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

From the Guidelines

Low HDL cholesterol levels should be managed through lifestyle modifications, including regular aerobic exercise and diet changes, as these have been shown to improve HDL levels and reduce the risk of heart disease 1. To raise HDL levels, it is essential to focus on lifestyle modifications. Regular aerobic exercise, aiming for at least 30 minutes most days, can help improve HDL levels. Maintaining a healthy weight and quitting smoking are also crucial. Diet changes are vital, including incorporating heart-healthy fats like olive oil, avocados, and nuts, while reducing trans fats and refined carbohydrates.

• Moderate alcohol consumption, such as one drink daily for women and up to two for men, may also help, but it is not recommended to start drinking solely for this benefit.
• Medications like niacin, fibrates, or statins may be prescribed if lifestyle changes are not sufficient, although raising HDL with medications has not consistently shown the same cardiovascular benefits as naturally high levels 1. The importance of HDL cholesterol lies in its role as the body's "good" cholesterol, helping remove LDL ("bad") cholesterol from arteries and transporting it back to the liver for processing.
• A desirable HDL level is 60 mg/dL or higher, while levels below 40 mg/dL for men or 50 mg/dL for women are considered low and warrant attention. It is essential to note that the primary target of therapy for individuals with low HDL cholesterol is LDL cholesterol, and ATP III guidelines for diet, exercise, and drug therapy should be followed to achieve the LDL cholesterol goal 1.
• After the LDL goal has been reached, emphasis shifts to other issues, such as achieving the non-HDL cholesterol goal or considering drugs to raise HDL, like fibrates or nicotinic acid, especially when triglycerides are less than 200 mg/dL.

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 The HDL-C levels remain depressed until fibrate therapy has been withdrawn; the response to withdrawal of fibrate therapy is rapid and sustained.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 levels have been reported in patients taking fenofibrate.

• The decrease in HDL-C can occur within 2 weeks to years after initiation of fibrate therapy.
• If a severely depressed HDL-C level is detected, fenofibrate therapy should be withdrawn and the HDL-C level monitored until it has returned to baseline. 2 2

From the Research

Low HDL Cholesterol

• Low levels of high-density lipoprotein cholesterol (HDL-C) represent a major cardiovascular risk factor, with a stronger relationship to coronary heart disease than that seen with elevated levels of low-density lipoprotein cholesterol (LDL-C) 3
• HDL-C has important antiatherogenic effects, including reverse cholesterol transport, inhibition of LDL-C oxidation, and antiplatelet and anti-inflammatory actions 3

Risk Factors Associated with Low HDL

• Patients with low HDL-C are also at an amplified risk of coronary heart disease due to the common coexistence of other risk factors, including excess adiposity, metabolic syndrome, type 2 diabetes mellitus, hypertriglyceridemia, and the atherogenic dyslipidemia characterized by small dense LDL-C 3

Treatment and Management

• First-line therapy of low HDL-C generally consists of nonpharmacologic measures such as improved fitness and weight loss 3
• Current pharmaceutical options include statins, fibrates, and nicotinic acid 3
• Fibrates are a class of drugs characterized by mainly lowering high triglyceride, raising high-density lipoprotein (HDL) cholesterol, and lowering the small dense fraction of low-density lipoprotein (LDL) cholesterol 4

Lifestyle Interventions

• 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 5
• Moderate alcohol consumption can be permitted in some cases 5
• Aerobic exercise has been shown to increase HDL-C and decrease triglycerides in adults with cardiovascular disease 6, 7

Effects of Aerobic Exercise

• Chronic aerobic exercise increases HDL-C and decreases triglycerides in adults, especially men, with cardiovascular disease 6
• Exercise is beneficial in terms of improving lipid profile, but for younger population, and those with kidney problems and CVD patients, more further preparations are needed under the supervision of experts in the field of sports and medicine to achieve the desired result 7