Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris

Background Lipid-lowering therapy reduces cardiac mor bidity and mortality. Le Methods and Results In a 2-year prospective randomized placebo-controlled study, the effect of pravastatin 40 mg on transient myocardial ischemia was assessed. Forty-eight-hour ambulatory ECGs with continuous ST-segment analysis were performed in 768 male patients with stable angina pectoris, documented coronary artery disease, and serum cholesterol between 4 and 8 mmol/L (155 and 310 mg/dL). During the trial, patients received routine antianginal treatment. In the patients randomized to pravastatin, transient myocardial ischemia was present at baseline in 28% and after treatment in 19%; in the placebo group, it was found in 20% and 23% of the patients, respectively (P=.021 for change in percentage between two treatment groups; odds ratio, 0.62; 95% CI, 0.41 to 0.93). Ischemic episodes decreased by 1.23 +/- 0.25 (SEM) episode with pravastatin and by 0.53 +/- 0.25 episode with placebo (P=.047). Under pravastatin, the duration of ischemia decreased from 80 +/- 12 minutes to 42 +/- 10 minutes (P=.017) and with placebo, from 60 +/- 13 minutes to 51 +/- 9 minutes (P=.56). The total ischemic burden decreased from 41 +/- 5 to 22 +/- 5 mm ... min in the pravastatin group (P=.0058) and from 34 +/- 6 to 26 +/- 4 mm ... min in the placebo group (P=.24). Adjusted for independent risk factors for the occurrence of ischemia, the effect of pravastatin on the reduction of risk for ischemia remained statistically significant (odds ratio, 0.45; 95% CI, 0.22 to 0.91; P=.026). Conclusions In men with documented coronary artery disease and optimal antianginal therapy, pravastatin reduces transient myocardial ischemia

Genetic variant showing a positive interaction with beta-blocking agents with a beneficial influence on lipoprotein lipase activity, HDL cholesterol, and triglyceride levels in coronary artery disease patients.:The Ser447-stop substitution in the lipoprotein lipase gene. REGRESS Study Group

BACKGROUND: Lipoprotein lipase (LPL) is the rate-limiting enzyme in the lipolysis of triglyceride-rich lipoproteins, and the gene coding for LPL is therefore a candidate gene in atherogenesis. We previously demonstrated that two amino acid substitutions in LPL, the Asn291-Ser and the Asp9-Asn, are associated with elevated triglycerides and lower HDL cholesterol and are present with greater frequency in coronary artery disease (CAD) patients than in normolipidemic control subjects. Conversely, a third frequent mutation in this gene, the Ser447-Stop, is reported by some investigators to underlie higher HDL cholesterol levels and would represent a beneficial genetic variant in lipoprotein metabolism. We therefore sought conclusive evidence for these allegations by investigating the effects of the LPL Ser447-Stop mutation on LPL and hepatic lipase (HL) activity, HDL cholesterol, and triglycerides in a large group of CAD patients (n = 820) with normal to mildly elevated total and LDL cholesterol levels. METHODS AND RESULTS: Carriers of the Ser447-Stop allele (heterozygotes and homozygotes) had significantly higher postheparin LPL activity (P = .034), normal postheparin HL activity (P = .453), higher HDL cholesterol levels (P = .013), and lower triglyceride levels (P = .044) than noncarriers. The influence of the Ser447-Stop allele on LPL activity was pronounced in patients using beta-blockers (P = .042) and not significant in those not using them (P = .881), suggesting a gene-environment interaction between the Ser447-Stop mutation and beta-blockers. CONCLUSIONS: We conclude that the LPL Ser447-Stop mutation has a significant positive effect on LPL activity and HDL cholesterol and triglyceride levels and that certain subgroups of CAD patients carrying the Ser447-Stop mutation will have less adverse metabolic effects when placed on beta-blockers. The LPL Ser447-Stop mutation therefore should have a protective effect against the development of atherosclerosis and subsequent CA

Acute Myocardial Infarction: Comparison of T2‐Weighted and T1‐Weighted Gadolinium‐DTPA Enhanced MR Imaging

Magnetic resonance images were obtained from 32 patients with acute myocardial infarction, using a four‐echo technique (echo time (TE) = 30, 60, 90, and 120 ms) pre‐gadolinium(Gd)‐DTPA injection and a TE = 30 ms sequence pre‐ and post‐Gd‐DTPA. Intensity ratios of infarcted and normal myocardium were calculated, as were contrast‐to‐noise and signal‐to‐noise ratios. The four intensity ratios pre‐Gd‐DTPA were 1.20 ±0.15, 1.42 ± 0.22, 1.78 ± 0.38, and 1.99 ± 0.60 for TE = 30, 60, 90, and 120 ms, respectively, and 1.42 ± 0.19 post‐Gd‐DTPA (p = NS for post‐Gd‐DTPA vs TE = 60, p = 0.007 for TE = 90 vs TE = 120, p < 0.0001 for all other comparisons). The four contrast‐to‐noise ratios pre‐Gd‐DTPA were 1.69 ± 0.97, 2.69 ± 1.13, 3.17 ± 1.15, and 2.90 ± 1.09 for TE = 30, 60, 90, and 120 ms, respectively, and 2.71 ± 1.26 post‐Gd‐DTPA (p = NS for post‐Gd‐DTPA vs TE = 60, 90, and 120, p = NS for TE = 120 vs TE = 60 and 90, p< 0.01 for all other comparisons). The four signal‐to‐noise ratios pre‐Gd‐DTPA were 8.67 ± 1.47, 6.52 ± 0.76, 5.20 ± 0.64, 4.17 ± 0.53 for TE = 30, 60, 90, and 120 ms, respectively, and 9.17 ± 1.92 post‐Gd‐DTPA (p = 0.03 for post‐Gd‐DTPA vs TE = 30, p < 0.0001 for all other comparisons). In conclusion, the detectabilities of acute myocardial infarction were similar at TE = 60 ms and at Gd‐DTPA enhanced short‐TE MR imaging. However, image quality proved to be superior using the Gd‐DTPA enhanced short‐TE technique. © 1991 Academic Press, Inc