From the Guidelines
High HDL cholesterol is generally considered cardioprotective, though the relationship is more complex than once thought. HDL (high-density lipoprotein) functions by removing excess cholesterol from the bloodstream and transporting it to the liver for elimination, a process called reverse cholesterol transport 1. Traditional guidelines suggest that HDL levels above 60 mg/dL are protective against heart disease, while levels below 40 mg/dL for men and below 50 mg/dL for women increase cardiovascular risk. However, recent research indicates that extremely high HDL levels (above 90-100 mg/dL) may not provide additional protection and might even be associated with increased risk in some populations.
The quality and functionality of HDL particles appear more important than just their quantity. While medications like niacin can raise HDL levels, they haven't consistently shown cardiovascular benefits in clinical trials 1. Lifestyle modifications remain the most effective approach for optimizing HDL levels, including:
- Regular physical activity
- Maintaining a healthy weight
- Consuming a Mediterranean-style diet rich in olive oil, nuts, and fatty fish
- Moderate alcohol consumption
- Avoiding smoking
These measures improve both HDL quantity and functionality, potentially enhancing its cardioprotective effects. According to the European guidelines on cardiovascular disease prevention in clinical practice, HDL cholesterol <1.0 mmol/l (40 mg/dl) in men and <1.2 mmol/l (46 mg/dl) in women serve as markers of increased cardiovascular risk 1.
In terms of management, lifestyle modifications should be the primary approach to optimize HDL levels and reduce cardiovascular risk. If the 10-year risk of cardiovascular death is ≥5%, or will become ≥5% if the individual's risk factor combination is projected to age 60, a full analysis of plasma lipoproteins should be performed, and intensive lifestyle advice, particularly dietary advice, should be given 1.
From the Research
HDL and Cardiovascular Disease
- The relationship between high-density lipoprotein (HDL) cholesterol and cardiovascular disease is complex, with some studies suggesting that high HDL levels may not always be protective against cardiovascular disease 2, 3.
- HDL cholesterol has been shown to have various cardioprotective properties, including the ability to uptake and return surplus cholesterol from peripheral tissues back to the liver, which can help prevent atherosclerosis and myocardial infarction 2.
- However, recent evidence suggests that the functionality of HDL, rather than its concentration, may be more important in determining its cardioprotective effects 4, 3.
HDL Functionality and Cardiovascular Risk
- HDL functionality, including its ability to facilitate cholesterol efflux from macrophages, has been shown to be inversely associated with cardiovascular risk, independent of HDL-C levels 4.
- Studies have found that very high HDL-C levels (≥80 mg/dL in men, ≥100 mg/dL in women) may be paradoxically associated with higher all-cause and cardiovascular disease-related mortality 3.
- The use of fibrates, which can increase HDL-C levels, has been shown to have a greater effect on reducing cardiovascular risk in patients with high triglyceride levels or atherogenic dyslipidemia profile 5.
Clinical Implications
- The current evidence suggests that HDL-C should not be used as the sole indicator of cardiovascular risk, and that other factors, such as HDL functionality and triglyceride levels, should also be considered 4, 3.
- Further research is needed to fully understand the relationship between HDL and cardiovascular disease, and to develop effective strategies for reducing cardiovascular risk in patients with low HDL-C levels or other lipid abnormalities 2, 3.