High HDL May Not Protect All Women Against Heart Disease

With Samar R. El Khoudary, PhD, MPH, and Alan Tall, MD

Sure you finally figured out the status of your blood cholesterol and whether you have enough “good” cholesterol and not too much “bad” cholesterol. And yet, as women approach menopause, you are told that your risks for heart disease, high blood pressure, and stroke risk will rise.1

Now, it seems even those with higher “good” cholesterol may face unexpected—and increased—risks.

When carotid artery is block by cholesterol, blood cannot pass to brain. Even with a high HDL, the risk of heart disease may rise in women around menopause. Photo 123rf.

Questions Raised about the Protective Effects of HDL Cholesterol

In a study published in Arteriosclerosis, Thrombosis, and Vascular Biology,2 investigators offer evidence that postmenopausal women with higher levels of high-density lipoprotein (HDL) cholesterol (the so-called “good” cholesterol) are more likely to develop atherosclerosis, a thickening and narrowing of the arteries that is a risk factor for heart attack and stroke.

"This study was not designed to define at what level HDL cholesterol is considered too high,” lead author Samar R. El Khoudary, PhD, MPH, FAHA, associate professor of epidemiology and clinical and Translational Science Institute of the University of Pittsburgh, explains. Instead, “it mainly assessed for an increase in risk in postmenopausal women” as HDL cholesterol levels climbed. 

It seems that a closer look at the total number and size of HDL cholesterol particles (HDL-P) may offer a clearer picture of women’s cardiovascular risk, which appears to vary with age.2

“This atherogenic association was more evident in women with later age at menopause who were more than 10 years postmenopausal,” tells EndocrineWeb. In addition, it looks like HDL particles might offer more insight into women’s postmenopausal cardiovascular risk, which can vary with age. For instance, postmenopausal women with more large-sized HDL particles seem to have a greater risk of heart disease at midlife, than later on.2

Why HDL Might Matter in  Women’s Heart Disease Risk

Cholesterol is a waxy substance found in every cell.  Blood cholesterol tests measure levels of total cholesterol, HDL, low-density lipoproteins (LDL), and triglycerides. Our cholesterol numbers reflect the amounts of cholesterol produced by the liver and that we consume in the form of saturated fats. 

Dietary fats that influence our blood cholesterol levels come primarily from a variety of animal products, mostly red meat and dairy.3 While an elevated total blood cholesterol, in general, is associated with a host of cardiovascular-related risks such as heart disease, high blood pressure, and stroke, a high HDL-cholesterol is considered “cardioprotective,” or beneficial.4 That’s because HDL moves less-healthy forms of cholesterol into the liver, where it is then removed from the body. 

 Cholesterol’s bad reputation comes from LDL. High levels of LDL cholesterol can lead to the build-up of plaque (a combination of cholesterol and other substances) on the artery walls. As plaque accumulates, the arteries thicken and can become blocked. This process, called atherosclerosis, can slow or stop the flow of blood through the arteries and raises your risk of heart disease, stroke, high blood pressure, and other medical challenges.

Current recommendations include HDL levels above 60 mg/dL, while triglycerides should be below 150 mg/dL. Optimal LDL levels vary, depending on whether or not you have, or are at risk for, heart disease or diabetes.

 A Closer Look at Good Cholesterol in Heart Disease  

To assess the beneficial role of HDL, Dr.  El Khoudary and her team identified 1,380 middle-aged or older women from the MESA (Multi-Ethnic Study of Atherosclerosis) study and analyzed their ultrasound images of the carotid (neck) artery to determine arterial wall thickness. The carotid artery is the main channel for delivering blood to the brain.

The researchers also measured both the size and number of lipoprotein (a combination of fats and proteins) particles present. Study participants are broken into several groups based on menopausal status: 

  • Surgical menopause (mean age, 63.3 years)
  • Natural Menopause (mean age 65.1 years),
  • Perimenopause (mean age 48.4).

According to investigators,2 the surgical menopause group's mean total HDL particle concentration was 27.47  μmol/L. In the natural menopause group, it was 26.60  μmol/L, and in the perimenopause group, it was 25.81  μmol/L. In all groups, large HDL particles numbered between  6.51 μmol/L and 7.08 μmol/L, while the number of small HDL particles ranged from 19.30 μmol/L to 20.39 μmol/L. 

"Our findings suggest that associations between concentrations of large HDL particles and atherosclerosis depend on time elapsed since menopause,” Dr. El Khoudary says. “On the other hand, small HDL particles—as well as the total number of HDL particles—appear to be protective, irrespective of time elapsed since menopause.”

The results, which were similar to data reported from previous studies,5,6  “suggest that total HDL-particles offers a better indicator of HDL antiatherogenic features than HDL cholesterol in women at midlife and in older women…who, in our work as well as in other studies cited in the introduction of the paper, did not show the expected protective effect from HDL-C,” Dr. El Khoudary explains.

HDL, Carotid Artery Plaque, and Heart Disease Risk In Women

While the study is well-conducted, the issue may not be the size or number of HDL particles but rather the use of carotid artery plaque to assess HDL’s benefits, says Alan Tall, MD, professor of medicine at Columbia University Medical Center in New York City.

Based on Dr. Tall's research,6 “HDL is not protective for carotid plaque or stoke...The real message may be that HDL has a different relationship in carotid plaque than it does to coronary heart disease.”

“We found that HDL cholesterol mass efflux [the process by which cholesterol is collected for delivery to the liver] is strongly protective against coronary heart disease, but not carotid plaque or stroke,”6 says Dr. Tall.  "Although the measurements that [Dr. El Khoudary and others] made on carotid plaque are consistent with our findings, our data apply to a broader population, not just postmenopausal women," he says.

What does this mean for patients?

“I still think that HDL is related to a lower risk of coronary artery disease,” Dr. Tall tells EndocrineWeb. “Whether it’s a direct effect or a marker, there is a measure of protection there.” However, “if there are other risk factors such as high LDL, or high blood pressure, those still need to be treated.”

What, if anything, does this mean for women who are looking to reduce their risks of heart disease, especially early in menopause when concerns about cardiovascular risk increase substantially?

“Women (and others) need to know their HDL, LDL, and triglyceride numbers, and their blood pressure. And, people with diabetes also need to know what their hemoglobin A1c is,” Dr. Tall says. “These are basic medical values that need to be under control.” Dr. Tall explains that while particle number is inversely related to coronary disease risk, the lab-based tests used by Dr. El Khoudary and her team are not yet widely available.

No Change in Recommendations for Heart Disease Risk  

Regardless of the laboratory measurements used to assess HDL cholesterol, if your blood cholesterol numbers put you at risk, the treatment recommendations remain the same: “For women with high LDL cholesterol, dietary changes and statins remain the first lines of treatment,” Dr. Tall says, “and for people with diabetes, good blood sugar control has modest effects as protection against coronary disease.”

“While interesting, these new insights about HDL cholesterol are not urgent enough to suggest a change in current strategies regarding risk reduction for heart disease in post-menopausal women,” says Dr. Tall.  In addition to blood cholesterol levels, other factors that will raise your heart disease risk include poorly controlled diabetes and blood pressure.

“For now, women should stick to their physician’s current medical advice: follow a heart-healthy diet that also helps you to avoid gaining weight, and include walking or other physical activity daily,” says Dr. Tall. 

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