Effect of l-Arginine on Human Coronary Endothelium-Dependent and Physiologic Vasodilation

AbstractObjectives. We hypothesized that l-arginine would improve abnormal coronary vasodilation in response to physiologic stress in patients with atherosclerosis and its risk factors by reversing coronary endothelial dysfunction.Background. Studies have demonstrated that physiologic coronary vasodilation correlates with endothelial function and that l-arginine, the substrate for nitric oxide synthesis, improves the response to acetylcholine (Ach).Methods. Changes in coronary blood flow and epicardial diameter response to Ach, adenosine and cardiac pacing were measured in 32 patients with coronary atherosclerosis or its risk factors and in 7 patients without risk factors and normal coronary angiograms.Results. Intracoronary l-arginine did not alter baseline coronary vascular tone, but the epicardial and microvascular responses to Ach were enhanced (both p < 0.001). The improvement after l-arginine was greater in epicardial segments that initially constricted with Ach; similarly, l-arginine abolished microvascular constriction produced by higher doses of Ach. Thus, there was a negative correlation between the initial epicardial and vascular resistance responses to Ach and the magnitude of improvement with l-arginine (r = −0.55 and r = −0.50, respectively, p < 0.001). d-Arginine did not affect the responses to Ach, and adenosine responses were unchanged with l-arginine. Cardiac pacing-induced epicardial constriction was abolished by l-arginine, but microvascular dilation remained unaffected.Conclusions. Thus, l-arginine improved endothelium-dependent coronary epicardial and microvascular function in patients with endothelial dysfunction. Prevention of epicardial constriction during physiologic stress by l-arginine in patients with endothelial dysfunction may be of therapeutic value in the treatment of myocardial ischemia

Relationship between antidepressant therapy and risk for cardiovascular events in patients with and without cardiovascular disease

Objective: The American Heart Association has endorsed depression as a cardiac risk factor and recommends screening as part of routine practice. This has been met with controversy due to inconsistencies in the data linking depression treatment to better cardiovascular outcomes. Our objective was to prospectively assess the association between depression treatment (defined as being prescribed antidepressant medication) and major adverse cardiovascular events (MACE) in patients referred for exercise stress tests. Methods: 2385 consecutive patients presenting for myocardial perfusion exercise stress tests underwent a sociodemographic, medical, and psychiatric interview (PRIME-MD) and completed the Beck Depression Inventory (BDI). History of CVD and antidepressant use was self-reported and verified via chart review. Participants followed over an 8.8 year follow-up, and information regarding MACE incidence (including cardiac mortality, non-fatal myocardial infarction, revascularization procedures, cerebrovascular events) was obtained from provincial administrative databases. Results: 8% (n=190) of the sample were taking antidepressants at baseline, 41% (n=916) had a history of CVD, and 38.7% (n=921) had depression according to the PRIME-MD or BDI. Antidepressant treatment was associated with a 30% reduced risk of MACE (HR=0.697; 95%CI=0.504-0.964; p=.029). A 46% reduction in risk was associated with antidepressant treatment among those without CVD (HR=0.542; 95%CI=0.299-0.981; p=.043). In depressed patients, a 33% reduction in risk of MACE associated with antidepressant use was seen (adjusted HR=0.674; 95%CI=0.440-1.033; p=.07). Conclusions: Antidepressants may be cardio-protective among patients presenting for stress testing independent of risk factors including CVD and depression. Results support treating depression with antidepressants in this population to reduce risk of MACE