Background: Level of alcohol consumption is associated with differential risk of atherosclerosis, but little research has investigated this association among HIV + persons. We evaluated the association between long-term alcohol use and incident atherosclerosis among HIV + persons. Methods: We utilized data from HIV + participants of the Women's Interagency HIV Study (n = 483) and the Multicenter AIDS Cohort Study (n = 305) without history of cardiovascular disease. Atherosclerosis was assessed two times by B-mode carotid artery ultrasound imaging from 2004 to 2013. Presence of plaque was defined as focal carotid intima-media thickness over 1.5 mm. Those with no plaque at baseline and plaque at follow-up were considered incident cases of atherosclerosis. Group-based trajectory models were used to categorize participants into 10-year drinking patterns representing heavy, moderate, or abstinent-low. Multivariable logistic regressions were conducted to assess the association of long-term moderate and heavy use on atherosclerosis, compared to abstinent-low. Results: Heavy alcohol consumption was not statistically significantly associated with risk for incident atherosclerosis in women (AOR 1.10, CI 0.40-3.02) or men (AOR 1.31, CI 0.43-4.00), compared to abstinence-low. Moderate consumption was associated with 54% lower odds for incident disease in men (AOR 0.46, CI 0.21-1.00), but not in women (AOR 1.08, CI 0.58-2.00). In cohort-combined analyses, alcohol consumption was not statistically significantly association with incident atherosclerosis (moderate AOR 0.78, CI 0.48-1.27; heavy AOR 1.33, CI 0.66-2.69). Conclusion: Moderate alcohol consumption was associated with a significant protective effect on incident atherosclerosis in men only. No other levels of alcohol consumption significantly predicted atherosclerosis in men and women compared to abstinent-low.

BACKGROUND:People living with HIV-infection (PLWH) have higher prevalence and earlier onset of cardiovascular disease (CVD), compared to uninfected populations. It is unclear how alcohol consumption is related to CVD among PLWH. OBJECTIVES:To summarize the current literature and strength of evidence regarding alcohol consumption as a risk factor for CVD among PLWH, to generate summary estimates for the effect of alcohol consumption on CVD outcomes, and to make recommendations for clinical practice and future research based on the findings and limitations of existing studies. METHODS:A systematic review was conducted using Pubmed/Medline to identify relevant peer-reviewed articles published between 1 January 1999 and 1 January 2014. After critical review of the literature, 13 studies were identified. Risk ratios were extracted or calculated and sample size weighted summary estimates were calculated. RESULTS:The prevalence of a CVD diagnosis or event ranged from 5.7-24.0%. The weighted pooled crude effect sizes were 1.75 (95% CI 1.06, 3.17) for general and 1.78 (95% CI 1.09, 2.93) for heavy alcohol use on CVD. The pooled adjusted effect size was 1.37 (95% CI 1.02, 1.84) for heavy alcohol use on CVD. Pooled estimates differed by CVD outcome and alcohol measure; alcohol consumption was most significant for cerebral/ischemic events. CONCLUSION:HIV clinicians should consider risk factors that are not included in the traditional risk factor framework, particularly heavy alcohol consumption. Neglect of this risk factor may lead to underestimation of risk, and thus under-treatment among PLWH.

OBJECTIVE:This study investigated the relation between psychotropic medication use and adverse cardiovascular (CV) events in women with symptoms of myocardial ischaemia undergoing coronary angiography.METHOD:Women enrolled in the Women's Ischemia Syndrome Evaluation (WISE) were classified into one of four groups according to their reported antidepressant and anxiolytic medication usage at study intake: (1) no medication (n = 352); (2) anxiolytics only (n = 67); (3) antidepressants only (n = 58); and (4) combined antidepressant and anxiolytics (n = 39). Participants were followed prospectively for the development of adverse CV events (for example, hospitalisations for non-fatal myocardial infarction, stroke, congestive heart failure and unstable angina) or all-cause mortality over a median of 5.9 years.RESULTS:Use of antidepressant medication was associated with subsequent CV events (HR 2.16, 95% CI 1.21 to 3.93) and death (HR 2.15, 95% CI 1.16 to 3.98) but baseline anxiolytic use alone did not predict subsequent CV events and death. In a final regression model that included demographics, depression and anxiety symptoms, and risk factors for cardiovascular disease, women in the combined medication group (that is, antidepressants and anxiolytics) had higher risk for CV events (HR 3.98, CI 1.74 to 9.10, p = 0.001 and all-cause mortality (HR 4.70, CI 1.7 to 2.97, p = 0.003) compared to those using neither medication. Kaplan-Meier survival curves indicated that there was a significant difference in mortality among the four medication groups (p = 0.001).CONCLUSIONS:These data suggest that factors related to psychotropic medication such as depression refractory to treatment, or medication use itself, are associated with adverse CV events in women with suspected myocardial ischaemia.

Background: Depression is associated with increased risk of death among patients with coronary disease. Cardiovascular autonomic dysregulation may be one of the mechanisms by which depression exerts its effects on cardiovascular function. The purpose of this study was to determine whether depressive symptoms are associated with low heart rate variability (HRV) and prolonged HR recovery after exercise testing in patients with coronary artery disease (CAD). Methods: The Psychophysiological Investigation of Myocardial Ischemia (PIMI) was a large, multicenter study designed to assess psychological and physiological correlates of stress in patients with CAD. One hundred and eighty-dight patients with CAD as evidenced by at least 50% blockage of one major artery and a previous positive exercise stress test were included in this study. Patients included in this report were not taking beta blockers. Cardiovascular functioning was. assessed by a modified Bruce protocol treadmill stress test. Measures of psychological functioning including the Beck Depression Inventory (BDI), were also obtained. Results: BDI scores were negatively correlated with HR recovery (r = -0.15,p =.04). Depression scores accounted for 3.5% of the variance in HR recovery when controlling for participant age (p < .01). Depressive symptoms were related to two HRV indices (ultra-low frequency, high frequency). Conclusions: Depressive symptoms are associated with cardiovascular autonomic nervous system dysfunction as assessed by HR recovery. This relationship is not merely due to an association of depression severity with beta blocker usage or a failure of depressed patients to achieve art adequate chronotropic response.

OBJECTIVES The purpose of this study was to investigate the possibility that some patients with coronary artery disease (CAD) but negative exercise or chemical stress test results might have mental stress-induced ischemia. The study population consisted solely of those with negative test results.BACKGROUND Mental stress-induced ischemia has been reported in 20% to 70% of CAD subjects with exercise-induced ischemia. Because mechanisms of exercise and mental stress-induced ischemia may differ, we studied whether mental stress would produce ischemia in a proportion of subjects with CAD who have no inducible ischemia with exercise or pharmacologic tests.METHODS Twenty-one subjects (14 men, 7 women) with a mean age of 67 years and with a documented history of CAD were studied. All subjects had a recent negative nuclear stress test result (exercise or chemical). Subjects completed a speaking task involving role playing a difficult interpersonal situation. A total of 30 mCi Tc-99m-sestamibi was injected at one minute into the speech, and imaging was started 40 min later. A resting image obtained within one week was compared with the stress image. Images were analyzed for number and severity of perfusion defects. The summed difference score based on the difference between summed stress and rest scores was calculated. Severity was assessed using a semiquantitative scoring method from zero to four.RESULTS Six of 21 (29%) subjects demonstrated reversible ischemia (summed difference score >= 3) with mental stress. No subject had chest pain or electrocardiographic changes during the stressor. Mean systolic and diastolic blood pressure and heart rate all increased between resting and times of peak stress.CONCLUSIONS Mental stress may produce ischemia in some subjects with CAD and negative exercise or chemical nuclear stress test results.

BACKGROUND:Depressive symptoms have been associated with increased cardiac morbidity and mortality rates, but the pathophysiologic mechanism linking depressive symptoms to cardiovascular outcome has yet to be fully understood. Lower heart rate variability has also been associated with increased risk of cardiac events in healthy individuals and in patients with coronary artery disease. Findings regarding a relationship between depressive symptoms and heart rate variability that could explain increased cardiovascular risk have been inconsistent across studies.METHODS:As an ancillary study to the Women's Health Initiative Observational Study, 3372 postmenopausal women aged 50 to 83 years were enrolled for further evaluation using 24-hour ambulatory electrocardiographic monitoring. A shortened version of the Center for Epidemiological Studies Depression Scale and the Diagnostic Interview Schedule were administered. Women with adequate electrocardiographic data and depressive symptom information and without coronary artery disease were analyzed (n = 2627).RESULTS:Two hundred sixty-nine women (10.2%) had depressive symptoms as measured using the 2 instruments. Women with depressive symptoms had a higher mean +/- SD heart rate (77.4 +/- 9.6 vs 75.5 +/- 8.5 beats/min) and lower heart rate variability than women without depressive symptoms. All differences remained significant after adjusting for age (P<.01).CONCLUSIONS:Women with depressive symptoms had significant reductions in heart rate variability and higher heart rates, suggestive of increased sympathetic tone. These findings may contribute to the increased cardiac morbidity and mortality rates associated with depression in other studies.

Department of Psychiatry; Washington University School of Medicine; St. Louis, Missouri; [email protected] (Freedland) Department of Medicine, Division of Cardiovascular Medicine; University of Florida, Malcom Randall VA Medical Center; Gainesville, Florida (Sheps)

During the past two years, Psychosomatic Medicine joined many of the leading medical journals in adopting the CONSORT, MOOSE, QUOROM, and STARD guidelines for reporting clinical trials, meta-analyses, and diagnostic studies. This year, we are implementing our own set of statistical analysis guidelines. In doing so, we are joining a much smaller number of journals. Whether we are setting a trend, or simply going out on a limb, remains to be seen. We decided to implement these new guidelines for several reasons. First, they will advance the journal’s mission of promoting methodologically rigorous psychosomatic research. Second, they will enable our contributors to avoid some of the most common statistical criticisms when they submit manuscripts for review, and they will spare our reviewers from having to consider these problems. Third, they will reduce uncertainty about the acceptability of certain statistical methods. The new guidelines address several basic statistical problems that frequently appear among the hundreds of manuscripts that are submitted to Psychosomatic Medicine every year. Some of these problems result from simple failures to follow well-established statistical practices, or from adherence to statistical practices that were once widely accepted but that have since become obsolete. Others reflect legitimate differences of opinion among statisticians, or decades-long methodological controversies that have sewn persistent uncertainty and confusion among the rest of us. Still others stem from the multidisciplinary nature of psychosomatic research: Certain statistical practices are extolled in some of our constituent disciplines but are anathema in others. We are starting out with a very small set of guidelines concerning 1) directional (one-tailed) hypothesis tests; 2) artificial categorization of continuous variables; 3) automated selection (eg, stepwise selection) regression models; and 4) covariate adjustment. We will implement additional guidelines only as the need arises, and we expect the list to grow rather slowly. Although a number of newer, more advanced statistical methods such as growth curve models have begun to supercede their older, less sophisticated analytical ancestors, we are not yet establishing any guidelines favoring the former over the latter. We may do so in the future, but this is currently a low priority. We are also in the process of developing guidelines regarding testing interactions, subgroup analysis of clinical trials, and the rather complex issue of multiple testing. It is important to note that we are implementing statistical guidelines, not requirements. Although the guidelines discourage the use of certain methods, they do not prohibit them under all circumstances. For example, categorizing a continuous variable into several groups may be a reasonable approach if the functional form of the relation under study is not linear and difficult to capture using a mathematical function such as the logarithm or exponent (though there are still preferred alternatives, such as modern curve fitting algorithms). The burden will be on the contributor to make a convincing case for deviations from the guidelines. Our guidelines primarily address the choice, use, and description of statistical methods, rather than the presentation of statistical results. Our Instructions to Authors includes only a limited set of specifications for tables and illustrations. Furthermore, the CONSORT and other statements listed above comprise general reporting guidelines for specific types of articles, but they provide little guidance as to the best ways to report statistical results. However, our reviewers frequently raise questions or concerns about the presentation of statistical results in tables, graphs, or text. Consequently, we are also adopting the statistical reporting recommendations presented in two standard manuals, How to Report Statistics in Medicine (1) and the Publication Manual of the American Psychological Association, 5th edition (2). In addition, we also recommend referring to Cleveland’s 1994 book, The Elements of Graphing Data (3) as a general guide to the effective graphical presentation of data. Contributors are asked to consult these manuals as needed when deciding how to present their results, and to cite supporting material from these sources in their response if they disagree with a reviewer’s position on a statistical reporting issue. Since these manuals offer little guidance on how to report the results of some of the newer, more advanced methods, it may be necessary to consult other authoritative sources as well. Our statistical guidelines are described in a document linked to the Instruction to Authors page on our journal’s web site, www.psychosomaticmedicine.org and on our manuscript management web site, psymed.editorialmanager.com. We welcome comments on the initial guidelines and suggestions for additional ones.

From the Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Malcom Randall VA Medical Center, Gainesville, Florida D.S.S.); and the Division of Cardiology, St. Luke's–Roosevelt Hospital Center, and the Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY (A.R.). Address correspondence and reprint requests to David S. Sheps, MD, MSPH, Department of Medicine, Division of Cardiovascular Medicine, University of Florida, Malcom Randall VA Medical Center, Gainesville, FL 32610-0277. E-mail: [email protected] Accepted for publication March 18, 2005. In accordance with CME accreditation guidelines, author David S. Sheps disclosed that he has served on the speakers' bureau for Pfizer. Alan Rozanski disclosed no real or potential conflicts of interest.

Purpose of review Coronary artery disease (CAD) is the leading cause of death in the United States and other developed countries. Along with a number of other factors thought to contribute to the high prevalence of CAD in developed societies (longer life expectancy, obesity, sedentary lifestyles), various psychological and social factors appear to promote the development or worsening of heart disease. It is well recognized that stress can be harmful to the cardiovascular system. The combination of the preexisting vulnerability and the major stressor are believed to result in cardiac arrhythmias and/or plaque rupture leading to death. Recent findings Recently, the epidemiologic evidence of a link between stress and CAD is very convincing, yet the biopsychosocial pathway that would explain how stress can lead to disease is less clear. Different types of psychological stress have been found to be associated with increased cardiovascular events. Evidence regarding the efficacy of psychosocial interventions is also presented. Summary It is suggested that, taken as a whole, evidence for a psychological and social impact on CAD morbidity and mortality is convincing.

Background: Mental stress testing is considered a reliable method for diagnosing patients with coronary heart disease (CHD) who may be at risk for future events. It has been shown recently that myocardial ischemia induced during mental stress tests is specifically associated with peripheral arterial vasoconstriction.Hypothesis: The study was undertaken to test the diagnostic capability of peripheral arterial tonometry (PAT) to detect peripheral arterial vasomotor changes.Methods: We monitored pulsatile finger blood volume changes using a specially designed finger plethysmograph, PAT that can detect peripheral arterial vasomotor changes. Equilibrium radionuclide angiography (ERNA) was simultaneously performed in 18 male patients at rest and during a mental arithmetic stress test with harassment. All patients had previously diagnosed coronary disease and positive exercise tests. Myocardial ischemia was diagnosed by ERNA when global ejection fraction fell greater than or equal to 8% during mental stress or new (or worsened) focal wall motion abnormalities occurred. Peripheral arterial tonometry tracings were considered abnormal when the pulse wave amplitude decreased by greater than or equal to 20% from baseline.Results: In 18 patients there were 16 usable studies. In eight patients, both ERNA and PAT were abnormal, and in six patients the tests were negative by both methods. In two cases, the results were discordant. Therefore, when considering an abnormal PAT tracing as indicative of mental stress-driven myocardial ischemia, concordance of the two methods was 88%.Conclusion: The use of PAT may facilitate both clinical testing and research during mental stress.

This issue of Psychosomatic Medicine marks the debut of the Statistical Corner. The goals of this new feature are to promote good statistical practices, to introduce readers to advanced statistical methods, to provide practical guides to specific techniques, and to address methodological issues in psychosomatic research. The articles will be invited and peer reviewed. We decided to launch this feature because there is a growing statistics gap in our field, and it is hindering the progress of psychosomatic research. Many of us are statistical dinosaurs, having been trained years ago when power analysis was an arcane art, practiced only by mysterious old wizards in the dark basements of biostatistics departments, and when ordinary analysis of variance was the most advanced technique we were required to study. Most of us thought that the statistical stone tools available to us at the time were the only ones we would ever need, and we had no idea that great advances in methodology would be achieved in the coming decades. Those advances have begun to transform our field, and the dinosaurs among us have to adapt to this evolving environment to avoid extinction. The gap has grown has grown large enough to swallow more recent trainees as well. Some of us were trained as behavioral scientists, but we find ourselves working at the interdisciplinary interface between behavioral science and medical research. We were trained in statistical methods for the behavioral and social sciences, and we lack formal training in biostatistics and epidemiology. Some of us have the opposite problem. Many psychologists, for example, learn nothing about survival analysis during their graduate training, and many epidemiologists learn nothing about structural equation modeling. Many physicians receive limited training in basic biostatistical methods and no training at all in most of the new, advanced methods. Regardless of our educational background, after we graduate and embark on our research careers, we soon discover that expert statistical consultation and collaboration are scarce resources. Consequently, many of us find ourselves struggling to understand a multitude of unfamiliar and formidable statistical methods and blithely misusing the familiar ones. The statistics gap is also an unintended consequence of our well-justified disdain for methodologically sophisticated trivia, ie, studies in which fancy, complicated statistical techniques are used to investigate dull, unimportant phenomena. Unfortunately, some of us are so turned off by fancy, complicated statistics that we assume that any study that employs them must be dull and unimportant, or at least not worth the effort to read. This attitude is becoming increasingly untenable because advanced methods are entering the mainstream of medical research and appearing in papers that have unquestionable scientific significance. We cannot afford to ignore these studies, so we have to equip ourselves to understand them. Some may grumble that these advanced methods are vexatious nuisances inflicted on us by statistical zealots who know nothing about the real world of clinical research, but that is, of course, nonsense. They are some of our most useful scientific tools. They are our Hubble telescopes, our CERN particle accelerators, our scanning tunneling microscopes. If we embrace them, they will enable us to study phenomena that were previously beyond our analytical grasp, and to see relationships that were previously invisible. They will also give us more accurate and replicable answers to our questions, and help us make the best use of our hard-earned data. Our first Statistical Corner paper is an excellent illustration of this point (1). In it, Dr. Maria Llabre and her colleagues at the University of Miami introduce us to an advanced technique called latent growth curve (LGC) modeling and illustrate its utility by meticulously dissecting some original data on cardiovascular recovery from stress. They show us how LGC modeling yields new insights that would never have been uncovered with less sophisticated methods. The paper includes some moderately difficult material, but readers who are fortunate enough to have attended Dr. Llabre’s workshop on growth curve modeling know that she is a very talented teacher and methodologist who makes the hard parts understandable. Some of the articles in the Statistical Corner may be easier to read than this one, and others may be harder, but all of them will be written for a broad audience rather than for expert statisticians. Some of them will, like this one, introduce readers to new advances in methodology. Others will help us to use familiar techniques more effectively, or show us where we are making methodological mistakes and how we can overcome them in order to improve the quality, credibility, and impact of psychosomatic research. We hope that our readers, reviewers, and contributors will find them to be useful. We also hope that they will find their way into the classrooms where the next generation of psychosomatic researchers is currently being trained. Although the Statistical Corner is unique in that it is tailored to the needs of the psychosomatic research community, Psychosomatic Medicine is not the first journal to throw out a methodological life preserver to save its readers from drowning in a sea of statistics. Some of the most informative papers have been published in the Journal of the American Medical Association in a series entitled “User’s Guides to the Medical Literature.” The entire series is available to subscribers through a link on JAMA’ s web site. The British Medical Journal has published many excellent and highly informative methodological papers in its “Education and Debate” series. They are available at www.bmj.org. Another outstanding resource is a book published by the American College of Physicians, entitled How to Report Statistics in Medicine(2). The Statistical Corner joins our recent endorsement of the CONSORT, MOOSE, and QUOROM guidelines as efforts to improve the quality and reporting of statistical methods in medical research. See www.consort-statement.org for further details on CONSORT for reporting clinical trials, MOOSE for reporting meta-analyses of epidemiological and other observational studies, and QUOROM for reporting meta-analyses of clinical trials. We are proud to launch the Statistical Corner and grateful to Dr. Llabre and her colleagues for getting the series off to an impressive start. The Statistical Corner will appear in every other issue of the journal. We welcome your feedback and suggestions for future articles. Department of Psychiatry Washington University School of Medicine St. Louis, MO Maryland Psychiatric Research Center Baltimore, MD Division of Cardiovascular Medicine Department of Medicine University of Florida Gainesville, FL

Psychosomatic Medicine: May 2004 - Volume 66 - Issue 3 - p 372 doi: 10.1097/01.PSY.0000129696.13858.43

In a recent editorial, Lane et al. [(1)][1]conclude that depression is probably not a risk factor for cardiac mortality. They assert that the SADHART and ENRICHD trials were designed to determine whether depression after myocardial infarction (MI) is causally linked to clinical prognosis and that

BACKGROUND:The Thrombolysis in Myocardial Infarction risk score (TIMI-RS) for unstable angina/non-ST elevation myocardial infarction (MI) was developed in patients presenting with unstable angina accompanied by high-risk features or non-ST elevation MI to determine early risk stratification. HYPOTHESIS:The validity in patients presenting for emergency care with symptoms suggestive of acute coronary syndrome (ACS) has not been well established, and the present study sought to do so by evaluating the TIMI-RS in a prospective fashion. METHODS:A prospective TIMI-RS using seven variables was calculated in 245 patients admitted to the hospital with symptoms suggestive of ACS: (1) age > 65, (2) three or more cardiac risk factors, (3) ST deviation, (4) aspirin use within 7 days, (5) two or more anginal events over 24 h, (6) history of coronary stenosis, and (7) elevated troponin. Patients were contacted at 30 days and data were collected concerning major adverse cardiac events. RESULTS:In patients presenting with chest pain, a higher TIMI-RS was associated with an increase in major adverse cardiac events within 30 days. We found that the 30-day event rate was 0% for a score of 1, 20% for a score of 2, 24% for a score of 3, 42% for a score of 4, 52% for a score of 5, and 70% for a score of 6 or 7 (p < 0.0001). CONCLUSIONS:The TIMI-RS successfully differentiates early risk for major adverse cardiac events in a general population presenting with symptoms suggestive of acute coronary syndrome. A simple bedside calculation of the TIMI-RS provides rapid risk stratification, allowing facilitation of therapeutic decision making in patients with symptoms suggestive of ACS.

OBJECTIVE:To describe factors influencing chest pain expression in patients with cardiac or noncardiac disease. METHODS:The authors conducted a case presentation and review of literature. RESULTS:Causes of chest pain are diverse. Psychologic factors influence chest pain expression commonly in patients with or without cardiac disease. CONCLUSIONS:Physicians and other therapists must be aware of psychologic influences on chest pain expression to provide optimal treatment to their patients.

Division of Cardiovascular Medicine Department of Medicine University of Florida Gainesville, FL 32610 Email: [email protected]

Sheps, David S. MD, MSPH; Freedland, Kenneth E. PhD; Golden, Robert N. MD; McMahon, Robert P. PhD Author Information