What are the implications of low High-Density Lipoprotein (HDL) cholesterol?

From the Guidelines

Low HDL cholesterol levels should be managed by first targeting LDL cholesterol through dietary modification, weight loss, and/or physical exercise, as outlined in the ATP III guidelines, with a focus on achieving the LDL cholesterol goal before considering medications to raise HDL levels. According to the acc/aha 2002 guideline update for the management of patients with chronic stable angina 1, a low HDL cholesterol level is defined as less than 40 mg/dL. Patients with established coronary disease and low HDL cholesterol are at high risk for recurrent events and should be targeted for aggressive nonpharmacological treatment.

Some key considerations for managing low HDL cholesterol include:

• Dietary modification to reduce trans fats and refined carbohydrates
• Weight loss, if necessary
• Regular physical exercise, such as at least 30 minutes of moderate exercise most days of the week
• Quitting smoking, if applicable
• Moderate alcohol consumption, if recommended by a healthcare provider

After the LDL goal has been reached, emphasis shifts to other issues, such as achieving the non-HDL cholesterol goal if triglycerides are high (200 to 499 mg/dL), or considering medications to raise HDL levels, such as fibrates or nicotinic acid, if triglycerides are less than 200 mg/dL 1. It's essential to work with a healthcare provider to determine the best approach for managing low HDL cholesterol and to monitor progress regularly.

From the FDA Drug Label

There have been post-marketing and clinical trial reports of severe decreases in HDL cholesterol levels (as low as 2 mg/dL) occurring in diabetic and non-diabetic patients initiated on fibrate therapy. The decrease in HDL-C is mirrored by a decrease in apolipoprotein A1 This decrease has been reported to occur within 2 weeks to years after initiation of fibrate therapy. The HDL-C levels remain depressed until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is rapid and sustained. The clinical significance of this decrease in HDL-C is unknown It is recommended that HDL-C levels be checked within the first few months after initiation of fibrate therapy. If a severely depressed HDL-C level is detected, fibrate therapy should be withdrawn, and the HDL-C level monitored until it has returned to baseline, and fibrate therapy should not be re-initiated

Low HDL can be a result of fenofibrate therapy, as there have been reports of severe decreases in HDL cholesterol levels in patients taking fenofibrate.

• The clinical significance of this decrease is unknown.
• It is recommended to check HDL-C levels within the first few months after initiation of fenofibrate therapy.
• If a severely depressed HDL-C level is detected, fenofibrate therapy should be withdrawn 2 2.

From the Research

Low HDL Cholesterol

• Low levels of HDL cholesterol are a significant predictor of atherosclerotic cardiovascular events 3
• HDL is believed to protect against atherosclerosis by promoting reverse cholesterol transport, and potentially through anti-inflammatory, antioxidative, antithrombotic and nitric oxide effects 3
• The main lifestyle interventions to modify serum HDL cholesterol include physical exercise, weight loss with either caloric restriction or specific dietary approaches, and smoking cessation 4
• Moderate alcohol consumption can be permitted in some cases, but it is often difficult to discern which intervention is responsible for improvement in HDL outcomes 4

Therapeutic Options

• Niacin therapy is currently the most effective means for raising HDL levels, and should be initiated in patients with isolated low HDL 5
• Patients who have both low HDL and elevated LDL should receive a statin or statin-niacin combination therapy 5
• Patients with concomitant low HDL and elevated TGs should receive a fibrate initially, with a statin, niacin, or ezetimibe added thereafter as needed 5
• Long-chain omega-3 fatty acids may be a well-tolerated and effective alternative to fibrates and niacin for reducing triglyceride levels 6

Dietary Treatment

• Dietary measures to lower levels of LDL-C and triglyceride and reduce cardiovascular outcomes include minimizing saturated fats and refined carbohydrates, eliminating trans-fat, and increasing fruits, vegetables, whole grains, low-fat dairy, and fish or other omega-3 fatty acids 7
• Adhering to a Mediterranean diet is strongly recommended because of its ability to lower CVD and total mortality 7
• High-dose omega-3 fatty acids can lower triglyceride, reduce CVD, and prevent coronary plaque progression 7