Long-term effects of statin treatment in elderly people: extended follow-up of the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

Background: The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), a placebo-controlled trial of pravastatin, demonstrated a 19% reduction in coronary outcomes (p=0.006) after a mean of 3.2 years, with no impact on stroke outcomes or all-cause mortality.

Long-term impact on healthcare resource utilization of statin treatment, and its cost effectiveness in the primary prevention of cardiovascular disease: a record linkage study.

Aims: To assess the impact on healthcare resource utilization, costs, and quality of life over 15 years from 5 years of statin use in men without a history of myocardial infarction in the West of Scotland Coronary Prevention Study (WOSCOPS).

Methods: Six thousand five hundred and ninety-five participants aged 45-54 years were randomized to 5 years treatment with pravastatin (40 mg) or placebo. Linkage to routinely collected health records extended follow-up for secondary healthcare resource utilization to 15 years.

Blood pressure variability and cardiovascular risk in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER).

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70-82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.

Genome-wide study of gene variants associated with differential cardiovascular event reduction by pravastatin therapy.

Statin therapy reduces the risk of coronary heart disease (CHD), however, the person-to-person variability in response to statin therapy is not well understood. We have investigated the effect of genetic variation on the reduction of CHD events by pravastatin. First, we conducted a genome-wide association study of 682 CHD cases from the Cholesterol and Recurrent Events (CARE) trial and 383 CHD cases from the West of Scotland Coronary Prevention Study (WOSCOPS), two randomized, placebo-controlled studies of pravastatin.

The effect of omega-3 fatty acids on the atherogenic lipoprotein phenotype in patients with nephrotic range proteinuria.

Aims: Patients with nephrotic range proteinuria are known to have an increased risk of cardiovascular disease partly due to possessing the atherogenic lipoprotein phenotype. The aim of this study was to examine the effect of high dose omega-3 fatty acids on atherogenic triglyceride rich lipoproteins in patients with nephrotic range proteinuria, comparing their effect on lipoprotein profiles in age and sex matched controls.

Methods: 17 patients with nephrotic range proteinuria and 17 age and sex matched controls were studied.

Apolipoprotein E genotype and the cardiovascular disease risk phenotype: impact of sex and adiposity (the FINGEN study).

Here the impact of APOE genotype on CHD risk in UK adults is reported, along with an analysis of APOE genotype × BMI/age/sex interactions. APOE genotype had a significant impact on fasting total:LDL-cholesterol (TC:LDL-C) ratio, triglycerides, % HDL3, and the Framingham 10-year CVD risk score (P<0.05), with an overall trend towards lower and higher risk in E2- and E4-carriers, respectively, relative to the wild-type E3/E3 genotype.

Genetic variants in the KIF6 region and coronary event reduction from statin therapy.

A single nucleotide polymorphism (SNP) in KIF6, a member of the KIF9 family of kinesins, is associated with differential coronary event reduction from statin therapy in four randomized controlled trials; this SNP (rs20455) is also associated with the risk for coronary heart disease (CHD) in multiple prospective studies. We investigated whether other common SNPs in the KIF6 region were associated with event reduction from statin therapy. Of the 170 SNPs in the KIF6 region investigated in the Cholesterol and Recurrent Events trial (CARE), 28 were associated with differential event reduction from statin therapy (P (interaction) < 01 in Caucasians, adjusted for age and sex) and were further investigated in the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI22) and West of Scotland Coronary Prevention Study (WOSCOPS).

Activation of hemostasis and decline in cognitive function in older people.

Objective: To determine whether activation of hemostatic function (thrombosis and fibrinolysis) is associated with cognitive decline in older people.

Methods And Results: We studied 5804 people (age, 70-82 years) in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Mean follow-up was 3.

Omega-3 fatty acids improve postprandial lipaemia in patients with nephrotic range proteinuria.

Background: Patients with nephrotic range proteinuria have a marked increase in the risk of cardiovascular disease. Qualitative and quantitative changes in lipids and lipoproteins contribute to this increased risk with an abundance of atherogenic triglyceride (TG) rich apolipoprotein B containing lipoproteins. TG rich lipoproteins predominate postprandially and are associated with increased risk of coronary heart disease (CHD).

Familial hypobetalipoproteinemia due to a novel early stop mutation.

Background: Familial hypobetalipoproteinemia (FHBL) is a co-dominant disorder associated with low circulating levels of low-density lipoprotein (LDL) cholesterol and apolipoprotein B100 (ApoB). A proband was identified in whom the condition was due to an E110X mutation of APOB, creating a particularly early truncation of ApoB in the region of the molecule necessary for very-low-density lipoprotein (VLDL) assembly. The mutation was also associated with nonalcoholic fatty liver disease.

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.

Fractionation of cholesteryl ester rich intermediate density lipoprotein subpopulations by chondroitin sulphate.

IDL is considered an atherogenic lipoprotein but little progress has been made on methods to subfractionate this density class. Furthermore, previous work suggests that lipoproteins retained by the arterial wall, of which chondoitin sulphate is the major arterial wall proteoglycan, are potentially atherogenic. The aim of this study was to assess the subfractionation of IDL particles using chondroitin sulphate (CS).

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.

Insight into the nature of the CRP-coronary event association using Mendelian randomization.

Background: It is unclear wheather the association between C-reactive protein (CRP) and incident coronary events is free from bias and confounding. Individuals homozygous for a +1444C>T polymorphism in the CRP gene have higher circulating concentrations of CRP. Since the distribution of this polymorphism occurs at random during gamete formation, its association with coronary events should not be biased or confounded.

Microsomal triglyceride transfer protein -493T variant reduces IDL plus LDL apoB production and the plasma concentration of large LDL particles.

The microsomal triglyceride transfer protein (MTP) is essential for the synthesis and secretion of apolipoprotein B (apoB)-containing lipoproteins. We investigated the role the MTP -493G/T gene polymorphism in determining the apoB-100 secretion pattern and LDL heterogeneity in healthy human subjects. Groups of carriers of the T and the G variants (n = 6 each) were recruited from a cohort of healthy 50-yr-old men.

Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease.

Objective: Activated inflammation and activated blood coagulation are believed to increase the risk of coronary thrombosis and are related. We therefore compared plasma IL-6 (a key cytokine in the inflammatory process), fibrin D-dimer (a marker of fibrin turnover), and coagulation factors VII and XIIa (initiators of extrinsic and intrinsic blood coagulation, respectively) as predictors of coronary risk in the West of Scotland Coronary Prevention Study of pravastatin in men with hypercholesterolemia.

Methods And Results: 485 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or revascularization) were matched for age and smoking status with 934 controls.

The microsomal triglyceride transfer protein gene-493T variant lowers cholesterol but increases the risk of coronary heart disease.

Background: The microsomal triglyceride transfer protein (MTP) transfers lipids into apolipoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. The T-variant of a functional polymorphism in the MTP promoter, MTP-493G/T, has been associated with reduced low-density lipoprotein cholesterol concentrations. We hypothesize that this polymorphism impacts on coronary heart disease (CHD) risk.

Supraphysiological concentrations of estradiol in menopausal women given repeated implant therapy do not adversely affect lipid profiles.

Background: The effects of oral estrogen therapy (ERT) on lipids and metabolic parameters are well known, in contrast to the effects of subcutaneously administered estrogen, particularly high concentrations of estrogen. We examined metabolic parameters in cohorts of women with and without subcutaneous estrogen therapy with concomitant supra-normal concentrations of estradiol (SE).

Methods: Lipids and lipoprotein concentrations, low density lipid (LDL) subfractions, and activity of hepatic lipase (HL) were assessed in 30 menopausal women with SE and 19 control subjects not using ERT, matched for body mass index and age.

Goals of statin therapy: three viewpoints.

The "lipid hypothesis" is now universally recognized as a law. Few issues in medicine are as completely resolved as the question of whether reducing serum cholesterol increases longevity. However, there are a few questions that remain, and the most important uncertainty is to what extent cholesterol should be reduced.

Comparative effects of cerivastatin and fenofibrate on the atherogenic lipoprotein phenotype in proteinuric renal disease.

Patients with nephrotic-range proteinuria have impaired clearance of triglyceride-rich lipoproteins. This results in the atherogenic lipoprotein phenotype (mild hypertriglyceridemia, low high-density lipoproteins [HDL], and excess small, dense low-density lipoproteins [LDLIII]). Excess remnant lipoproteins (RLP) are linked to hypertriglyceridemia and may contribute to the atherogenicity of nephrotic dyslipidemia.