Relation of nonalcoholic fatty liver disease and Framingham Risk Score to flow-mediated dilation in patients with cardiometabolic risk factors.

Nonalcoholic fatty liver disease (NAFLD) has a high prevalence in the general population. Brachial artery flow-mediated dilation (FMD) is a surrogated marker of early atherosclerosis. Few data investigating the relation between FMD, NAFLD, and cardiovascular (CV) risk are available. We recruited 367 consecutive outpatients with cardiometabolic risk factors who underwent ultrasound scanning for liver steatosis and FMD. Mean age was 54.2 ± 12.2 years, and 37% were women. NAFLD was present in 281 patients (77%). Median FMD was 5.1%. FMD was significantly reduced in patients with NAFLD (p <0.001), diabetes (p = 0.001), history of coronary heart disease (p = 0.034), and metabolic syndrome (p = 0.050) and in those taking antihypertensive drugs (p = 0.022). Women disclosed greater FMD than males (p = 0.033). Moreover, FMD inversely correlated with age (Spearman rank correlation test [Rs], -0.171; p = 0.001), waist circumference (Rs, -0.127; p = 0.016), fasting blood glucose (Rs, -0.204; p <0.001), and gamma-glutamyl transpeptidase (Rs, -0.064; p = 0.234). At multivariate regression analysis, fasting blood glucose (ß, -0.148; p = 0.008), age (ß, -0.158; p = 0.005), and the presence of NAFLD (ß, -0.132; p = 0.016) inversely correlated with FMD, whereas female gender predicted a better FMD (ß, 0.125; p = 0.022). FMD and Framingham Risk Score (FRS) were inversely correlated (Rs, -0.183; p <0.001). After dividing patients into low (FRS <10; FMD, 5.5% [3.1% to 8.9%]), intermediate (FRS 10 to 20; FMD, 4.9% [2.7% to 7.5%]), and high (FRS >20; FMD, 3.3% [1.7% to 4.5%]) risk, FMD significantly decreased across risk classes of FRS (p = 0.003). At multivariate regression analysis, both FRS (ß, -0.129; p = 0.016) and NAFLD (ß, -0.218; p <0.001) were variables independently associated with FMD. In conclusion, the presence of NAFLD and FRS inversely correlated with FMD.

Dark chocolate acutely improves walking autonomy in patients with peripheral artery disease.

BACKGROUND: NOX-2, the catalytic subunit of NADPH oxidase, has a key role in the formation of reactive oxidant species and is implicated in impairing flow-mediated dilation (FMD). Dark chocolate exerts artery dilatation via down-regulating NOX2-mediated oxidative stress. The aim of this study was to investigate whether dark chocolate improves walking autonomy in peripheral artery disease (PAD) patients via an oxidative stress-mediated mechanism. METHODS AND RESULTS: FMD, serum levels of isoprostanes, nitrite/nitrate (NOx) and sNOX2-dp, a marker of blood NOX2 activity, maximal walking distance (MWD) and maximal walking time (MWT) were studied in 20 PAD patients (14 males and 6 females, mean age: 69±9 years) randomly allocated to 40 g of dark chocolate (>85% cocoa) or 40 g of milk chocolate (≤35% cocoa) in a single blind, cross-over design. The above variables were assessed at baseline and 2 hours after chocolate ingestion. Dark chocolate intake significantly increased MWD (+11%; P<0.001), MWT (+15%; P<0.001), serum NOx (+57%; P<0.001) and decreased serum isoprostanes (-23%; P=0.01) and sNOX2-dp (-37%; P<0.001); no changes of the above variables were observed after milk chocolate intake. Serum epicatechin and its methylated metabolite significantly increased only after dark chocolate ingestion. Multiple linear regression analysis showed that Δ of MWD was independently associated with Δ of MWT (P<0.001) and Δ of NOx (P=0.018). In vitro study demonstrated that HUVEC incubated with a mixture of polyphenols significantly increased nitric oxide (P<0.001) and decreased E-selectin (P<0.001) and VCAM1 (P<0.001). CONCLUSION: In PAD patients dark but not milk chocolate acutely improves walking autonomy with a mechanism possibly related to an oxidative stress-mediated mechanism involving NOX2 regulation. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947712.