High-density lipoprotein metabolism in familial hypercholesterolaemia: significance, mechanisms, therapy

Watts et al., 2002 | Nutr Metab Cardiovasc Dis | Meta Analysis

Citation

Watts G F, Barrett P H. High-density lipoprotein metabolism in familial hypercholesterolaemia: significance, mechanisms, therapy. Nutr Metab Cardiovasc Dis. 2002-Feb;12(1):36-41

Abstract

AIM: To assess the significance, mechanisms and therapy of impaired high-density lipoprotein (HDL) metabolism in patients with heterozygous familial hypercholesterolaemia (FH). METHODS: Review of epidemiological, metabolic and clinical literature with synthetic analysis of data referring to HDL. PRINCIPAL FINDINGS AND SYNTHESIS: Low HDL is a powerful risk factor for coronary artery disease (CAD) in FH. Low HDL in FH is a metabolic sequel of insulin resistance, which is the central feature of the visceral accumulation of adipose tissue acquired in later life. Insulin resistance increases hepatic secretion of triglycerides that subsequently results in remodelling of holo-HDL particles and enhanced catabolism of apolipoprotein A-I. Gene-gene and gene-environment interactions may contribute to the pathogenesis of low HDL in FH. Low HDL may also point to other cardiovascular risk factors, such as hyper-remnantaemia, increased small dense low-density lipoproteins (LDL), procoagulopathy and vascular insulin resistance. Visceral obesity should be vigorously identified and treated in FH. Judicious addition of fish oils, niacin and fibrates to a statin may be required to optimise HDL metabolism. Extracorporeal removal of LDL cholesterol should aim not to extract HDL from plasma. CONCLUSIONS: With the increasing incidence of obesity in the community, the metabolic syndrome will overmanifest in patients with FH. Impaired HDL metabolism is an important consequence of this syndrome for FH patients, because it will per se or in collusion with other associated risk factors accelerate the progression of atherosclerosis and CAD. Dysregulation of HDL metabolism principally results from hepatic insulin resistance and remodelling of HDL particles. Obesity should be prevented and aggressively treated in FH and use of a safe combination drug regimen considered to correct the dysmetabolism of HDL in these patients.

Key Findings

With the increasing incidence of obesity in the community, the metabolic syndrome will overmanifest in patients with FH. Impaired HDL metabolism is an important consequence of this syndrome for FH patients, because it will per se or in collusion with other associated risk factors accelerate the progression of atherosclerosis and CAD. Dysregulation of HDL metabolism principally results from hepatic insulin resistance and remodelling of HDL particles. Obesity should be prevented and aggressively t

Outcomes Measured

• Requires manual extraction

Population

MeSH Terms

• Body Composition
• Humans
• Hyperlipoproteinemia Type II
• Lipoproteins, HDL
• Metabolic Syndrome
• Obesity

Evidence Classification

• Level: Meta Analysis
• Publication Types: Journal Article, Meta-Analysis, Research Support, Non-U.S. Gov't
• Vertical: niacin

Provenance

• PMID: 12125229
• DOI: (not available)
• PMCID: Not in PMC
• Verified: 2026-04-09 via PubMed E-utilities API

Source extracted via PubMed E-utilities API on 2026-04-09