Interplay of HDL cholesterol and apoB and the risk of incident atherosclerotic cardiovascular disease in UK Biobank

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Abstract
Aims: Apolipoprotein B (apoB) is the most accurate causal lipid factor associated with increased risk of atherosclerotic cardiovascular disease (ASCVD). While high HDL cholesterol has been considered protective, HDL-C–raising therapies have not shown benefit. Objective: To assess whether HDL-C provides independent information from apoB and whether HDL-C modifies the effect of apoB on ASCVD risk. Methods and results: 293 872 UK Biobank participants aged 37–73, free of CVD, not on lipid-lowering medication, and with complete standard risk factor data were followed for 10 years for incident ASCVD. Cox proportional hazard models, adjusted for standard risk factors, including log-triglycerides, used apoB and HDL-C residuals (regressed on each other) as primary exposures. Interaction between apoB and HDL-C was tested separately. When HDL-C residual was added to a model with apoB, both were significant: hazard ratios (HRs) per 1 SD were 1.16 (95% confidence interval, CI: 1.15–1.18; P < 0.001) for apoB and 0.85 (95% CI: 0.84–0.87; P < 0.001) for HDL-C residual. Similarly, adding apoB residual to a model with HDL-C yielded HRs of 1.14 (95% CI: 1.12–1.16; P < 0.001) for apoB residual and 0.84 (95% CI: 0.82–0.85; P < 0.001) for HDL-C. The apoB–HDL-C interaction was significant: HR 0.95 (95% CI: 0.93–0.96; P < 0.001), consistent across sexes. Conclusion: High HDL-C is associated with lower ASCVD risk, independent of apoB, and it attenuates the effect of high apoB on ASCVD risk. These findings suggest HDL-C’s role in primary ASCVD prevention warrants re-evaluation. However, findings from an observational study, such as this, do not establish causation.
Funding Information
  • Mike and Valeria Rosenbloom Foundation

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