Thrombogenic and BMI in Newly Menopausal Women
Published: 2010-08-28 - Updated: 2022-09-18
Author: American Physiological Society | Contact: physiology.org
Peer-Reviewed Publication: Yes
Additional References: Female Health Publications
Synopsis: Early menopause is a time to address life style changes that will reduce BMI and cardiovascular risk. As BMI increases, so do traditional cardiovascular risk factors such as blood pressure, blood glucose, total cholesterol, LDL cholesterol, triglycerides, and high-sensitive C-reactive protein. The researchers assessed conventional cardiovascular risk factors such as blood pressure, cholesterol, triglycerides, fasting blood glucose, and liver function.
Thrombogenicity refers to the tendency of a material in contact with the blood to produce a thrombus or clot. It refers not only to fixed thrombi but also to emboli, which have become detached and travel through the bloodstream. Thrombogenicity can also encompass events such as the activation of immune pathways and the complement system.
Although having a high body mass index (BMI) is a known risk factor for cardiovascular disease, researchers are only beginning to understand how BMI affects the physiological processes involved in developing the disease.
Now, a study of a subset of women in the Kronos Early Estrogen Prevention Study (KEEPS) suggests that as BMI increases, so do platelet reactivity and thrombogenic microvesicles, and activated protein C in the blood, all of which contribute to the formation of atherothrombosis and associated cardiovascular events. Moreover, as BMI increases, so do traditionally established cardiovascular risk factors such as blood pressure, blood glucose, total cholesterol, LDL cholesterol, triglycerides, and high-sensitive C-reactive protein.
Muthuvel Jayachandran, Assistant Professor of Physiology in the Mayo Clinic's Department of Physiology and Biomedical Engineering in Rochester, Minn., is the lead author of the study which is entitled "Body Mass Index and Thrombogenic Factors in Newly Menopausal Women."
The Mayo researchers assessed cardiovascular risk factors in 118 newly enrolled women in the KEEPS, an ongoing multi-center study designed to evaluate the effectiveness of hormone replacement therapy in preventing cardiovascular disease in post-menopausal women aged 42 to 58. All women in the study had their final menstrual period less than 36 months before enrollment.
The Mayo subset study is a baseline study that determined cardiovascular risk parameters in women before they were randomized to receive hormone replacement therapy or placebo in the KEEPS. The researchers divided the 118 women into three groups according to BMI, with women in the low, moderate, and high groups having BMIs of less than 25, 25 to 29.9, and 30 to 34.9, respectively.
The researchers assessed conventional cardiovascular risk factors such as blood pressure, cholesterol, triglycerides, fasting blood glucose, and liver function. They also analyzed the women's blood for platelet count, platelet reactivity, populations of activated cell membrane-derived thrombogenic microvesicles, and the amount of high-sensitive C-reactive protein and activated protein C. Finally; the women underwent computer tomography scans to test for the presence of calcium in their coronary arteries, an indicator of cardiovascular disease.
Although most of the conventional risk factors were in the normal range in all women, the researchers found that these parameters were significantly greater in the moderate and high BMI groups compared to the low BMI group. For example, the mean blood pressure in the low BMI group was 115/72 mmHg, but 124/77 mmHg and 127/78 mmHg in the moderate and high BMI groups, respectively.
Likewise, mean fasting blood glucose was 89 mg/dL in the low BMI group but 92 mg/dL and 95 mg/dL in the moderate and high BMI groups.
The exception was LDL, which was normal in the low BMI group with a mean of 122 mg/dL, but borderline high in the moderate and high BMI groups, each having a mean of 138 mg/dL and 140 mg/dL, respectively.
The researchers found elevated levels of platelets, thrombogenic microvesicles, high-sensitive C-reactive protein, and activated protein C in the moderate and high BMI groups. The mean platelet count in the low BMI group was 220 x103/mL, but 233 x103/mL and 255 x103/mL in the moderate and high BMI groups, respectively. The mean high-sensitive C-reactive protein in the low group was one pg/mL, but two pg/mL in the moderate BMI group and four pg/mL in the high BMI group. Mean activated protein C was 0.6 ng/mL in the low group but one ng/mL in both the moderate and high BMI groups.
Finally, researchers assessed the risk of coronary artery calcium according to the number of women in each group who tested positive for it. Women in the low BMI group had an 8% risk, but women in the moderate and high BMI groups had a 17% and 14% risk, respectively
According to Dr. Jayachandran, the upward trend in risk parameters among women in the moderate and high BMI groups should be taken seriously.
"It indicates that there may be more risk for cardiovascular disease. Early menopause is a time to address lifestyle changes that will reduce BMI and, therefore, cardiovascular risk," he said.
He added that studies like KEEPS would be pivotal in clearing up the controversy surrounding menopausal hormone therapy and cardiovascular risk. Previous studies, such as the Women's Health Initiative and the Heart and Estrogen/Progestin Replacement Study, did not show any cardiovascular benefit, but the demographics in those studies were different.
"Those studies examined women with a mean age of 62 years. They were further away from their menopause before starting treatment, and the hormones may not reduce existing atherosclerosis," Dr. Jayachandran said. "We want to know how the hormone treatments might work early on to prevent the development of cardiovascular disease."
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