Abstract 2456: High HDL-cholesterol Levels Are Paradoxically Associated With Increased Atherosclerosis And Increased Coronary Heart Disease (CHD) Events In Metabolic Syndrome Subjects: The Multi-ethnic Study Of Atherosclerosis (MESA)
Background: In population studies high HDL is associated with fewer CHD events, however in certain people high HDL does not appear to protect and recent work suggests that HDL can become dysfunctional in settings of inflammation. Since Metabolic Syndrome (MetSyn) patients often have systemic inflammation, we hypothesized that high HDL might not be protective in this group.
Methods: We analyzed data from 6,814 subjects in MESA; 2,362 of whom had MetSyn. Subjects were stratified by HDL into low (< 40), mid (40 –59) and high (≥ 60 mg/dL) groups. Outcomes were cIMT, coronary calcium (CAC), and CHD events over 3 years of follow up. Cox proportional hazards models assessed the association of HDL with CHD events.
Results: In non-MetSyn subjects, outcomes were worst in the low HDL group and improved as HDL increased. In MetSyn subjects, however, an unexpected U-shaped relationship was seen. The most favorable results were in MetSyn subjects with mid HDL (40 –59), while worse outcomes were seen with either low (< 40) or high (≥ 60) HDL. cIMT was 1.23, 1.14 and 1.26 mm for low, mid and high HDL respectively (p mid vs. high = 0.04). Loge CAC was 4.63, 4.37 and 4.66 for low, mid and high HDL (p = 0.09). CHD rates were 3.7%, 1.8% and 4.1% for low, mid and high HDL (p = 0.027). In multivariate analysis, high (vs. mid) HDL remained associated with CHD events in MetSyn (HR 2.44 [1.03–5.82]).
Conclusion: Although HDL is associated with decreased CHD in general populations, in certain people HDL doesn’t protect. In our data MetSyn subjects with HDL ≥ 60 had poorer outcomes than those with HDL 40 –59, which suggests that HDL-C is a complex marker that must be interpreted in light of a person’s metabolic profile and inflammatory status.