Study finds link between low numbers of progenitor cells, CVD in older women

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Women have lower numbers of circulating progenitor cells, a study published in the Journal of the American Heart Association reported, possibly explaining the rise in adverse cardiovascular events in women after they reach menopause and start to age.

Progenitor cells (PCs) are key to vascular repair and regeneration, Matthew L. Topel, MD, MSc, and colleagues wrote in their paper, but research hasn’t shed much light on how these malleable cells differ between men and women. Circulating PCs are largely derived from the bone marrow mononuclear cell population and can transform to perform a limited number of functions. Two of these functions, Topel and his team reported, are as hematopoietic and endothelial cells.

The researchers monitored circulating PC levels in 642 heart disease-free patients, who were a majority women and an average of 48 years old at the time. They measured PC counts using flow cytometry and found women recorded lower levels of circulating hematopoietic PCs than men in matched age groups.

Prior research has shown the risk of cardiovascular disease (CVD) morbidity and mortality increases substantially in women after they experience menopause. Before menopause, CVD rates tend to be lower in women than in men of the same age bracket. To this point, Topel and co-authors wrote, that jump has been attributed to estrogens, and studies have suggested estradiol can be protective against endothelial dysfunction and atherosclerosis in reproductive-aged women.

This study, though, lends a new idea to the existing paradigm: poor CVD outcomes in older women could be attributed to fewer circulating PCs. According to Topel’s research, lower PC levels have been associated with adverse CVD events in the past.

While estrogen levels correlate with the number of PCs in women, the researchers found the same was not true of testosterone levels in men, suggesting possible sex-based differences in regenerative capacity.

“Female sex was associated with 20 percent to 24 percent fewer PCs after adjusting for common cardiovascular risk factors,” the authors wrote. Although estradiol was associated with hematopoietic PC counts, there were no differences in PCs between premenopausal and menopausal women, and age-matched men for each cohort had significantly higher PC counts than either subset of women.”

The researchers said this was also true in a separate cohort of older patients with CVD. Women in that group recorded 12 percent to 19 percent fewer PCs than men.

“We and others have shown that PC counts decrease with aging, exposure to CVD risk factors or prevalent CVD, and low levels of PCs are associated with increased risk of CVD events," the authors wrote. "Because women have lower PC counts compared with men, they are likely to reach a critically low level with aging that is associated with increased risk of adverse CVD outcomes.”