Prospective study of coronary heart disease vs. HDL2, HDL3, and other lipoproteins in Gofman's Livermore Cohort

ObjectiveTo assess the relationship of lipoprotein subfractions to coronary heart disease (CHD).MethodsProspective 29.1-year follow-up of 1905 men measured for lipoprotein mass concentrations by analytic ultracentrifugation between 1954 and 1957. Vital status was determined for 97.2% of the cohort. Blinded physician medical record and death certificate review confirmed 179 CHD deaths. Follow-up questionnaires identified 182 nonfatal myocardial infarctions and 93 revascularization procedures from 1346 (98.3%) of the surviving cohort and from the next-of-kin of 153 men who died.ResultsWhen adjusted for age, total incident CHD was inversely related to HDL2-mass (P = 0.0001) and HDL3-mass (P = 0.02), and concordantly related to LDL-mass (P < 10−11), IDL-mass (P < 10−7), and small (P < 10−7) and large VLDL-mass concentrations (P = 0.003). The hazard reduction per mg/dl of HDL was greater for HDL2-mass than HDL3-mass (P = 0.04). The lowest quartiles of both HDL2-mass (P = 0.007) and HDL3-mass (P = 0.001) independently predicted total incident CHD when adjusted for traditional risk factors. Risk for premature CHD (≤65 years old) was significantly greater in men within the lowest HDL2 (P = 0.03) and HDL3 quartiles (P = 0.04) and having higher LDL-mass concentrations (P = 0.001). Serum cholesterol's relationship to incident CHD (P < 10−8) was accounted for by adjustment for LDL-mass concentrations (adjusted P = 0.90).ConclusionsLipoprotein subfractions differ in their relationship to CHD.