OBJECTIVE: Small vessel disease is more common in Afro-Caribbeans than Caucasians. We investigated underlying differences in metabolic, inflammatory, and vascular responses that may predispose Afro-Caribbeans to small vessel pathology. METHODS AND RESULTS: Seventy-eight Afro-Caribbeans aged 35-75 years, with no vascular disease or medications, were compared with 82 matched Caucasians for metabolic variables, fasting insulin, interleukin 6, tumor necrosis factor (TNF) alpha, and cytoplasmic repressor protein levels. Carotid intima media thickness (CIMT) was measured ultrasonographically. Small vessel function was assessed by measuring the absolute change from baseline in the reflectance index (RI) of the digital volume pulse during IV infusion of albuterol (5 microg/min, DeltaRIALB) and glyceryl tri nitrate (5 microg/min, DeltaRIGTN). Large artery elasticity was measured as the stiffness index (SI) and derived from the time to pulse wave reflection adjusted for subject height. Afro-Caribbeans had significantly higher diastolic blood pressure (80.3 versus 77.6 mm Hg; P=0.033), fasting insulin (14.0 versus 10.6 microU/mL; P=0.026), TNF-alpha (6.7 versus 4.3; pg/mL; P=0.001), and interleukin 6 (2.3 versus 1.5 pg/mL; P=0.036) levels compared with Caucasians. CIMT was greater (0.81+/-0.20 versus 0.75+/-0.18 mm; P=0.02) and small vessel reactivity attenuated (mean DeltaRIALB 6.8+/-8.0% versus 12.3+/-8.%; P<0.0001) in Afro-Caribbeans, but their large artery elasticity (mean index of large artery stiffness 9.9 versus 9.7 m/s; P=0.48) was comparable with Caucasians. CIMT was independently associated with an index of large artery stiffness (beta=0.03; P=0.002) in Caucasians but not in Afro-Caribbeans. There were independent relationships among Afro-Caribbean ethnicity, TNF-alpha, and insulin levels. CONCLUSIONS: Selective impairment of small artery function may contribute to excess small vessel disease in Afro-Caribbeans.