Why is raising High-Density Lipoprotein (HDL) not important for coronary artery disease?

From the Guidelines

Raising HDL cholesterol is not a primary target for heart disease prevention due to lack of evidence showing its direct benefit in reducing cardiovascular events. The relationship between HDL and heart health is complex, and the quality and functionality of HDL particles may be more important than their quantity 1. While low HDL levels are associated with increased risk, clinical trials have failed to demonstrate that artificially increasing HDL levels reduces cardiovascular risk.

Key points to consider in managing heart disease include:

• Lowering LDL cholesterol as the primary target of therapy, using medications such as statins, ezetimibe, or PCSK9 inhibitors
• Controlling blood pressure, not smoking, maintaining a healthy weight, and regular exercise
• Managing diabetes as part of a comprehensive approach to reducing cardiovascular risk
• Considering medications to raise HDL, such as fibrates or nicotinic acid, only in specific cases, such as when triglycerides are less than 200 mg/dL and HDL is isolatedly low

The current guidelines, as outlined in the acc/aha 2002 guideline update for the management of patients with chronic stable angina, do not specify a goal for HDL raising, and emphasis is placed on achieving the LDL cholesterol goal first 1. This approach prioritizes strategies with proven benefits in reducing cardiovascular events, rather than focusing solely on raising HDL levels.

From the FDA Drug Label

To reduce elevated TC, LDL-C, Apo B and TG, and to increase HDL-C in patients with primary hyperlipidemia and mixed dyslipidemia. Limitations of use: Addition of niacin extended-release tablets did not reduce cardiovascular morbidity or mortality among patients treated with simvastatin in a large, randomized controlled trial ( 5.1). The FDA drug label does not answer the question.

From the Research

Raising HDL and Heart Disease

• The importance of raising HDL (high-density lipoprotein) cholesterol for heart disease prevention has been debated in various studies 2, 3, 4.
• While some research suggests that increasing HDL cholesterol can lead to a risk reduction of 2-3% for coronary heart disease 3, other studies have found that the relationship between HDL cholesterol and cardiovascular risk is more complex.
• For example, a study published in 2009 found that niacin, a drug that increases HDL cholesterol, also lowers triglycerides and LDL cholesterol, but its potential to decrease vascular risk remains to be proven 2.
• Another study published in 2012 noted that established drug therapies resulting in substantial HDL-C increase are scarce and their effect is controversial 3.
• More recent studies have focused on the role of LDL (low-density lipoprotein) cholesterol in cardiovascular disease, with evidence suggesting that reducing LDL cholesterol is a more effective strategy for preventing heart disease 5, 6.
• The 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidemias recommend the use of PCSK9 inhibitors to very high-risk ASCVD patients who are not achieving treatment goals on a maximum tolerated dose of a statin and ezetimibe 6.
• Overall, the current evidence suggests that while raising HDL cholesterol may have some benefits, it is not as important as reducing LDL cholesterol for preventing heart disease 2, 3, 5, 6, 4.

Key Findings

• Reducing LDL cholesterol is a more effective strategy for preventing heart disease than raising HDL cholesterol 5, 6.
• PCSK9 inhibitors can reduce LDL-C by 50-60% above that achieved by statin therapy alone and may reduce cardiovascular events and all-cause mortality in patients with clinical ASCVD 6.
• Niacin, a drug that increases HDL cholesterol, also lowers triglycerides and LDL cholesterol, but its potential to decrease vascular risk remains to be proven 2.
• Established drug therapies resulting in substantial HDL-C increase are scarce and their effect is controversial 3.