While low HDL-C is considered a traditional risk factor for atherosclerotic cardiovascular disease (ASCVD) and embedded in ASCVD risk scores such as the Pooled Cohort Equation and the European SCORE, large epidemiologic cohort studies have demonstrated that the risk of death is also increased at the highest HDL-C levels. Alcohol intake, some medications, and rare genetic syndromes can contribute to high HDL-C levels. Some people with extreme HDL-C levels may actually have dysfunctional HDL rather than atheroprotective HDL-C. This poses a clinical conundrum when evaluating patients with very high HDL-C levels for ASCVD risk.
I was part of a research team that presented an abstract at #AHA23 that sought to identify whether coronary calcium score (CAC) could help risk-stratify people with very high HDL-C levels. In this study, a total of 335 primary prevention patients enrolled in the CAC consortium with high HDL-C (> 80 mg/dL in men; > 100 mg/dL in women) were analyzed. The participants had a median age of 58.6 years; 51% were women, 51% with prevalent CAC, and had a median HDL-C of 100 mg/dL. Analyzing a total of 20 deaths, seven of which were attributable to CVD, an increasing CAC score was associated with higher all-cause mortality (HR per 100 Agatston unit increase: 1.07; 95% CI 1.01-1.12). Those with a CAC > 1,000 had an almost sixfold increased risk of mortality compared to those with a CAC = 0.