Abstract
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.
Highlights
Hyperalphalipoproteinemia (HALP) is a condition characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels > 90th percentile of the distribution of HDL-C values in the general population [1], associated or not with overt clinical manifestations and predisposition to atherosclerotic coronary artery disease (CAD) [2]
Mutations in the genes coding for cholesteryl ester transfer protein (CETP), hepatic lipase (LIPC), and apolipoprotein C-III (APOC3) are known causes of primary HALP [1]
The pathophysiology of other forms of HALP is not well characterized, and it is still unknown if the increased production or reduced catabolism of HDL are the cause of this lipid disorder [1]
Summary
Hyperalphalipoproteinemia (HALP) is a condition characterized by elevated plasma high-density lipoprotein cholesterol (HDL-C) levels > 90th percentile of the distribution of HDL-C values in the general population [1], associated or not with overt clinical manifestations and predisposition to atherosclerotic coronary artery disease (CAD) [2]. Epidemiological studies have demonstrated a strong inverse relationship between low HDL-C levels and risk for developing atherosclerotic cardiovascular disease (ASCVD) [3,4]. Low plasma HDL-C levels strongly correlate with high CV risk, but genetically determined low HDL-C levels are not associated with an increased risk for ASCVD, suggesting that low HDL-C levels per se are not a cause of cardiovascular diseases [5,6]. Besides the major involvement in RCT, HDLs exert several anti-inflammatory effects that may prevent endothelial dysfunction [10], which is considered one of the first events in atherogenesis [11]
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