The association between baseline circulating progenitor cells and vascular function: The role of aging and risk factors.

BACKGROUND: To investigate the cross-sectional and longitudinal relationships between vascular function and circulating progenitor cell (CPC) counts with respect to aging and exposure to risk factors. METHODS: In 797 adult participants, CPCs were enumerated by flow cytometry as CD45med mononuclear cells expressing CD34 epitope and its subsets co-expressing CD133, and chemokine C-X-C motif receptor 4 (CXCR4+). Arterial stiffness was evaluated by tonometry-derived pulse wave velocity (PWV) and microvascular function was assessed as digital reactive hyperemia index (RHI). RESULTS: In cross-sectional analyses, for every doubling in CD34+ cell counts, PWV was 15% higher and RHI was 9% lower, after adjusting for baseline characteristics and risk factors (p for all < 0.01). There were significant CPC-by-age-by-risk factor interactions (p <0.05) for both vascular measures. Among younger subjects (< 48 years), CPC counts were higher in those with risk factors and vascular function was better in those with higher compared to those with lower CPC counts (p for all < 0.0l). In contrast, in older participants, CPCs were not higher in those with risk factors, and vascular function was worse compared to the younger age group. A lower CPC count at baseline was an independent predictor of worsening vascular function during 2-year follow-up. CONCLUSION: A higher CPC count in the presence of risk factors is associated with better vascular function among younger individuals. There is no increase in CPC count with risk factors in older individuals who have worse vascular function. Moreover, a higher CPC count is associated with less vascular dysfunction with aging.

Circulating stem cells and cardiovascular outcomes: from basic science to the clinic.

The cardiovascular and haematopoietic systems have fundamental inter-relationships during development, as well as in health and disease of the adult organism. Although haematopoietic stem cells (HSCs) emerge from a specialized haemogenic endothelium in the embryo, persistence of haemangioblasts in adulthood is debated. Rather, the vast majority of circulating stem cells (CSCs) is composed of bone marrow-derived HSCs and the downstream haematopoietic stem/progenitors (HSPCs). A fraction of these cells, known as endothelial progenitor cells (EPCs), has endothelial specification and vascular tropism. In general, the levels of HSCs, HSPCs, and EPCs are considered indicative of the endogenous regenerative capacity of the organism as a whole and, particularly, of the cardiovascular system. In the last two decades, the research on CSCs has focused on their physiologic role in tissue/organ homoeostasis, their potential application in cell therapies, and their use as clinical biomarkers. In this review, we provide background information on the biology of CSCs and discuss in detail the clinical implications of changing CSC levels in patients with cardiovascular risk factors or established cardiovascular disease. Of particular interest is the mounting evidence available in the literature on the close relationships between reduced levels of CSCs and adverse cardiovascular outcomes in different cohorts of patients. We also discuss potential mechanisms that explain this association. Beyond CSCs' ability to participate in cardiovascular repair, levels of CSCs need to be interpreted in the context of the broader connections between haematopoiesis and cardiovascular function, including the role of clonal haematopoiesis and inflammatory myelopoiesis.

Marital status and outcomes in patients with cardiovascular disease.

The national burden of cardiovascular disease (CVD) continues to impose significant risk of morbidity, mortality and increased costs. While traditional risk factors have been well-established, the evolving role of non-traditional risk factors, including socioeconomic and psychosocial factors, is increasingly being recognized. Several studies have acknowledged an association between marital status and the presence of CVD and its associated adverse outcomes. Across multiple U.S. and international cohorts, patients who are unmarried, including those who are divorced, separated, widowed, or never married, have an increased rate of adverse cardiovascular events when compared to their married counterparts. Some studies suggest that marriage may have a more protective role for men compared to women. Furthermore, dissatisfaction in a marriage and marriage quality have significant impact on cardiovascular risk. Psychosocial and socioeconomic factors, as well as other acute stressors, may contribute to the association between marital status and CVD outcomes, but the underlying mechanisms are not completely clear. Further investigation is required to identify potential targets for intervention and to determine whether more aggressive targeting of standard anti-atherosclerotic therapies can favorably impact CVD risk in unmarried patients.