Even before a highly publicized study from Emory University in 2018, several studies found an association between both low and high HDL-C levels and increased cardiovascular disease and death rates—that is, a U-shaped risk curve, with the lowest risk in the middle range. The studies vary in their estimates of the level at which high HDL-C starts to be associated with significant risk, with some pointing to very high levels.
For instance, a large Danish study in the European Heart Journal in 2017 found that cardiovascular mortality rates rose significantly at HDL-C above 97 mg/dL for men and above 116 for women, after adjustment for LDL and many other factors. Such high HDL-C levels are undoubtedly due to genetic factors, which may also increase cardiovascular risk.
Women and HDL
Women tend to have higher HDL-C than men, but this may not be beneficial during and after menopause. Notably, a study in Arteriosclerosis, Thrombosis, and Vascular Biology in 2018 found that HDL-C ceases to be cardioprotective in many postmenopausal women, and that high levels may mask significant atherosclerosis and cardiovascular risk.
The study involved 1,380 women, ages 45 to 84, and the researchers controlled for age, LDL, weight, hormone use, and other factors. “We hypothesize that higher HDL-C in older women could be a marker of underlying HDL dysfunction,” the researchers concluded. However, they found that HDL particle size made a difference: While a high number of small HDL particles was linked to lower risk, large HDLparticles were linked to elevated risk in women who recently went through menopause.
The researchers theorized that the decrease in estrogen and other metabolic changes that occur during and after menopause can trigger inflammation, which may impair the cholesterol-removing function of HDL over time.
This article first appeared in the UC Berkeley Wellness Letter.