Lipoprotein lipase activity is decreased in a large cohort of patients with coronary artery disease and is associated with changes in lipids and lipoproteins

Lipoprotein lipase (LPL) is crucial in the hydrolysis of triglycerides (TG) in TG-rich lipoproteins in the formation of HDL particles. As both these lipoproteins play an important role in the pathogenesis of atherosclerotic vascular disease, we sought to assess the relationship between post-heparin LPL (PH-LPL) activity and lipids and lipoproteins in a large, well-defined cohort of Dutch males with coronary artery disease (CAD). These subjects were drawn from the REGRESS study, totaled 730 in number and were evaluated against 75 healthy, normolipidemic male controls. Fasting mean PH-LPL activity in the CAD subjects was 108 46 mU/ml, compared to 138 44 mU/ml in controls (P < 0.0001). When these patients were divided into activity quartiles, those in the lowest versus the highest quartile had higher levels of TG (P < 0.001), VLDLc and VLDL-TG (P = 0.001). Conversely, levels of TC, LDL, and HDLc were lower in these patients (P = 0.001, P = 0.02, and P = 0.001, respectively). Also, in this cohort PH-LPL relationships with lipids and lipoproteins were not altered by apoE genotypes. The frequency of common mutations in the LPL gene associated with partial LPL deficiency (N291S and D9N carriers) in the lowest quartile for LPL activity was more than double the frequency in the highest quartile (12.0% vs. 5.0%; P = 0.006). By contrast, the frequency of the S447X LPL variant rose from 11.5% in the lowest to 18.3% (P = 0.006) in the highest quartile. This study, in a large cohort of CAD patients, has shown that PH-LPL activity is decreased (22%; P = 0.001) when compared to controls; that the D9N and N291S, and S447X LPL variants are genetic determinants, respectively, in CAD patients of low and high LPL PH-LPL activities; and that PH-LPL activity is strongly associated with changes in lipids and lipoproteins

Diagnostic significance of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in thrombolytic treatment for acute myocardial infarction: its potential in assessing reperfusion.

The diagnostic value of gadolinium-DTPA (diethylenetriamine penta-acetic acid) enhanced magnetic resonance imaging in patients treated by thrombolysis for acute myocardial infarction was assessed in 27 consecutive patients who had a first acute myocardial infarction (14 anterior, 13 inferior) and who underwent thrombolytic treatment and coronary arteriography within 4 hours of the onset of symptoms. Magnetic resonance imaging was performed 93 hours (range 15-241) after the onset of symptoms. A Philips Gyroscan (0.5 T) was used, and spin echo measurements (echo time 30 ms) were made before and 20 minutes after intravenous injection of 0.1 mmol/kg gadolinium-DTPA. In all patients contrast enhancement of the infarcted areas was seen after Gd-DTPA. The signal intensities of the infarcted and normal values were used to calculate the intensity ratios. Mean (SD) intensity ratios after Gd-DTPA were significantly increased (1.15 (0.17) v 1.52 (0.29). Intensity ratios were higher in the 17 patients who underwent magnetic resonance imaging more than 72 hours after the onset of symptoms than in the 10 who underwent magnetic resonance imaging earlier, the difference being significantly greater after administration of Gd-DTPA (1.38 (0.12) v 1.61 (0.34). When patients were classified according to the site and size of the infarcted areas, or to reperfusion (n = 19) versus non-reperfusion (n = 8), the intensity ratios both before and after Gd-DTPA did not show significant differences. Magnetic resonance imaging with Gd-DTPA improved the identification of acutely infarcted areas, but with current techniques did not identify patients in whom thrombolytic treatment was successful

The role of a common variant of the cholesteryl ester transfer protein gene in the progression of coronary atherosclerosis. The Regression Growth Evaluation Statin Study Group

BACKGROUND: The high-density lipoprotein (HDL) cholesterol concentration is inversely related to the risk of coronary artery disease. The cholesteryl ester transfer protein (CETP) has a central role in the metabolism of this lipoprotein and may therefore alter the susceptibility to atherosclerosis. METHODS: The DNA of 807 men with angiographically documented coronary atherosclerosis was analyzed for the presence of a polymorphism in the gene coding for CETP. The presence of this DNA variation was referred to as B1, and its absence as B2. All patients participated in a cholesterol-lowering trial designed to induce the regression of coronary atherosclerosis and were randomly assigned to treatment with either pravastatin or placebo for two years. RESULTS: The B1 variant of the CETP gene was associated with both higher plasma CETP concentrations (mean [+/-SD], 2.29+/-0.62 microg per milliliter for the B1B1 genotype vs. 1.76+/-0.51 microg per milliliter for the B2B2 genotype) and lower HDL cholesterol concentrations (34+/-8 vs. 39+/-10 mg per deciliter). In addition, we observed a significant dose-dependent association between this marker and the progression of coronary atherosclerosis in the placebo group (decrease in mean luminal diameter: 0.14+/-0.21 mm for the B1B1 genotype, 0.10+/-0.20 mm for the B1B2 genotype, and 0.05+/-0.22 mm for the B2B2 genotype). This association was abolished by pravastatin. Pravastatin therapy slowed the progression of coronary atherosclerosis in B1B1 carriers but not in B2B2 carriers (representing 16 percent of the patients taking pravastatin). CONCLUSIONS: There is a significant relation between variation at the CETP gene locus and the progression of coronary atherosclerosis that is independent of plasma HDL cholesterol levels and the activities of lipolytic plasma enzymes. This common DNA variant appears to predict whether men with coronary artery disease will benefit from treatment with pravastatin to delay the progression of coronary atherosclerosis

An evaluation of the inappropriate prescribing in older residents in long term care facilities in the greater Cork and Northern Ireland regions using the STOPP and Beers’ criteria.

This work has highlighted a number of areas of prescribing concern, for example, the long term use of both benzodiazepines and hypnotics, in older residents residing in long term care facilities. Each of these individual areas should be further investigated to determine the underlying reason(s) for the prescribing concerns in these areas and strategic methods of addressing and preventing further issues should be developed on a national level

No gender bias in referral for coronary angiography after myocardial perfusion scintigraphy with technetium-99m tetrofosmin

Background. Several studies have shown that the application of diagnostic and invasive procedures varies between men and women. The purpose of this study was to assess if referral for coronary angiography after technetium-99m tetrofosmin myocardial perfusion scintigraphy in 616 patients with undiagnosed chest pain might demonstrate gender bias, Methods and Results. The primary end point for this study was coronary angiography within 90 days of myocardial perfusion scintigraphy. Women had more normal perfusion images than men (207 [70.9%] vs 160 [50.5%], P <.05), Of 242 patients with abnormal images (157 men, 85 women), 28 men (17.7%) and 17 women (20.0%) were referred for further invasive testing (P = not significant). Referral for coronary angiography increased relative to the number of defects. Univariate analysis showed that reversible and persistent defects were the most predictive variables for referral to coronary angiography (odds ratio [OR] 5.45, 95% confidence interval [CI] 3.10-9.58, P <.001, and OR 2.67, 95% CI 1.52-4.67, P =.001, respectively). More importantly, multivariate analysis showed that reversible perfusion defects (OR 4.77, 95% CI 2.48-9.17, P <.001) and persistent perfusion defects (OR 2.14, 95 % CI 1.11-4.14, P = .02) were predictive of subsequent coronary angiography, No significant association between gender and subsequent coronary angiography was found both in univariate and multivariate logistic regression analysis (OR 0.64, 95% CI 0.37-1.12, P = .12, and OR 0.70, 95% CI 0.36-1.36, P = .28, respectively). Conclusions, Our study reveals that after correction for the presence and the severity of myocardial perfusion abnormalities, men and women were referred to coronary angiography at a similar rate. Thus, based on the results of technetium-99m tetrofosmin myocardial perfusion imaging, no substantial evidence for a gender-related bias could be found in the referral for further invasive testin