EFFECTS OF LONG-TERM WEIGHT GAIN ON ENDOTHELIAL FUNCTION

Abstract

Endothelial dysfunction is the first stage of the atherosclerotic cascade, and is independently associated with future cardiovascular (CV) events. Obesity is a risk factor for CV diseases, but the long-term effects of weight gain on endothelial function remains unknown. To fill this knowledge gap, we evaluated the associations of longitudinal changes in weight, waist circumference (WC), body fat percentage (BF%) and lean mass index (LMI) with changes in endothelial function. 521 community-based subjects who belonged to hypertensive sibships and had no history of myocardial infarction or stroke had their height, weight, WC and endothelial function assessed a mean of 8.5 years apart. BF% was estimated with a validated formula [(1.20 × BMI) + (0.23 × Age) − (10.8 × sex) − 5.4; sex=1 for men and 0 for women]. LMI was calculated as BMI x (1-BF%). Endothelial function was assessed with brachial artery ultrasound according to guidelines, yielding measures of brachial artery flow-mediated dilation (FMD, a measure of conduit artery endothelial function) and reactive hyperemia (RH, a measure of microvascular endothelial function). We used multivariate linear and logistic regression with generalized estimating equations to assess the associations of longitudinal changes (Δ) in weight, WC, BF% and LMI with ΔFMD and ΔRH, and with worsening of FMD and RH, respectively. Models were adjusted for sex, baseline age, blood pressure, renal function, lipids, FMD and RH, follow-up time, history of hypertension, diabetes and smoking, and use of statins and anti-hypertensives. Mean±SD age was 57.6±8.7 years, 58% were women, and 72% were hypertensive. Mean±SD weight, BMI, WC, BF%, LMI, FMD and RH at baseline were 87.6±19.4Kg, 30.7±5.8Kg/m2, 100.2±15.7cm, 50.9±8.6% and 14.7±2.0Kg/m2, 5.9±4.9% and 805±452%, respectively. At end of follow-up, mean± SD weight, WC, BF, FMD and RH increased by 0.4±8.1Kg, 0.4±8.7cm, 1.9±3.4%, 1.9±7.6% and 51.2±605.8%, respectively, and LMI decreased by 0.6±0.4Kg/m2. In multivariable regression, Δweight, ΔWC, ΔBF% and ΔLMI were not associated with ΔFMD or FMD worsening. However, Δweight, ΔWC and ΔBF% were inversely associated with ΔRH, and significantly associated with greater odds of RH worsening over time (Table). Absolute changes in RH based on magnitude of weight change are illustrated in the Figure. ΔLMI was not associated with ΔRH or RH worsening. Long-term increases in weight, WC and BF% are associated with progressive worsening of microvascular endothelial function, but not conduit vessel endothelial function, in subjects without a history of CV events, independently of CV risk factors.View Large Image Figure ViewerDownload (PPT)