCI have enrolled only small numbers of patients with diabetes. A pooled analysis of 10 randomized trials involving 1233 patients with diabetes confirmed that such patients had a particular survival advantage after CABG, as compared with PCI.3 But this evidence was discounted because drug-eluting stents were not used in PCI procedures in the earlier trials, and more recent trials in which drug-eluting stents were used4,5 enrolled relatively few patients with diabetes. Settling this controversy would require a trial with a large number of patients with both diabetes and multivessel coronary artery disease in whom CABG or PCI would be performed with the use of contemporary methods.

Farkouh et al.6 now report in the Journal the results of the definitive Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) trial, in which 1900 patients with diabetes (about as many patients with diabetes as in all previous trials combined) were randomly assigned to undergo either CABG or PCI with drug-eluting stents.

As a cardiologist who does not perform either procedure, I find that the FREEDOM trial provides compelling evidence of the comparative effectiveness of CABG versus PCI in patients with diabetes and multivessel coronary artery disease. After 5 years of follow-up, the 947 patients assigned to undergo CABG had significantly lower mortality (10.9% vs. 16.3%) and fewer myocardial infarctions (6.0% vs. 13.9%) than the 953 patients assigned to undergo PCI. However, patients in the CABG group had significantly more strokes (5.2% vs. 2.4%), mostly because of strokes that occurred within 30 days after revascularization. In the CABG group, the primary composite outcome of death, myocardial infarction, or stroke over 5 years was reduced by 7.9 percentage points, or a relative decrease of 30%, as compared with PCI (18.7% vs. 26.6%, P=0.005). These results are consistent with the findings of multiple previous trials comparing CABG and PCI in patients with diabetes,3 as well as the most recent trials in which drug-eluting stents were used during PCI.4,5

Despite the results of BARI and other trials, over time more and more patients with diabetes have undergone PCI rather than CABG to treat multivessel coronary disease.7,8 The reasons for this trend are uncertain, yet there are two broad potential explanations. First, because PCI technology continues to evolve, many cardiologists simply have dismissed the results of earlier randomized studies as outdated because they used earlier techniques. This is a catch-22, since long-term studies are needed to compare hard outcomes, but evidence from long-term studies may be ignored if therapies are evolving. The results of the FREEDOM trial suggest that the comparative effectiveness of CABG and PCI on hard outcomes remains similar whether PCI is performed without stents, with bare-metal stents, or with drug-eluting stents. Mortality has been consistently reduced by CABG, as compared with PCI, in more than 4000 patients with diabetes who have been evaluated in 13 clinical trials. The controversy should finally be settled.

Another potential reason for the increasing use of PCI in patients with multivessel coronary disease is that the clinical-decision pathway leads patients toward PCI over alternative treatments. Many PCIs today are ad hoc procedures, performed at the time of diagnostic coronary angiography, with the same physician making the diagnosis, recommending the treatment, and performing the procedure. There is little time for informed discussion about alternative treatment options, either medical therapy on the one hand or CABG on the other. Well-informed patients might choose any of those options on the basis of their concerns about the various outcomes of treatment, such as survival, stroke, myocardial infarction, angina, and recovery time. This is a complicated decision, and clinical guidelines in the United States9 and Europe10 now emphasize the importance of more deliberate decision making about coronary revascularization, including discussions with a multidisciplinary heart team.

The results of the FREEDOM trial suggest that patients with diabetes ought to be informed about the potential survival benefit from CABG for the treatment of multivessel disease. These discussions should begin before coronary angiography in order to provide enough time for the patient to digest the information, discuss it with family members and members of the heart team, and come to an informed decision.

Disclosure forms provided by the author are available with the full text of this article at NEJM.org.

This article was published on November 4, 2012, at NEJM.org.

SOURCE INFORMATION

From Stanford University School of Medicine, Stanford, CA.

REFERENCES:

REFERENCES

  1. National Heart, Lung, and Blood Institute (NHLBI). Clinical alert: bypass over angioplasty for patients with diabetes. US National Library of Medicine, National Institutes of Health, September 21, 1995 (http://www.nlm.nih.gov/databases/alerts/bypass_diabetes.html).
  2. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators. Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. N Engl J Med 1996;335:217-225[Erratum, N Engl J Med 1997;336:147.]Full Text | Web of Science
  3. Hlatky MA, Boothroyd DB, Bravata DM, et al. Coronary artery bypass surgery compared with percutaneous coronary interventions for multivessel disease: a collaborative analysis of individual patient data from ten randomised trials. Lancet 2009;373:1190-1197CrossRef | Web of Science | Medline
  4. Kappetein AP, Feldman TE, Mack MJ, et al. Comparison of coronary bypass surgery with drug-eluting stenting for the treatment of left main and/or three-vessel disease: 3-year follow-up of the SYNTAX trial. Eur Heart J 2011;32:2125-2134CrossRef | Web of Science
  5. Hall R. Coronary Artery Revascularisation in Diabetes trial: five year follow-up data. ESC Clinical Trial and Registry update, Munich, August 27, 2012 (http://www.escardio.org/congresses/esc-2012/congress-reports/Pages/710-5-CARDia.aspx).
  6. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012. DOI: 10.1056/NEJMoa1211585.
  7. Hassan A, Newman A, Ko DT, et al. Increasing rates of angioplasty versus bypass surgery in Canada, 1994-2005. Am Heart J 2010;160:958-965CrossRef | Web of Science
  8. Frutkin AD, Lindsey JB, Mehta SK, et al. Drug-eluting stents and the use of percutaneous coronary intervention among patients with class I indications for coronary artery bypass surgery undergoing index revascularization: analysis from the NCDR (National Cardiovascular Data Registry). JACC Cardiovasc Interv 2009;2:614-621CrossRef | Web of Science
  9. Hillis LD, Smith PK, Anderson JL, et al. 2011 ACCF/AHA guideline for coronary artery bypass graft surgery: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists and Society of Thoracic Surgeons. J Am Coll Cardiol 2011;58:e123-e210CrossRef | Web of Science
  10. Wijns W, Kolh P, Danchin N, et al. Guidelines on myocardial revascularization. Eur Heart J2010;31:2501-2555CrossRef | Web of Science | Medline

SOURCE:

http://www.nejm.org/doi/full/10.1056/NEJMe1212278?query=OF

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