RESUMEN
BACKGROUND: Cardiovascular disease is associated with endothelial dysfunction in humans and studies of plasma biomarkers suggest that dogs with myxomatous mitral valve disease (MMVD) might also have endothelial dysfunction. HYPOTHESIS: That progression of mitral regurgitation (MR) is associated with development of endothelial dysfunction. ANIMALS: Forty-three Cavalier King Charles Spaniels (CKCS) with MR of varying severity. METHODS: Privately owned CKCS were prospectively recruited and divided in 4 groups: (1) 12 CKCS with minimal MR; (2) 9 CKCS with mild MR; (3) 11 CKCS with moderate-severe MR; and (4) 11 CKCS with moderate-severe MR and clinical signs compatible with heart failure. Dogs underwent blood sampling, echocardiography, blood pressure (BP) recordings, and flow-mediated vasodilation (FMD) measurements. The effect of progressive MR on FMD was determined by multivariate analyses. RESULTS: Flow-mediated vasodilation decreased with progression of MR. Group 4 (4.79 ± 3.22%) had significantly lower FMD than groups 1 (10.40 ± 4.58%) and 2 (10.14 ± 3.67%) (P < .005) and group 3 (6.79 ± 3.98%) had a significantly lower FMD than group 1 (P = .03). Increasing left ventricular end-diastolic diameter (P = .0004, R(2) = 0.27) and the combination of age (P = .01) and body weight (P = .002) (R(2) = 0.31) were significantly associated with reduced FMD. FMD did not correlate with sex, BP, or plasma markers. CONCLUSIONS AND CLINICAL IMPORTANCE: Reduced FMD indicates that increased disease severity in CKCS with MMVD is associated with development of endothelial dysfunction which might be a future therapeutic and/or diagnostic target.