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.