Change in High-Density Lipoprotein Cholesterol and Incident Coronary Heart Disease in Apparently Healthy Male Physicians

The association between change in high-density lipoprotein (HDL) cholesterol and risk of subsequent coronary heart disease (CHD) is unclear. Change in HDL cholesterol was calculated in a prospective cohort of 4,501 male physicians enrolled in the Physician's Health Study (PHS) I who had HDL cholesterol measured in 1982 and again approximately 14 years later. Subjects were divided into categories of those with a decrease (≥−2.5 mg/dl), no change (change −2.5 to 2.5 mg/dl), a small increase of 2.5 to 12.5 mg/dl, or a large increase of ≥12.5 mg/dl. Cox proportional hazards was used to examine the association between change in HDL cholesterol and incident CHD (confirmed acute myocardial infarction or cardiac death). Hazard ratios (HRs) were adjusted for age, initial HDL cholesterol, diabetes mellitus, hypertension, non-HDL cholesterol, and history of cholesterol medication. Compared with subjects with a decrease in HDL cholesterol, multivariable-adjusted HRs for CHD were 0.66 (95% confidence interval [CI] 0.40 to 1.09) in subjects with no change, 0.56 (95% CI 0.35 to 0.89) for subjects with an increase of 2.5 to 12.5 mg/dl, and 0.43 (95% CI 0.23 to 0.83) for subjects with an HDL cholesterol increase ≥12.5 mg/dl. In conclusion, our findings were consistent with an inverse graded relation between 14-year increase in HDL cholesterol and risk of subsequent CHD.