Abstract 4028: A High Level of High Density Lipoprotein Cholesterol Does Not Protect Against Incident Coronary Artery Disease in Families with Premature Coronary Disease
Background: The Adult Treatment Panel III (ATP III) Guidelines support the concept that high levels of high density lipoprotein cholesterol (HDL-C) are protective across all thresholds of low density lipoprotein cholesterol (LDL-C) and that points should be subtracted from global risk scores for anyone with an HDL-C ≥60 mg/dl. We have previously shown that apparently healthy siblings (SIBS) of persons with premature CAD < 60 years of age have a high prevalence of all major risk factors and a higher 10-year incidence of CAD than would be predicted by traditional risk scoring systems. To determine whether HDL-C levels ≥ 60 mg/dl are protective in this population, we examined lipoprotein predictors of incident CAD in high risk families with a history of premature CAD.
Methods: Risk factor screening was performed in 754 apparently healthy SIBS from hospitalized index cases with a CAD event < 60 years of age. SIBS were then followed for incident total CAD events, documented by medical records and adjudicated by an external endpoints committee.
Results: The 754 SIBS were 46±7 yrs old at baseline, 50% female, 17% African American, 33% smokers, 6% diabetics, and 44% hypertensives. Incident CAD occurred in 130 SIBS (17%) during 11.6±3.8 yrs of follow-up. In Cox proportional hazard models (Table⇓), it can be seen that incident CAD events are not lower at any of the 3 thresholds of LDL-C examined (≥ 130, 160, or 190 mg/dl). There is no significant protection when HDL-C is ≥60 mg/dl, even with adjustment for all other risk factors, for statin therapy, and for race, sex, and age.
Conclusion: In families at high risk for premature CAD, a high HDL-C does not appear to afford protection against incident CAD at therapeutic LDL-C thresholds recommended by ATP III. This finding suggests that the convention of subtracting points from global risk scores for anyone with an HDL-C ≥ 60 mg/dl may result in underestimation of risk in families with premature CAD.