Racial disparities in cardiovascular disease risk: mechanisms of vascular dysfunction

Abstract

Cardiovascular disease (CVD) accounts for a third of all deaths in the United States making it the leading cause of morbidity and mortality. Although CVD affects individuals of all races/ethnicities, the prevalence of CVD is highest in non-Hispanic black (BL) individuals relative to other populations. The mechanism(s) responsible for elevated CVD risk in the BL population remains incompletely understood. However, impaired vascular vasodilator capacity and exaggerated vascular vasoconstrictor responsiveness are likely contributing factors, both of which are present even in young, otherwise healthy BL individuals. Within this review, we highlight some historical and recent data, collected from our laboratories, of impaired vascular function, in terms of reduced vasodilator capacity and heightened vasoconstrictor responsiveness, in the peripheral and cerebral circulations in BL individuals. We provide data that such impairments may be related to elevated oxidative stress and subsequent reduction in nitric oxide bioavailability. In addition, divergent mechanisms of impaired vasodilatory capacity between BL men and women are discussed. Finally, we propose several directions where future research is needed to fill in knowledge gaps, which will allow for better understanding of the mechanisms contributing to impaired vascular function in this population. Ultimately, this information will allow for better lifestyle and therapeutic approaches to be implemented in an effort to minimize the increased CVD burden in the BL population.

Keywords: African American; hypertension; vascular function; vasoconstriction; vasodilation.

Fig. 1.

Group × treatment comparisons in white (n = 15) and black (n = 15) individuals. A: plateau cutaneous vascular conductance [CVC, %maximum (max)] at control, apocynin, and allopurinol sites during 39°C local heating in white and black groups. The control site in the black group was attenuated compared with the control site in the white group. Apocynin and allopurinol increased this response in the black group only. B: nitric oxide (NO) contribution determined by the difference in CVC between local heating responses before and after NO synthase inhibition via N^ω-nitro-l-arginine methyl ester. The NO contribution in the black group was blunted at the control site relative to the white group. In the black group, allopurinol significantly increased the NO contribution vs. the control site. Data are presented as means ± SD; n = no. of individuals. ***P < 0.001 vs. the control site in the white group. [Modified from Patik et al. (101) with permission.]

Fig. 2.

Sex × treatment comparisons in black men (n = 8) and black women (n = 7). A: cutaneous vascular conductance [CVC, %maximum (max)] at control, apocynin, and allopurinol sites during 39°C local heating in white and black groups. Responses were similar between sexes at the control site. Apocynin and allopurinol increased this response in black men only. B: nitric oxide (NO) contribution determined by the difference in CVC between local heating response before and after NO synthase inhibition via N^ω-nitro-l-arginine methyl ester. The NO contribution was similar for black men and black women at the control site; however, in black men, apocynin and allopurinol both increased the NO contribution vs. the control site. All data are presented as means ± SD; n = no. of individuals. [Modified from Patik et al. (101) with permission.]

Fig. 3.

Effect of spontaneous muscle sympathetic nerve activity (MSNA) bursts on total vascular conductance (TVC) and mean arterial pressure (MAP). A: percent decreases in TVC over the 10 cardiac cycles immediately following spontaneous MSNA bursts. B: peak decreases in TVC following spontaneous MSNA bursts. C: absolute increases in MAP over the 10 cardiac cycles immediately following spontaneous MSNA bursts. D: peak increases in MAP following spontaneous MSNA bursts. Blacks are denoted by closed symbols and bars, and whites are denoted by open symbols and bars. *P < 0.05, blacks vs. whites. [Modified from Vranish et al. (125) with permission.]

Fig. 4.

Effect of beverage high in flavanol content or beverage with no flavanol content (placebo) on maximal percentage increase (y0) in cerebral vascular conductance index (CVCi) during rebreathing‐induced hypercapnia (A) and individual responses in non-Hispanic black (BL) individuals after flavanol consumption (B). In A, BL individuals (closed bars) have a reduced y0 before flavanol consumption relative to non-Hispanic white (WH) individuals (open bars), but this difference was not significant following consumption. Likewise, y0 was lower in WH individuals before consumption of the placebo; however, this difference remained following consumption. In B, y0 was significantly increased overall in BL individuals after flavanol consumption. Significant interactions (type of drink × before-after × race) were observed (P = 0.010). Values are shown as means + SD. AA, African American; CA, Caucasian American. *P < 0.05 compared with before-beverage value in the same treatment conditions by three‐way mixed-model ANOVA. [From Hurr et al. (61) with permission.]

Fig. 5.

Schematic illustrations of known findings related to racial differences. A: summary of the primary findings related to mechanisms of impaired microcirculatory vasodilatory capacity in non-Hispanic black (BL) relative to non-Hispanic white (WH) individuals. The vasodilatory response in the cutaneous circulation to a standard local heating protocol is attenuated in BL men and women. ALLO, allopurinol; APO, apocynin; BH₄, tetrahydrobiopterin; eNOS, endothelial nitric oxide synthase; l-Arg, l-arginine; l-NAME, N^G-nitro-l-arginine methyl ester; Max, maximum; NO, nitric oxide; NOS, nitric oxide synthase; ${\text{O}}_2^{-}$,  superoxide; ONOO⁻, peroxynitrite; TEM, tempol; ♂ indicates signaling pathways that resulted in augmented function in BL men only. B: the vasoconstrictor response to a given burst of sympathetic nerve activity is exaggerated in BL relative to WH individuals (i.e., greater sympathetic vascular transduction). NE, norepinephrine. C: a blunted vasodilator response in the middle cerebral artery during rebreathing-induced hypercapnia in BL relative to WH individuals. However, this group difference is abolished following acute consumption of a beverage high in flavanol content. MCAvmean, mean blood velocity in the middle cerebral artery. Please refer to the related article text for in-depth discussion of each of these responses.