From the Guidelines
For patients with low HDL cholesterol who are already on statin and ezetimibe therapy, the primary management approach should focus on lifestyle modifications, with consideration of adding specific medications to further reduce cardiovascular risk, as evidenced by the 2018 American Heart Association/American College of Cardiology guidelines 1.
Lifestyle Modifications
Lifestyle changes are foundational in managing low HDL cholesterol. These include:
- Regular aerobic exercise, such as 30 minutes of moderate-intensity exercise most days of the week, which can increase HDL by 5-10%
- Dietary adjustments like reducing refined carbohydrates and increasing consumption of omega-3 fatty acids from fatty fish or supplements (2-4 grams daily)
- Moderate alcohol consumption, if appropriate (1 drink daily for women, up to 2 for men)
- Weight loss if the patient is overweight
- Smoking cessation, as smoking is known to lower HDL levels
Medication Considerations
If lifestyle modifications are insufficient, consideration can be given to adding medications that can help raise HDL levels or further reduce cardiovascular risk. Options may include:
- Niacin, starting at 500mg daily and gradually increasing to 1-2g daily, taken with aspirin to reduce flushing, which can raise HDL by 15-35%
- Fibrates like fenofibrate (145mg daily), which can increase HDL by 10-20% and are particularly useful in patients with high triglycerides
- PCSK9 inhibitors, which may modestly increase HDL while significantly lowering LDL, as recommended for patients at very high risk for ASCVD with LDL-C levels above 1.8 mmol/L (70 mg/dL) despite maximally tolerated statin therapy 1
Primary Focus
It's crucial to remember that while raising HDL is beneficial, the primary focus should remain on LDL reduction and overall cardiovascular risk management, as some trials of HDL-raising drugs have not shown improved outcomes despite increasing HDL levels. Therefore, management should be tailored to the individual's overall risk profile, with a focus on reducing LDL cholesterol levels as recommended by the guidelines 1.
From the Research
Management Options for Low HDL
In patients already on statin (HMG-CoA reductase inhibitor) and ezetimibe, management options for low high-density lipoprotein (HDL) include:
- Considering the use of fenofibrate, which reduces triglycerides and cardiovascular risk in patients with type 2 diabetes when triglycerides are elevated and HDL is low 2
- Evaluating the potential benefits of adding a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, which can reduce LDL-C and cardiovascular risk 2, 3
- Assessing the use of omega-3 fatty acids, although their role in reducing cardiovascular risk remains controversial 2
- Considering combination therapy with ezetimibe and statin, which has been shown to be effective in reducing LDL-C and cardiovascular risk 4, 5, 3
Specific Treatment Considerations
- For patients with type 2 diabetes, fenofibrate may be considered for both macro- and microvascular benefits 3
- In high and very-high-risk patients with mild to moderately elevated triglyceride levels, treatment with either a fibrate or high-dose omega-3 fatty acids (icosapent ethyl) may be considered, weighing the benefit versus risks 3
- The combination of low-dose statin plus ezetimibe and/or nutraceuticals may be a valuable therapeutic option for patients intolerant to high-dose statin treatment 6