A prospective, multicenter biobank cohort study in the UK and US revealed that very high high-density lipoprotein cholesterol (HDL-C) levels were associated with higher mortality risk in patients with coronary artery disease (CAD). There were 14 478 UK participants (from 2006; mean age 62.1 years, 76.2% men) and 5467 US participants (from 2003; mean age 63.8 years, 66.4% men). Over a median follow-up of 8.9 years in the UK and 6.7 years in the US, a U-shaped association with outcomes was observed with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (>80 mg/dL) were associated with increased risk of all-cause death (hazard ratio [HR], 1.96) and cardiovascular death (HR, 1.71) compared with those with HDL-C levels in the range of 40 to 60 mg/dL in the UK after adjustment for confounding factors. These results were replicated in the US. These associations persisted after adjustment for the HDL-C genetic risk score within the UK cohort. Sensitivity analyses demonstrated that the risk of all-cause mortality in the very high HDL-C group was higher among men than women in the UK (HR, 2.63 vs HR, 1.39). The findings suggest that although previous studies have shown lower cardiovascular risk with higher HDL-C levels, very high HDL-C levels are paradoxically associated with higher mortality risk in patients with CAD, independent of the common polymorphisms associated with high HDL-C levels. Source: https://jamanetwork.com/
