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Objective: The age at which arteriosclerosis begins to contribute to events is uncertain. We determined, across the adult lifespan, the extent to which arteriosclerosis-related changes in arterial function occur in those with precipitous arterial events (stroke and critical limb ischemia). Approaches and Results: In 1082 black South Africans (356 with either critical limb ischemia [n=238] or stroke [n=118; 35.4% premature], and 726 age, sex, and ethnicity-matched randomly selected controls), arterial function was evaluated from applanation tonometry and velocity and diameter measurements in the outflow tract. Compared with age- and sex-matched controls, over 10-year increments in age from 20 to 60years, multivariate-adjusted (including steady-state pressures) aortic pulse wave velocity, characteristic impedance (Zc), forward wave pressures (Pf), and early systolic pulse pressure amplification were consistently altered in those with arterial events. Increases in Zc were accounted for by aortic stiffness (no differences in aortic diameter) and Pf by changes in Zc and not aortic flow or wave re-reflection. Multivariate-adjusted pulse wave velocity (7.48±0.30 versus 5.82±0.15 m/s, P <0.0001), Zc ( P <0.0005), and Pf ( P <0.0001) were higher and early systolic pulse pressure amplification lower ( P <0.0001) in those with precipitous events than in controls. In comparison to age- and sex-matched controls, independent of risk factors, pulse wave velocity, and Zc ( P <0.005 and <0.05) were more closely associated with premature events than events in older persons and Pf and early systolic pulse pressure amplification were at least as closely associated with premature events as events in older persons. Conclusions: Arteriosclerosis-related changes in arterial function are consistently associated with arterial events beyond risk factors from as early as 20 years of age.

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Aim We hypothesized that arterial function and N‐terminal natriuretic peptide (NT‐proBNP) levels as a marker of volume overload, relate differently to E/e′ as an index of diastolic function in dialysis compared with non‐dialysis patients with chronic kidney disease. We further examined whether cardiovascular risk factors attenuated these relationships. Methods We assessed cardiovascular risk factors and determined arterial function indices by applanation tonometry using SphygmoCor software and E/e′ by echocardiography in 103 (62 non‐dialysis and 41 dialysis) patients. Results In established confounder adjusted analysis, dialysis status impacted the pulse wave velocity‐E/e′ relationship (interaction p = .01) but not the NT‐proBNP level‐E/e′ association (interaction p = .1). Upon entering arterial function measures and NT‐proBNP levels simultaneously in regression models, arterial function measures were associated with E/e′ (p = .008 to .04) in non‐dialysis patients whereas NT‐proBNP levels were related to E/e′ in dialysis patients (p = .009 to .04). Bivariate associations were found between diabetes (p < .0001) and E/e′ in non‐dialysis patients, and haemoglobin concentrations and E/e′ (p = .02) in those on dialysis. Upon adjustment for diabetes in non‐dialysis patients, only central pulse pressure remained associated with E/e′ (p = .02); when haemoglobin concentrations were adjusted for in dialysis patients, NT‐proBNP levels were no longer associated with E/e′ (p = .2). In separate models, haemoglobin levels were associated with E/e′ independent of left ventricular mass index and preload and afterload measures (p = .02 to .03). Conclusion The main determinants of E/e′ may differ in non‐dialysis compared with dialysis patients. These include arterial function and diabetes in non‐dialysis patients, and volume overload and anaemia in dialysis patients.

Background and Objectives. The extent to which chronic kidney disease (CKD) impacts cardiovascular disease (CVD) in black Africans is uncertain. We compared cardiovascular risk factors and CVD between black and other African CKD patients. Methods. Cardiovascular risk factors, aortic and cardiac function, atherosclerosis extent, and cardiovascular event rates were assessed in 115 consecutive predialysis (n = 67) and dialysis patients (n = 48) including 46 black and 69 other (32 Asian, 28 white, and 9 mixed race) participants. Data were analysed in multivariable regression models. Results. Overall, black compared to other African CKD patients had less frequent carotid artery plaque (OR (95% CI) = 0.38 (0.16–0.91)) despite an increased cardiovascular risk factor burden. In receiver operator characteristic curve analysis, the Framingham score performed well in identifying non-black but not black CKD patients with carotid plaque (area under the curve (AUC) (95% CI) = 0.818 (0.714–0.921) and AUC (95% CI) = 0.556 (0.375–0.921), respectively). Black compared to other African predialysis patients experienced larger Framingham scores and more adverse nontraditional cardiovascular risk factors, impaired arterial and diastolic function but similar cardiovascular event rates (OR (95% CI) = 0.93 (0.22 to 3.87)). Among dialysis patients, black compared to other Africans had an overall similar traditional and nontraditional cardiovascular risk factor burden, similar arterial and diastolic function but increased systolic function (partial R = 0.356, p  = 0.01 and partial R = 0.315, p  = 0.03 for ejection fraction and stroke volume, respectively) and reduced cardiovascular event rates (OR (95% CI) = 0.22 (0.05 to 0.88)). Conclusion. Black compared to other African CKD patients have less frequent very high risk atherosclerosis and experience weaker cardiovascular risk factor-atherosclerotic CVD relationships. These disparities may be due to differences in epidemiological health transition stages. Among dialysis patients, black compared to other Africans have less cardiovascular events, which may represent a selection bias as previously documented in black Americans.