Jan Buch

Circulating Lipid Hydroperoxides Predict Cardiovascular Events in Patients With Stable Coronary Artery Disease : The PREVENT Study

OBJECTIVES This study was designed to determine the predictive value of lipid hydroperoxide (LOOH) levels for adverse cardiovascular outcomes in patients with stable coronary artery disease (CAD). BACKGROUND Oxidative modification of circulating lipids contributes to inflammation and endothelial dysfunction, which are hallmark features of atherosclerosis. A serum biomarker of oxidation is LOOH, which is a primary product of fatty acid peroxidation. METHODS Serum LOOH levels were measured and correlated with clinical events over a 3-year period in 634 patients with angiographic evidence of CAD. RESULTS Baseline LOOH levels in the highest quartile were associated with hazard ratios of 3.24 (95% confidence interval [CI] 1.86 to 5.65; p = 0.0001) for nonfatal vascular events (n = 149), 1.80 (95% CI 1.13 to 2.88; p = 0.014) for major vascular procedures (n = 139), and 2.23 (95% CI 1.44 to 3.44; p = 0.0003) for all vascular events and procedures. Baseline LOOH levels correlated with serum levels of soluble intercellular adhesion molecule-1 (p = 0.001) and thiobarbituric acid reactive substances (p = 0.001) as well as the mean percent change in stenosis for large segments >50% stenosed (p = 0.048). A multivariate proportional hazards model, adjusted for traditional risk factors and inflammatory markers, showed an independent effect of LOOH on nonfatal vascular events, vascular procedures, and all events or procedures. Amlodipine treatment was associated with reduced cardiovascular events and changes in LOOH levels compared with placebo. CONCLUSIONS Elevated LOOH levels were predictive of nonfatal vascular events and procedures in patients with stable CAD, independent of traditional risk factors and inflammatory markers.

Potent anti-ischaemic effects of statins in chronic stable angina: incremental benefit beyond lipid lowering?

Aims The DoUble-blind Atorvastatin AmLodipine (DUAAL) trial investigated whether atorvastatin decreases ischaemia by a vascular benefit, independent of low-density lipoprotein cholesterol lowering, in patients with coronary artery disease (CAD), both alone and in combination with the traditional anti-anginal therapy, amlodipine. Methods and results Randomized, double-blind, parallel-group, multicountry trial (2 weeks run-in and 24 weeks active therapy) comparing three treatments: amlodipine, atorvastatin, and amlodipine + atorvastatin; in 311 patients (78% male; mean age 62 years) with stable angina (≥2 attacks/week), CAD history, ≥3 transient myocardial ischaemia (TMI) episodes, and/or ≥15 min ischaemia on 48 h ambulatory electrocardiographic (AECG) monitoring. Efficacy variables were change in TMI by AECG, exercise ischaemia, angina diary data, and inflammatory biomarkers at Week 26. There was a comparable, highly significant decrease in TMI with amlodipine and atorvastatin, but no additional benefit for the combination. More than 50% of patients became TMI-free in all three groups and this was accompanied by a comparable, marked reduction in angina and nitroglycerin consumption. High-sensitivity C-reactive protein fell by 40% in patients receiving atorvastatin but there was no change with amlodipine. Adverse events were comparable among groups. Conclusion Atorvastatin was as potent an anti-ischaemic agent as amlodipine. Future studies of combination therapies will be instructive. Clinical trial registration information: National clinical trial number: NCT00159718, protocol number A0531031 listed on http://clinicaltrials.gov/.