Is a high high‑density lipoprotein (HDL) cholesterol level harmful?

Is High HDL Cholesterol Harmful?

High HDL cholesterol is not harmful and does not require treatment—it remains protective against cardiovascular disease, though extremely elevated levels (>60 mg/dL) may simply indicate that cardiovascular events occur at a more advanced age rather than being prevented entirely. 1, 2

HDL as a Protective Factor, Not a Treatment Target

The evidence consistently demonstrates that HDL cholesterol functions as a negative risk factor in cardiovascular risk assessment:

• An HDL-C level ≥60 mg/dL is considered protective and allows you to subtract one risk factor when calculating coronary heart disease risk using the Framingham scoring system. 1

• Epidemiological studies show an inverse relationship between HDL-C levels and coronary heart disease risk across all ranges—subjects with HDL-C >60 mg/dL have lower CHD risk than those with 40-60 mg/dL, who in turn have lower risk than those with <40 mg/dL. 3

• No upper limit for the beneficial effect of HDL-C on CHD risk has been identified in population studies. 3

The Critical Distinction: HDL Level vs. HDL Function

Recent research has fundamentally changed our understanding of HDL:

• Genetic studies and large randomized controlled trials have found no evidence that artificially raising HDL-C levels reduces cardiovascular events, questioning whether HDL-C itself is causally protective. 4

• The focus has shifted from HDL quantity to HDL quality—the functional properties and composition of HDL particles matter more than the absolute cholesterol level. 4

• In inflammatory conditions, HDL can transform from an anti-atherogenic particle to a pro-atherogenic equivalent despite normal or elevated levels, demonstrating that HDL function is more important than HDL concentration. 4

Clinical Reality: High HDL Patients Still Develop CAD

A prospective study of 2,322 patients with chronic coronary artery disease provides important nuance:

• Patients with elevated HDL-C (>60 mg/dL) still develop coronary artery disease and cardiac events, but at a more advanced age (3-5 years older) compared to those with normal or low HDL-C. 2

• These patients were less frequently male, smokers, diabetic, or obese, suggesting their high HDL reflects a healthier overall metabolic profile. 2

• After adjusting for age, the apparent prognostic benefit of elevated HDL-C disappeared, indicating that high HDL delays rather than prevents cardiovascular events. 2

Treatment Implications: What NOT to Do

Guidelines explicitly state that HDL cholesterol should NOT be used as a therapeutic target, despite its value for risk assessment. 1

Key points for clinical practice:

• LDL cholesterol remains the primary target for lipid-lowering therapy because virtually all successful drug trials have used LDL-C reduction as the treatment endpoint. 1

• While ratios involving HDL (such as LDL/HDL or total cholesterol/HDL) are useful for risk estimation, the components must be considered separately for treatment decisions. 1

• There is insufficient evidence to recommend therapies aimed at raising HDL cholesterol, even when HDL is low. 1

Common Pitfalls to Avoid

1. Do not attempt to lower high HDL cholesterol—it is not harmful and reflects favorable cardiovascular risk. 1, 3

2. Do not assume that high HDL eliminates the need to treat elevated LDL cholesterol—patients with high HDL still require LDL-lowering therapy if their LDL exceeds risk-based targets. 1

3. Do not use HDL-raising medications (such as CETP inhibitors or niacin) as primary prevention strategies—these have not demonstrated cardiovascular benefit in clinical trials. 4

4. Do not ignore other cardiovascular risk factors in patients with high HDL—age, smoking, hypertension, diabetes, and family history still require assessment and management. 1, 2

Practical Clinical Algorithm

When encountering a patient with high HDL cholesterol:

1. Count it as a negative risk factor (subtract one risk factor) when calculating 10-year cardiovascular risk using Framingham scoring. 1

2. Focus treatment decisions on LDL cholesterol targets based on the patient's overall cardiovascular risk category (very high risk: LDL <70 mg/dL; high risk: LDL <100 mg/dL; moderate risk: LDL <130 mg/dL). 1

3. If triglycerides are elevated (≥150 mg/dL), calculate non-HDL cholesterol (total cholesterol minus HDL cholesterol) as a secondary target, with goals 30 mg/dL higher than corresponding LDL goals. 1

4. Reassure the patient that high HDL is favorable and requires no specific intervention. 3