Ronnier J. Aviles

Inflammation as a Risk Factor for Atrial Fibrillation

Background—The presence of systemic inflammation determined by elevations in C-reactive protein (CRP) has been associated with persistence of atrial fibrillation (AF). The relationship between CRP and prediction of AF has not been studied in a large population-based cohort. Methods and Results—CRP measurement and cardiovascular assessment were performed at baseline in 5806 subjects enrolled in the Cardiovascular Health Study. Patients were followed up for a mean of 6.9±1.6 (median 7.8) years. AF was identified by self-reported history and ECGs at baseline and by ECGs and hospital discharge diagnoses at follow-up. Univariate and multivariate analyses were used to assess CRP as a predictor of baseline and future development of AF. At baseline, 315 subjects (5%) had AF. Compared with subjects in the first CRP quartile (<0.97 mg/L), subjects in the fourth quartile (>3.41 mg/L) had more AF (7.4% versus 3.7%, adjusted OR 1.8, 95% CI 1.2 to 2.5; P =0.002). Of 5491 subjects without AF at baseline, 897 (16%) developed AF during follow-up. Baseline CRP predicted higher risk for developing future AF (fourth versus first quartile adjusted hazard ratio 1.31, 95% CI 1.08 to 1.58; P =0.005). When treated as a continuous variable, elevated CRP predicted increased risk for developing future AF (adjusted hazard ratio for 1-SD increase, 1.24; 95% CI 1.11 to 1.40; P <0.001). Conclusions—CRP is not only associated with the presence of AF but may also predict patients at increased risk for future development of AF.

Statins Promote Potent Systemic Antioxidant Effects Through Specific Inflammatory Pathways

Background—The pleiotropic actions of hydroxymethylglutaryl CoA reductase inhibitors (statins) include antiinflammatory and antioxidant actions. We recently reported that statins induce reductions in plasma protein levels of nitrotyrosine (NO2Tyr), a modification generated by nitric oxide–derived oxidants. Whether alternative oxidative pathways are suppressed in vivo after statin administration has not yet been reported. Methods and Results—As an extension of our prior study, hypercholesterolemic subjects with no known coronary artery disease were evaluated at baseline and after 12 weeks of atorvastatin therapy (10 mg/d). Plasma levels of protein-bound chlorotyrosine, NO2Tyr, dityrosine, and orthotyrosine, specific molecular fingerprints for distinct oxidative pathways upregulated in atheroma, were determined by mass spectrometry. In parallel, alterations in lipoproteins and C-reactive protein were determined. Statin therapy caused significant reductions in chlorotyrosine, NO2Tyr, and dityrosine (30%, 25%, and 32%, respectively; P <0.02 each) that were similar in magnitude to reductions in total cholesterol and apolipoprotein B-100 (25% and 29%, P <0.001 each). Nonsignificant decreases in orthotyrosine and C-reactive protein levels were observed (9% and 11%, respectively; P >0.10 each). Statin-induced reductions in oxidation markers were independent of decreases in lipids and lipoproteins. Conclusions—Statins promote potent systemic antioxidant effects through suppression of distinct oxidation pathways. The major pathways inhibited include formation of myeloperoxidase-derived and nitric oxide–derived oxidants, species implicated in atherogenesis. The present results suggest potential mechanisms that may contribute to the beneficial actions of statins. They also have important implications for monitoring the antiinflammatory and antioxidant actions of these agents.

Usefulness of Myeloperoxidase Levels in Healthy Elderly Subjects to Predict Risk of Developing Heart Failure

Increased systemic myeloperoxidase (MPO) has been associated with both the presence and severity of heart failure (HF). This study tested the hypothesis that increased systemic MPO in apparently healthy elderly subjects may predict increased risk of developing HF. Systemic MPO was measured in all available samples from the 1992 to 1993 visit of the Cardiovascular Health Study (CHS). After excluding subjects without available blood samples or with a history of prevalent HF, myocardial infarction (MI), or stroke, 3,733 subjects were included. A total of 569 subjects developed incident HF during 7.2 +/- 2.3 years of follow-up. Patients in the highest MPO quartile (>432 pmol/L) showed higher risk of developing incident HF after adjusting for MI, age, gender, systolic blood pressure, smoking, low-density lipoprotein cholesterol, diabetes mellitus, and any subclinical cardiovascular disease (hazard ratio 1.34, 95% confidence interval 1.06 to 1.72, p = 0.013). However, the relation was more apparent after censoring subjects with incident MI before incident HF, even when adjusted for C-reactive protein and cystatin C (hazard ratio 1.46, 95% confidence interval 1.08 to 1.97, p = 0.02). Interestingly, stratified analyses showed that the relation between increased MPO and HF risk was stronger in subjects without traditional cardiovascular risk factors (<or=75 years old, systolic blood pressure <or=136 mm Hg, no subclinical cardiovascular disease, and no diabetes mellitus). In conclusion, an independent association between increased MPO and the development of HF in apparently healthy elderly subjects was observed, particularly beyond MI and traditional cardiac risk factors.

Antiplatelet therapies in combination for the treatment of patients with stable and unstable coronary artery disease.

There have been several recent trials of antiplatelet therapy that are relevant to the management of patients with coronary artery disease. The CURE, PCI-CURE, ESPRIT, TACTICS-TIMI 18, and TARGET studies were all major randomized clinical trials that have advanced the field of cardiovascular medicine tremendously. Additionally, the CREDO trial will soon be presented. It is evident from these trials that clopidogrel therapy improves upon the results seen with aspirin alone in patients with acute coronary syndromes. This is true even of patients undergoing an invasive approach, which is clearly the preferred strategy in moderate and high risk patients with acute coronary syndromes. It is imperative that this invasive approach be coupled with intravenous blockade of the glycoprotein IIb/IIIa receptor. The benefits of clopidogrel and glycoprotein IIb/IIIa inhibitors appear complementary. Questions remain about the optimal duration of clopidogrel treatment after elective stenting and of the particular choice of glycoprotein IIb/IIIa inhibitor both in acute and elective settings.