Endothelial dysfunction and high cardiovascular risk profile in severe alcoholics improve only partially following a medium-term alcohol withdrawal

Background: Little is known about brachial artery flow-mediated vasodilatation (FMD) in active and medium-term withdrawing heavy alcoholics (HA). Methods: FMD and some parameters of cardiovascular (CV) risk were measured in 29 HA (average alcohol intake 135, range 86 to 215 g per day) at baseline and after a 9 ± 7 months withdrawal and in 35 teetotalers. Results: HA showed baseline impaired maximal % FMD (8.5 ± 5.4 SD vs. 14.9 ± 7.4, <0.001 vs. teetotalers), higher systolic (SBP) and diastolic (DBP) blood pressure (+24 mm Hg, <0.001; +15 mm Hg, <0.01), uric acid (5.3 ± 1.1 vs. 4.4 ± 0.8 mg⁄ dl, <0.05), high-sensitivity C-reactive protein (hs-CRP; 2.7 ± 2.0 vs. 1.0 ± 0.9 mg ⁄ l, <0.02), endothelin-1 (ET-1, 0.88 ± 0.36 vs. 0.37 ± 0.10 pg ⁄ ml,<0.001), asymmetric dimethylarginine (ADMA, 0.50 ± 0.21 vs. 0.41 ± 0.12 lmol/l, p < 0.001), homeostasis model assessment of insulin resistance (HOMAIR) (2.3 ± 1.1 vs. 1.2 ± 0.4, <0.001), and urinary 8-isoprostane (U8-iso-PGF2a) (237.2 ± 172.4 vs. 168.5 ± 96.6 pg ⁄ mg creatinine, <0.05). After withdrawal, SBP fell by 15 mm Hg, DBP by 11 mm Hg (p < 0.001), and hs-CRP by 0.94 mg ⁄l (p < 0.02), all remaining still higher than teetotalers (<0.05, 0.01, 0.05 respectively). ET-1, HOMA-IR, and U8-iso-PGF2a were unchanged (p = NS vs. baseline, <0.05 to 0.001 vs. teetotalers). Maximal % FMD rose (to 10.6 ± 6.2, p < 0.04), but it still remained impaired (<0.04 vs. teetotalers). ADMA increased further to 0.64 ± 0.15 lmol/l (<0.05 vs. baseline, <0.02 vs. teetotalers). Conclusions: HA show marked endothelial dysfunction (ED) and high BP, impaired insulin sensitivity, inflammation, increased oxidative stress, and elevated ET-1 and ADMA, which are unaffected or only partially reversed by a medium-term alcohol withdrawal. ED and related abnormalities persist in detoxified alcoholics, thus contributing to a greater CV morbidity and mortality.