C Reactive protein, moderate alcohol consumption, and long term prognosis after successful coronary stenting: four year results from the GENERATION study.

OBJECTIVES: To determine the impact of moderate alcohol consumption on long term prognosis after successful coronary stenting, and whether it could be related to preprocedural plasma C reactive protein (CRP). DESIGN: Part of the prospectively designed GENERATION study which investigated the impact of several biochemical factors, including plasma CRP, on long term prognosis after coronary stenting. SETTING: Tertiary referral centre. PATIENTS: 483 consecutive patients with stable or unstable coronary artery disease who underwent successful coronary stenting and were followed for up to four years. Information about alcohol consumption was collected prospectively. INTERVENTIONS: Successful coronary stenting. MAIN OUTCOME MEASURES: The incidence of the composite end point of readmission to hospital for unstable angina, non-fatal myocardial infarction, or cardiac death, whichever occurred first. RESULTS: By the end of follow up the incidence of the composite end point was 22.8%. Patients with a baseline plasma CRP concentration of < 0.68 mg/dl (defined by ROC analysis) did not show any difference in the composite end point (p = 0.9) or its components, regardless of the amount of alcohol consumed during follow up. However, among patients with plasma CRP concentration of > or = 0.68 mg/dl, those who drank moderately had a lower incidence of the composite end point (p < 0.001) or its components. CONCLUSIONS: Moderate alcohol consumption may have a beneficial impact on the long term prognosis following successful coronary stenting. The extent of this effect is positively related to preprocedural inflammatory status. An anti-inflammatory action of moderate alcohol consumption cannot be excluded.

Dysfunctional endothelial nitric oxide biosynthesis in healthy smokers with impaired endothelium-dependent vasodilatation.

BACKGROUND: The mechanisms involved in the dysfunction of both endothelium-dependent vasodilatation (EDV) and NO biosynthesis related to smoking are unclear. In this study, EDV was assessed in healthy smokers and nonsmokers in vivo and, using serum from the same individuals, was related to the NO biosynthetic pathway in vitro. METHODS AND RESULTS: Flow-mediated EDV of the brachial artery was measured in 23 male patients (8 nonsmokers and 15 smokers). Serum was collected, added to confluent ( approximately 85%) monolayers of human umbilical vein endothelial cells (HUVECs), and incubated for 12 hours. Basal and substance P-stimulated NO production was measured. The HUVECs used for measuring basal NO production were lysed, and both endothelial NO synthase (eNOS) protein expression and eNOS activity were determined. EDV was lower in smokers compared with nonsmokers (P<0.001). HUVECs treated with serum from smokers compared with nonsmokers showed significantly lower basal (P<0.0001) and stimulated (P<0.02) NO production, higher eNOS expression (P<0.0001), but lower eNOS activity (P<0.004). There was a significant positive correlation between in vivo EDV and in vitro substance P-stimulated NO production (rho=0.57, P<0.01) and between basal NO production and eNOS activity (r=0.54, P<0.008) and a negative correlation between basal NO production and eNOS protein expression (r=-0.60, P<0.003). CONCLUIONS: This is the first study to combine an in vivo model with a near-physiological in vitro model to demonstrate an association between decreased NO production and reduced EDV. Cigarette smoking was associated with reduced EDV, NO generation, and eNOS activity in the presence of increased eNOS protein expression.