When "Good” Cholesterol Goes "Bad”

Just as beauty is in the eye of the beholder, the terms “good” and “bad” have always been somewhat subjective. For cardiovascular health, physicians regularly monitor the levels of “good cholesterol” (high-density lipoproteins or HDL) and “bad cholesterol” (low-density lipoproteins or LDL). Traditionally, cardiovascular risk is assessed by measuring levels of HDL and LDL.

However, new evidence from investigators at University of Pittsburgh Graduate School of Public Health indicates that this specific type of blood cholesterol measurement may not translate into a lowered risk of cardiovascular disease in older women – bringing into question the current use of HDL cholesterol in a common equation designed to predict heart disease risk, particularly for women.

Findings from the new study were published in Arteriosclerosis, Thrombosis, and Vascular Biology through an article titled “HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women.”

“The results of our study are particularly interesting to both the public and clinicians because total HDL cholesterol is still used to predict cardiovascular disease risk,” explains lead study investigator Samar El Khoudary, Ph.D., associate professor in Pitt Public Health’s department of epidemiology. “This study confirms our previous work on a different group of women and suggests that clinicians need to take a closer look at the type of HDL in middle-aged and older women, because higher HDL cholesterol may not always be as protective in postmenopausal women as we once thought. High total HDL cholesterol in postmenopausal women could mask a significant heart disease risk that we still need to understand.”

HDL is a family of particles found in the blood that vary in sizes and cholesterol contents. HDL has traditionally been measured as the total cholesterol carried by the HDL particles, known as HDL cholesterol. HDL cholesterol, however, does not necessarily reflect the overall concentration, the uneven distribution, or the content and function of HDL particles. Previous research has demonstrated the heart-protective features of HDL. This good cholesterol carries fats away from the heart, reducing the build-up of plaque and lowering the potential for cardiovascular disease.

The Pitt researchers examined data from 1138 women aged 45 through 84 enrolled across the U.S. in the Multi-Ethnic Study of Atherosclerosis (MESA), a medical research study sponsored by the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH). MESA began in 1999 and is still following participants today.

Interestingly, the researchers found that the traditional measure of the good cholesterol, HDL cholesterol, fails to portray an accurate depiction of heart disease risk for postmenopausal women.

Women are subject to a variety of physiological changes in their sex hormones, lipids, body fat deposition, and vascular health as they transition through menopause. The authors hypothesized that the decrease of estrogen, a cardio-protective sex hormone, along with other metabolic changes, can trigger chronic inflammation over time, which may alter the quality of HDL particles.

“We have been seeing an unexpected relationship between HDL cholesterol and postmenopausal women in previous studies, but have never deeply explored it,” notes Dr. El Khoudary.

In the current study, the number and size of the HDL particles and total cholesterol carried by HDL particles were observed. Moreover, the researchers looked at how age when women transitioned into postmenopause, and the amount of time since transitioning, may impact the expected cardio-protective associations of HDL measures.

The harmful association of higher HDL cholesterol with atherosclerosis risk was most evident in women with older age at menopause and who were greater than, or equal to, 10 years into postmenopause.

In contrast to HDL cholesterol, a higher concentration of total HDL particles was associated with lower risk of atherosclerosis. Additionally, having a high number of small HDL particles was found beneficial for postmenopausal women. These findings persist irrespective of age and how long it has been since women became postmenopausal.

“Identifying the proper method to measure active ‘good’ HDL is critical to understanding the true cardiovascular health of these women,” concludes senior study investigator Matthew Budoff, M.D., professor of medicine, David Geffen School of Medicine, UCLA, and program director, Los Angeles Biomedical Research Institute.