口袋女优

Fewer stem cells are mobilized from the bone marrow of black individuals, suggesting a diminished compensatory response to chronic ischemia and a potential explanation for African Americans' elevated risk of cardiovascular disease, researchers said.

Blacks had fewer CD34+ circulating progenitor cells (CPCs) overall compared with whites (-17.6%, P<0.001), Arshed Quyyumi, MD, of Emory University School of Medicine in Atlanta, and colleagues reported online in .

These patients also had lower CPC counts, quantified by flow cytometry, regardless of their risk factors or underlying cardiovascular disease. Lower CD34+ counts were predictive of mortality over a median of 2.2 years in both blacks (HR 2.83, 95% CI 1.12-7.20) and whites (HR 1.79, 95% CI 1.09-2.94) without significant interaction.

"Across the U.S., Blacks compared to Whites suffer from a greater burden of cardiovascular disease (CVD) including incident MI, heart failure, stroke, and other adverse cardiovascular events. This can only partly be explained by a higher prevalence of traditional risk factors such as obesity, hypertension, diabetes mellitus, or tobacco use and it has been suggested that socioeconomic factors account for the remaining disparity," Quyyumi's group wrote.

"Because Blacks have lower CPC counts, this reduced endogenous regenerative capacity may be one additional reason for the observed disparities in CVD outcomes between Blacks and Whites," they suggested.

Progenitor cells are mobilized from the bone marrow into the circulation in response to ischemia, contributing to cellular repair and regeneration, according to the authors, though they found that CPC levels decline with age, reaching on average half the levels at age 80 compared to age 20.

The study included 1,747 patients from the Emory Cardiovascular Biobank, a prospective registry of patients undergoing cardiac catheterization; the Mental Stress Ischemia Prognosis Study, which recruited patients with stable coronary artery disease; and the Emory Predictive Health Initiative, a study of individuals without overt CVD.

In all, 26% of the cohort self-reported themselves as being black.

An analysis of CPC-mobilizing factors -- stromal cell-derived factor-1α (SDF-1α), vascular endothelial growth factor (VEGF), and matrix metallopeptidase-9 (MMP-9) -- showed that blacks had significantly lower plasma MMP-9 levels, which attenuated the association between low CD34+ and black race by 19%. On other hand, VEGF and SDF-1α levels were not significantly different between the races.

Subpopulations of CD34+ cells also reduced in black versus white individuals included:

• CD34+/CD133+ cells (-15.5%, P<0.001)
• CD34+/CXCR4+ cells (-17.3%, P<0.001)
• CD34+/VEGF2R+ cells (-27.9%, P=0.04)

"Under specific conditions such as acute MI, progenitor cell-mobilizing factors ... permit progenitor cell release from their bone marrow niches, and their subsequent proliferation, differentiation, and mobilization into the circulation," Quyyumi and colleagues wrote.

They validated the main findings of their study in a separate cohort of 411 patients recruited from Emory University-affiliated hospitals.

Among 91 individuals with acute MI, CPC levels had generally risen by the time of the angiogram (typically within 24 hours after presentation), presumably as a result of mobilization due to injury. Blacks had 30%-35% lower CPC mobilization in the setting of acute MI as well.

Nevertheless, the findings should be noted with the caveats that race was self-reported and that the researchers lacked data on sickle cell traits that could have confounded the overall results.

Comment