RANGE OF SERUM-CHOLESTEROL VALUES IN THE POPULATION DEVELOPING CORONARY-ARTERY DISEASE

Blood lipids have been established as fundamental to atherogenesis, and there is a better understanding of the pathogenesis of atherosclerosis and of the various pharmacologic agents available to counter the mechanisms involved. However, more optimal lipid levels must be established for treatment of both the healthy population and persons already with coronary artery disease (CAD). In the Framingham Study cohort, those with elevated serum total cholesterol (>275 mg/dl) had an increased risk of adverse outcomes whether healthy or with CAD. Com pared with persons with cholesterol levels <200 mg/dl (<5.17 mmol/liter), the risk ratios for patients with elevated cholesterol levels were 3.8 for reinfarction, 2.6 for CAD mortality, and 1.9 for overall mortality. The prevalence of cholesterol levels greater than or equal to 240 mg/dl (greater than or equal to 6.21 mmol/liter) in persons who had sustained myocardial infarction was 35-52% in men and 66% in women, but 20% of myocardial infarctions occurred in people who had cholesterol levels <200 mg/dl (<5.17 mmol/liter). The average levels of serum total cholesterol and low density lipoprotein (LDL) cholesterol (225 mg/dl [5.82 mmol/liter] and 150 mg/dl [3.88 mmol/liter], respectively) at which CAD events occurred in men were below the levels recommended for treatment according to the guidelines of the National Cholesterol Education Program. In women, these levels were only slightly above the guideline levels. The average cholesterol levels at which CAD events occurred were substantially higher in women and decreased with age. Also, a steady decline in the average cholesterol levels of patients over the decades reflected chiefly the aging of the cohort. More recent data comparing CAD patients from the Tufts-New England Medical Center with matched control subjects from the Framingham Study under age 60 years indicate significantly higher levels for triglycerides, total cholesterol, LDL cholesterol, apolipoprotein B, and lipoprotein(a), and lower levels for high density lipoprotein (HDL) cholesterol and apolipoprotein A-1. Major overlapping of distributions with control values was noted. The most frequent dyslipidemias were reduced HDL cholesterol a lone (19%), lipoprotein(cr) (15.8%), and elevated LDL cholesterol alone (12%). Reduced levels of HDL cholesterol were the best predictor, occurring alone or in combination in 32% of CAD patients versus 9% of control subjects. Approximately 35% of Tufts CAD patients had total cholesterol levels <200 mg/dl (<5.17 mmol/liter) and 73% of these had HDL cholesterol levels <35 mg/dl (<0.91 mmol/liter). Thus, the CAD patients with cholesterol levels in the desired range have significant dyslipidemia. The data suggest that more aggressive efforts are needed to lower LDL cholesterol levels to <100 mg/dl (<2.59 mmol/liter), and raising HDL cholesterol levels should be considered. Conservative indications for therapy in men and women would be total cholesterol levels >225 mg/dl (>5.82 mmol/liter) and >240 mg/dl (>6.21 mmol/liter), respectively, and LDL cholesterol levels >150 mg/dl (>3.88 mmol/liter) and >160 mg/dl (>4.14 mmol/liter), respectively. Also, at any level of serum total or LDL cholesterol, a total cholesterol to HDL cholesterol ratio greater than or equal to 5 for women and greater than or equal to 5.5 for men warrants treatment. An optimal ratio would be approximately 3.5. Data from ongoing trials are urgently needed to determine whether patients with CAD with moderate dyslipidemia (comprising most patients) benefit from treatment.