Association of the Trp719Arg polymorphism in kinesin-like protein 6 with myocardial infarction and coronary heart disease in 2 prospective trials: the CARE and WOSCOPS trials.

Objectives: We asked whether 35 genetic polymorphisms, previously found to be associated with cardiovascular disease, were associated with myocardial infarction (MI) in the CARE (Cholesterol and Recurrent Events) trial and with coronary heart disease (CHD) in the WOSCOPS (West of Scotland Coronary Prevention Study) trial and whether the risk associated with these polymorphisms could be reduced by pravastatin treatment.

Background: Identification of genetic polymorphisms associated with CHD may improve assessment of CHD risk and understanding of disease pathophysiology.

Methods: We tested the association between genotype and recurrent MI in the CARE study and between genotype and primary CHD in the WOSCOPS trial using regression models that adjusted for conventional risk factors: Cox proportional hazards models for the CARE study and conditional logistic regression models for a nested case-control study of the WOSCOPS trial.

Association between ADAMTS1 matrix metalloproteinase gene variation, coronary heart disease, and benefit of statin therapy.

Objective: The purpose of this study was to investigate the association between the Ala227Pro polymorphism in the ADAMTS1 metalloproteinase gene and coronary heart disease and benefit from statin therapy in 2 independent cohorts.

Methods And Results: The frequency of the ADAMTS1 227Pro minor allele was 0.24 in 2421 male subjects from CARE, a randomized trial of pravastatin versus placebo.

Relation Between Red Blood Cell Distribution Width and Cardiovascular Event Rate in People With Coronary Disease.

BACKGROUND: Higher levels of red blood cell distribution width (RDW) may be associated with adverse outcomes in patients with heart failure. We examined the association between RDW and the risk of all-cause mortality and adverse cardiovascular outcomes in a population of people with coronary disease who were free of heart failure at baseline. METHODS AND RESULTS: We performed a post hoc analysis of data from the Cholesterol and Recurrent Events study.

Acceptability of sodium-reduced research diets, including the Dietary Approaches To Stop Hypertension diet, among adults with prehypertension and stage 1 hypertension.

Objective: Examine the acceptability of sodium-reduced research diets.

Design: Randomized crossover trial of three sodium levels for 30 days each among participants randomly assigned to one of two dietary patterns.

Participants/setting: Three hundred fifty-four adults with prehypertension or stage 1 hypertension who were participants in the Dietary Approaches to Stop Hypertension (DASH-Sodium) outpatient feeding trial.

Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women.

Context: The association of triglycerides with incident cardiovascular disease remains controversial. Although triglyceride levels are typically obtained in the fasting state, postprandial hypertriglyceridemia may play an important role in atherosclerosis.

Objective: To determine the association of triglyceride levels (fasting vs nonfasting) and risk of future cardiovascular events.

A trilogy of primary prevention statin trials. Panel discussion.

Presented is a report of a panel discussion held as part of the ISA 2006 Sankyo Forum titled "A Trilogy of Primary Prevention Statin Trials--The Impact of These Landmark Studies on Clinical Practice," Rome, Italy, June 2006. The themes of the panel discussion were the design features of three trials, WOSCOPS, AFCAPS/TexCAPS, and Japan's MEGA Study; comparison of their primary endpoints; and the implications of their results. Among the topics discussed by the panel of experts from Japan, USA, and UK were observations on the benefits associated with pravastatin at low dose as demonstrated in the MEGA Study as well as that study's implications for women, who represented the majority of subjects.

Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions.

The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III.

Apolipoprotein CIII-induced THP-1 cell adhesion to endothelial cells involves pertussis toxin-sensitive G protein- and protein kinase C alpha-mediated nuclear factor-kappaB activation.

Objective: Plasma apolipoprotein CIII (apoCIII) independently predicts risk for coronary heart disease (CHD). We recently reported that apoCIII directly enhances adhesion of human monocytes to endothelial cells (ECs), and identified the activation of PKC alpha as a necessary upstream event of enhanced monocyte adhesion. This study tested the hypothesis that apoCIII activates PKC alpha in human monocytic THP-1 cells, leading to NF-kappaB activation.

Asp92Asn polymorphism in the myeloid IgA Fc receptor is associated with myocardial infarction in two disparate populations: CARE and WOSCOPS.

Objective: Statins reduce inflammation and risk of myocardial infarction (MI). Because the myeloid IgA Fc receptor encoded by FCAR mediates inflammation, we hypothesized that the FCAR Asp92Asn polymorphism is associated with risk of MI and that this risk would be modified by pravastatin.

Methods And Results: In the placebo arm of the Cholesterol and Recurrent Events (CARE) study, male carriers of the 92Asn allele had an adjusted hazard ratio for incident MI of 1.

Apolipoprotein CIII induces expression of vascular cell adhesion molecule-1 in vascular endothelial cells and increases adhesion of monocytic cells.

Background: Activation of vascular endothelial cells (ECs) plays an important role in atherogenesis and plaque instability. Lipoproteins containing apolipoprotein CIII (apoCIII) predict coronary heart disease (CHD). We recently reported that apoCIII has a proinflammatory effect on human monocytes.

The apolipoprotein story.

The importance of different lipid and lipoprotein measurements, including LDL particle concentration and levels of apolipoproteins and triglycerides, in the prediction of future cardiac events continues to be debated. In summary, apo B is a strong, independent predictor of initial and recurrent coronary events, even during statin treatment, and recent studies show its predictive superiority over LDL and non-HDL cholesterol. Importantly, determination of apo B levels is unaffected in a non-fasted or hypertriglyceridemic state and is not derived from other measurements.

Healthy lifestyle factors in the primary prevention of coronary heart disease among men: benefits among users and nonusers of lipid-lowering and antihypertensive medications.

Background: Healthy lifestyle choices such as eating a prudent diet, exercising regularly, managing weight, and not smoking may substantially reduce coronary heart disease (CHD) risk by improving lipids, blood pressure, and other risk factors. The burden of CHD that could be avoided through adherence to these modifiable lifestyle factors has not been assessed among middle-aged and older US men, specifically men taking medications for hypertension or hypercholesterolemia.

Methods And Results: We prospectively monitored 42 847 men in the Health Professionals Follow-up Study, 40 to 75 years of age and free of disease in 1986.

Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee.

Improving diet and lifestyle is a critical component of the American Heart Association's strategy for cardiovascular disease risk reduction in the general population. This document presents recommendations designed to meet this objective. Specific goals are to consume an overall healthy diet; aim for a healthy body weight; aim for recommended levels of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides; aim for normal blood pressure; aim for a normal blood glucose level; be physically active; and avoid use of and exposure to tobacco products.

Proteinuria, impaired kidney function, and adverse outcomes in people with coronary disease: analysis of a previously conducted randomised trial.

Objectives: To determine whether data on proteinuria are useful for refining estimates of risk based on kidney function alone, and whether the results of kidney function tests can be a useful adjunct to data on proteinuria.

Design: Analysis of data from a randomised trial. Impaired kidney function was defined as low glomerular filtration rate (< 60 ml/min/1.

Metabolism of apoB lipoproteins of intestinal and hepatic origin during constant feeding of small amounts of fat.

We aimed to identify mechanisms by which apolipoprotein B-48 (apoB-48) could have an atherogenic role by simultaneously studying the metabolism of postprandial apoB-48 and apoB-100 lipoproteins. The kinetics of apoB-48 and apoB-100, each in four density subfractions of VLDL and intermediate density lipoprotein (IDL), were studied by stable isotope labeling in a constantly fed state with half-hourly administration of almond oil in five postmenopausal women. A non-steady-state, multicompartmental model was used.

Effect of pravastatin on blood pressure in people with cardiovascular disease.

Experimental evidence and several small studies in humans suggest that HMG-CoA (3-hydroxy 3-methylglutaryl coenzyme A) reductase inhibitors (statins) reduce blood pressure, perhaps through effects on endothelial function or by reducing inflammation. We tested the hypothesis that pravastatin would reduce blood pressure at 3 months and the risk of developing new hypertension over a follow-up period of 5 years. This was a post hoc subgroup analysis of a randomized double-blind placebo-controlled trial of pravastatin 40 mg daily vs placebo in 4159 participants with previous myocardial infarction and total plasma cholesterol <240 mg/dl (6.

Apolipoprotein CIII in apolipoprotein B lipoproteins enhances the adhesion of human monocytic cells to endothelial cells.

Background: Lipoproteins containing apolipoprotein (apo) CIII predict coronary heart disease and associate with components of the metabolic syndrome. ApoCIII inhibits lipoprotein catabolism in plasma. However, it is unknown whether apoCIII itself, or in association with VLDL, LDL, or HDL, directly affects atherogenic mechanisms in vascular cells.

Dietary approaches to prevent and treat hypertension: a scientific statement from the American Heart Association.

A substantial body of evidence strongly supports the concept that multiple dietary factors affect blood pressure (BP). Well-established dietary modifications that lower BP are reduced salt intake, weight loss, and moderation of alcohol consumption (among those who drink). Over the past decade, increased potassium intake and consumption of dietary patterns based on the "DASH diet" have emerged as effective strategies that also lower BP.

Rationale and design of the Optimal Macro-Nutrient Intake Heart Trial to Prevent Heart Disease (OMNI-Heart).

Background: The DASH (Dietary Approaches to Stop Hypertension) diet is a carbohydrate-rich, reduced-fat diet that lowers blood pressure (BP) and LDL-cholesterol. Whether partial replacement of some carbohydrate (C) with either protein (P) or unsaturated fat (U) can further improve these and other cardiovascular (CVD) risk factors is unknown.

Methods: OmniHeart is a randomized, three-period, crossover feeding study designed to compare the effects on BP and blood lipids of a carbohydrate-rich diet (CARB, similar to the DASH diet) with a diet rich in protein (PROT, predominantly from nonmeat sources) and a diet rich in unsaturated fat (UNSAT, predominantly monounsaturated).

Soy protein, isoflavones, and cardiovascular health: an American Heart Association Science Advisory for professionals from the Nutrition Committee.

Soy protein and isoflavones (phytoestrogens) have gained considerable attention for their potential role in improving risk factors for cardiovascular disease. This scientific advisory assesses the more recent work published on soy protein and its component isoflavones. In the majority of 22 randomized trials, isolated soy protein with isoflavones, as compared with milk or other proteins, decreased LDL cholesterol concentrations; the average effect was approximately 3%.

Lipoprotein lipase bound to apolipoprotein B lipoproteins accelerates clearance of postprandial lipoproteins in humans.

Objective: Experiments in cells and animal models show that lipoprotein lipase (LpL) bound to apolipoprotein (apo)B lipoproteins enhances their uptake by receptor mediated pathways. It is unknown whether this pathway is important in humans.

Methods And Results: ApoB lipoproteins with LpL were isolated from normal subjects after oral fat loading by immunoaffinity chromatography and were further separated into apoB100 and apoB48 lipoproteins.