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Beyond LDL-C--the importance of raising HDL-C
Anthony S Wierzbicki1, Dimitri P Mikhailidis
1Dept of Chemical Pathology, King's College London, Guy's, King's and St Thomas' Medical School, UK. anthony.wierzbicki@kcl.ac.uk
Insights
Low high-density lipoprotein cholesterol (HDL-C) significantly elevates coronary heart disease (CHD) risk. Raising HDL-C levels, as shown in the VA-HIT study, effectively reduces CHD events, highlighting its therapeutic importance.
Area of Science:
- Cardiology
- Lipidology
- Preventive Medicine
Background:
- Low high-density lipoprotein cholesterol (HDL-C) is a significant risk factor for coronary heart disease (CHD).
- Combined lipid abnormalities, including low HDL-C, high triglycerides, and high total cholesterol, independently predict increased coronary events.
- Existing lipid-modifying therapies that increase HDL-C have demonstrated a reduction in major coronary events.
Purpose of the Study:
- To evaluate the impact of raising HDL-C levels in patients with low-density lipoprotein cholesterol (LDL-C) within guideline-recommended ranges but with low HDL-C.
- To assess the efficacy of gemfibrozil in reducing CHD-related events in this specific patient population.
Main Methods:
- The study involved patients with LDL-C levels meeting current guidelines but exhibiting low HDL-C.
- Gemfibrozil was administered to raise HDL-C levels.
- The trial monitored CHD-related events as the primary outcome.
Main Results:
- The VA-HIT trial demonstrated that gemfibrozil significantly reduced the risk of CHD-related events in patients with low HDL-C.
- Raising HDL-C levels proved effective in mitigating cardiovascular risk in this cohort.
Conclusions:
- Low HDL-C is a critical, independent risk factor for CHD, necessitating consideration in treatment strategies.
- Therapeutic interventions aimed at increasing HDL-C levels, such as gemfibrozil, are valuable for reducing cardiovascular events.
- Future drug development should focus on agents that beneficially impact both HDL-C and LDL-C levels for comprehensive dyslipidemia management.
Abstract:
Epidemiological studies have established that low levels of high-density lipoprotein cholesterol (HDL-C) are associated with an increased risk of coronary heart disease (CHD). Recent studies have demonstrated that low HDL-C levels, and high triglycerides and total cholesterol levels are independent predictors of CHD, and that the combination of these lipid abnormalities increases the risk of coronary events. In lipid-modifying intervention studies, agents that raise HDL-C levels have been shown to reduce the incidence of major coronary events. The VA-HIT study consisted of patients with low-density lipoprotein cholesterol (LDL-C) levels similar to those recommended by several guidelines but with low levels of HDL-C. This trial demonstrated that raising HDL-C levels with gemfibrozil reduced the risk of CHD-related events. While the mechanisms by which HDL-C exerts its anti-atherogenic effects have yet to be fully elucidated, its role in the reverse transport of cholesterol and the beneficial effects on endothelial function are plausible explanations for these actions. Although LDL-C reduction is the primary goal in the treatment of dyslipidaemia, current guidelines recognise low HDL-C levels as a major risk factor for CHD. Indeed, the NCEP ATP III guidelines suggest that the treatment of isolated low HDL-C levels in CHD patients or individuals with CHD risk equivalents should be considered. The differing abilities of statins to raise HDL-C levels may be an important factor when making treatment decisions. New lipid-modifying drugs with beneficial effects on both HDL-C and LDL-C levels would be desirable additions to the currently available therapeutic options.