Asymmetric dimethylarginine is an independent risk factor for coronary heart disease: results from the multicenter Coronary Artery Risk Determination investigating the Influence of ADMA Concentration (CARDIAC) study.

BACKGROUND: Asymmetric dimethylarginine (ADMA) plasma levels have been shown to be elevated in diseases related to endothelial dysfunction such as hypertension, hyperlipidemia, diabetes mellitus, and others. It has been shown that ADMA predicts cardiovascular mortality in patients who have coronary heart disease (CHD). However, the question whether ADMA is an independent risk factor for CHD still remains unresolved. METHODS: The CARDIAC study is a multicenter case-control study, designed to detect differences in ADMA plasma levels between patients with CHD and controls from the general population. We included in our analysis 131 cases and 131 controls, matched for age, sex, and body mass index. RESULTS: We found that cases had higher ADMA plasma levels than controls (0.70 micromol/L [0.59-0.87 micromol/L] vs 0.60 micromol/L [0.54-0.69 micromol/L], P < .001). To evaluate the predictive power of ADMA regarding CHD, we calculated 2 multivariate logistic regression models including laboratory parameters and traditional risk factors. The odds ratio for ADMA in the multivariate model including the laboratory characteristics was 2.59 (1.61-4.17; P < .001); the odds ratio for the multivariate model including other risk factors was 6.04 (2.56-14.25; P < .001) for the third tertile (>0.72 micromol/L) versus the first (<0.58 micromol/L). CONCLUSIONS: We conclude from the results of our study that ADMA is an independent risk factor for CHD.

PMN/platelets coinfused in guinea pig hearts Exposed to low-flow ischemia have no additive cardiodepressive effect.

Recent studies revealed an additive cardiodepressive effect of polymorphonuclear granulocytes (PMN) and thrombocytes in hearts exposed to a no-flow ischemia. To find out whether or not this is also true for isolated guinea pig hearts exposed to a low-flow ischemia, the current study was performed. PMN or thrombocytes, together or separately, were applied as a 1-min bolus (1,000/microl or 20,000/microl, respectively) during ischemia or in reperfusion in the presence of thrombin (0.3 U/ml perfusate). Recovery of external heart work and intracoronary cell retention were quantified in percent. Sole application of PMN or platelets during ischemia and reperfusion significantly compromised myocardial function, whereas coapplication of PMN and platelets did not exhibit any further cardiodepressive effect. Coapplication of cells almost prevented intracoronary platelet retention during ischemia and in reperfusion, as opposed to sole platelet application. Known blockers of endogenously released anti-platelet substances like nitric oxide, PGI(2) or adenosine did not mediate a further aggravation of myocardial dysfunction. The platelet-activating factor (PAF) antagonist WEB 2170 BS, however, significantly improved recovery of external heart work during ischemia and in reperfusion. This indicates that an additive cardiodepressive effect of PMN and platelets in working guinea pig hearts exposed to a low-flow ischemia, cannot be demonstrated, whereas PAF antagonists seem to be cardioprotective, under these conditions. Even addition of fibrinogen to the perfusate, did not show an additive cardiodepressive effect of coapplication of PMN and platelets.

Influence of lipid-lowering therapy on the progression of coronary artery calcification: a prospective evaluation.

BACKGROUND: Coronary calcification measured by fast computed tomography techniques is a surrogate marker of coronary atherosclerotic plaque burden. In a cohort study, we prospectively investigated whether lipid-lowering therapy with a cholesterol synthesis enzyme inhibitor reduces the progression of coronary calcification. METHODS AND RESULTS: In 66 patients with coronary calcifications in electron beam tomography (EBT), LDL cholesterol >130 mg/dL, and no lipid-lowering treatment, the EBT scan was repeated after a mean interval of 14 months and treatment with cerivastatin was initiated (0.3 mg/d). After 12 months of treatment, a third EBT scan was performed. Coronary calcifications were quantified using a volumetric score. Cerivastatin therapy lowered the mean LDL cholesterol level from 164+/-30 to 107+/-21 mg/dL. The median calcified volume was 155 mm3 (range, 15 to 1849) at baseline, 201 mm3 (19 to 2486) after 14 months without treatment, and 203 mm3 (15 to 2569) after 12 months of cerivastatin treatment. The median annualized absolute increase in coronary calcium was 25 mm3 during the untreated versus 11 mm3 during the treatment period (P=0.01). The median annual relative increase in coronary calcium was 25% during the untreated versus 8.8% during the treatment period (P<0.0001). In 32 patients with an LDL cholesterol level <100 mg/dL under treatment, the median relative change was 27% during the untreated versus -3.4% during the treatment period (P=0.0001). CONCLUSIONS: Treatment with the cholesterol synthesis enzyme inhibitor cerivastatin significantly reduces coronary calcium progression in patients with LDL cholesterol >130 mg/dL.