Preventative Cardiology in the Office: Part I
Preventative Cardiology in the Office: Part I
Author: James J. Maciejko, MS, PhD, FACC, Director, Lipid Clinic, Botsford General Hospital, Farmington Hills, MI; and Associate Professor of Medicine, Wayne State University School of Medicine, Detroit, MI.
Peer Reviewers: Sydney Goldstein, MD, Division Head Emeritus, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, MI; and Jon M. Sweet, MD, Assistant Professor of Medicine, Wright State University School of Medicine, OH.
Editor’s Note—Although mortality rates for coronary heart disease (CHD) have been declining in recent years, CHD still remains the no. 1 cause of death and disability in the United States. The cost of our interventional procedures and drugs to manage symptomatic CHD (e.g., balloon angioplasty, stents, low-molecular-weight heparins, glycoprotein II-b-IIIa inhibitors, and bypass surgery) should lead us to pause and reconsider the benefits of prevention and risk stratification. This two-part series will explore the identification of these risk factors and our better understanding of them and provide the primary care physcian effective strategies for intervention. The next issue will highlight Category II, III, and IV risk factors and provide a summary of the recommendations in order of importance.
Introduction
Control or cure of most infectious diseases in the industrialized countries has led to chronic illnesses, becoming the major health problems in those nations. Although a decline in rates has been observed over the past 30 years,1,2 cardiovascular diseases remain the leading cause of death and disability in the United States. Approximately 75% of cardiovascular disease deaths are the result of atherosclerosis, which causes coronary heart, cerebral vascular, and peripheral vascular diseases. Forty percent of first major CHD episodes result in death within 30 days,3 and survivors of a first myocardial infarction (MI) have a several-fold increase in the probability of death during the next 5-10 years compared to the risk for persons without a prior history of CHD.4 These facts highlight the importance of primary prevention as a major clinical strategy for better control of this epidemic. This does not suggest that prevention to reduce reoccurrence of clinical events for those already afflicted with CHD is not of value (i.e., secondary prevention), rather, it emphasizes that secondary prevention, emergency service, and long-term medical and surgical interventions alone are not sufficient to reduce this healthcare burden. A major challenge of healthcare professionals is to control and significantly reduce atherosclerotic cardiovascular disease (ASCVD) in the United States.
Implementation of a strategy combining public health efforts for the general population and specific clinical efforts for persons and families at high risk for ASCVD are necessary. An essential component of this approach involves efforts beginning early in life that promote healthy habits in children. Physicians can contribute to this prevention effort by effectively interacting with their patients and families.
People who develop ASCVD have common predisposing characteristics. These characteristics are called risk factors and are reliable predicators of an individual’s likelihood of developing ASCVD. Risk factors have been categorized in several ways including modifiable vs. nonmodifiable, acquired vs. biochemical/physiological, causal vs. associative, and chronic vs. acute. The 27th Bethesda Conference held in 1995 ("Matching the Intensity of Risk Factor Management with the Hazard for Coronary Disease Events") classified ASCVD risk factors according to "descending levels of evidence to support direct management."5,6 This format allows for prioritization of ASCVD risk factors relative to their significance. Four risk factor categories have been proposed: 1) risk factors for which interventions have been proved to reduce the incidence of coronary artery disease (CAD) events; 2) risk factors associated with increased CAD risk that, if modified, will likely reduce the incidence of CAD events; 3) risk factors associated with increased CAD risk that, if modified, might reduce the incidence of CAD events; and 4) risk factors associated with increased CAD risk that cannot be modified or whose modification would be unlikely to change the incidence of CAD events (see Table 1). This categorization format allows the primary care physician to focus on those risk factors for which there is evidence that their modification favorably affects outcome.
| Table 1. Risk Factors for Atherosclerosis Based on Priority | ||||
| Category |
|
|
|
|
| Risk Factors | Smoking | Diabetes Mellitus | Psychosocial Factors | Age |
| Hypercholesterolemia | Sedentary Lifestyle | Hypertriglyceridemia | Gender | |
| Hypertension | Hypoalphalipoproteinemia | Hyper-Lp(a)lipoproteinemia | Positive Family History | |
| Hypercoagulability | Obesity | Hyperhomocystemia | ||
| Postmenopause | Oxidative Stress | |||
| Excess Alcohol Consumption | ||||
|
Adapted from: Pasternak RC, et al. Task Force 3. Spectrum of risk factors for coronary heart disease. J Am Coll Cardiol 1996;27:979-990. ________________________________________________________________________________________ |
||||
Category I Risk Factors (Highest Priority)
Cigarette Smoking. Cigarette smoking is the single most obvious and important risk factor for CAD and other atherosclerotic vascular diseases.7,8 Smoking accelerates atherosclerosis9 and leads to abnormalities of coronary arterial tone,10 of thrombogenesis,11 and of lipoprotein metabolism.12,13 The net consequence of smoking is an increased incidence of all clinical CAD sequelae including MI,14 unstable angina pectoris,15 sudden death,16 and ventricular dysfunction.17
The incidence of CHD in men by smoking status was examined in five prospective cardiovascular epidemiological studies in the United States as part of the National Cooperative Pooling Project.18 All of the studies documented higher incidences of CHD in smokers than in nonsmokers. Additionally, a definitive dose-response relationship between the amount smoked and CHD risk in current smokers was also apparent. A study in women indicated a distinct relation between smoking and CHD mortality, with smoking accounting for half of all cardiovascular deaths.19 This study also demonstrated that casual women cigarette smokers were at enhanced risk of CHD.
Clinical data have shown that smoking cessation produces a substantial and prompt reduction in CHD death rates.20,21 Prospective smoking cessation studies demonstrate that CAD events decline more rapidly than overall death from CHD, with the greatest proportion of risk reduction occurring in the first several months after smoking cessation.8 Patients who continue to smoke after acute MI have an increase in the risk of death from reinfarction that is, on average, 33% higher than in patients who terminate smoking.22
Exposure to second-hand (passive) smoke may also increase risk. Second-hand smoke may be the third leading cause of preventable death in this country. It is estimated that passive smoking accounts for about 40,000 CHD deaths annually in this country.23
Healthcare professionals should set an example by not smoking and should take an active role in programs designed to dissuade all individuals, especially teenagers, from starting to smoke. A smoking history should be routinely obtained, and all patients should be informed that cigarette smoking causes ASCVD and lung cancer. All patients who smoke should be counseled to quit and should receive personal assistance both to stop smoking and to maintain an ex-smoker status. Patients with ASCVD and chronic obstructive pulmonary disease (COPD), as well as asymptomatic patients at high CHD risk, should receive special attention. Patients who are candidates for coronary artery bypass graft surgery (CABG) or arterial reconstructive surgery of the lower extremities should be advised of smoking-related surgical risks. Patients receiving oral contraceptives and a wide variety of cardiopulmonary medications should be instructed about possible adverse interactions between cigarette smoking and these medications.
Hypercholesterolemia. Hypercholesterolemia (i.e., elevated low-density lipoprotein [LDL]-cholesterol concentrations) is causally related to the development of atherosclerosis. The evidence linking an elevated LDL-cholesterol and ASCVD is derived from extensive epidemiologic and clinical trial data. The landmark epidemiologic (observational) studies are the Framingham Heart Study,24 the Seven Countries Study,25 and the PROCAM Study.26 These epidemiologic studies indicated a 2% increase in risk for CHD per 1% increase in the plasma LDL-cholesterol concentration.
Extensive interventional data from both primary- and secondary-prevention trials have demonstrated that lowering total and LDL-cholesterol concentrations reduces coronary events (unstable angina pectoris, acute MI), coronary mortality, and total mortality (see Table 2).27-36 The clinical benefit appears to be related to the degree of LDL-cholesterol reduction.35
| Table 2. Primary and Secondary Prevention Lipid-Lowering Trials | |||
|
|
|
MI/CAD Death |
|
| Primary Prevention Trials | |||
| LRC-CPPT | cholestyramine |
|
|
| WOSCOPS | pravastatin |
|
|
| AF/Tex CAPS | lovastatin |
|
|
| Secondary Prevention Trials | |||
| CDP | nicotinic acid |
|
|
| POSCH | partial ileal bypass |
|
|
| 4(S) | simvastatin |
|
|
| CARE | pravastatin |
|
|
| Post-CABG | lovastatin |
|
|
| LIPID | pravastatin |
|
|
|
Key: LRC-CPPT: Lipid Research Clinics-Coronary Primary Prevention Trial27 WOSCOPS: West of Scotland Coronary Prevention Study28 AF/TexCAPS: Air Force/Texas Coronary Atherosclerosis Prevention Study29 CDP: Coronary Drug Project30,31 POSCH: Program on the Surgical Control of the Hyperlipidemias32 4S: Scandinavian Simvastatin Survival Study33 CARE: Cholesterol and Recurrent Events Study34 Post-CABG: Post Coronary Artery Bypass Graft Study35 LIPID: Long-Term Intervention with Pravastatin in Ischemic Disease36 _________________________________________________________________________________ |
|||
Recently, three landmark trials with clinical end points, each using an HMG-CoA Reductase Inhibitor (i.e., statin) in conjunction with dietary therapy, have been completed and extend the evidence demonstrating that lowering LDL-cholesterol can increase overall survival in secondary and primary prevention, and can reduce CHD risk in patients without hypercholesterolemia. The Scandinavian Simvastatin Survival Study (4S),33 the West of Scotland Coronary Prevention Study (WOSCOPS),28 and the Cholesterol and Recurrent Events Study (CARE)34 collectively enrolled more than 15,000 patients. The 4S provided the first evidence that aggressive LDL-cholesterol lowering can significantly reduce all-cause mortality (30%) in patients with CHD. The risk of all-cause mortality was also reduced by 22% in the WOSCOP primary prevention study. Additionally, both of these studies demonstrated significant reductions in nonfatal MI and CHD death rate, the need for revascularization procedures, and stroke. The beneficial effect on nonfatal MI and CHD death applied to all subgroups including patients 55 years and older, patients 54 years and younger, and patients with and without multiple CHD risk factors (i.e., smokers, hypertensives, diabetics).
The CARE trial34 was a secondary prevention study in survivors of MI with average plasma levels of cholesterol (mean LDL-cholesterol, 137 mg/dL). The results from CARE indicated that LDL-cholesterol lowering can reduce coronary morbidity and mortality rates in CHD patients without hypercholesterolemia.
Although some of the lipid-lowering interventional trials were conducted in men only, treatment of women with hypercholesterolemia is also warranted. The Air Force/Texas Coronary Artery Prevention Study (AF/Tex CAPS)29 demonstrated that the effect of treatment with lovastatin on the rate of first acute major coronary events was greater in women than in men (46% vs 37% reduction in relative risk). 4S33 found that the reduction in risk of CHD morbidity and mortality from LDL-cholesterol lowering by simvastatin was equal in both genders.
Treatment of hypercholesterolemia in patients older than 70 years and without clinical evidence of atherosclerosis remains controversial. Although total cholesterol levels are slightly lower in older age groups, as compared to younger people, the prevalence of hypercholesterolemia in the elderly is substantial. Treatment of elevated total cholesterol or LDL-cholesterol levels is often advocated to prevent CHD, which is a leading cause of mortality and morbidity in this population. A current study, the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack (ALLHAT), is designed to address this issue by recruiting men and women older than 65 years of age.37 The results of the Established Populations for Epidemiologic Studies of the Elderly (EPESE)38 indicated that low high-density lipoprotein (HDL)-cholesterol predicts CHD mortality and occurrence of new CHD events in persons older than 70 years. The EPESE results suggest that lipid-lowering therapy should be considered in hyperlipidemic elderly patients with low HDL-cholesterol concentrations (< 35 mg/dL).
Approximately 35% of all American adults have a total cholesterol level that is associated with an increased risk of developing CHD. Initially, most individuals are candidates for lifestyle and dietary modifications. However, if such measures fail to improve LDL-cholesterol levels adequately, then combined diet and drug treatment should be considered.
A number of cholesterol-modifying drugs, including bile acid sequestrants, niacin, and statins, are effective in lowering LDL-cholesterol and have been shown to prevent coronary events. Statins have the advantage of a low side-effects profile and high compliance rate.
Current evidence indicates that cholesterol lowering is underused in patients with established CHD because of confusion over the degree of benefit they provide in patients with and without established CHD.39,40 Given the conclusive evidence of the benefits of cholesterol lowering in patients with established ASCVD, withholding cholesterol-lowering medication in such patients is irrational and dangerous. It is imperative that monitoring of cholesterol levels be incorporated into the management of patients with established CHD and that treatment be prompt and effective. The National Cholesterol Education Program (NCEP) provides guidelines for the selection of individuals for diet and pharmacologic therapy for hypercholesterolemia.41
Hypertension. Elevated blood pressure (BP) is a significant risk factor for ASCVD. Numerous studies have indicated a continuous relationship between systolic and diastolic arterial blood pressures and ASCVD risk.42,43 The Joint National Committee (JNC) VI report defines hypertension as a systolic BP of 140 mmHg or greater or a diastolic BP of 90 mmHg or greater.44 The diagnosis of hypertension is based on an average of two or more readings taken at two or more visits after an initial screening visit (see Table 3).
| Table 3. Classification of Blood Pressure for Adults 18 Years and Older | |
| Classification |
Pressure (mmHg) Pressure (mmHg) |
| Optimal |
|
| Normal |
|
| High-normal |
|
| Hypertension: | |
|
Stage 1
Stage 2 Stage 3 |
160-179 or 100-109 >= 180 or >= 110 |
|
Note: Based on the average of two or more readings taken at each of two or more visits after the initial screening. Adapted from: National Heart, Lung, and Blood Institute. Sixth Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure; Bethesda, MD: U.S. Department of Health and Human Services. National Institutes of Health, 1997.
|
|
Lifestyle modifications (e.g., weight reduction, smoking cessation, exercise) to reduce BP are highly encouraged with medications used as necessary to normalize BP. One of the new features of the JNC VI report is the use of risk stratification.44 It was reasoned that the risk of cardiovascular disease in hypertensive patients is related not only to the level of BP but also to the presence of additional risk factors, and target organ damage or clinical cardiovascular disease. The need for pharmacologic therapy is determined according to the components of risk stratification and the level of blood pressure (see Table 4). Risk group A is associated with no risk factors other than an elevation in BP and no target organ damage or clinical signs of cardiovascular disease. Risk group B has at least one risk factor (not including diabetes mellitus), in addition to hypertension, and no target organ damage or clinical cardiovascular disease. Risk group C has target organ damage or clinical cardiovascular disease and/or diabetes mellitus with or without other cardiovascular risk factors. Patients with proteinuria greater than 1 g/d should be treated to a goal BP of 125/75 mmHg. Diabetics and patients with renal insufficiency and less than 1 g/d of proteinurea should be treated to a goal BP of 130/85 mmHg.44
| Table 4. Recommendations for Treating High Blood Pressure Based on Risk | |||
|
(no risk factors or TOD/CCD)* |
(at least 1risk factor, not including diabetes; no TOD/CCD) |
(TOD/CCD and/or diabetes, with or without other risk factors) |
|
| Blood Pressure Stages | |||
| High-normal | Lifestyle modification | Lifestyle modification | Drug Therapy |
| Stage 1 | Lifestyle modification
(up to 12 months) |
Lifestyle modification
(up to 6 months) |
Drug Therapy |
| Stages 2 or 3 | Drug Therapy | Drug Therapy | Drug Therapy |
|
Note: Lifestyle modification should be adjunctive therapy for all patients recommended for pharmacologic therapy. * TOD/CCD, target organ disease/clinical cardiovascular disease For patients with heart failure, renal insufficiency, or diabetes mellitus For patients with multiple risk factors, physicians should consider pharmacologic agents as initial therapy with lifestyle modifications. _________________________________________________________________________________ |
|||
Lifestyle modifications including weight loss, sodium restriction (< 2.4 g sodium/d), smoking cessation, increase in aerobic activity, and reduction in alcohol intake should always be included in the treatment of hypertension. For patients with uncomplicated conditions, diuretics or beta blockers are preferred as initial therapy.
Certain clinical situations require specific anti-hypertensive medications. MI requires beta-blocker therapy without intrinsic sympathomimetic activity and angiotensin-converting enzyme (ACE) inhibitors when systolic dysfunction is present. Patients with Type 1 diabetes mellitus and proteinurea would benefit from ACE inhibitors. For congestive heart failure, ACE inhibitors and diuretics are preferred. Diuretics are suggested for older patients with isolated systolic hypertension, although long-acting dihydropyridine calcium antagonists may be used.44
There is evidence that reducing BP decreases the development of cardiovascular disease including CAD, cerebralvascular disease, and heart failure.45,46 Although the reduction in coronary events in some of these studies was less than expected from the magnitude of BP reduction,45 this observation should not diminish acceptance of the role of hypertension in the production of ASCVD or the importance of its treatment.5
It is essential to recognize, evaluate, and treat every patient with an elevated arterial pressure. Lowering BP reduces the risk of complication from hypertension, stroke, and CHD, and decreases the occurrence of cardiovascular morbidity and mortality. In future years, newer and improved therapies should become available and they will likely be associated with even lower morbidity and mortality from hypertension. However, this cannot be achieved without constantly screening for new patients with unrecognized hypertension.
Thrombogenic Factors. Acute MI generally follows occlusion of a coronary artery by a thrombus. Aspirin has been documented to reduce both primary and secondary CHD events, affirming that reduction of thrombogenic potential improves outcome.47 A number of prothrombotic factors have been identified and quantified, and these factors have been shown to be associated with increased CHD risk and events. However, treatment of any single thrombogenic variable has not yet been adequately shown to significantly lower CHD risk.
Low-dose aspirin therapy is a useful pharmacologic intervention for the prevention and treatment of acute thrombotic events. Aspirin irreversibly inhibits platelet cyclooxygenase and thromboxane A2 production, resulting in an inhibition of platelet aggregation. This inhibition of platelet function dramatically reduces the risk of acute thrombosis, an effect that can be achieved with a dose of 80 mg aspirin each day (i.e., "baby" aspirin).48
Randomized clinical trials have demonstrated the benefit of aspirin in both the secondary and primary prevention of cardiovascular disease. In a recent overview of 25 trials of antiplatelet therapy among patients with established vascular disease, the use of aspirin was associated with a 32% overall reduction in subsequent nonfatal MI, a 27% reduction in subsequent nonfatal stroke, and a 15% reduction in total cardiovascular mortality.49 Among subjects with unstable angina, aspirin therapy has been associated with a 37% reduction in cardiovascular death.50,51 The Second International Study of Infarct Survival (ISIS-2) demonstrated that aspirin therapy reduced nonfatal reinfarction by 50%, reduced nonfatal stroke by 46%, and reduced total cardiovascular mortality by 23%.52
Aspirin has been shown to reduce the risk of a first acute MI in people without ASCVD. Two randomized trials of the primary prevention of occlusive vascular disease have been reported—the Physicians’ Health Study53 and the British Doctors’ Trial.54 The Physicians’ Health Study, which included 22,000 males, demonstrated a 44% reduction in the incidence of MI in the physicians (ages 40-84 years) receiving aspirin (325 mg every other day) compared to the physicians taking a placebo. However, the British Doctor’s Trial of 5000 male physicians found no difference in MI or cardiovascular death between the group taking aspirin (500 mg/d) and the group not taking aspirin. There was a very small increase in disabling strokes in the aspirin-treated group.54 Based on the current data, the United States Preventative Services Task Force recommends that physicians consider aspirin therapy to prevent a first MI among men at heightened risk.55 Although no randomized trial data of aspirin therapy in women are available, epidemiologic studies have suggested similar benefit.56
There are several disease states that are associated with hypercoagulability and increased incidence of thrombosis (see Table 5). Although the number of patients with these disorders is small, it is important to consider them since early identification can lead to significant improvements in clinical care.
| Table 5. Clinical States Associated with Hypercoagulability and Increased Risk of Thrombosis |
| Primary abnormalities of coagulation and fibrinolysis |
Antithrobin III deficiency |
| Secondary abnormalities of coagulation and fibrinolysis |
Malignant neoplasm |
| Abnormalities of platelet function |
Myeloproliferative disorders |
| Abnormalities of blood vessels and rheology |
Venous stasis__________________________________________________ |
References
1. Gillum R. Trends in acute myocardial infarction and coronary heart disease in the United States. J Am Coll Cardiol 1994;23:1273-1277.
2. Rosamon WD, et al. Trends in the incidence of myocardial infarction and in mortality due to coronary heart disease, 1987 to 1994. N Engl J Med 1998;339:861-867.
3. Stamler J, Foreword, in Pearson, TA, Criqui, MH, Luepker, RV, Oberman, A, Winston, M. (eds.): Primer in Preventative Cardiology. Dallas, American Heart Association, 1994; i-iv.
4. Kannel WB, et al. Prognosis after initial myocardial infarction: The Framingham Study. Am J Cardiol 1979;44:53-59.
5. Pasternak RC, et al. Task Force 3. Spectrum of risk factors for coronary heart disease. J Am Coll Cardiol 1996; 27:978-990.
6. Furberg CD, et al. Task Force 2. Clinical epidemiology: The conceptual basis for interpreting risk factors. J Am Coll Cardiol 1996;27:976-978.
7. Holbrook JH, et al. Cigarette smoking and cardiovascular diseases. A statement for health professionals by a task force appointed by the steering committee of the American Heart Association. Circulation 1984;70:114A-1117A.
8. The Health Consequence of Smoking: Cardiovascular Disease. A Report of the Surgeon General, publication DHHS (PHS) 84-50204. U.S. Department of Health and Human services, Public Health Services, Office on Smoking and Health. Rockville, Md, 1983.
9. Moise A, et al. Factors associated with progression of coronary artery disease in patients with normal and minimally narrowed coronary arteries. Am J Cardiol 1985; 56:30-34.
10. Fried LP, et al. Long-term effects of cigarette smoking and moderate alcohol consumption on coronary artery diameter. Am J Med 1986;80:37-44.
11. Folts JD, Bonebrake FC. The effects of cigarette smoke and nicotine on platelet thrombus formation in stenosed dog coronary arteries: Inhibition by phentolamine. Circulation 1982;65:465-470.
12. Stamford BA, et al. Cigarette smoking, exercise and high density lipoprotein cholesterol. Atherosclerosis 1984;52:73-83.
13. Fortmann SP, et al. Changes in plasma high density lipoprotein cholesterol after changes in cigarette use. Am J Epidemiol 1986;317:1303-1309.
14. Hartz AJ, et al. Smoking, coronary artery occlusion, and nonfatal myocardial infarction. JAMA 1981;246:851-853.
15. Ouyant P, et al. Variables predictive of successful medical therapy in patients with unstable angina; selection by multivariate analysis from clinical electrocardiographic, and angiographic evaluations. Circulation 1984;70:367-376.
16. Hallstrom AP, et al. Smoking as a risk factor for recurrence of sudden death. N Engl J Med 1986;314:271-275.
17. Hartz AJ, et al. The association of smoking with cardiomyopathy. N Engl J Med 1984;311:1201-1206.
18. Pooling Project Research Group: Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: Final report of the Pooling Project. J Chronic Dis 1978;31:201-306.
19. Willet WC, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med 1987;317:1303-1309.
20. Hermanson B, et al. Beneficial six year outcome of smoking cessation in older men and women with coronary artery disease. Results from the CASS registry. N Engl J Med 1988;319:1365-1369.
21. Rosenberg L, et al. The risk of myocardial infarction after quitting smoking in men under 55 years of age. N Engl J Med 1985;313:1511-1514.
22. Friedman GD, et al. Mortality in cigarette smokers and quitters. Effects of base-line differences. N Engl J Med 1981;304:1407.
23. Glantz SA, Parmley WW. Passive smoking and heart disease. Mechanisms and risk. JAMA 1995;273:1047-1053.
24. Kannel WP, et al. Serum cholesterol, lipoproteins, and the risk of coronary heart disease: The Framingham Study. Ann Intern Med 1971;74:1-12.
25. Keys A (ed): Coronary heart disease in seven countries. Circulation 1970;41(suppl 1):1-198.
26. Assmann G, Schulte H. Relation of high-density lipoprotein cholesterol and triglycerides to incidence of atherosclerotic coronary artery disease (the PROCAM experience). Am J Cardiol 1992;70:733-737.
27. Lipid Research Clinics coronary Primary Prevention Trial Results. I. Reduction in incidence of coronary heart disease. JAMA 1984;251:351-364.
28. Shepherd J, et al. For the West of Scotland Coronary Prevention Study Group. Prevention of coronary heart disease with pravastatin in men and hypercholesterolemia. N Engl J Med 1995;333:1301-1307.
29. Downs JR, et al. For the Air Force/Texas Coronary Atherosclerosis Prevention Study Group. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels. JAMA 1998;279:1615-1622.
30. The Coronary Drug Project Group. Clofibrate and niacin in coronary heart disease. JAMA 1975;231:360-381.
31. Canner PL, et al. Fifteen year mortality in the coronary drug project patients: Long-term benefit with patients. J Am Coll Cardiol 1988;8:1245-1255.
32. Buchwald H, et al. Effects of partial ileal bypass surgery on mortality and morbidity from coronary heart disease in patients with hypercholesterolemia: Report of the Program on the Surgical Control of the Hyperlipidemias (POSCH). N Engl J Med 1990;323:946-955.
33. Scandinavian Simvastatin Survival Study Group. Randomized trial of cholesterol lowering in 4444 patients with coronary heart disease: The Scandinavian simvastatin Survival Study (4S). Lancet 1994; 344:1383-1389.
34. Sacks FM, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. N Engl J Med 1996;335:1001-1009.
35. Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med 1997;336:153-162.
36. The Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med 1998;339:1349-1357.
37. Davis BR, et al. Rationale and design for the Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Am J Hypertens 1996;9:342-360.
38. Corti MC, et al. HDL-cholesterol predicts coronary heart disease mortality in older persons. JAMA 1995; 274:539-544.
39. Clinical Quality Improvement Network (CQIN) Investigators. Low incidence of assessment and modification of risks in acute care patients at high risk for cardiovascular events, particularly among females and the elderly. Am J Cardiol 1995;76:570-573.
40. Shepherd J, Pratt M. Prevention of coronary heart disease in clinical practice: a commentary on current treatment patterns in six European countries in relation to published recommendations. Cardiology 1996;87:1-5.
41. National Cholesterol Education Program Expert panel. Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). JAMA 1993; 269:3015-3023.
42. McGill HC, et al. General findings of the International Atherosclerosis Project. Lab Invest 1968;18:498-502.
43. MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part I, prolonged differences in blood pressure: Prospective, observational studies corrected for the regression dilution bias. Lancet 1990;335:765-774.
44. National Heart, Lung, and Blood Institute. Sixth Report of the Joint National Committee on Prevention, Detection, and Treatment of High Blood Pressure. Bethesda, MD: U.S. Department of Health and Human Services. National Institutes of Health. 1997.
45. Collins R, et al. Blood pressure, stroke, and coronary heart disease. Part II, short-term reductions in blood pressure: Overview of randomized drug trials in their epidemiological context. Lancet 1990;335:827-838.
46. Cutler JA, et al. Public Health Issues in Hypertension Control; What has Been Learned from Clinical Trials. In: Laragh JH, Brenner BM, eds. Hypertension: Pathophysiology, Diagnosis Management. 2nd ed. NY: Raven Press, 1995:253-270.
47. Hennekens CH, et al. Aspirin and other antiplatelet agents in the secondary and primary prevention of cardiovascular disease. Circulation 1989;80:746-756.
48. Ridker PM, Hennekens CH. Risk factors for acute thrombosis, in Pearson TA, Criqui MH, Luepker RV, Oberman A, Winston M (eds.): Primer in Preventative Cardiology. Dallas, American Heart Association, 1994; 205-216.
49. Antiplatelet Trialists’ Collaboration: Secondary prevention of vascular disease by prolonged antiplatelet therapy. Br Med J (Clin Res Ed) 1988;291:320-331.
50. Lewis HD, Jr., et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina. N Engl J Med 1983;309:396-403.
51. Cairns JA, et al. Aspirin, sulfinpyrazone, or both in unstable angina: Results of a Canadian multicenter trial. N Engl J Med 1985;313:1369-1375.
52. ISIS-2 (Second International Study of Infarct Survival) Collaborative Group: Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-360.
53. Steering Committee of the Physicians’ Health Study Research Group: Final report on the aspirin component of the ongoing Physicians’ Health Study. N Engl J Med 1989;321:129-135.
54. Peto R, et al. A randomized trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) 1988;29:313-316.
55. U.S. Preventive Services Task Force: Aspirin prophylaxis, in Guide to Clinical Preventive Services: An Assessment of the Effectiveness of 169 Interventions. Report of the U.S. Preventive Services Task Force. Baltimore, William and Wilkins, 1989.
56. Manson JE, et al. A prospective study of aspirin use and primary prevention of cardiovascular disease in women. Presented at 31st Annual Conference on Cardiovascular Epidemiology, March 14-16, Orlando, FL. 1992.
Readers are Invited
Readers are invited to submit questions or comments on material seen in or relevant to Primary Care Reports. Send your questions to: Robin Mason—Reader Questions, Primary Care Reports, c/o American Health Consultants, P.O. Box 740059, Atlanta, GA 30374. Or, you can reach the editors and customer service personnel for Primary Care Reports via the Internet by sending e-mail to [email protected]. You can also visit our home page at http://www.ahcpub.com. We look forward to hearing from you.
Subscribe Now for Access
You have reached your article limit for the month. We hope you found our articles both enjoyable and insightful. For information on new subscriptions, product trials, alternative billing arrangements or group and site discounts please call 800-688-2421. We look forward to having you as a long-term member of the Relias Media community.