Luther T. Clark

Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines

The Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued an evidence-based set of guidelines on cholesterol management in 2001. Since the publication of ATP III, 5 major clinical trials of statin therapy with clinical end points have been published. These trials addressed issues that were not examined in previous clinical trials of cholesterol-lowering therapy. The present document reviews the results of these recent trials and assesses their implications for cholesterol management. Therapeutic lifestyle changes (TLC) remain an essential modality in clinical management. The trials confirm the benefit of cholesterol-lowering therapy in high-risk patients and support the ATP III treatment goal of low-density lipoprotein cholesterol (LDL-C) <100 mg/dL. They support the inclusion of patients with diabetes in the high-risk category and confirm the benefits of LDL-lowering therapy in these patients. They further confirm that older persons benefit from therapeutic lowering of LDL-C. The major recommendations for modifications to footnote the ATP III treatment algorithm are the following. In high-risk persons, the recommended LDL-C goal is <100 mg/dL, but when risk is very high, an LDL-C goal of <70 mg/dL is a therapeutic option, ie, a reasonable clinical strategy, on the basis of available clinical trial evidence. This therapeutic option extends also to patients at very high risk who have a baseline LDL-C <100 mg/dL. Moreover, when a high-risk patient has high triglycerides or low high-density lipoprotein cholesterol (HDL-C), consideration can be given to combining a fibrate or nicotinic acid with an LDL-lowering drug. For moderately high-risk persons (2+ risk factors and 10-year risk 10% to 20%), the recommended LDL-C goal is <130 mg/dL, but an LDL-C goal <100 mg/dL is a therapeutic option on the basis of recent trial evidence. The latter option extends also to moderately high-risk persons with a baseline LDL-C of 100 to 129 mg/dL. When LDL-lowering drug therapy is employed in high-risk or moderately high-risk persons, it is advised that intensity of therapy be sufficient to achieve at least a 30% to 40% reduction in LDL-C levels. Moreover, any person at high risk or moderately high risk who has lifestyle-related risk factors (eg, obesity, physical inactivity, elevated triglycerides, low HDL-C, or metabolic syndrome) is a candidate for TLC to modify these risk factors regardless of LDL-C level. Finally, for people in lower-risk categories, recent clinical trials do not modify the goals and cutpoints of therapy.

Prevention Conference V Beyond Secondary Prevention : Identifying the High-Risk Patient for Primary Prevention : Noninvasive Tests of Atherosclerotic Burden : Writing Group III

Writing Group I of Prevention Conference V considered the role of routine office-based measures for assessing global risk in asymptomatic persons. With the physician-directed office risk assessment as a foundation, further risk stratification may be valuable, especially when the risk estimate is neither clearly low risk nor high risk (intermediate risk). For the intermediate-risk patient, further testing might include ≥1 noninvasive measure of atherosclerotic burden. Pathology studies have documented that levels of traditional risk factors are associated with the extent and severity of atherosclerosis. However, at every level of risk factor exposure, there is substantial variation in the amount of atherosclerosis. This variation in disease is probably due to genetic susceptibility; combinations and interactions with other risk factors, including life habits; duration of exposure to the specific level of the risk factors; and such factors as biological and laboratory variability. Thus, subclinical disease measurements, representing the end result of risk exposures, may be useful for improving coronary heart disease (CHD) risk prediction. Noninvasive tests such as carotid artery duplex scanning, electron beam–computed tomography (EBCT), ultrasound-based endothelial function studies, ankle/brachial blood pressure ratios, and magnetic resonance imaging (MRI) techniques offer the potential for directly or indirectly measuring and monitoring atherosclerosis in asymptomatic persons. High-sensitivity testing for C-reactive protein (hs-CRP) may also represent a measure of atherosclerosis “burden” and may therefore be considered another potential marker of atherosclerosis disease risk. The Prevention Conference V participants considered the status of several measures of subclinical disease in CHD risk assessment. The discussion that follows is a summary of the data reviewed and discussed at Prevention Conference V. During the discussion groups at Prevention Conference V, the ankle-brachial blood pressure index (ABI) was considered as a means of predicting CHD events. The ABI is a simple, inexpensive diagnostic test for lower-extremity peripheral arterial disease (PAD). …

Cardiovascular Preparticipation Screening of Competitive Athletes A Statement for Health Professionals From the Sudden Death Committee (Clinical Cardiology) and Congenital Cardiac Defects Committee (Cardiovascular Disease in the Young), American Heart Association

The sudden death of a competitive athlete is a personal tragedy with great impact on the lay and medical communities.1 Sudden deaths in athletes are usually caused by previously unsuspected cardiovascular disease.2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 Such an event often assumes a high public profile because of the generally held perception that trained athletes constitute the healthiest segment of our society. The death of a well-known elite athlete often emphasizes this visibility.1 21 Athletic field catastrophes strike to the core of our sensibilities and often galvanize us. They also inevitably raise a number of practical and ethical issues. This statement is a response to these considerations and represents the consensus of a panel appointed by the American Heart Association Science Advisory and Coordinating Committee. The panel comprised cardiovascular specialists, other physicians with extensive clinical experience with athletes of all ages, and a legal expert. The panel (1) assessed the benefits and limitations of preparticipation screening for early detection of cardiovascular abnormalities in competitive athletes; (2) addressed cost-efficiency and feasibility issues as well as the medical and legal implications of screening; and (3) developed consensus recommendations and guidelines for the most prudent, practical, and effective screening procedures and strategies (the recommendations are listed at the end of this statement). This endeavor seems particularly relevant and timely, given the large number of competitive athletes in this country, recent public health initiatives on physical activity and exercise, and the staging of the 1996 Olympic Games in the United States. The competitive athlete has been described as one who participates in an organized team or individual sport requiring systematic training and regular competition against others while placing a high premium on athletic excellence and achievement.20 The …

Impact of Completeness of Percutaneous Coronary Intervention Revascularization on Long-Term Outcomes in the Stent Era

Background— The importance of completeness of revascularization by percutaneous coronary intervention in patients with multivessel disease is unclear in that there is little information on the impact of incomplete revascularization outside of randomized trials. The objective of this study is to compare long-term mortality and subsequent revascularization for percutaneous coronary intervention patients receiving stents who were completely revascularized (CR) with those who were incompletely revascularized (IR). Methods and Results— Patients from New York States Percutaneous Coronary Interventions Reporting System were subdivided into patients who were CR and IR. Then subsets of IR patients were contrasted with CR patients. Differences in long-term survival and subsequent revascularization for CR and IR patients were compared after adjustment for differences in preprocedural risk. A total of 68.9% of all stent patients with multivessel disease who were studied were IR, and 30.1% of all patients had total occlusions and/or ≥2 IR vessels. At baseline, the following patients were at higher risk: those who were older and those with more comorbid conditions, worse ejection fraction, and more renal disease and stroke. After adjustment for these baseline differences, IR patients were significantly more likely to die at any time (adjusted hazard ratio=1.15; 95% confidence interval, 1.01 to 1.30) than CR patients. IR patients with total occlusions and a total of ≥2 IR vessels were at the highest risk compared with CR patients (hazard ratio=1.36; 95% confidence interval, 1.12 to 1.66). Conclusions— IR with stenting is associated with an adverse impact on long-term mortality, and consideration should be given to either achieving CR, opting for surgery, or monitoring percutaneous coronary intervention patients with IR more closely after discharge.

Volume-outcome relationships for percutaneous coronary interventions in the stent era.

Background—Most studies that are the basis of recommended volume thresholds for percutaneous coronary interventions (PCIs) predate the routine use of stent placement. Methods and Results—Data from New York’s Percutaneous Coronary Interventions Reporting System in 1998 to 2000 (n=107 713) were used to examine the impact of annual hospital volume and annual operator volume on in-hospital mortality, same-day coronary artery bypass graft (CABG) surgery, and same- stay CABG surgery after adjustment for differences in patients’ severity of illness. For a hospital-volume threshold of 400, the odds ratios for low-volume hospitals versus high-volume hospitals were 1.98 (95% CI, 1.17, 3.35) for in-hospital mortality, 2.07 (95% CI, 1.36, 3.15) for same-day CABG surgery, and 1.51 (95% CI, 1.03, 2.21) for same-stay CABG surgery. For an operator-volume threshold of 75, the odds ratios for low-volume versus high-volume operators were 1.65 (95% CI, 1.05, 2.60) for same-day CABG surgery and 1.55 (95% CI, 1.10, 2.18) for same-stay CABG surgery. Operator volume was not significantly associated with mortality. Also, for hospital volumes below 400 and operator volumes below 75, the respective odds of mortality, same-day CABG surgery, and same-stay CABG surgery were 5.92, 4.02, and 3.92 times the odds for hospital volumes of 400 or higher and operator volumes of 75 or higher. Conclusions—Higher-volume operators and hospitals continue to experience lower risk-adjusted PCI outcome rates.

Primary stent implantation compared with primary balloon angioplasty for acute myocardial infarction: a meta-analysis of randomized clinical trials

The clinical efficacy of primary angioplasty for acute myocardial infarction (AMI) is limited by recurrent myocardial ischemia during the hospital stay and restenosis in the months thereafter. 1 With the application of more effective poststenting antithrombotic regimens 2 and the improvement in stent implantation techniques, 3 coronary stenting is no longer considered contraindicated in thrombus-containing lesions and has gained substantial popularity in the setting of AMI. Recently, several randomized clinical trials have been conducted that compared coronary stenting and balloon angioplasty as the primary revascularization strategy for AMI. 4 ‐14 In the present study, we performed a meta-analysis of all the reported randomized trials to assess the overall comparative efficacy of these 2 strategies on major clinical outcomes in AMI.

Improving compliance and increasing control of hypertension: Needs of special hypertensive populations

Approximately 60 million people in the United States have hypertension. More than half are either untreated or treated without blood pressure control, despite the well-known risks of hypertension and the established benefits of treatment. The major reason for inadequate control of hypertension is poor adherence to treatment. Approximately 50% of patients with hypertension fail to keep follow-up appointments, and only 60% take their medications as prescribed. Barriers to effective therapeutic adherence include poor doctor-patient communication, cost of antihypertensive therapy, and side effects of the drugs. To increase control of hypertension, compliance with therapy must be improved. Physicians and patients must be mutually committed to achieving control of blood pressure. Physicians should communicate instructions clearly and prescribe therapies that are effective, affordable, and have minimal or no adverse effects on patient quality of life or overall cardiac risk profile. The needs of special hypertensive populations (i.e., elderly, black, and young patients) must also be recognized and addressed. Patients must follow recommendations and alert their physicians to any problems with their medications--particularly those relating to side effects and cost. When selecting drug therapy it should be noted that older patients are sensitive to volume depletion and sympathetic inhibition. In this group of patients, initial drug doses should be low and increments smaller and more gradual than in younger patients. Black patients with hypertension show an accentuated response to diuretics and blunted responses to beta-blockers and angiotensin-converting enzyme (ACE) inhibitors as monotherapy. However, when used with a diuretic, there are no racial differences in the blood pressure lowering effects of beta-blockers and ACE inhibitors.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronary Heart Disease in African Americans

African Americans have the highest overall mortality rate from coronary heart disease (CHD) of any ethnic group in the United States, particularly out-of-hospital deaths, and especially at younger ages. Although all of the reasons for the excess CHD mortality among African Americans have not been elucidated, it is clear that there is a high prevalence of certain coronary risk factors, delay in the recognition and treatment of high-risk individuals, and limited access to cardiovascular care. The clinical spectrum of acute and chronic CHD in African Americans is similar to that in whites. However, African Americans have a higher risk of sudden cardiac death and present more often with unstable angina and non-Q-wave myocardial infarction than whites. African Americans have less obstructive coronary artery disease on angiography, but may have a similar or greater total burden of coronary atherosclerosis. Ethnic differences in the clinical manifestations of CHD may be explained largely by the inherent heterogeneity of the coronary syndromes, and the disproportionately high prevalence and severity of hypertension and type 2 diabetes in African Americans. Identification of high-risk individuals for vigorous risk factor modification-especially control of hypertension, regression of left ventricular hypertrophy, control of diabetes, treatment of dyslipidemia, and smoking cessation--is key for successful risk reduction.

Discovering the full spectrum of cardiovascular disease: Minority Health Summit 2003: report of the Obesity, Metabolic Syndrome, and Hypertension Writing Group.

This article provides an overview of our current understanding of the epidemiology of obesity, the metabolic syndrome, and hypertension among racial/ethnic groups. Three presentations made at the conference by the present writing group are summarized and updated with other information on ethnic groups, and recommendations developed by the writing group for programs, public policy, and research are put forward.

Meta-analysis of the association of platelet glycoprotein IIIa PlA1/A2 polymorphism with myocardial infarction

This meta-analysis examined all the published reports up to October 1999 that studied the association between PlA2 polymorphism of platelet glycoprotein IIIa gene and myocardial infarction. The PlA2 polymorphism was not found to be associated with an increased risk of myocardial infarction, either overall or in selected subgroups, which were patients with premature disease onset (age < or = 60 years), first acute myocardial infarction, and patients who were men, women, and exclusively Caucasian.