President, Chairman, Chief Executive Officer

We are extremely excited to present you with the February 2013 issue of 

 on iPad—a new way to deliver the current information you need for your daily practice. The cardiovascular landscape is evolving rapidly, and now more than ever physicians rely on the latest published research for education, guidance, and insight. This issue of 

 brings clear, concise, timely reviews of current studies under the expert guidance of a prestigious Editorial Advisory Board and esteemed Editor-in-Chief Debabrata Mukherjee, MD, MS, FACC. The carefully selected editorial content, matched with cutting-edge expert commentary by these leaders in the field, is a valuable resource right at your fingertips. Plus, with iPad, we also provide multimedia and relevant resources—literally a tap away&mdash;for your use as you delve into these important topics. Then, when ready, you can go online to the CME activity and test your knowledge right away. We invite cardiologists, internal medicine physicians, family practitioners, and endocrinologists, as well as related disciplines to take full advantage of all this iPad edition has to offer, and to pass it along to their colleagues.

The February issue covers a multitude of vital topics ranging from venous thromboembolism and diabetes to acute myocardial infarction and the future and formation of the Affordable Care Act. This issue also introduces a new department called “Clinical Forum,” where we ask clinicians to discuss a hot topic, so I invite you to see what is being discussed enthusiastically by your peers right now.

Our mission is to review and report on the most relevant, timely, and thought-provoking content in the field of cardiology. The myriad of information available from journals, the Internet, and other communication vehicles can be overwhelming and largely unmanageable. With 

on iPad, now available 6 times a year, we supply a muchneeded solution for physicians. Also look for additional news and reports on HCPLive.com, where 

In our “Meeting Report” coverage in this edition, we summarize important studies from the American Society of Echocardiography 23rd Annual Echo Hawaii conference, held in late January—fulfilling our promise to bring you the most relevant, timely information from the meetings you may not be able to attend yourself. Watch for more useful summaries down the road&mdash;fresh from important meetings&mdash; and enjoy this inaugural iPad edition of 

	President, Chairman, Chief Executive Officer

Articles

Letter from the Publisher

Cardiology Review on iPad!

As winter loosens its grip on the country, I hope most of us are ready to shake off the blues and enjoy spring. In line with the season for rejuvenation, renewal, resurrection, and regrowth, this particular issue of 

 discusses many important articles and viewpoints that I hope will rejuvenate our minds.

Dr. Saurav Chatterjee discusses low-dose aspirin to prevent recurrent venous thromboembolism (VTE) and opines that the ASPIRE study substantiates earlier evidence of a possible therapeutic benefit of aspirin when given to patients after initial anticoagulant therapy for a first episode of unprovoked VTE. Dr. Harry Davis reviews the evidence for fasting time and lipid levels in a community-based population and suggests that because many patients are in the habit of obtaining fasting lab tests prior to a scheduled visit, this is probably a reasonable habit to continue. But if the patient is seen first, the random collection of the lipid profile may be justified based on this study.

Drs. Sachin Goel and Mehdi Shishebhor look at strategies for multivessel revascularization in patients with diabetes and suggest that further research should help identify those patients with diabetes and multivessel coronary disease who will benefit from percutaneous coronary intervention; however, until then, coronary artery bypass graft appears to be superior in the majority of these individuals. Dr. Thomas Whayne comments on social challenges and the effects of unemployment stress on the risk of acute myocardial infarction and points out that for most workers, unemployment represents a major life stress. Such stress in and of itself could lead to post-traumatic stress disorder and has well-established mechanisms associated with acute cardiovascular (CV) events. He thinks that these findings impose on employment counselors and physicians the reality of added CV risk and emphasize the importance of maximizing the prevention of psychosocial and traditional CV risk factors.

Dr. Jimena Blandon, our budding nephrologist, discusses the impact of aliskiren on patients with Type 2 diabetes and notes that until more data are gathered about adding aliskiren to angiotensin-converting enzyme inhibitors or angiotensin receptor blocker therapies, we should follow current recommendations regarding renin-angiotensin-aldosterone system inhibition to add years of life to our diabetic patients and their kidneys. Dr. Timor Paul, one of our new board members, examines the increased mortality seen among patients taking digoxin, and suggests that low-dose, close monitoring of digoxin level and clinical symptoms is key and he would not necessarily eliminate the use of digoxin in this population— particularly in cases of low serum digoxin levels.

Dr. Diana Fancher comments on the future and formation of the US Affordable Care Act (ACA)—Obamacare&mdash;and reminds us that although 2 major obstacles to the implementation of the ACA have been cleared, powerful threats to its full realization remain in the future. Deep spending cuts and increased taxes being considered by Congress would certainly have an impact on the implementation of the ACA.

In this issue we introduce a new section, Clinical Forum, in which clinicians discuss a question about a hot topic. For our inaugural section, Drs. Tracy Macaulay, Rabab Mohsin, and Karla Quevedo opine on statins and the risk for diabetes, and whether such a concern should impact therapy. Please enjoy the lively conversation on this topic.

Finally, the insightful compilation of studies presented at the American Society of Echocardiography’s 23rd Annual Echo Hawaii conference, held January 21-25, 2013, at Kohala Coast, Big Island, HI, by our excellent managing editor, Ms. Jackie Syrop, should keep you updated on the latest happenings in the imaging field. She discusses several key items in the news, namely the impact of epicardial adipose tissue, utility of pocket ultrasound, and prognostic value of left atrial volume index change, among others.

I hope that you will find these commentaries to be valuable and enjoyable. I encourage you to share your insights, thoughts, and personal experiences on the topics touched upon in this issue. On a broader level, I would love to hear feedback on how we can make this journal even better. My goal continues to be to make you look forward to every issue of 

Editor's Page

A New Year of Cardiology Review

CME Test

Conference Calendar

Migrane with Aura in Women May Be Linked to MI, Blood Clots

Women who have migraine with aura may have a higher risk of heart attacks and blood clots, according to 2 recent studies to be presented at the annual meeting of the American Academy of Neurology in March.

The first study followed nearly 28,000 women in the ongoing Women’s Health Study, 1400 of whom had migraine with aura. After 15 years of follow-up, the study found that more than 1000 women had a heart attack, stroke, or died from cardiovascular causes. Only hypertension was a stronger predictor of cardiovascular problems, said lead author Tobias Kurth, MD, MSc, ScD, of the French National Institute of Health and Medical Research in Bordeaux, France, and Brigham and Women’s Hospital in Boston. The risk associated with migraine with aura was even stronger than that associated with diabetes, smoking, obesity, and family history of heart disease.   

It is not known if controlling migraines would reduce the risk for heart disease, and no causeand- effect relationship between migraine with aura and cardiovascular problems has been demonstrated. Noah Rosen, MD, Director of the Headache Center at Cushing Neuroscience Institute at North Shore-Long Island Jewish Health System in Manhasset, NY, said the study raises the concern that migraine with aura is more of a risk than diabetes, and that it might change the way risk is stratified based on a history of migraine. Dr Rosen didn’t think migraine control would reduce cardiovascular risk because migraine is likely a genetic phenomenon and is not a modifiable risk factor. “It makes sense to control the other risk factors for cardiovascular disease,” he said.

A second study that will also be presented at the neurology meeting found that women with migraine with aura who take hormonal contraceptives have a higher risk of blood clots than women with migraine without aura. The study, which followed 145,000 women who used hormonal contraceptives, shows that 7.6% of the women with migraine with aura who used a newer-generation hormonal contraceptive that combines estrogen and progestin had deep vein thrombosis, compared with 6.3% of women with migraine without aura.

What Your Patients Are Reading

Apixaban Approved for Reduction of Risk of Stroke, Blood Clots in AF Patients

In the last few days of 2012, the FDA approved the oral factor Xa inhibitor anticoagulant apixaban (Eliquis) to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF).

The agency based the approval decision on data from the ARISTOTLE clinical trial comparing apixaban with warfarin, which involved more than 18,000 patients. The trial showed that patients taking apixaban had fewer strokes than those who took warfarin.

Apixaban labeling contains a boxed warning stating that patients who discontinue apixaban are at an increased risk of thrombotic events. An increased risk of stroke was observed following discontinuation of apixaban in clinical trials in patients with nonvalvular atrial fibrillation. If anticoagulation with apixaban must be discontinued for a reason other than pathological bleeding, coverage with another anticoagulant should be strongly considered.

Product labeling also notes that apixaban increases the risk of bleeding and can cause serious, potentially fatal bleeding. The most common and serious adverse events associated with the medication were related to bleeding.

Apixaban is a product of Bristol-Myers Squibb (BMS) and will be co-marketed by BMS and Pfizer.

Dabigatran Should Not Be Used in Patients with Mechanical Prosthetic Heart Valves

The FDA has notified health care practitioners and patients that dabigatran etexilate mesylate (Pradaxa) should not be used to prevent stroke or major thromboembolic events in patients with mechanical prosthetic heart valves. The agency is communicating this recommendation after the RE-ALIGN clinical trial was halted because study subjects who used dabigatran were more likely to experience strokes, heart attacks, and the formation of blood clots on mechanical heart valves than were users of warfarin. There was also more bleeding after valve surgery in the patients using dabigatran than in the warfarin users. The FDA’s recommendations can be found at 

http://www.fda.gov/Drugs/DrugSafety/ucm332912.htm

Dabigatran is not approved for patients with AF caused by heart valve problems, and the FDA is requiring a contraindication to be added to the labeling of dabigatran warning against use in patients with mechanical heart valves.

Niacin/Laropiprant Products Will Be Suspended Worldwide

The marketing, supply, and authorizations of 3 identical niacin/laropiprant products (Tredaptive, Pelzont, and Trevaclyn) used to treat adults with dyslipidemia will be suspended across the European Union following the recommendation of the European Medicines Agency (EMA) at its January 2013 meeting. Merck, which markets the combination, has begun working with regulatory agencies in all countries where the medication is currently available to suspend availability of the product and work on communications for health care providers. The timetable for the suspension will be based on the regulations and processes of each individual nation.

The decision was made based on EMA’s assessment of data related to safety concerns about the products. The HPS-2 THRIVE study failed to show any clinical benefit of adding extendedrelease niacin/laropiprant to statin therapy. The combination did not significantly reduce the risk of the composite of coronary deaths, nonfatal myocardial infarctions, strokes, or coronary revascularizations compared with statin therapy, but it did significantly increase the risk of nonfatal but serious side effects.

Merck announced that it did not intend to seek approval for the drug from the FDA. The company recommends that physicians cease prescribing Tredaptive or the identical products, and review patients’ treatment plans in a timely manner to discontinue it and consider other changes in therapy.

News & Trends

, we ask several clinicians to answer a question of current interest to health care practitioners. Please send your comments and suggestions for future topics to Editor-in-Chief Dr Debabrata Mukherjee at: debabrata.mukherjee@ttuhsc.edu.

Q: Should concerns about developing diabetes impact the use of statins?

In 2008 the Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein Trial (better known as JUPITER) demonstrated that rosuvastatin was beneficial in the primary prevention of cardiovascular disease in atrisk individuals.

 Although the study received a lot of press, perhaps one of the more heavily debated findings was the demonstration that rosuvastatin-treated patients were also more likely to have physician-reported new-onset diabetes (0.030% vs 0.024%, P = 0.01).

	As far as objective evidence to support these findings, there was no difference in fasting glucose or glycosuria, but there was a statically significant difference in A1C (5.9% vs 5.8%, P = 0.001). Further analysis by the same team published in 

 in 2012 showed that those who developed diabetes during the study follow-up had 1 or more diabetes risk factors at baseline and, importantly, had a cardiovascular and mortality benefit similar to the intention-to-treat population.

 One could easily argue that with in-depth analysis of a study this large (17,802 participants), findings can be statically significant and not necessarily be clinically important. Although many clinicians believed this to be the case with the original JUPITER trial, the findings were appropriately hypothesis-generating and led to further investigations. A metaanalysis of 13 clinical trials by Sattar et al

 investigating the association of diabetes and statin use that collectively enrolled over 90,000 patients demonstrated the actual risk increase of new-onset diabetes to be around 0.09% in statin-treated participants (1.22% vs 1.13%; odds ratio [OR], 1.09; 95% confidence interval [CI], 1.02-1.17).

	The authors’ conclusions were cautious, describing the slight association, but emphasizing the benefit of statin therapy, and recommending no change in practice. However, these findings did result in a change in statin labeling by the FDA, which now warns of the increased incidence in new-onset type 2 diabetes in statintreated patients. The lay press also took note, resulting in much discussion as to whether statins should be used more cautiously.

	Although safety surveillance is important, particularly with such a widely utilized class of medications, many conclusions have now been made based on evidence that is not entirely up to the rigorous standards for which the cardiology community prides itself. For example, there was no trial-specified definition of diabetes uniformly pressed upon the investigators in JUPITER. Nor is a meta-analysis the prospective evaluation that a question of this importance might deserve. Many questions remain that simply cannot be answered by a meta-analysis; for example, were each of the 13 included trials equally regimented about tracking of blood glucose (at baseline and throughout) or were other known diabetes contributors controlled for adequately? That being said, given the vast numbers of patients included in these evaluations, there certainly appears to be an association between diabetes and statins. Importantly, in neither JUPITER nor the subsequent meta-analysis did this linkage alter the morbidity and mortality benefits incurred by statin users in these high-risk patient populations.

	Therefore, use of statins in populations similar to those studied and in whom treatment benefits have been shown is important. However, these studies’ findings are yet another indication that we do not entirely understand all the mechanisms underlying statin therapy. And to that end, the “put them in the water” approach to prescribing statins is also not supported by clinical evidence. Use of statin therapy in less carefully evaluated low-risk individuals may also not be prudent, as some have suggested.

	The most interesting juxtaposition posed by this question—“Should concerns about developing diabetes impact the use of statins?”&mdash;is that once a patient develops diabetes (statin instigated or not), is there a better-known medication to prevent the vascular complications of diabetes than an HMG co-A reductase inhibitor? Not even most medications designed and developed to treat diabetes have had as great an impact on the course of cardiovascular complications as statins have had. So, it is my wholehearted opinion that concerns over the development of diabetes should certainly NOT impact the use of statins. But as always, use of statins should mirror the clinical trial populations in which any hazard of developing diabetes was outweighed by the cardiovascular benefit.

	1. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. 

	2. Ridker PM, Pradhan A, MacFadyen JG, et al. Cardiovascular benefits and diabetes risks of statin therapy in primary prevention: an analysis from the JUPITER trial. 

	3. Sattar N, Preiss D, Murray HM. Statins and risk of incident diabetes: a collaborative meta-analysis of randomised statin trials. 

In the early 1950s, the act of adding fluoride to the drinking water supply to prevent tooth decay became the official policy of the US Public Health Service. Over the past 20 years, the popularity of statin therapy has physicians and medical experts theorizing about the possibility of adding statins to our water supply due to their proven and substantial cardiovascular benefits.

Today, preventive medicine is at the forefront of healthcare policies, and statins have become one of the most promoted medical therapies to reduce cardiovascular events in multiple patient populations. Many physicians and health care experts have hypothesized that early initiation of statin therapy would reduce cardiovascular risk effectively. One of the most aggressive management plans for lipid control is directed to the diabetic population.

In recent years, meta-analyses and clinical trials have raised a concern that statins can potentiate the incidence of diabetes. Sattar et al recently explored 13 clinical trials that enrolled more than 90,000 patients and found that there was a 9% increased risk of developing diabetes while on statin therapy. However, the absolute incidence of diabetes did not change, and the patients were shown to have a reduction in coronary events.

The 2008 American Diabetes Association’s (ADA’s) standards of care call for an initiation of statin therapy for all patients with diabetes. A “treat-to-target” approach for low-density lipoprotein (LDL) of <100 mg/dL is used in addition to lifestyle therapy in the ADA guidelines versus an evidence-based “fixed-dose” approach.

 In the JUPITER trial, there was a significant but mild increase in new-onset diabetes in patients started on rosuvastatin (3% vs. 2.4% in placebo).

 It has been observed in many of the statin studies that the average BMI was over 24 kg/m

, which adds to the development of diabetes. Small observational and cohort studies have shown that all statins are not created equal and have different adverse effects on glucose metabolism.

The pleiotropic effects of statins, including a reduction of inflammation, plaque stabilization, a reduction in microvascular complications, and reversal of endothelial dysfunction, have all been implicated as beneficial phenomena to reduce cardiovascular risk.

 A final point to address would be the intensivedose therapy versus low-dose therapy in the development of diabetes. In Preiss et al’s meta- analysis of 5 statin trials, which included approximately 33,000 patients without diabetes at baseline, 8.4% were found to have new-onset diabetes.

 The intensive-dose statin therapy was associated with increased risk of diabetes as compared with moderate-dose therapy.

Regardless of the mild increase in the diabetic population observed in the above studies, the substantial benefit in reducing cardiovascular events leaves the prescriber utilizing statins both for primary and secondary prevention. The most important guideline is to use good clinical judgment and close followup when prescribing statins in preventive medicine. It is a good reminder to healthcare staff that statins are an adjunctive therapy to lifestyle changes, including encouragement of daily exercise. Although adding statins to the public water supply may not be the best application of preventive medicine, statins remain a proven therapy for patients with cardiovascular risks.

1. Sattar N, Preiss D, Murray H, et al. Statins and risk of incident diabetes: a collaborative meta- analysis of randomised statin trials. 

2. Eldor R, Raz I. American Diabetes Association indications for statins in diabetes: is there evidence? 

3. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. 

4. Belalcazar LM, Raghavan VA, Ballantyne CM. Statin-induced diabetes: will it change clinical practice? 

5. Preiss D, Seshasai S, Welsh P, et al. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta analysis. 

Chronic diseases, such as heart disease, stroke, cancer, diabetes, and arthritis, are among the most common, costly, and preventable health problems in the United States. Heart disease, cancer, and stroke account for more than 50% of all US deaths each year. From 1980 through 2010, the number of adults in the United States between the ages of 18 to 79 with newly diagnosed type 2 diabetes mellitus more than tripled from 493,000 in 1980 to over 1.7 million in 2010. Adults with diabetes are 2 to 4 times more likely to have heart disease or a stroke than adults without diabetes. The American Heart Association considers diabetes to be one of the 6 major controllable risk factors for cardiovascular disease.

Coronary heart disease has been directly linked to disorders of metabolic homeostasis, which are characterized by endothelial dysfunction and insulin resistance. The overall benefits observed with statins seem to be greater than would be expected from lowering lipid levels alone, suggesting statins’ effects beyond cholesterol control. These cholesterol-independent or “pleiotropic” effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. These properties of statins have not being completely elucidated.

Statins may regulate normal glucose metabolism in either beneficial or adverse ways. One of the newest and more controversial effects is the development of new-onset type 2 diabetes mellitus. Statins, particularly at a high dose, may cause unfavorable pleiotropic effects such as impairment in insulin secretion and worsening of insulin resistance.

Statins’ effects related to worsening insulin resistance are:

• inhibition of glucose-stimulated elevations of free calcium in the cytoplasm of beta cells, leading to impaired insulin secretion;

• down-regulation of expression of the insulin- responsive glucose transporter GLUT4 and up-regulation of glucose transporter GLUT1;

• and inhibition of isoprenoid biosynthesis, an intermediate product of cholesterol formation.

In order to determine whether individual statins may have differential effects on insulin sensitivity in patients without pre-existing diabetes mellitus, a systematic review and metaanalysis was conducted through December 2008.

 Each statin was analyzed separately versus placebo. Pravastastin significantly improved insulin sensitivity, atorvastatin and rosuvastatin tended to mildly worsen insulin sensitivity, and simvastatin significantly worsened insulin sensitivity. This systematic review and meta-analysis demonstrates that statins do not have a “class effect” on insulin sensitivity in patients without diabetes.

Another meta-analysis of randomized controlled trials suggest potential differences between individual statins, with pravastatin showing a trend toward a reduction in risk and atorvastatin, rosuvastatin, and simvastatin together demonstrating a significant increase in risk versus placebo.

 A recent meta-analysis reported that statin therapy is associated with a 9% increase in risk for incident diabetes. Risk of development of diabetes with statins was highest in trials of older patients.

 The 2 trials with the lowest calculated occurrence of diabetes (AFCAPS/TexCAPS and WOSCOPS) were primary prevention trials with low diabetes risk.

 The 4 trials with the highest frequency of incident diabetes included participants known to be at high risk of diabetes: PROSPER (participants were 70 to 82 years of age with or at high risk of cardiovascular disease), GISSI Prevenzione (myocardial infarction within the last 6 months), GISSI HF, and CORONA (patients with heart failure, a well-known diabetogenic state).

 Studies have also shown some evidence of a dose-dependent association of statin use with development of type 2 diabetes. Use of higher-dose statin compared with a moderatedose statin has been associated with a higher incidence of new-onset diabetes.

These multiple trials highlight the need for more prospective, large, randomized clinical trials to examine the effects on overall mortality as well as cardiovascular and metabolic morbidity with the use of different statins. Until then, it is difficult to weigh the risk of adverse metabolic consequences of statins against their beneficial effects on cardiovascular events. Whether new-onset diabetes or worsening of diabetes is causally related to cardiovascular outcomes remains unknown. Clinical trials designed to maintain optimal glucose control in a diabetic population have shown a reduction in the incidence of myocardial infarction, suggesting that glucose itself might play some role in the physiopathology of cardiovascular disease.

Even with the possible side effect of statins worsening glycemic control and increasing the risk of new-onset type 2 diabetes mellitus, the risk of statin use remains absolutely outweighed by the cardiovascular benefit in patients with an indication for statin use. One important consideration that can be extrapolated from this new evidence is that statin use should not being recommended for patients at low cardiovascular risk or patients in whom cardiovascular benefit has not been proved and in whom a potential risk for development of diabetes has to be considered. The magnitude of statins’ benefit matches or exceeds benefits with other secondary prevention medications such as aspirin, ß-blockers, and angiotensin-converting enzyme inhibitors in patients after myocardial infarction. In clinical practice, statins are still recommended for primary and secondary prevention of coronary heart disease.

1. Baker WL, Talati R, White CM, Coleman CI. Differing effect of statins on insulin sensitivity in non-diabetics: a systematic review and meta-analysis. 

2. Koh KK, Sakuma I, Quon M. Differential metabolic effects of distinct statins. 

3. Sattar N, Preiss D. Statins and risk of incident diabetes: a collaborative meta-analysis of randomized statin trials. 

4. Primary Prevention of Acute Coronary Events with Lovastatin in Men and Women with Average Cholesterol Levels Results of AFCAPS/TexCAPS. 

5. West of Scotland Coronary Prevention Group. West of Scotland Coronary Prevention Study: identification of high-risk groups and comparison with other cardiovascular intervention trials. 

6. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomized controlled trial. 

7. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomized, double-blind, placebo-controlled trial. 

8. Effects of Statin Therapy According to Plasma High-Sensitivity C - reactive protein Concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). 

9. Preiss D, Welsh P. Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy. 

Clinical Forum

Should Concerns About Developing Diabetes Impact the Use of Statins?

 summarizes 6 studies presented at the 23rd Annual Echo Hawaii conference, held January 21-25, 2013, at Kohala Coast, Big Island, HI. The Echo Hawaii conference presents the latest information on established and emerging cardiovascular ultrasound technologies, with a focus on how state-of-the-art technologies can be effectively applied in the clinical setting. The meeting is jointly sponsored by the American Society of Echocardiology (ACE) and the ACE Foundation.

Aortic Knob Calcification on Chest X-ray Predicts Atheroma of Distal Aortic Arch on TEE

Kyung Won Yun, MD, of the Pusan National University Yangsan Hospital, Yangsan, Republic of Korea, presented data showing a correlation between aortic knob calcification (AKC) on chest x-ray and atheroma of the distal aortic arch detected by transesophageal echocardiography (TEE). The study was the first to show the correlation, and suggests that chest x-ray is a useful screening method to provide important clinical information about aortic atheroma.

From January to December 2011, 410 patients who were to undergo TEE at the cardiovascular center at Pusan National University Yangsan Hospital were selected for possible inclusion in the study. After excluding patients who did not undergo chest x-ray or who had an unknown family history or lipid profile, 322 consecutive patients (197 male, 125 female; mean age, 62.2) were included in the final study.

Atheroma thickness was measured in the distal aortic arch and the proximal descending thoracic aorta. Atheroma thickness was divided into <5 mm and ≥5 mm. Atheroma was classified as simple (presence of calcification only) and complex (presence of calcification with ulceration or mobile plaque or hypoechoic area).

Chest x-rays were rated for presence or absence of calcification in the aortic knob, and graded as grade 0 (no calcification), grade 1 (localized in the aortic arch, below the 50% girth and thickness[<2 mm]), or grade 2 (presence of multiple calcification beyond aortic knob or 50% circumference of aortic knob or heavy thickness [≥ 2 mm]) of calcification.

Patients with higher-grade calcification were more likely to be female (P = 0.16), older (P <0.001), have a history of diabetes mellitus (DM) (P <0.001), and lower highdensity lipoprotein (HDL) cholesterol level (P = 0.007). Hypertension was more frequent in the group of patients with grade 1 calcification (P <0.001).

The study showed that the higher the grade of AKC observed, the thicker the atheroma. More patients with grade 2 AKC had ≥5 mm atheroma thickness and complex atheroma (P <0.001) than did patients with lower grades of AKC.

After adjustment for age, sex, DM status, hypertension, and HDL, grade 1 AKC was associated with a 4.7-fold increase of ≥5 mm atheroma thickness (95% confidence interval [CI], 1.907-11.450) and 4.6-fold increased risk of complex atheroma (95% CI, 2.056- 10.356). Grade 2 AKC was associated with a 7.2-fold increased risk of ≥5 mm atheroma thickness (95% CI, 2.139-24.319) and a 21.1- fold increased risk of complex atheroma (95% CI, 6.312-70.797).

Epicardial Adipose Tissue: Can It Predict Metabolic Syndrome in the Elderly?

Interest has grown in the assessment of epicardial adipose tissue (EAT) because of its potential clinical association with metabolic syndrome (MetS). Previous studies have largely been conducted on a younger population (<50 years) for predicting cardiovascular risk. Researchers from Hofstra North Shore Long Island Jewish School of Medicine and St Luke’s- Roosevelt Hospital Center in New York used echocardiography to assess EAT in the elderly population (>70 years) of patients referred for echo evaluation between January 2010 and May 2012. Patients with prior cardiac surgery or pericardial disease were excluded.

EAT thickness (EAT-th) was determined in the parasternal long axis view by measuring the echo-free space between the outer RV free wall myocardium and the visceral pericardium at end-systole. MetS was determined based on clinical chart review using currently accepted NCEP ATP III guidelines.

EAT-th was measured in 101 patients (30% male; 72 ±10 years; BMI 30±8 kg/m2). Mean EAT-th was higher in patients with MetS (P = 0.008). In univariate analysis, EAT correlated with the presence of MetS, hypertension, and diabetes mellitus. In multivariate analysis, hypertension and DM correlated with EAT.

The AUC for EAT-th as a predictor of MetS was 0.67 (SE, 0.06; 95% CI, 0.54-0.79; P = 0.01), with an EAT-th cutoff of 7.6 mm, yielding a sense of 71% and spec of 56% for detecting MetS.

The study confirmed the positive correlation between EAT-th and MetS risk factors in an elderly population. The clinical relevance of the findings is not yet determined. If found at a later time, EAT could suggest an underlying metabolic disorder that would merit further investigation.

Is Pocket Ultrasound Accurate for Assessment of LV Function?

Rapid bedside assessments of cardiac function are extremely valuable in critical care settings. Pocket ultrasound devices promise high-quality 2-dimensional (2D) images at a reasonable price, ease of use, and extreme portability.

Australian doctors from Princess Alexandra Hospital in Brisbane studied 45 consecutive patients with clinically indicated transthoracic echocardiograms (TTEs) and limited 2D imaging of the LV with a pocket-sized device to assess whether these pocket devices are accurate at predicting left ventricular (LV) function. All examinations were performed by an experienced sonographer. LV function was assessed from the standard views by an experienced and novice physician and sonographer, and graded to be of normal, mild, moderate, and severe dysfunction. Presence or absence of regional wall motion abnormalities (RWMAs) were also noted.

Of the 45 patients examined, 53% were males and the median age was 60 years; all patients had images of acceptable quality. Normal LV function was seen in 68.9% of patients. Cohen’s kappa (k) showed a strong agreement between the standard and pocket devices in LV function assessed by an experienced reader (91%, k = 0.82; P <0.01)and sonographer (86%, k = 0.73; P <0.01) . Novice sonographers and readers could accurately interpret LV function 79% and 62% of the time, respectively. RWMAs were accurately detected with the pocket device.

The researchers concluded that pocket devices can be used to reliably assess LV function. “They are easy to use, with results comparable to standard equipment and little interobserver variability,” they said, and can be used effectively by novice users with a limited learning curve.

Effect of Bariatric Surgery on Cardiac Mechanics in Obese Patients

Bariatric surgery is considered a therapeutic option for morbidly obese patients, with data showing that this surgery may improve major cardiovascular morbidity and mortality. South Korean researchers, led by Sung-Hee Shin, MD, of Inha University Hospital in Seoul, assessed the changes in left ventricular (LV) mechanics after bariatric surgery in 23 obese patients. Patients had undergone Roux-en-Y gastric bypass for obesity (age = 39 ± 12 years; males:females = 6:17).

	measurements were measured. LV global longitudinal, circumferential, and radial deformations were assessed using 2-dimensional speckle tracking software.

	Bariatric surgery resulted in a significant weight reduction of 27.8 ± 17.5 kg over 14.7 ± 3.8 

	months (P <0.001). LV size and mass decreased significantly and the ratio of early-to-late diastolic mitral inflow and early diastolic tissue Doppler velocity increased postoperatively. While LV ejection fraction did not significantly change, LV longitudinal strain significantly increased after surgery. LV circumferential and radial strains were comparable at follow-up. (Figure)

	The researchers concluded that in obese patients, significant weight loss by bariatric surgery led to regression of LV hypertrophy and improvement in LV longitudinal deformation and diastolic function. Therefore, they believe their findings may lend support to other data showing that bariatric surgery has beneficial effects for future cardiovascular outcomes in obese patients.

Determinant Factors of Elevated Plasma B-Type Natriuretic Peptide Level in Severe Aortic Stenosis

	Elevated plasma B-type natriuretic peptide (BNP) level is a predictor of outcome and can help predict risk stratification in aortic stenosis (AS). However, progression of left ventricular (LV) diastolic dysfunction with aging may influence plasma BNP levels in elderly patients with AS. Japanese researchers led by Shunsuke Sasaki, MD, of the Sakakibara Heart Institute in Tokyo hypothesized that determinant factors for elevated plasma BNP level may be different in elderly versus younger patients with AS.

	They performed echocardiography in 341 patients with severe AS (aortic valve area [AVA] <1.0 cm2), and classified them into 2 groups by age (elderly ≥75 years, n = 201; younger <75 years, n = 140). Patients with chronic renal failure and other significant valvular disease were excluded. Multivariate linear regression analysis was used to assess determinant factors for plasma BNP level separately in both groups.

	Both elderly and younger patients had similar AVA indices: 0.46 ± 0.13 cm2/m2 and 0.46 ± 0.12 cm2/m2 (P = 0.06), respectively. However, elderly patients had an increased ratio of mitral peak velocity of early filling (E’) to early diastolic mitral annular velocity (E’) (E/e’) (20 ± 8 and 16 ± 6; P <0.01) compared with younger patients.

	LV ejection fraction, LV mass index, E/e’, estimated systolic pulmonary artery pressure, and the presence of atrial fibrillation were found to be independent determinants of plasma BNP level in both elderly patients and younger patients.

	The researchers concluded that there may be differences in determinant factors of plasma BNP level between elderly and younger patients with AS. In elderly patients with AS, plasma BNP levels may be more influenced by diastolic dysfunction rather than AS severity compared with younger patients.

Prognostic Value of Left Atrial Volume Index Change After Primary Coronary Intervention in Patients With STEMI

	Left atrial volume index (LAVI) is 1 prognostic indicator for acute myocardial infarction. Values of 32.0 mL/m2 or more have been associated with poor prognosis. However, little is known about the usefulness of LAVI dynamic changes after primary coronary intervention (PCI) in patients with STelevation myocardial infarction (STEMI).

	Donghan Kim, MD, and colleagues from the Republic of South Korea analyzed 244 eligible STEMI patients undergoing PCI, performing echocardiographic studies at baseline and at 12 months, with clinical follow-up at 30.8 ± 7.5 months. Patients were divided into 2 groups according to the degree of change in LAVI derived from the previous report: change in LAVI ≤2.5 mL/m2 (n = 146) and change in LAVI >2.5 mL/m2 (n = 98). The primary end point was the composite of major adverse cardiac events including death, atrial fibrillation, hospitalization on heart failure, and revascularization.

	In multivariate Cox regression analysis adjusted for male gender, glomerular filtration rate (GFR), smoking, Killip class (≥III), heart rate, history of ischemic heart disease, statin use, BNP, left ventricular (LV) systolic function, LV end-diastolic dimension, LAVI, change in LAVI, stent diameter, successful PCI, follow-up LV systolic function, and diabetes mellitus, the change in LAVI >2.5 mL/ m2 group had significantly increased major adverse cardiac events (MACEs) in STEMI patients. However, there were no differences in death rates, including cardiac or noncardiac death and revascularization. Change in LAVI >2.5 mL/m2 was the independent prognostic factor of MACEs as well as GFR, and LV systolic function using ejection fraction.

	Dr. Kim and colleagues concluded that in STEMI patients undergoing primary PCI, change in LAVI is a useful parameter to predict MACE, including atrial fibrillation and hospitalizations for heart failure.

Prior to surgery patients had undergone echocardiography, which was repeated at least 1 year after bariatric surgery. Parameters including tissue Doppler 

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Vice Chairman, Department of Internal Medicine

Texas Tech University Health Sciences Center

Professor of Medicine and the Michael and

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Philip J. and Harriet L. Goodhart Professor of

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	In their study on unemployment’s effect on risks for acute myocardial infarction (AMI), Dupre et al 

			used statistical multivariate models to show that the risk for AMI was significantly higher among 

			unemployed individuals, with the risk especially elevated during the first year of unemployment.

 These significant results held even after adjustments for multiple clinical, socioeconomic, and behavioral risk factors.

			The study population consisted of adults in a continuing prospective cohort study of adults aged 51 to 75 years in the Health and Retirement Study (HRS), which is sponsored by the National Institute on Aging and the Institute for Social Research at the University of Michigan in Ann Arbor. The analytic sample was described as including a total of 13,451 participants from the original HRS birth cohort (1931-1941), the war baby cohort (1942 to 1947), and the early baby-boomer cohort (1948 to 1953). The first interviews for the authors’ study on unemployment were carried out in 1992, 1998, and 2004, respectively. The participants in HRS on average contributed approximately 8 person-years of exposure during the 18-year study period, with a total of1061 AMI events or occurrences reported during 165,169 person-years of observation. This AMI incidence was 7.9% over the study period and it was the primary outcome analyzed. Participants in the study were asked at each biennial interview whether a “heart attack” or myocardial infarction had happened to them in the preceding approximately 24-month interval since the last interview. The authors considered that the relatively short interval between interviews and the seriousness of the evaluated events decreased the potential for recall bias.

			It was found that adults who had experienced an AMI were more likely to be males in an older age group, non-Hispanic, and to live in the South than those who did not suffer an event. The initial model showed that unemployment status, the cumulative number of job losses, and the cumulative time without employment were all associated with AMI. This was independent of other aspects of the patients’ work history. The fully adjusted model demonstrated an independent association with incident AMI as assessed by hazard ratio (HR) and confidence interval (CI). This association with incident AMI by work history was as follows: status as unemployed (HR, 1.35 [95% CI, 1.10-1.66]); 1 job loss (HR, 1.22 [95% CI, 1.04-1.42]); 2 job losses (HR, 1.27 [95% CI, 1.05-1.54]); 3 job losses (HR, 1.52 [95% CI, 1.22-1.90]); and 4 or more total job losses (HR, 1.63 [95% CI, 1.29-2.07]). These findings were significant and comparable to AMI association with other major risk factors such as smoking (HR, 1.44 [95% CI, 1.24-1.68]) and diabetes mellitus (HR, 1.51 [95% CI, 1.30-1.75]). The risk for AMI was most significant in the first year of unemployment. The significance of rate for age-specific AMI for employed/unemployed was P <0.001; for the cumulative number of job losses, it was P <0.001. In contrast to job loss, it appears that a voluntary cessation of work, such as retirement, was not associated with increased AMI.

			1. Dupre M, George LK, Liu G, Peterson ED. The cumulative effect of unemployment on risks for acute myocardial infarction. 

			2. Crombie IK, Kenicer MB, Smith WC, et al. Unemployment, socioenvironmental factors, and coronary heart disease in Scotland. 

			3. Kritz-Silverstein D, Wingard DL, Barrett-Connor E. Employment status and heart disease risk factors in middle-aged women: the Rancho Bernardo Study. 

			4. Hintikka J, Lehto SM, Niskanen L, et al. Unemployment and ill health: a connection through inflammation? 

			5. Marmot MG, Rose G, Shipley M, et al. Employment grade and coronary heart disease in British civil servants. 

			6. Marmot MG, Bosma H, Hemingway H, et al. Contribution of job control and other risk factors to social variations in coronary heart disease incidence. 

			7. Wamala SP, Mittleman MA, Horsten M, et al. Job stress and the occupational gradient in coronary heart disease risk in women. The Stockholm Female Coronary Risk Study. 

			8. Kivimäki M, Nyberg ST, Batty GD, et al. Job strain as a risk factor for coronary heart disease: a collaborative meta-analysis of individual participant data. 

			9. Eller NH, Netterstrom B, Gyntelberg F, et al. Work-related psychosocial factors and the development of ischemic heart disease: a systematic review. 

			10. Skodova Z, Nagyova I, van Dijk JP, et al. Socioeconomic differences in psychosocial factors contributing to coronary heart disease: a review. 

			11. Ladwig KH, Emeny RT, Hafner S, et al. [Depression. An underestimated risk for the development and progression of coronary heart disease]. 

Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz

			What’s Behind Unemployment’s Heart Risks?

The findings of Dupre et al focus on stress as a cause of increased risk of AMI in the involuntarily unemployed. 

 An association between unemployment and coronary heart disease (CHD) has been reported but not with such an extensive analysis. Crombie et al analyzed unemployment, socioenvironmental factors, and CHD in Scotland in 1989,

 and found a strong association with several measures of social disadvantage in 56 local districts; the strongest association was with percentage of male unemployment. The Rancho Bernardo Study studied 242 women, aged 40 to 59 years, and found that those in management were healthier than unemployed women.

 Employed women smoked less, drank less alcohol, and exercised more, and although these differences were not statistically significant, their total cholesterol and fasting glucose levels were significantly lower. In searching for a mechanism for unemployment and ill health, Hintikka et al reported a possible link with unemployment as a source of acute and long-term psychosocial stress.

 Preliminary findings suggested stress-induced, low-grade inflammation as a link, due to increased interleukin-6 and high-sensitivity C-reactive protein levels in 225 general population Finnish subjects below the usual retirement age of 65 years. Inflammation and CHD appear associated.

			Marmot et al found a strong inverse association between employment grade and CHD mortality in British male civil servants.

 Men in the lowest employment grade had 3 to 6 times the CHD mortality of men in the highest employment grade. The lowest-grade employees were heavier for their height, had higher blood pressures and plasma glucose, smoked more, and participated in less leisure physical activity. The authors concluded the higher CHD mortality of British working-class men, also present in national statistics, could only partially be explained by known CHD risk factors. Besides unemployment, job control also appears to be a factor in CHD. Marmot et al also reported on the second Whitehall Study,

 in which self-reported angina and chest pain, and physiciandiagnosed ischemia, were studied. Men in the lowest employment grade had an ageadjusted odds ratio for new CHD of 1.50 compared with men in the highest grade; the result for women was similar, with an odds ratio for the lowest grade of 1.47. The largest factor in socioeconomic gradient in CHD frequency appeared to be a low level of control at work. In the Stockholm Female Coronary Risk Study in 292 women, Wamala et al found the lowest occupational class (semi/unskilled) had a 4-fold (95% CI, 1.75-8.83) increased risk for CHD compared with the highest class (executive/ professional).

 However, job stress in the lowest occupational classes could not alone explain their increased CHD risk, resulting in consideration of interacting sources of work/non-work stress mediated by behavioral/ biological factors. In a metaanalysis of 13 European cohort studies involving men and women, Kivimäki et al found that there was an association between job strain and CHD for sex, age groups, socioeconomic strata, and region.8 After adjusting for socioeconomic status, lifestyle risk factors, and conventional risk factors, the population-attributable risk for job strain was 3.4%.

 In a systematic review, Eller et al reported that in more recent studies, the association between work and CHD was better explained by the association between demands and CHD risk.

 There was insufficient evidence to establish a relationship between CHD and effort-reward imbalance, injustice, job insecurity, or long working hours. Thus, job control may be important, but establishing nontraditional CHD risk is not proven science.

			Depression appears to be an important psychosocial factor in CHD. Skodova et al reported in a review of 301 articles published from 1994 to 2007 that socioeconomic status including education, occupation, or income was adversely associated with psychosocial factors linked to CHD, especially evident with hostility and depression.

 There were similar trends with social support, health perception, and decreased optimism. Anger and perceived stress had a lesser association. Ladwig et al looked at depression as an underestimated cardiovascular (CV) disease risk factor in 4 meta-analyses considering psychobiological pathways.

 They reported depressed individuals have an unhealthier lifestyle (poor nutrition, smoking, and less physical activity). Ladwig et al considered the possible effect of depression acting on 3 major psychobiological pathways directly acting on the circulation: (1) hyperregulation of the autonomic nervous system; (2) overshooting endocrine stress responses with impaired feedback such as cortisol release; and (3) modified immune system with altered release of acute phase proteins and proinflammatory cytokines, leading to platelet activation and flow-mediated endothelial dysfunction.

			For most workers, unemployment represents a major life stress. Such stress in and of itself could lead to PTSD and has well-established mechanisms associated with acute CV events. Dupre et al

 have defined the significance of unemployment in the causation of AMI as a major CV event. Their findings impose on employment counselors and physicians the reality of added CV risk and emphasize the importance of maximizing the prevention of psychosocial and traditional CV risk factors.

			Thomas F. Whayne, Jr, MD, PhD, is Professor of Internal Medicine in the Division of Cardiovascular Medicine at the Gill Heart Institute at the University of Kentucky in Lexington. He received his MD from the University of Pennsylvania, and did his internships and residency at The New York Hospital-Cornell Medical Center. Dr Whayne has a PhD in Biochemistry from the University of California in San Francisco. He has been named one of America’s Top Physicians since 2004 and a Top Cardiologist since 2006. He is fluent in Spanish and has authored numerous publications in both Spanish and English and presented his work nationally and internationally.

Dupre ME, George LK, Liu G, Peterson ED. The cumulative effect of unemployment on risks for acute myocardial infarction. 

CME Reviews

Effects of Unemployment Stress on the Risk of Acute MI

	In his recent commentary, “The Future of Obamacare,” published in the 

, Jonathan Oberlander, PhD, of the University of North Carolina, Chapel Hill, expresses his views on the imminent implementation of the Patient Protection and Affordable Care Act (ACA), passed in 2010 and upheld by the US Supreme Court in June 2012.

 Republicans have few or minimal options for repeal or derailment of the ACA after the November 2012 reelection of President Obama and the retention of majority Senate control by Democrats. 

	Dr. Oberlander points out that Republicans are left without viable options for overturning the ACA through legislative or executive action, as the earliest a Republican will potentially be in the White House is 2017, which is why the GOP considered the 2012 elections to be pivotal to the future and formation of US health care. The basic tenets of the ACA will have been implemented and in effect for 3 years by the time the next presidential election is held. It will be difficult to take health care benefits away from the public once they are actualized.

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Effects of Unemployment Stress on the Risk of Acute MI

The Future and Formation of US Health Care

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