Key result
Genetic and trial data show high HDL-C lacks causal atheroprotective benefit against cardiovascular disease.
Why the study?
Epidemiological studies suggested an inverse correlation between HDL-C and cardiovascular risk, but recent Mendelian randomization data demonstrated a lack of atheroprotective causal effects.
This review reinforces the paradigm shift that pharmacologically or genetically raising HDL-C levels does not intrinsically reduce cardiovascular risk.
Hyperalphalipoproteinemia (HALP) is a lipid disorder characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels above the 90th percentile of the distribution of HDL-C values in the general population. Secondary non-genetic factors such as drugs, pregnancy, alcohol intake, and liver diseases might induce HDL increases. Primary forms of HALP are caused by mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (HL), apolipoprotein C-III (apo C-III), scavenger receptor class B type I (SR-BI) and endothelial lipase (EL). However, in the last decades, genome-wide association studies (GWAS) have also suggested a polygenic inheritance of hyperalphalipoproteinemia. Epidemiological studies have suggested that HDL-C is inversely correlated with cardiovascular (CV) risk, but recent Mendelian randomization data have shown a lack of atheroprotective causal effects of HDL-C. This review will focus on primary forms of HALP, the role of polygenic inheritance on HDL-C, associated risk for cardiovascular diseases and possible treatment options.
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Giammanco et al. (2021) conducted a review in Hyperalphalipoproteinemia. High HDL-C levels and HDL-raising therapies was evaluated. Mendelian randomization data and clinical trials of HDL-raising therapies show a lack of atheroprotective causal effects of high HDL-C on cardiovascular disease.
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