Pathogenesis of aortic sclerosis: association with low BMI, tissue nitric oxide resistance, but not systemic inflammatory activation.

Aortic sclerosis (ASc) represents the earliest stage of development of aortic valve thickening, and may eventually progress to aortic valve stenosis (AS). ASc is associated with intra-valvular inflammatory activation, and potentially with attenuation of the anti-inflammatory effect of nitric oxide (NO). We have shown that ASc occurs less frequently in obese individuals, in whom systemic inflammatory activity is generally increased. We explored these relationships further by stratifying a population of 253 ageing individuals according to BMI. Increasing BMI was associated with increased hs-CRP concentrations (r=0.43; p<0.001). However, presence/absence of ASc did not significantly modify this relationship. Furthermore, increasing BMI was independent of tissue responsiveness to NO, as measured via inhibition of platelet aggregation by the NO donor sodium nitroprusside. Therefore the association of low BMI with increased risk of ASc appears to interact neither with systemic inflammatory activation in such individuals, nor with any "paradoxical" occurrence of NO resistance.