Tobacco smoke exposure and endothelial dysfunction in patients with advanced coronary artery disease

Exposure to tobacco smoke is associated with a higher cardiovascular risk, especially in patients with coronary artery disease (CAD).

The aim of the study was to evaluate the effect of active and passive tobacco smoking on the activity of endothelial markers in advanced atherosclerosis.

We studied 181 consecutive patients with advanced CAD (53 women and 128 men) aged 60 ±8 years, including 102 active self‑declared smokers (56.3%). We determined plasma asymmetric dimethylarginine (ADMA), thrombomodulin (TM), and plasminogen activator inhibitor‑1 (PAI‑1) levels, along with serum cotinine concentrations as a marker of tobacco smoking.

Plasma ADMA levels were higher in active smokers compared with nonsmokers (0.60 ±0.09 μmol/l vs. 0.49 ±0.08 μmol/l, P <0.001). There were similar intergroup differences in TM (4.60 ±2.11 ng/ml vs. 3.0 ±1.7 ng/ml, P <0.0001) and PAI‑1 levels (30.3 ±12.4 ng/ml vs. 23.6 ±11.3 ng/ml, P <0.0001). We observed positive correlations between cotinine and ADMA (r = 0.71, P <0.0001), TM (r = 0.53, P <0.0001), and PAI‑1 (r = 0.58, P <0.0001). In 21 patients (26.6%) who declared to be nonsmokers, cotinine levels (mean, 6.30 ±22.5 ng/ml) significantly correlated with ADMA, TM, and PAI‑1 (all P <0.001). A multivariate regression analysis showed that cotinine was an independent predictor of ADMA, TM, and PAI‑1 in the whole patient group.

Despite long‑lasting endothelial injury in advanced CAD, continued cigarette smoking is able to further enhance endothelial damage by increasing ADMA levels and resultant inhibition of fibrinolysis.