How can I increase high-density lipoprotein (HDL) and lower low-density lipoprotein (LDL) levels to reduce the risk of cardiovascular disease?

How to Increase HDL and Lower LDL

Start with comprehensive lifestyle modifications including reduction of saturated fat to <7% of total calories, regular aerobic exercise, weight loss if overweight, and smoking cessation; if LDL remains elevated after 3-6 months, initiate statin therapy as first-line pharmacological treatment, with consideration of adding niacin or fibrates specifically to raise HDL if it remains low after LDL goals are achieved. 1, 2

Lifestyle Modifications: The Foundation

Dietary Changes

• Reduce saturated fat to <7-10% of total calories and cholesterol intake to <200-300 mg/day 1, 2, 3
• Eliminate trans-fatty acids to <1% of energy intake 1, 3
• Increase monounsaturated and polyunsaturated fats (olive oil, canola oil, nuts) to 15-20% of calories, as replacing saturated fats with these healthier fats lowers LDL without the adverse effect of raising triglycerides that occurs with high-carbohydrate diets 1, 4
• Increase dietary fiber through fruits, vegetables, whole grains, and legumes 1, 2
• Consider plant stanols/sterols (2 grams daily) which interfere with intestinal cholesterol absorption and can lower LDL by an additional amount 1

Physical Activity and Weight Management

• Engage in at least 30 minutes of moderate-intensity aerobic exercise most days of the week, as regular physical activity raises HDL levels and lowers triglycerides 1, 2, 3, 4
• Achieve and maintain BMI between 18.5-24.9 kg/m² and waist circumference <35 inches in women 2, 3
• Weight loss combined with healthy diet and exercise can increase HDL by 10-13% 4

Smoking Cessation

• Stop smoking immediately, as smoking cessation can increase HDL levels by up to 30% 1, 5

Pharmacological Treatment Algorithm

When to Initiate Drug Therapy

For LDL Lowering:

• Start statins immediately if LDL ≥190 mg/dL regardless of other risk factors 3
• Start statins if LDL ≥160 mg/dL after 3-6 months of lifestyle modifications in patients with multiple risk factors 2
• Consider statins if LDL 100-159 mg/dL in patients over age 40 with diabetes or established cardiovascular disease 1

First-Line: Statin Therapy

Statins are the drugs of choice for LDL lowering and should be used as first-line pharmacologic therapy 1, 6, 7

• Start with moderate-to-high intensity statin: atorvastatin 20-40 mg daily or simvastatin 20-40 mg daily 3, 6, 7
• Target at least 30-50% LDL reduction from baseline 1, 2, 3
• Primary LDL goal is <100 mg/dL for most patients; <70 mg/dL for very high-risk patients with established cardiovascular disease 1
• Recheck lipid panel in 4-12 weeks after initiation and adjust dose as needed 3

Second-Line: Adding Agents for Inadequate LDL Response

If LDL remains elevated despite maximally tolerated statin therapy:

1. Add ezetimibe as the initial nonstatin agent (lowers LDL by inhibiting intestinal absorption) 1
2. Consider PCSK9 inhibitors (evolocumab or alirocumab) if <50% LDL reduction achieved or LDL ≥55 mg/dL on statin plus ezetimibe, particularly in very high-risk patients 1
3. May consider bempedoic acid as an alternative, though no cardiovascular outcomes data exist yet 1

Targeting Low HDL and High Triglycerides

After achieving LDL goals, address persistently low HDL (<40 mg/dL in men, <50 mg/dL in women) and elevated triglycerides (≥150 mg/dL):

For Low HDL:

• Fibrates are first-line for raising HDL when LDL is controlled, particularly in patients with established cardiovascular disease and low HDL 1
• Niacin is the most effective drug for raising HDL (can increase by 15-35%), though it may modestly increase blood glucose in diabetics at doses of 750-2,000 mg/day 1, 8, 9
• Target HDL >40 mg/dL in men, >50 mg/dL in women 1

For Elevated Triglycerides:

• Target triglycerides <150 mg/dL 1
• Optimize glycemic control first in diabetics, as improved glucose control can significantly reduce triglycerides 1
• Consider fibrates (fenofibrate preferred) or omega-3 fatty acids (2-4 grams EPA+DHA daily) 3

Combination Therapy Considerations

When combining statins with fibrates or niacin:

• Fenofibrate is preferred over gemfibrozil when combining with statins to minimize myopathy risk 1
• Take fibrates in the morning and statins in the evening to minimize peak dose concentrations and reduce myopathy risk 1
• Monitor for muscle symptoms (myalgia, weakness) and check creatine kinase if symptoms develop 6
• Combination therapy has not been fully evaluated in outcomes studies for cardiovascular event reduction, but may be necessary to achieve multiple lipid targets 1

Monitoring Strategy

• Recheck lipid panel 4-12 weeks after any medication change 3
• Once at goal, monitor lipids annually or every 2 years if low-risk values achieved (LDL <100 mg/dL, HDL >50 mg/dL, triglycerides <150 mg/dL) 1
• Monitor liver enzymes and creatine kinase at baseline and as clinically indicated with statin therapy 3, 6

Common Pitfalls to Avoid

• Don't rely solely on LDL lowering - residual cardiovascular risk remains even with optimal LDL control if HDL is low and triglycerides are elevated 10, 9
• Don't combine gemfibrozil with statins due to increased myopathy risk; use fenofibrate instead 1
• Don't forget to address secondary causes of dyslipidemia (hypothyroidism, diabetes, medications) before escalating therapy 1
• Don't abandon lifestyle modifications once medications are started - they remain critical throughout treatment 1