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THE LATE US SENATOR (D, KY) AND VICE PRESIDENT Alben Barkley enjoyed telling the story of his encounter with a disgruntled constituent. “ ‘I recalled how I had helped get an access road built to his farm, how I had visited him in a military hospital . . . , how I had assisted in securing him veteran benefits, . . . how I had got him a disaster loan. . . . Surely you remember all these things I have done for you?’ ‘Yeah,’ the fellow said, ‘I remember. But what have you done for me lately?’” In 1948, when Barkley was elected vice president (under President Harry S Truman), the National Heart Institute launched the Framingham Heart Study, an innovative and now internationally recognized population-based epidemiological project that brought together prominent scientists with members of the community of Framingham, Massachusetts. Thirteen years later, in 1961, the Framingham investigators introduced the term risk factor into the medical lexicon. They described the links between incident coronary heart disease and hypertension, hypercholesterolemia, and electrocardiographic left ventricular hypertrophy. Later reports described other risk factors, including smoking and diabetes. These early discoveries led to further research in risk factor elucidation and management, management that has contributed to the remarkable 50-year decline in cardiovascular mortality in the United States. Yet today, despite these extraordinary contributions, the value of epidemiology is questioned. Critics cite excess expense, repudiated findings, studies that offer small incremental knowledge, inability to innovate at reasonable cost, and failure to identify research questions with the greatest merit. At a time of unprecedented budgetary constraints, these critics wonder what epidemiology has done for medical science lately. A survey of the field suggests 2 answers: much and not enough. That epidemiology continues to provide important knowledge is evident in 2 reports published in this issue of JAMA. In one report, Safford and colleagues analyzed the course of more than 24 000 participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Compared with white men and women, black men and women, who comprised more than 40% of the cohort, were more likely to smoke; be obese; and have diabetes, hypertension, and renal dysfunction. During 4 years of follow-up, black men and women had substantially higher rates of fatal coronary heart disease; in regression models, these higher rates were largely accounted for by the risk factors. The REGARDS findings are consistent with other reports of persistent health disparities and highlight the likely important role of risk factors, some of which are reversible, among some racial/ethnic groups. In another report in this issue of JAMA, Daviglus and colleagues describe the prevalence of cardiovascular risk factors in a large, diverse population-based cohort of US Hispanic and Latino individuals, including more than 15 000 participantsofCuban,Dominican,Mexican,PuertoRican,Central American, and South American origin. The burden of risk factors was high: 80% of men and 71% of women had at least 1 risk factor. Persons of Puerto Rican origin carried an especially high burden, with 25% having at least 3 risk factors. Risk factor burden was also associated with levels of education, immigration history, and preferred language. The reports by Safford et al and by Daviglus et al send a powerful and sobering message: despite 50 years of epidemiological knowledge and despite numerous therapeutic advances, risk factor burdens among minority populations are unacceptably high and consequential. Both reports offer, with appropriately cautious language, how their findings might translate into clinical and public health interventions that could reduce disparities. Still, critics of the US biomedical research enterprise suggest that not enough is being done. More specifically, they wonder why researchers are not working more closely with patients, clinicians, and policy makers to improve public health in a more direct way. Some authorities note that clinical and population research takes place within separate spheres from clinical care and public health and that long-standing US models for governing and executing epidemiological studies are being eclipsed by non-US studies that are much larger, yet considerably less expensive. How then can researchers more effectively work across the boundaries prescribed by traditional stakeholder roles— epidemiologists, clinicians, patients, policy makers, funders, regulators, foodanddrugmanufacturers,urbanplanners, and others—where suchboundariesmightbe impediments to scientificdiscoveriesandthe translationsandusesof suchdiscoveries that will best improve public health? Oneapproachtostrategicdecisionmaking, results-basedaccountability,offersatransformativeprincipleforworkingacross boundaries.First,definetheconditionsofwell-beingforwhich nosingle stakeholdercanbesolelyaccountableand thenwork

ON OCTOBER 31, 1940, PRESIDENT FRANKLIN Delano Roosevelt dedicated the new Bethesda, Maryland, campus of the National Institutes of Health. As cardiovascular disease was emerging as the biggest threat to the nation’s health, and as threats of war loomed from Europe, Roosevelt declared, “Total defense . . . which the nation seeks, involves a great deal more than building airplanes, ships, guns, and bombs. We cannot be a strong nation unless we are a healthy nation. And so we must recruit not only men and materials but also knowledge and science in the service of national strength.” Nearly 61 years after Roosevelt’s dedication, the US government announced the Million Hearts initiative with a goal of preventing 1 million myocardial infarctions and strokes over 5 years “by implementing proven, effective, inexpensive interventions.” Centers for Disease Control and Prevention director Thomas Frieden and Centers for Medicare & Medicaid Services administrator Donald Berwick seek to implement the ABCS, namely, aspirin prophylaxis, reduction of blood pressure levels, reduction of cholesterol levels, and cessation of smoking. For each of these interventions, the research enterprise can take credit for discovering the problem and rigorously demonstrating, often through large-scale randomized trials, the value of clinical and public health interventions. The profound influence of cardiovascular research has been remarkable. Between 1960 and 2000, life expectancy in the United States increased by 7 years, with 70% of the increase attributable to fewer cardiovascular deaths. Improved cardiovascular health can be attributed to “high-technology” medicine, including cardiac surgery, acute revascularization, and defibrillators; “low-technology” medicine, including clinical and community management of blood pressure and cholesterol levels; and behavioral changes, in particular marked reductions in cigarette smoking. For each intervention, researchers played critical roles. Echoing Roosevelt, knowledge and science served admirably to improve national health. Yet all is not well. Cardiovascular disease remains the leading cause of death in the United States and in most of the world. In the United States, the nature of cardiovascular disease is changing, as thepopulationbecomesolder,moreobese, and more urban with substantial changes in nutrition, work, physical activity, and transportation.The incidenceandprevalence of acute ST-segment elevation myocardial infarction and rheumatic heart disease are decreasing while they are increasing for heart failure, degenerative aortic stenosis, peripheral arterial disease, and atrial fibrillation, conditions for which there is much to learn. Clinical cardiology has been criticized, as a recent magazine headline declared that “Cardiac care is a money-making machine that too often favors profit over science.” Nearly 90% of professional society recommendations are based on suboptimal evidence. Even though some cardiovascular research has been successful, much more needs to be accomplished. What is next for cardiovascular research? Several areas are likely to be of major importance.

SINCE BARACK OBAMA BECAME THE 44TH PRESIDENT OF the United States in January 2009, nearly all sectors of society have engaged in intense discussions about the best ways to stimulate the nation’s economy and reform the US health care system. The National Institutes of Health (NIH) has been—and will continue to be—in the middle of such conversations, emphasizing the power of biomedical research to show what health interventions yield the greatest benefits. Health reform and economic concerns may have moved comparative effectiveness research (CER) from relative obscurity into the public policy spotlight. However, CER is not a new concept to NIH, which has long recognized and supported the value of CER for providing evidence-based, wellvalidated approaches to medical care. For instance, nearly 2 decades ago, NIH-supported researchers published results of the Cardiac Arrhythmia Suppression Trial (CAST). To the surprise of many, 3 drugs that suppressed ventricular premature beats (encainide, flecainide, and moricizine) not only failed to reduce the risk of sudden cardiac death, but actually increased arrhythmic death rates. About 14 years later, the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), a comparative effectiveness trial funded by NIH, demonstrated that oral administration of the antiarrhythmic drug amiodarone proved no better than standard heart failure care (such as -blockade), whereas implantation of an internal cardioverter defibrillator reduced mortality by 23%. Despite the positive results of SCD-HeFT, only a subset of patients with heart failure derives benefit from implantable defibrillators. Consequently, NIH, the Agency for Healthcare Research and Quality (AHRQ), and the American College of Cardiology have joined together to support an observational CER study of 3500 patients receiving implantable cardioverter-defibrillators. The 31⁄2-year study, launched in January 2010, should help clinicians better gauge whether a patient is likely to benefit from a defibrillator. Other major CER efforts supported by NIH have compared antipsychotic drugs for the treatment of schizophrenia, strategies for preventing deaths from prostate cancer, antihypertensive medications, treatments for bullous emphysema, and approaches to preventing diabetes. A 2007 report by the CongressionalBudgetOfficecitedNIH’scomparativeeffectiveness studies asprimeexamplesof government-sponsored research that could directly inform clinical practice and public policy. Today, the biomedical research community has an unprecedented opportunity to build on this foundation. The United States urgently needs the evidence to design a system that offers health interventions that are both beneficial and cost-effective. The American Recovery and Reinvestment Act (ARRA) of 2009 appropriated $1.1 billion for CER, with $400 million of that funding allocated to NIH and the remainder to AHRQ and the Office of the Secretary of the Department of Health and Human Services. While the ARRA-mandated report of the Federal Coordinating Council acknowledged that NIH historically has been the largest source of federal support for CER, NIH has important partners in other government agencies, particularly AHRQ. NIH generally contributes to CER by supporting primary research, including both observational studies and randomized control trials. AHRQ’s strength is in conducting secondary comprehensive meta-analyses of multiple studies, seeking to identify overarching conclusions and propose practice guidelines. By the end of September 2009, NIH had committed most of its $400 million ARRA allocation for CER through a variety of mechanisms, including Challenge grants, larger-scale Grand Opportunity grants, pay line expansions, competitive revisions, and administrative supplements. To prioritize these spending decisions, a high-level, trans-NIH committee considered a variety of criteria that met the Federal Coordinating Council’s definition of CER. These criteria included potential public health benefit, variability in practice, low probability for support by nongovernmental sectors, potential for multiplicative effect, focus on diverse populations and subgroups, engagement of communities in research, and application to the stated priorities of the Medicare Modernization Act and the Institute of Medicine (IOM). In addition to providing a much-needed funding boost for CER, ARRA-related activities helped delineate 5 important challenges facing NIH as it considers how to use science to benefit health care reform.

Following the first convincing trials in humans on the benefits of cholesterol lowering for preventionof atheroscleroticrelated events, in 1985, then-Director of the National Heart, Lung, and Blood Institute Robert Levyasserted that the cholesterol“question”wasno longer whether to treat high cholesterol levels, but rather when, inwhom,andhow.1For 30years, it hasbeenwell known that lowering blood cholesterol concentrations by a variety of drugs and other approaches reduces cardiovascular disease (CVD) risk.2Withmore trials in patient groupswith lower risk, including thosewith relatively low levels of low-density lipoprotein cholesterol (LDL-C),3 it has become clear that atherosclerotic cardiovascular disease (ASCVD) canbeprevented by loweringLDL-C levels, especiallywith statindrugs,2,3 in broad segments of the general population. However, the critical questions—when, in whom, and how to lower cholesterol— still remain. This Editorial, with new evidence from 2 reports in this issueof JAMA, addresses 2 of thesequestions: inwhom and how to treat cholesterol levels in 2015. The 2013 American College of Cardiology/American Heart Association (ACC/AHA) cholesterol guidelines2 recommended consideration of statin treatment for 4 clinical scenarios: (1) patients with clinical ASCVD including those with myocardial infarction, angina, or previous coronary revascularization; (2) patients without clinical ASCVD but with an LDL-C level higher than 190 mg/dL and without secondary cause; (3) patients aged 40 through 75 years without clinical ASCVD but with diabetes mellitus and LDL-C levels from 70 through 189mg/dL; and (4) patients aged 40 through 75 years without clinical ASCVD and diabetes, but with an LDL-C level of 70 through 189 mg/dL and an estimated 10-year ASCVD risk of 7.5% or higher. For the first 3 clinical scenarios there was almost universal acceptance with general agreement that the new recommendations were based on strong and consistent data.4 However, nearly immediately after release of the guidelines therewas considerable scrutiny and controversy regarding the fourth clinical scenario: primary prevention in adults without diabetes butwith an estimated 10-yearASCVD risk of 7.5% or higher. One group reported a set of analyses suggesting that the new ACC/AHA Pooled Cohort Equation overestimated risk in various populations,5 whereas others reported that, in properly selected cohorts, the new equation performedmore accurately thanpreviouslyused risk equations.6 Uncertainties about the accuracy of the risk calculator raised concerns about the wisdom of the newly lowered treatment threshold.Would the new guidelines lead tomassive and unjustified overtreatment ofmillions of people? Thequestionof in whom to use statins lingered. Basedonevidence frommultipleclinical trials, statindrugs havebeenshownto lowerCVDrisk forprimarypreventioneven among relatively low-risk people and even among thosewith relatively low LDL-C concentrations.3 Although a 10-year ASCVD risk threshold of 7.5%orhighermight initially seem to be a low threshold, many, indeed most, CVD events occur among the low-riskmembers of thepopulation.7Rose first described theseemingparadox8 that relatively fewASCVDevents occur in high-risk individuals simply because there are so few high-risk people in the population. The vast majority ofASCVDeventsoccuramong lower-riskpersonsbecause they comprise the greatest portion of the population.9 To prevent manymoreASCVDevents, it is reasonable to considerwhether statin drugs should be used in lower-risk individuals, and whether risk assessment by the new Pooled Cohort Equation leads to a reasonable level of treatment of at-risk people and a rational use of medical resources, even if potentially billions of people worldwide would be recommended for statin drugs.10 In this issue of JAMA, 2 reports suggest that the new risk threshold is likely to be reasonable and cost-effective; it may not even go far enough. If true, even a risk calculator that overestimates risk might be reasonable to use in the clinical setting. In the first report, using FraminghamOffspring Study data, Pursnani et al11 sought to determine whether the 2013 ACC/AHA guidelines improved identification of individuals who developed incident ASCVD, had evidence of coronary artery calcium, or had both compared with the National Cholesterol Education Program’s 2004 Updated Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III) guidelines. As expected, among 2435 statin-naive people, the new Pooled Cohort Equation led to many more people being eligible for statin therapy (39% for ACC/AHA guidelines vs 14% for ATP III guidelines). However, the newly statin-eligible people were at markedly increased risk for experiencing clinical events, for having elevated levels of coronary calcium, or for having both. These findings offer assurance that the 2013 Pooled Cohort Equation can efficiently and appropriately identify those destined to develop a major ASCVD event in the near future. However, identifying those at risk with reasonable accuracy is only part of the decision-making process. An imporRelated articles pages 134 and 142 Opinion

ContextThe usefulness of exercise stress test results and global cardiovascular risk systems for predicting all-cause mortality in asymptomatic individuals seen in clinical settings is unclear.ObjectivesTo determine the validity for prediction of all-cause mortality of the Framingham Risk Score and of a recently described European global scoring system Systematic Coronary Risk Evaluation (SCORE) for cardiovascular mortality among asymptomatic individuals evaluated in a clinical setting and to determine the potential prognostic value of exercise stress testing once these baseline risks are known.Design, Setting, and ParticipantsProspective cohort study of 3554 asymptomatic adults between the ages of 50 and 75 years who underwent exercise stress testing as part of an executive health program between October 1990 and December 2002; participants were followed up for a mean of 8 years.Main Outcome MeasuresGlobal risk based on the Framingham Risk Score and the European SCORE. Prospectively recorded exercise stress test result abnormalities included impaired physical fitness, abnormal heart rate recovery, ventricular ectopy, and ST-segment abnormalities. The primary end point was all-cause mortality.ResultsThere were 114 deaths. The c-index, which corresponds to receiver operating characteristic curve values, and the Akaike Information Criteria found that the European SCORE was superior to the Framingham Risk Score in estimating global mortality risk. In a multivariable model, independent predictors of death were a higher SCORE (for 1% predicted increase in absolute risk, relative risk [RR], 1.07; 95% confidence interval [CI], 1.04-1.09; P

Randomized clinical trials remain the most reliable means of identifying the drugs, devices, and treatment strategies that will improve human health. There is increasing interest in the possibility that “personalized” medicine can be evaluated in much smaller trials because the average treatment effect is expected to be larger in highly selected cohorts. Smaller, biomarkerdriven trials can provide major insights into whom to treat and may be sufficient for selected disease states in which considerable treatment effects may be observed. However, a precise biological understanding of most chronic illnesses and biomarkers that might predict response has eluded investigators. Moreover, treatment effect sizes in chronic conditions are expected to be modest in most cases. As a result, determining the long-term balance of risk and benefit, particularly in comparative effectiveness trials, often requires large numbers of clinical events in representative populations. The conduct of large trials by government agencies, industry sponsors, academicians, and advocacy groups is limited by complexity and cost. As a result, many trials are too small to provide reliable estimates of the risk-benefit balance. Without adequate trials, clinicians will have insufficient guidance on how to meaningfully affect individual and population health. Achieving the “triple aim” (improving patient experience of care, improving health of populations, and reducing per

ContextAlthough aspirin has been shown to reduce cardiovascular morbidity and short-term mortality following acute myocardial infarction, the association between its use and long-term all-cause mortality has not been well defined.ObjectivesTo determine whether aspirin is associated with a mortality benefit in stable patients with known or suspected coronary disease and to identify patient characteristics that predict the maximum absolute mortality benefit from aspirin.Design and SettingProspective, nonrandomized, observational cohort study conducted between 1990 and 1998 at an academic medical institution, with a median follow-up of 3.1 years.PatientsOf 6174 consecutive adults undergoing stress echocardiography for evaluation of known or suspected coronary disease, 2310 (37%) were taking aspirin. Patients with significant valvular disease or documented contraindication to aspirin use, including peptic ulcer disease, renal insufficiency, and use of nonsteroidal anti-inflammatory drugs, were excluded.Main Outcome MeasureAll-cause mortality according to aspirin use.ResultsDuring 3.1 years of follow-up, 276 patients (4.5%) died. In a simple univariable analysis, there was no association between aspirin use and mortality (4.5% vs 4.5%). However, after adjustment for age, sex, standard cardiovascular risk factors, use of other medications, coronary disease history, ejection fraction, exercise capacity, heart rate recovery, and echocardiographic ischemia, aspirin use was associated with reduced mortality (hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.51-0.87; P = .002). In further analysis using matching by propensity score, 1351 patients who were taking aspirin were at lower risk for death than 1351 patients not using aspirin (4% vs 8%, respectively; HR, 0.53 ; 95% CI, 0.38-0.74; P = .002). After adjusting for the propensity for using aspirin, as well as other possible confounders and interactions, aspirin use remained associated with a lower risk for death (adjusted HR, 0.56; 95% CI, 0.40-0.78; P

ContextBoth attenuated heart rate recovery following exercise and the Duke treadmill exercise score have been demonstrated to be independent predictors of mortality, but their prognostic value relative to each other has not been studied.ObjectiveTo assess the associations among abnormal heart rate recovery, treadmill exercise score, and death in patients referred specifically for exercise electrocardiography.Design and SettingProspective cohort study conducted in an academic medical center between September 1990 and December 1997, with a median follow-up of 5.2 years.PatientsA total of 9454 consecutive patients (mean [SD] age, 53 [11] years; 78% male) who underwent symptom-limited exercise electrocardiographic testing. Exclusion criteria included age younger than 30 years, history of heart failure or valvular disease, pacemaker implantation, and uninterpretable electrocardiograms.Main Outcome MeasuresAll-cause mortality, as predicted by abnormal heart rate recovery, defined as failure of heart rate to decrease by more than 12/min during the first minute after peak exercise, and by treadmill exercise score, defined as (exercise time) − (5 × maximum ST-segment deviation) − (4 × treadmill angina index).ResultsThree hundred twelve deaths occurred in the cohort. Abnormal heart rate recovery and intermediate- or high-risk treadmill exercise score were present in 20% (n = 1852) and 21% (n = 1996) of patients, respectively. In univariate analyses, death was predicted by both abnormal heart rate recovery (8% vs 2% in patients with normal heart rate recovery; hazard ratio [HR], 4.16; 95% confidence interval [CI], 3.33-5.19; χ2 = 158; P

Context Chronotropic incompetence, an attenuated heart rate response to exercise, is a predictor of all-cause mortality in healthy populations. This association may be independent of exercise-induced myocardial perfusion defects. Objective To examine the prognostic significance of chronotropic incompetence in a low-risk cohort of patients referred for treadmill stress testing with thallium imaging. Design Prospective cohort study conducted between September 1990 and December 1993. Setting Tertiary care academic medical center. Patients Consecutive patients (1877 men and 1076 women; mean age, 58 years) who were not taking {beta}-blockers and who were referred for symptom-limited treadmill thallium testing. Main Outcome Measures Association of chronotropic incompetence, defined as either failure to achieve 85% of the age-predicted maximum heart rate or a low chronotropic index, a heart rate response measure that accounts for effects of age, resting heart rate, and physical fitness, with all-cause mortality during 2 years of follow-up. Results Three hundred sixteen patients (11%) failed to reach 85% of the age-adjusted maximum heart rate, 762 (26%) had a low chronotropic index, and 612 (21%) had thallium perfusion defects. Ninety-one patients died during the follow-up period. After adjustment for age, sex, thallium perfusion defects, and other confounders, failure to reach 85% of the age-predicted maximum heart rate was associated with increased risk of death (adjusted relative risk [RR], 1.84; 95% confidence interval [CI], 1.13-3.00; P=.01), as was a low chronotropic index (adjusted RR, 2.19; 95% CI, 1.43-3.44; P

Context.—Approximately 0.5% of all patients who undergo exercise testing develop a transient left bundle-branch block (LBBB) during exercise, but its prognostic significance is unclear.Objective.—To determine whether exercise-induced LBBB is an independent predictor of mortality and cardiac morbidity.Design.—Matched control cohort study. Between September 1990 and February 10, 1994, 17277 exercise stress tests were performed on patients.Setting.—Tertiary care, academic medical center.Patients.—From the cohort, 70 cases of exercise-induced LBBB were identified. The controls comprised 70 individuals without LBBB at rest or during exercise that matched the 70 cases based on age, test date, sex, prior history of coronary artery disease, hypertension, diabetes, smoking, and β-blocker use.Main Outcome Measures.—All-cause mortality, percutaneous coronary intervention, open heart surgery, nonfatal myocardial infarction, documented symptomatic or sustained ventricular tachydysrhythmia, or implantation of a permanent pacemaker or an implantable cardiac defibrillator.Results.—A total of 37 events (28 events from the exercise-induced LBBB cases and 9 from the control cohort) occurred in 25 patients (17 exercise-induced LBBB patients and 8 control patients) during a mean follow-up period of 3.7 (0.9 years) (median, 3.8 years [range, 0.9-5.2 years]). There were 7 deaths, of which 5 occurred among patients with exercise-induced LBBB. Four-year Kaplan-Meier event rates were 19% among exercise-induced LBBB patients and 10% among controls (log rank χ2, 5.2; P =.02). After further adjusting for small differences in age, exercise-induced LBBB remained associated with a higher risk of primary events (adjusted relative risk, 2.78; 95% confidence interval, 1.16-6.65; P =.02).Conclusion.—Exercise-induced LBBB independently predicts a higher risk of death and major cardiac events.

Rigorous methodological standards help to ensure that medical research produces information that is valid and generalizable, and are essential in patient-centered outcomes research (PCOR). Patient-centeredness refers to the extent to which the preferences, decision-making needs, and characteristics of patients are addressed, and is the key characteristic differentiating PCOR from comparative effectiveness research. The Patient Protection and Affordable Care Act signed into law in 2010 created the Patient-Centered Outcomes Research Institute (PCORI), which includes an independent, federally appointed Methodology Committee. The Methodology Committee is charged to develop methodological standards for PCOR. The 4 general areas identified by the committee in which standards will be developed are (1) prioritizing research questions, (2) using appropriate study designs and analyses, (3) incorporating patient perspectives throughout the research continuum, and (4) fostering efficient dissemination and implementation of results. A Congressionally mandated PCORI methodology report (to be issued in its first iteration in May 2012) will begin to provide standards in each of these areas, and will inform future PCORI funding announcements and review criteria. The work of the Methodology Committee is intended to enable generation of information that is relevant and trustworthy for patients, and to enable decisions that improve patient-centered outcomes.

ContextLower socioeconomic status (SES) confers heightened cardiovascular risk and mortality, although the mediating pathways are unclear.ObjectiveTo evaluate the extent to which exercise physiologic characteristics account for the association between lower SES and mortality.Design, Setting, and ParticipantsProspective cohort study of 30 043 consecutive patients living in 7 counties in northeast Ohio referred between 1990 and 2002 for symptom-limited stress testing for evaluation of known or suspected coronary artery disease. Follow-up for mortality continued through February 2004.Main Outcome MeasuresEstimated functional capacity in metabolic equivalents and heart rate recovery, physiologic characteristics that are determined directly from exercise; testing and all-cause mortality during a median follow-up of 6.5 years.ResultsMultivariable models adjusting for demographics, insurance status, smoking status, and clinical confounders demonstrated a strong association between a composite SES score based on census block data and functional capacity (adjusted odds ratio comparing 25th with 75th percentile values, 1.72; 95% confidence interval [CI], 1.56-1.89; P

DURING THE PAST DECADE, THERE HAS BEEN TREMENdous progress in identifying novel risk factors and precisely delineating the role of traditional risk factors associated with coronary heart disease (CHD), with substantial research advances related to the role of lipoproteinsandlipidmetabolism.Observationalstudieshaveestablished the relationship of serum cholesterol and other lipoproteins with CHD in specific subgroups. Clinical trials have demonstrated convincing benefits of cholesterol lowering for reducing death and myocardial infarction among patients with CHD as well as beneficial effects of cholesterol lowering for decreasing the incidence of cardiac events in patients without established coronary disease. Accurately synthesizing and appropriatelyapplying this rapidlyaccumulatingevidence into clinicalpractice isessential for reducingthemorbidityandmortality associated with coronary disease. Thus, the Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel (Adult Treatment Panel III [ATP III]) published in this issue of THE JOURNAL is most welcome. The NCEP expert panel, a multidisciplinary group that includes leading clinicians and researchers, provides a detailed summary of updated clinical guidelines for the detection, evaluation, and management of high blood cholesterol in adults. The Executive Summary is based on the comprehensive ATP III document, a more than 200-page detailed report that includes numerous tables and over 800 references, and in which the NCEP panel thoroughly evaluates current scientific information on cholesterol, applies a rigorous evidencebased framework, and carefully outlines the clinical and scientific rationale for the guidelines and recommendations. The marked increase in new information on lipoproteins thathasbecomeavailablesincepublicationofAdultTreatment Panel II in1993 has resulted inmanynewand important features in ATP III. Although the authors summarize some of the new features of the updated guidelines (in their Table 1), several aspects of the ATP III Report deserve special mention. First, among patients without clinical coronary disease, emphasis is placed on prospectively estimating absolute risk. Most clinical research literature reports relative risks with statements such as, “Patients with finding X were Y times more likely to have an event than patients without finding X.” Although this information is helpful, it is an important step away from actual clinical practice. Real physicians caring for real patients care about real, that is, absolute, risk. The important clinical question is, “What is this patient’s actual likelihood for developing disease?” In ATP III, patients with an absolute 10-year risk of .20% for developing clinical coronary disease are considered candidates for very aggressive therapy. This includes a lowdensity lipoprotein (LDL) cholesterol treatment goal of ,100 mg/dL and a recommendation to initiate drug therapy at an LDL level of .130 mg/dL. Patients with diabetes are also considered candidates for aggressive therapy, whether or not clinical coronary disease is present, because their absolute risk for major events is also very high. For patients with an estimated absolute risk of 10%-20%, somewhat less aggressive therapy is recommended, although the guidelines do suggest pharmacotherapy if needed to keep LDL levels ,130 mg/dL. To calculate absolute risk for developing new coronary disease, the ATP III Report presents a modification of the Framingham Risk Prediction Score. The scheme presented is slightly, but importantly, different from a previously published version in that it does not include diabetes, because diabetes is now considered a CHD equivalent rather than a risk factor. The scheme takes into account important interactions of age with smoking, age with total cholesterol, and systolic blood pressure with treatment. Despite the sophistication of the sex-specific models, these risk prediction–scoring instruments should be easy to incorporate into clinical practice. A second important feature of the ATP III Executive Summary is the inclusion of lipid abnormalities that go beyond elevated LDL cholesterol. The metabolic syndrome is a recently recognized constellation of findings thought to arise from insulin resistance and includes hypertension, abdominal obesity, hyperglycemia, elevated triglyceride levels, and low levels of high-density lipoprotein (HDL) cholesterol. Specific recommendations for treatment include weight control, physical activity, and a seemingly paradoxi

Objective. —To determine the relationship of varying degrees of obesity with left ventricular mass and geometry. Design. —Survey. Setting. —Population-based epidemiologic study. Participants and Methods. —M-mode echocardiograms, which were adequate for estimation of left ventricular mass, were obtained in 3922 healthy participants of the Framingham Heart Study. Measured height and weight were used to calculate body-mass index, a measure of obesity. Results. —Body-mass index was strongly correlated with left ventricular mass. After adjusting for age and blood pressure, body-mass index remained a strong independent predictor of left ventricular mass, left ventricular wall thickness, and left ventricular internal dimension ( P 2 . Conclusions. —Obesity is significantly correlated with left ventricular mass, even after controlling for age and blood pressure. The increase in left ventricular mass associated with increasing adiposity reflects increases in both left ventricular wall thickness and left ventricular internal dimension. ( JAMA . 1991;266:231-236)