Increased body fat and reduced insulin sensitivity are associated with impaired endothelial function and subendocardial viability in healthy, non-Hispanic white adolescents.

BACKGROUND: Cardiovascular disease has its origins in adolescents. Endothelial dysfunction, arterial stiffness, and decreased endocardial oxygen supply: demand ratios are early functional markers of cardiovascular risk. The goal of this study was to determine the relationships of these markers to physical, inflammatory, and metabolic markers in healthy non-Hispanic, white adolescents. METHODS: Thirty-four of the 75 subjects were female. Mean age was 15.0 ± 1.7 years and mean body mass index (BMI) was 22.0 ± 5.8 kg/m2 (mean ± SD). Reactive hyperemia was measured using venous occlusion plethysmography. Arterial tonometry was used to measure the augmentation index (AIx75 ) and the Buckberg subendocardial viability ratio. Blood samples were taken to measure inflammatory and lipid markers and oral glucose tolerance test was used to assess insulin sensitivity. RESULTS: Reactive hyperemia decreased as body mass and fat mass increased. It also decreased with increasing neutrophil count. The Buckberg index was higher in males and was positively related to insulin sensitivity even when accounting for age, sex, and resting heart rate. AIx75 was not related to any of the other variables. CONCLUSIONS: These results demonstrate that increased fat mass and decreased insulin sensitivity are related to poorer vascular function and cardiac risk in adolescents before the development of actual cardiovascular disease.

Endothelium-dependent and cyclooxygenase-dependent cutaneous vasodilatation is blunted in young men with hypertensive parents.

BACKGROUND: Across ethnicities, offspring of hypertensive parents (OH) have higher risk of hypertension than offspring of normotensive parents (ON). Sympathetic hyperactivity and reduced nitric oxide availability have been reported in normotensive OH; but the role of vasodilator cyclooxygenase (COX) products is unclear. METHODS: In 12 OH and 12 ON men (19-24 years old), each group comprising six white Europeans and six South Asians with resting ABP less than 129/89 mmHg, reactive hyperaemia and responses evoked by iontophoresis pulses of acetylcholine (ACh) were recorded in forearm skin by laser Doppler fluximetry before and after COX inhibition. RESULTS: Peak reactive hyperaemia was larger in ON than OH (71.0 ±â€Š7.8 vs. 43.4 ±â€Š8.3 perfusion units (perf.units); P < 0.05). It was attenuated by COX inhibition in ON (24.8 ±â€Š5.2 perf.units, P < 0.01), not OH (54.2 ±â€Š7.5 perf.units). Similarly, increases in perfusion evoked by ACh were greater in ON than OH (169.1 ±â€Š20.4 vs. 142.1 ±â€Š19.9 perf.units; P < 0.05) and attenuated by COX inhibition in ON (94.5 ±â€Š13.7; P < 0.05), not OH (132.6 ±â€Š16.1 perf.units). Considering ethnicities, ACh-evoked dilation, though not reactive hyperaemia was greater in Europeans than Asians (176.8 ±â€Š21.7 vs. 130.4 ±â€Š15.0; P < 0.01; 61.0 ±â€Š8.7 vs. 51.7 ±â€Š9.2 perf.units). However, within both Europeans and Asians, COX inhibition attenuated reactive hyperaemia and ACh-induced dilatation in ON only. CONCLUSION: Reactive hyperaemia and ACh-evoked dilatation in cutaneous circulation are blunted in young, normotensive OH relative to ON men irrespective of white European, or South Asian ethnicity and are attributable to impaired contribution of COX vasodilator products in OH. These features may provide early markers of endothelial dysfunction that contribute to hypertensive risk in OH men.

Forearm vasodilator responses to environmental stress and reactive hyperaemia are impaired in young South Asian men.

PURPOSE: Prevalence of cardiovascular disease (CVD) is greater in South Asians (SAs) than White Europeans (WEs). Endothelial dysfunction and blunted forearm vasodilatation to environmental stressors have been implicated in CVD. We investigated whether these features are present in young SA men. METHODS: In 15 SA and 16 WE men (19-23 years), we compared changes in forearm blood flow, arterial blood pressure (ABP), forearm vascular conductance (FVC), heart rate, and electrodermal resistance (EDR; sweating) following release of arterial occlusion (reactive hyperaemia endothelium-dependent) and 5 single sounds at 5-10 min intervals (stressors). RESULTS: All were normotensive. Peak reactive hyperaemia was smaller in SAs than WEs (FVC increase: 0.36 ± 0.038 vs 0.44 ± 0.038 units; P < 0.05). Furthermore, in WEs, mean FVC increased at 5, 15, and 20 s of each sound (vasodilatation), but increased at 5 s only in SAs, decreasing by 20 s (vasoconstriction). This reflected a smaller proportion of SAs showing forearm vasodilatation at 15 s (5/15 SAs vs 11/16 WEs: P < 0.01), the remainder showing vasoconstriction. Concomitantly, WEs showed greater bradycardia and EDR changes. Intra-class correlation analyses showed that all responses were highly reproducible over five sounds in both WEs and SAs. Moreover, sound-evoked changes in ABP and FVC were negatively correlated in each ethnicity (P < 0.01). However, WEs showed preponderance of forearm vasodilatation and depressor responses; SAs showed preponderance of vasoconstriction and pressor responses. CONCLUSIONS: Endothelium-dependent vasodilatation is blunted in young SA men. This could explain their impaired forearm vasodilatation and greater pressor responses to repeated environmental stressors, so predisposing SAs to hypertension and CVD.

Endothelial Dysfunction and Racial Disparities in Mortality and Adverse Cardiovascular Disease Outcomes.

BACKGROUND: The contribution of arterial endothelial dysfunction (ED) to increased cardiovascular disease (CVD) risk among Blacks is not known. HYPOTHESIS: We investigated whether peripheral arterial ED explains racial disparity in CVD events. METHODS: Data from the Heart Strategies Concentrating on Risk Evaluation (Heart SCORE) study was used. Endothelial dysfunction was assessed by the Framingham reactive hyperemia index (fRHI), measured using pulse amplitude tonometry (PAT). Lower values of fRHI indicate more severe ED. The primary outcome of interest was combined CVD events and all-cause mortality. RESULTS: 1454 individuals (62% female, 40% Black, mean age 59 ± 8 years) had available data on fRHI (mean [SD]: 0.74 [0.46]). Over a mean follow-up period of 8.0 ± 2.4 years (11,186 person-years), 116 events were observed. Black race, male sex, smoking, diabetes, blood pressure, triglycerides, C-reactive protein, and interleukin-6 were inversely correlated with fRHI in univariate models. In an unadjusted Cox regression model, fRHI was associated with 20% lower risk of the primary outcome events (hazard ratio [HR] per 1-SD higher fRHI: 0.80, 95% confidence interval [CI]: 0.66-0.97). However, this association was no longer significant after adjustment for CVD risk factors (HR: 0.90, 95% CI: 0.74-1.11). In an age- and sex-adjusted model, Blacks had 1.68 (95% CI: 1.16-2.43) higher risk of primary outcome compared with Whites. This association was not significantly attenuated by addition of fRHI to the multivariable models. CONCLUSION: Black race is associated with increased risk of CVD events and mortality independent of its associations with ED, as measured by PAT.

Racial differences in arterial stiffness and microcirculatory function between Black and White Americans.

BACKGROUND: Compared with whites, black Americans suffer from a disproportionate burden of cardiovascular disease (CVD). We hypothesized that racial differences in the prevalence of CVD could be attributed, in part, to impaired vascular function in blacks after adjustment for differences in risk factor burden. METHODS AND RESULTS: We assessed vascular function in 385 black and 470 white subjects (mean age, 48±11 years; 45% male). Using digital pulse amplitude tonometry (EndoPAT) we estimated the reactive hyperemia index (RHI), a measure of microvascular endothelial function, and peripheral augmentation index (PAT-AIx). Central augmentation index (C-AIx) and pulse-wave velocity (PWV) were measured as indices of wave reflections and arterial stiffness, respectively, using applanation tonometry (Sphygmocor). Compared with whites, blacks had lower RHI (2.1±0.6 versus 2.3±0.6, P<0.001), greater arterial wave reflections assessed as both PAT-AIx (20.4±21.5 versus 17.0±22.4, P=0.01) and CAIx (20.8±12.3 versus 17.5±13.3, P=0.001), and greater arterial stiffness, measured as PWV (7.4±1.6 versus 7.1±1.6 m/s, P=0.001). After adjustment for traditional CVD risk factors, black race remained a significant predictor of lower RHI and higher PAT-AIx and CAIx (all P<0.001) in all subjects and of higher PWV in men (P=0.01). Furthermore, these associations persisted in a subgroup analysis of "healthy" individuals free of CVD risk factors. CONCLUSION: Black race is associated with impaired microvascular vasodilatory function, and greater large arterial wave reflections and stiffness. Because impairment in these vascular indices may be associated with worse long-term outcomes, they may represent underlying mechanisms for the increased CVD risk in blacks.

Impaired post-ischaemic microvascular hyperaemia in Indian Asians is unexplained by diabetes or other cardiovascular risk factors.

OBJECTIVE: People of Indian Asian descent have an increased risk of cardiovascular disease (CVD) that cannot be explained by diabetes and other established CVD risk factors. We investigated if microcirculatory function was impaired in a population-based sample of people of Indian Asian descent compared with Europeans in the UK and whether any differences could be accounted for by diabetes or other CVD risk factors. RESEARCH DESIGN AND METHODS: Cutaneous microvascular function was assessed using laser Doppler fluximetry in response to heating to 42 °C (maximum hyperaemia) and 3 min arterial occlusion (post occlusive reactive hyperaemia: PORH) in 148 Indian Asians and 147 Europeans. Blood pressure, anthropometry and fasting bloods were also measured. RESULTS: Maximum hyperaemia and minimum resistance did not differ significantly by ethnicity. Resting flux and PORH were lower in Indian Asians and time to peak of PORH was prolonged. Diabetes was associated with reduced maximum hyperaemia and PORH. Adjustment for diabetes accounted for differences in resting flux and time to peak but not differences in PORH (Europeans = 45.0 (40.3, 50.1)au, Indian Asians = 35.6 (31.9, 39.7)au, mean (95% confidence interval); p = 0.008 after adjustment). Differences in conventional CVD risk factors did not account for interethnic differences in microvascular responses. CONCLUSIONS: People of Indian Asian descent have impaired post-occlusive reactive hyperaemia unexplained by diabetes, dysglycaemia or other CVD risk factors. Abnormal microvascular function in response to ischaemia could represent a novel mechanism contributing to the elevated risk of CVD in Indian Asians.

Resistance exercise training reduces central blood pressure and improves microvascular function in African American and white men.

OBJECTIVE: African American men have stiffer large central arteries and impaired dilation of smaller peripheral arteries when compared to their white peers. The purpose of this study was to examine the effect of resistance exercise training (RT) on vascular function and central blood pressure (BP) in young (22 years) African American and white men. METHODS: Vascular and hemodynamic measures were made in 19 African American and 18 white men at baseline and following 6-weeks of RT. Carotid BP and carotid/brachial artery beta-stiffness were measured by tonometry and ultrasonography, respectively. Aortic BP was measured by radial artery tonometry and a generalized transfer function. Aortic stiffness was measured by pulse wave velocity (PWV). Forearm blood flow (FBF) was measured by strain-gauge plethysmography before and during reactive hyperemia (RH) induced by 5-min of brachial artery occlusion. RESULTS: There were similar reductions in central BP and similar increases in FBF-RH in both African American and white men following RT (p<0.05). There were no changes in brachial systolic BP, carotid stiffness, and aortic PWV in either group (p>0.05). There was an increase in brachial stiffness in African American but not white men following RT (p<0.05). CONCLUSIONS: RT led to reductions in central BP and increases in microvascular endothelial function with no effect on central artery stiffness in both groups of young men. RT increased brachial stiffness in African American men. Measurement of conventional brachial BP does not capture the central hemodynamic and vascular response to exercise training due to disparate racial changes in regional vascular properties.

Racial differences in central blood pressure and vascular function in young men.

Young African-American men have altered macrovascular and microvascular function. In this cross-sectional study, we tested the hypothesis that vascular dysfunction in young African-American men would contribute to greater central blood pressure (BP) compared with young white men. Fifty-five young (23 yr), healthy men (25 African-American and 30 white) underwent measures of vascular structure and function, including carotid artery intima-media thickness (IMT) and carotid artery beta-stiffness via ultrasonography, aortic pulse wave velocity, aortic augmentation index (AIx), and wave reflection travel time (Tr) via radial artery tonometery and a generalized transfer function, and microvascular vasodilatory capacity of forearm resistance arteries with strain-gauge plethysmography. African-American men had similar brachial systolic BP (SBP) but greater aortic SBP (P<0.05) and carotid SBP (P<0.05). African-American men also had greater carotid IMT, greater carotid beta-stiffness, greater aortic stiffness and AIx, reduced aortic Tr and reduced peak hyperemic, and total hyperemic forearm blood flow compared with white men (P<0.05). In conclusion, young African-American men have greater central BP, despite comparable brachial BP, compared with young white men. Diffuse macrovascular and microvascular dysfunction manifesting as carotid hypertrophy, increased stiffness of central elastic arteries, heightened resistance artery constriction/blunted resistance artery dilation, and greater arterial wave reflection are present at a young age in apparently healthy African-American men, and conventional brachial BP measurement does not reflect this vascular burden.

Low high-density lipoprotein cholesterol is associated with impaired endothelial function in Asian Indians.

This study was designed to assess the relationship between plasma lipid levels and endothelial function in Asian Indians without cardiovascular risk factors living in the United States. While traditional risk factors do not account for the increased incidence of coronary heart disease (CHD) in Asian Indians, low high-density lipoprotein (HDL) cholesterol, elevated triglycerides, elevated lipoprotein (a), and insulin resistance are consistently found in Asian Indians with CHD. Endothelial function was measured in 86 healthy Asian Indians (mean age 33 years) free of cardiac risk factors with LDL levels<160 mg/dL. Subjects were divided into two groups on the basis of HDL levels (low HDL<40 mg/dL and normal HDL-40 mg/dL). Endothelial function during reactive hyperemia was significantly impaired in Asian Indians in the low HDL group. After covariate adjustment, NTG-induced brachial vasodilation was not different between patients in the two HDL groups. These data indicate that low HDL is associated with endothelial dysfunction in this population.

Cutaneous reactive hyperaemia: racial differences induced by corticoid application.

The postocclusive hyperaemic reaction before and after a single 1 h application of a potent corticoid (clobetasol 0.05% in ointment) was recorded by means of laser Doppler velocimetry in order to elucidate different racial responses in skin vasoconstriction. Fourteen young male subjects entered the study (eight Caucasians, six Blacks). Reactive hyperaemia was recorded after 4 min of occlusion of the forearm blood flow. The following parameters of the hyperaemic reaction were investigated: area under the curve response, peak response, rise of blood flow slope to peak and decay of blood flow slope after peak. Different responses were recorded in the Black subjects after the vasoconstrictive stimulus compared to the Caucasians, namely: decreased area under the curve response (P less than 0.04); decreased peak response (P less than 0.01); decreased decay slope after peak blood flow (P less than 0.04). These data are consistent with a different reactivity of blood vessels in black skin and possibly not related to the transcutaneous penetration of the chemical compound.