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High HDL-Cholesterol Paradox: SCARB1-LAG3-HDL Axis.


ABSTRACT:

Purpose of the review

To evaluate recent studies related to the paradox of high HDL-C with mortality and atherosclerotic cardiovascular disease (ASCVD) risk.

Recent findings

Two observational studies (Cardiovascular Health in Ambulatory Care Research Team [CANHEART] and Copenhagen City Heart Study and the Copenhagen General Population Study [Copenhagen Heart Studies]) of adults without pre-existing ASCVD have shown a significant U-shaped association of HDL-C with all-cause and cause-specific mortality. Both studies showed that low HDL-C levels consistently increased hazard risk (HR) for all-cause and cause-specific mortality. In the CANHEART study, high HDL-C levels, HDL-C >?90 mg/dL, were associated with increased HR for non-CVD/non-cancer mortality. In the Copenhagen Heart Studies, women with HDL-C ??135 mg/dL showed increased HR for all-cause and CVD mortality, while men with HDL-C?>?97 mg/dL showed increased HR for all-cause and CVD mortality. Genetic association studies failed to show that genetic etiologies of high HDL-C significantly reduced risk for myocardial infarction (MI), while hepatocyte nuclear factor-4 (HNF4A) was significantly associated with high HDL-C and increased MI risk. Candidate gene studies have identified scavenger receptor B class I (SCARB1) and lymphocyte activation gene-3 (LAG3) as genes significantly associated with high HDL-C and increased MI risk. Low HDL-C remains as a significant factor for increased disease risk while high HDL-C levels are not associated with cardioprotection. Clinical CVD risk calculators need revision.

SUBMITTER: Rodriguez A 

PROVIDER: S-EPMC7782461 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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High HDL-Cholesterol Paradox: SCARB1-LAG3-HDL Axis.

Rodriguez Annabelle A  

Current atherosclerosis reports 20210105 1


<h4>Purpose of the review</h4>To evaluate recent studies related to the paradox of high HDL-C with mortality and atherosclerotic cardiovascular disease (ASCVD) risk.<h4>Recent findings</h4>Two observational studies (Cardiovascular Health in Ambulatory Care Research Team [CANHEART] and Copenhagen City Heart Study and the Copenhagen General Population Study [Copenhagen Heart Studies]) of adults without pre-existing ASCVD have shown a significant U-shaped association of HDL-C with all-cause and cau  ...[more]

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