Adverse effects of long-term weight gain on microvascular endothelial function

Background: Endothelial dysfunction is the first stage of the atherosclerotic cascade, and independently associated with cardiovascular events. We evaluated the associations of longitudinal changes in weight, waist circumference, body fat percentage and lean mass index with changes in endothelial function. Methods: 521 community-based subjects who belonged to hypertensive sibships and had no history of myocardial infarction or stroke had their anthropometric measures and endothelial function assessed a mean of 8.5 years apart. Endothelial function was assessed with brachial artery ultrasound, yielding measures of flow-mediated dilation and reactive hyperemia. We used multivariable linear regression with generalised estimating equations to assess the associations of longitudinal changes (Δ) in anthropometric measures with Δ flow-mediated dilation and reactive hyperemia, adjusting for potential confounders. Results: Mean ± standard deviation age was 57.6 ± 8.7 years, 58% were women, and 72% were hypertensive. Most (84%) were overweight or obese at baseline. At end of follow-up, flow-mediated dilation and reactive hyperemia increased by 1.9 ± 7.6% and 51.2 ± 605.8% on average, respectively. In multivariable linear regression, changes in anthropometric measures were not associated with changes in flow-mediated dilation. However, Δ weight (β ± SE: −9.00 ± 2.35), Δ waist circumference (−6.78 ± 2.21) and Δ body fat percentage (−19.72 ± 5.62, P < 0.0001 for each) were inversely associated with Δ reactive hyperemia. Δ lean mass index was not associated with Δ reactive hyperemia. Conclusions: Long-term increases in weight, waist circumference and body fat percentage are associated with progressive worsening of microvascular endothelial function, but not conduit vessel endothelial function, in subjects without a history of cardiovascular events, independently of risk factors.