Is Higher HDL Cholesterol Always Better?

No. Low HDL cholesterol goes with a higher risk of heart disease, which is why it’s called the “good” cholesterol, but higher isn’t better without limit. Genetic studies suggest HDL cholesterol itself doesn’t protect the heart, drugs that raise it haven’t prevented heart attacks, and very high levels have been linked to higher mortality. HDL is best read as one marker among several, mostly through what it says about the rest of your lipid profile.

This article is general information, not medical advice.

What HDL Cholesterol Measures

High-density lipoproteins (HDL) are particles that carry cholesterol away from tissues towards the liver. The test measures the cholesterol they carry, in mg/dL in the US or mmol/L elsewhere. MedlinePlus lists a healthy level as more than 40 mg/dL for men and more than 50 mg/dL for women aged 20 or older, and more than 45 mg/dL at 19 or younger. Smoking, excess weight, diabetes, and some medicines can lower it, MedlinePlus notes, and that company is much of why low HDL predicts risk.

Why Raising It Hasn’t Helped

• Genes. In a 2012 Mendelian randomisation study, Voight and colleagues found that people carrying a gene variant that raises HDL cholesterol had no lower risk of heart attack, while variants that raise LDL cholesterol raised risk as expected. Their conclusion: raising HDL cholesterol won’t uniformly lower risk.
• Drugs. In the AIM-HIGH trial, niacin added to a statin raised median HDL cholesterol from 35 to 42 mg/dL, yet cardiovascular events were no fewer than on placebo (16.4% against 16.2%), and the trial was stopped early.

So HDL cholesterol isn’t a target to push up with medication. The habits that tend to raise it, such as exercise, losing excess weight, and not smoking, are worth doing for their own sake.

Too High Is Not Protective

In over 116,000 adults from two Copenhagen cohorts, Madsen and colleagues found a U-shaped link between HDL cholesterol and death from any cause. The lowest mortality was at about 73 mg/dL in men and 93 mg/dL in women. Men with 116 mg/dL or more had about twice the risk of the lowest-risk group, and women with 135 mg/dL or more about 1.7 times. The authors called for confirmation in other studies, so treat very high HDL as unexplained rather than as a cause of harm.

The Ratio and Non-HDL Cholesterol

HDL is most useful alongside total cholesterol:

• Total cholesterol to HDL cholesterol ratio. Total cholesterol divided by HDL cholesterol; a lower ratio is better. Some risk calculators use it in place of the two numbers, such as the UK’s QRISK3.
• Non-HDL cholesterol. Total cholesterol minus HDL cholesterol: the cholesterol in all the particles that cause atherosclerosis. It works without fasting; see What Is ApoB, and Is It Better Than LDL Cholesterol?

Following It in Kaizora

HDL Cholesterol, Total Cholesterol to HDL Cholesterol Ratio, and Non-HDL Cholesterol are lab results on Labs, each logged with its time, laboratory, and printed range, so a result outside the lab’s range is flagged. A draw’s results share their time and laboratory, so your HDL lines up with the total cholesterol and triglycerides from the same blood. The Kaizora Longevity Score’s metabolic labs component scores non-HDL cholesterol by the American Heart Association’s Life’s Essential 8, using total cholesterol minus HDL cholesterol when your lab didn’t report non-HDL.

The Short Version

• Low HDL cholesterol marks higher heart risk, mostly through what comes with it.
• Raising HDL with drugs hasn’t prevented heart attacks, and genetic studies suggest it isn’t protective itself.
• Very high HDL has been linked to higher mortality in one large study.
• Read it through the cholesterol ratio and non-HDL cholesterol, with your doctor.

Sources

• MedlinePlus, HDL: The “Good” Cholesterol.
• Voight BF et al., “Plasma HDL cholesterol and risk of myocardial infarction: a mendelian randomisation study,” The Lancet 380, no. 9841 (2012): 572–580. doi:10.1016/S0140-6736(12)60312-2
• AIM-HIGH Investigators, “Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy,” New England Journal of Medicine 365, no. 24 (2011): 2255–2267. doi:10.1056/NEJMoa1107579
• Madsen CM et al., “Extreme high high-density lipoprotein cholesterol is paradoxically associated with high mortality in men and women: two prospective cohort studies,” European Heart Journal 38, no. 32 (2017): 2478–2486. doi:10.1093/eurheartj/ehx163
• Hippisley-Cox J et al., “Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease,” BMJ 357 (2017): j2099. doi:10.1136/bmj.j2099