HDL cholesterol and cardiovascular outcomes: what is the evidence?

Area of Science:

• Cardiology
• Biochemistry
• Pharmacology

Background:

• Low high density lipoprotein cholesterol (HDL-C) is a known risk factor for cardiovascular (CV) disease.
• The association between residual low HDL-C and excess CV risk in patients treated with statins is not well-established.
• Previous trials with niacin showed promise but were not validated with contemporary therapies.

Purpose of the Study:

• To evaluate the established link between low HDL-C and cardiovascular risk.
• To assess the efficacy of targeting HDL-C with pharmacological therapy in modern treatment paradigms.
• To explore the role of specific HDL particle subsets in cardiovascular disease.

Main Methods:

• Review of epidemiological studies and clinical trials.
• Analysis of data from recent trials involving contemporary anti-atherosclerotic therapies.
• Examination of emerging evidence on HDL particle heterogeneity.

Main Results:

• A consistent inverse relationship exists between HDL-C levels and CV disease risk in epidemiological studies.
• Recent trials have not validated the benefits of niacin in raising HDL-C for reducing CV events in patients on modern therapies.
• Evidence suggests that specific HDL particle subsets may have differential associations with CV disease.

Conclusions:

• The clinical benefit of targeting HDL-C with pharmacological therapy remains uncertain, particularly in patients receiving statins.
• Further clinical trials are needed to determine if raising HDL-C directly reduces hard cardiovascular events.
• Current evidence provides weak support for pharmacologically targeting HDL-C.