Coronary risk factors and plaque morphology in men with coronary disease who died suddenly.

BACKGROUND Cigarette smoking and abnormal serum cholesterol concentrations are risk factors for acute coronary syndromes, but the underlying mechanisms are poorly understood. We studied whether cigarette smoking and abnormal cholesterol values may precipitate acute coronary thrombosis and sudden death resulting from either rupture of vulnerable coronary plaques or erosion of plaques. METHODS We examined the hearts of 113 men with coronary disease who had died suddenly and also analyzed their coronary risk factors. We found an acute coronary thrombus in each of 59 men, and severe narrowing of the coronary artery by an atherosclerotic plaque without acute thrombosis (stable plaque) in 54. Cases of acute thrombosis were divided into two groups: 41 resulting from rupture of a vulnerable plaque (a thin fibrous cap overlying a lipid-rich core), and 18 resulting from the erosion of a fibrous plaque rich in smooth-muscle cells and proteoglycans. Vulnerable plaques that had not ruptured were counted in each heart. RESULTS Cigarette smoking was a risk factor in 44 (75 percent) of the men with acute thrombosis, as compared with 22 (41 percent) of the men with stable plaques (P<0.001). The mean (+/-SD) ratio of serum total cholesterol to high-density lipoprotein (HDL) cholesterol was markedly elevated in the men who died of acute thrombosis with plaque rupture (mean, 8.5+/-4.0) but only mildly elevated in the men without acute thrombosis (5.5+/-2.4; P<0.001) and in the men with thrombi overlying eroded plaques (5.0+/-1.8; P<0.001). Multivariate analysis showed an association between an elevated ratio of serum total cholesterol to HDL cholesterol and the presence of vulnerable plaques (P<0.001). CONCLUSIONS Among men with coronary disease who die suddenly, abnormal serum cholesterol concentrations - particularly elevated ratios of total cholesterol to HDL cholesterol - predispose patients to rupture of vulnerable plaques, whereas cigarette smoking predisposes patients to acute thrombosis.

[1]  L. Wilkins.  Natural history of aortic and coronary atherosclerotic lesions in youth. Findings from the PDAY Study. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[2]  C. Furberg,et al.  Reduction in coronary events during treatment with pravastatin. PLAC I and PLAC II Investigators. Pravastatin Limitation of Atherosclerosis in the Coronary Arteries. , 1995, The American journal of cardiology.

[3]  C. Brilla.  The cardiac structure‐function relationship and the renin‐angiotensin‐aldosterone system in hypertension and heart failure , 1994, Current opinion in cardiology.

[4]  D. Waters,et al.  Hyperlipidemia and coronary disease. Correction of the increased thrombogenic potential with cholesterol reduction. , 1995, Circulation.

[5]  S. Ellis,et al.  Pravastatin limitation of atherosclerosis in the coronary arteries (PLAC I): reduction in atherosclerosis progression and clinical events. PLAC I investigation. , 1995, Journal of the American College of Cardiology.

[6]  E. Arnesen,et al.  Smoking, serum lipids, blood pressure, and sex differences in myocardial infarction. A 12-year follow-up of the Finnmark Study. , 1996, Circulation.

[7]  J. Strong,et al.  Relation of glycohemoglobin and adiposity to atherosclerosis in youth. Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[8]  W. Kannel,et al.  Cardiac failure and sudden death in the Framingham Study. , 1988, American heart journal.

[9]  C. Furberg,et al.  Reduction in cardiovascular events during pravastatin therapy. Pooled analysis of clinical events of the Pravastatin Atherosclerosis Intervention Program. , 1995, Circulation.

[10]  S. Thompson,et al.  Hemostatic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. , 1995, The New England journal of medicine.

[11]  J. Hung,et al.  Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. , 1995, Circulation.

[12]  P. Ridker,et al.  Plasma concentration of cross-linked fibrin degradation product (D-dimer) and the risk of future myocardial infarction among apparently healthy men. , 1994, Circulation.

[13]  R. Virmani,et al.  Sudden coronary death. Frequency of active coronary lesions, inactive coronary lesions, and myocardial infarction. , 1995, Circulation.

[14]  R. Virmani,et al.  Effect of hypertension and cardiac hypertrophy on coronary artery morphology in sudden cardiac death. , 1996, Circulation.

[15]  M. Gheorghiade,et al.  Pharmacologic therapies after myocardial infarction. , 1996, American Journal of Medicine.

[16]  L. Chen,et al.  Clinical factors and angiographic features associated with premature coronary artery disease. , 1995, Chest.

[17]  V. Fuster,et al.  Coronary plaque disruption. , 1995, Circulation.

[18]  W. Vaughn,et al.  Comparison of angioscopy, intravascular ultrasound imaging and quantitative coronary angiography in predicting clinical outcome after coronary intervention in high risk patients. , 1996, Journal of the American College of Cardiology.

[19]  M J Davies,et al.  Plaque fissuring--the cause of acute myocardial infarction, sudden ischaemic death, and crescendo angina. , 1985, British heart journal.

[20]  W. Weintraub,et al.  Beneficial effects of cholesterol-lowering therapy on the coronary endothelium in patients with coronary artery disease. , 1995, The New England journal of medicine.

[21]  M-heart investigators.  Effect of simvastatin on coronary atheroma: the Multicentre Anti-Atheroma Study (MAAS) , 1994, The Lancet.

[22]  G. Anantharamaiah,et al.  Pathogenesis of atherosclerosis. , 1994, Current opinion in cardiology.

[23]  J. Kjekshus,et al.  Reducing the risk of coronary events: evidence from the Scandinavian Simvastatin Survival Study (4S). , 1995, The American journal of cardiology.

[24]  R D Kamm,et al.  Mechanical properties of model atherosclerotic lesion lipid pools. , 1994, Arteriosclerosis and thrombosis : a journal of vascular biology.

[25]  L. Tenkanen,et al.  Anti-cardiolipin antibodies and risk of myocardial infarction in a prospective cohort of middle-aged men. , 1995, Circulation.

[26]  G. Bearman,et al.  Thermal detection of cellular infiltrates in living atherosclerotic plaques: possible implications for plaque rupture and thrombosis , 1996, The Lancet.

[27]  C. White,et al.  Unstable angina. A comparison of angioscopic findings between diabetic and nondiabetic patients. , 1995, Circulation.

[28]  J D Thomas,et al.  Toward the quiescent coronary plaque. , 1993, Journal of the American College of Cardiology.

[29]  R. Virmani,et al.  Coronary plaque erosion without rupture into a lipid core. A frequent cause of coronary thrombosis in sudden coronary death. , 1996, Circulation.

[30]  V. Fuster.  Elucidation off the role of plaque instability and rupture in acute coronary events , 1995 .

[31]  W. Edwards,et al.  Age-related changes in normal human hearts during the first 10 decades of life. Part II (Maturity): A quantitative anatomic study of 765 specimens from subjects 20 to 99 years old. , 1988, Mayo Clinic proceedings.

[32]  J. Albers,et al.  Lipid Lowering and Plaque Regression New Insights Into Prevention of Plaque Disruption and Clinical Events in Coronary Disease , 1993, Circulation.

[33]  J. Weiss,et al.  A polymorphism of a platelet glycoprotein receptor as an inherited risk factor for coronary thrombosis. , 1996, The New England journal of medicine.