Abstract 015: Very-High Levels of HDL-C and Risks for CHD: The Lifetime Risk Pooling Project
Background: Whereas observational cohort data suggest the association between HDL-C and coronary heart disease (CHD) is inverse and linear, data are sparse at HDL-C values > 80mg/dL. Methods: We therefore pooled data from the NHLBI public-funded datasets of the Framingham, Framingham Offspring, and Atherosclerosis Risk in Communities studies. We used multivariable Cox Proportional-Hazards Models to adjust for age, systolic blood pressure, body mass index, smoking status, prevalent diabetes, non-HDL-C, antihypertension and lipid medication use. We calculated adjusted hazard ratios (HR) to assess the association between a priori strata of HDL-C (<30; >30-40; >40-50; >50-60; >60-70; >70-80; >80mg/dL) and CHD death and non-fatal myocardial infarction using HDL-C >40-50mg/dL as the referent. Results: Over 118,716 person*years of follow up, there were 562 events in 9,226 participants. As expected, hazard ratios for CHD events are greatest in the lowest category of HDL-C (HR 1.68, 95%CI: 1.31, 2.21) and there was generally a stepwise inverse trend in CHD hazards up to 80mg/dL. (See Figure) At HDL-C > 80mg/dL the hazard point estimate for CHD events was insignificantly higher (HR 0.52, 95% CI 0.29, 0.95) than the hazard observed at HDL-C >70-80mg/dl (HR 0.35, 95% CI 0.18-0.66). However, the hazard for CHD events for HDL-C > 80mg/dL was still significantly lower than the referent. Conclusions: These data suggest that the association between HDL-C and CHD risk may not be inverse and linear at HDL-C values > 80mg/dL. These data support investigation into qualitative differences in HDL molecules in individuals with very high levels of HDL-C.