Search

Objective: Activation of peroxisome proliferator-activated receptor (PPAR)-gamma signaling influences metabolic profiles and the propensity toward inflammation. Small-molecule stimulation of PPARgamma is investigated for secondary prevention of cardiovascular disease. The common PPARgamma Pro12Ala variant has functional and prognostic consequences. A protective effect of the 12Ala-allele carriership on diabetes and myocardial infarction in healthy populations has been suggested. The relevance of this pathway also needs exploration in patients with manifest vascular disease. We investigated the effects of carriership of the Pro12Ala variant on angiographic and cardiovascular event outcomes in male patients with symptomatic coronary artery disease (CAD).Research Design and Methods: The Regression Growth Evaluation Statin Study (REGRESS) cohort was genotyped for the Pro12Ala variant (rs1801282). Ten-year follow-up was derived from nation-wide registries, and risks were estimated using proportional hazards. Quantitative coronary angiography measurements were obtained and relations with genotype estimated using a generalized linear model.Results: Genotypes ascertained (n = 679) comprised 540 (80%) Pro/Pro, 126 (19%) Pro/Ala, and 13 (2%) Ala/Ala subjects. The 12Ala allele was associated with less extensive focal (P = 0.001) and diffuse (P = 0.002) atherosclerosis and lower 10-year cardiovascular risk. Hazard ratios were 0.10 (95% CI 0.01-0.70, P = 0.02) for ischemic heart disease and 0.24 (0.08-0.74, P = 0.013) for vascular death, per each added copy of 12Ala, respectively.Conclusions: Carriers of the 12Ala allele of PPARgamma have less widespread CAD and are considerably protected against 10-year (cardio)vascular morbidity and mortality. These long-term findings in patients with manifest CAD support an important role of PPARgamma in determining vascular risk. [ABSTRACT FROM AUTHOR]

Objective: To evaluate physicians' attitudes and adherence to the use of risk scores in the primary prevention of cardiovascular disease (CVD).Design and Methods: A cross-sectional survey of 2056 physicians involved in the primary prevention of CVD. Participants included cardiologists (47%), general practitioners (42%), and endocrinologists (11%) from several geographical regions: Brazil (n = 968), USA (n = 381), Greece (n = 275), Chile (n = 157), Venezuela (n = 128), Portugal (n = 42), The Netherlands (n = 41), and Central America (Costa Rica, Panama, El Salvador and Guatemala; n = 64).Results: The main outcome measure was the percentage of responses on a multiple-choice questionnaire describing a hypothetical asymptomatic patient at intermediate risk for CVD according to the Framingham Risk Score. Only 48% of respondents reported regular use of CVD risk scores to tailor preventive treatment in the case scenario. Of non-users, nearly three-quarters indicated that 'It takes up too much of my time' (52%) or 'I don't believe they add value to the clinical evaluation' (21%). Only 56% of respondents indicated that they would prescribe lipid-lowering therapy for the hypothetical intermediate-risk patient. A significantly greater proportion of regular users than non-users of CVD risk scores identified the need for lipid-lowering therapy in the hypothetical patient (59 vs. 41%; p < 0.0001).Conclusions: Based on a survey conducted in a 'real-world' setting, risk scores are generally not used by a majority of physicians to guide primary prevention in asymptomatic persons at intermediate risk for CVD. Appropriate prescribing of lipid-lowering therapy in such patients is equally neglected. Changing physicians' attitudes towards the use of CVD risk scores is one of several challenges that need to be addressed to reduce the world-wide burden of CVD. [ABSTRACT FROM AUTHOR]

OBJECTIVE:: Selective cyclooxygenase-2 inhibition by rofecoxib was associated with increased risk of cardiovascular events. We hypothesized that concomitant treatment with thromboxane prostanoid receptor antagonist S18886 might ameliorate possible negative effects. We evaluated the effects of S18886, rofecoxib, and the interaction of both compounds in a combined treatment on myocardial infarct (MI) size and cardiac function after experimental ischemia/reperfusion injury in hyperlipidemic APOE*3Leiden transgenic mice. DESIGN:: Prospective, randomized, control trial. SETTING:: Research laboratory. SUBJECTS:: Hyperlipidemic APOE*3Leiden transgenic mice. INTERVENTIONS:: After four weeks of feeding an atherogenic diet, MI was induced by a 30-min ligation of the left anterior descending coronary artery, followed by reperfusion. Oral compound treatment was initiated 90 mins before MI, and continued daily by gavage for seven days. Four treatment groups (n = 12, each) were studied: solvent (Control), S18886, rofecoxib, and S18886 plus rofecoxib. MEASUREMENTS AND MAIN RESULTS:: One week after MI, the mice were anesthetized and cardiac function was quantified by left ventricular (LV) pressure-volume relationships obtained by miniature pressure-conductance catheters. The ischemic area was measured by morphometry and expressed as percentage of LV area. No significant differences in infarct size were found between groups. Compared with control, treatment with S18886 did not affect heart function whereas the rofecoxib group had significantly lower cardiac output (4.5 +/- 0.8 vs. 3.2 +/- 1.1 mL/min, p < 0.01), lower ejection fraction (40 +/- 8 vs. 27 +/- 11%, p < 0.005), and increased end-systolic volume (18.6 +/- 5.7 vs. 28.6 +/- 9.0 muL, p < 0.05). The group with combined (S18886+rofecoxib) treatment was not different from control. Statistical analysis showed significant interactive effects between S18886 and rofecoxib indicating that negative effects of rofecoxib on cardiac function were prevented by S18886 treatment. CONCLUSIONS:: Rofecoxib treatment reduced global and systolic LV function after ischemia-reperfusion injury in APOE*3Leiden mice. These negative effects are prevented by combined treatment with thromboxane prostanoid-receptor antagonist S18886 (terutroban). [ABSTRACT FROM AUTHOR]

OBJECTIVE: Sudden cardiac (arrhythmic) death (SCD) is the single largest cause of death in dialysis patients. Prophylactic Implantable Cardioverter Defibrillator (ICD) therapy reduces SCD and reduces all-cause mortality in several groups of patients at high risk for arrhythmic death. Whether this also applies to dialysis patients is unknown. RESEARCH DESIGN AND METHODS: The Implantable Cardioverter Defibrillator in Dialysis patients (ICD2) trial is a prospective randomised controlled study. It has been designed to evaluate the efficacy and safety of prophylactic ICD therapy in reducing sudden cardiac death rates in dialysis patients aged 55-80 years. A total of 200 patients will be included. The primary endpoint of the study is sudden cardiac (arrhythmic) death. The mean follow-up time will be 4 years. TRIAL REGISTRATION: 'The Netherlands Trial Register'--ISRCTN20479861 CONCLUSION: The ICD2 trial--a pilot study--will be the first study to evaluate the possible benefit of ICD therapy for the primary prevention of sudden cardiac death in dialysis patients. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic accuracy of 64-slice multislice computed tomography (MSCT) coronary angiography between female and male patients using conventional coronary angiography as the reference standard. Design: Diagnostic accuracy study. Setting: University hospital. Patients: 103 consecutive patients (51 men, 52 women, mean (SD) age 60 (10) years) with known and suspected coronary artery disease underwent 64-slice MSCT. Main Outcome Measures: Diagnostic accuracy of 64-slice MSCT to detect obstructive (>or=50% luminal narrowing) stenoses in men and women. Results: One male and two female patients were excluded from the analysis owing to non-diagnostic MSCT scans as a result of increased heart rate and breathing during the scan. Accordingly, on segmental level, 728/762 coronary segments were of sufficient quality in women (96% (95% CI 95% to 97%)) and 704/723 segments were interpretable in men (97% (95% CI 96% to 98%)). In the remaining 100 patients included in the further analyses, the sensitivity and specificity on a segmental level in women and men were 85% (95% CI 75% to 95%) vs 85% (95% CI 78% to 92%) and 99% (95% CI 98% to 100%) vs 99% (95% CI 98% to 100%), respectively. On a patient level, the sensitivity in women and men was 95% (95% CI 87% to 100%) vs 100%, specificity 93% (95% CI 83% to 100%) vs 89% (95% CI 74% to 100%), positive predictive value 91% (95% CI 79% to 100%) vs 94% (95% CI 86% to 100%), and negative predictive value 96% (95% CI 89% to 100%) vs 100%, respectively. Conclusion: The findings confirm the high diagnostic accuracy of 64-slice MSCT coronary angiography in both male and female patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E(4) versus those without E(4) had poorer memory performance (mean score difference -0.20 (95% confidence interval (CI)=-0.31 to -0.09) for immediate recall and -0.32 (95% CI=-0.48 to -0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI=1.20-4.28); Letter-Digit score, -0.36, (95% CI=-0.77-0.05). Subjects with apolipoprotein E(4) showed a greater decline in immediate (-0.22, 95% CI=-0.33 to -0.11) and delayed (-0.30, 95% CI=-0.46 to -0.15) memory scores but no significant change in speed of information processing (Stroop, P=.17; Letter-Digit, P=.06). Memory scores decreased 2.5% from baseline in those without E(4), 4.3% in E(4) heterozygotes (P=.01 for immediate and P=.03 for delayed, vs no E(4)) and 8.9% to 13.8% in E(4) homozygotes (P=.04 for immediate and P=.004 for delayed, vs heterozygotes). Apolipoprotein E(4) was associated with greater decline in instrumental activities of daily living (P<.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E(4) is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Paraoxonase-1 (PON-1) is a high-density lipoprotein (HDL) associated enzyme involved in the protective mechanisms of HDL. Our aim was to compare the effect of treatment with rosuvastatin and atorvastatin on serum PON-1 activity. METHODS: We performed a prespecified prospective study in 68 patients, part of a larger, multicentre randomized study--RADAR (Rosuvastatin and Atorvastatin in different Dosages And Reverse cholesterol transport). Patients aged 40-80 years, all men, with established cardiovascular disease and high-density lipoprotein cholesterol (HDL-C) < 1.0 mmol/L (< 40 mg/dL) entered a 6-week dietary run-in period before receiving treatment with rosuvastatin 10 mg or atorvastatin 20 mg daily for 6-weeks. Doses were increased after 6 weeks to rosuvastatin 20 mg or atorvastatin 40 mg and after 12 weeks to rosuvastatin 40 mg or atorvastatin 80 mg daily. Serum PON-1 activity and lipid profile were determined at baseline, 6 and 18 weeks. RESULTS: After 18 weeks, the rosuvastatin arm showed a significant increase of PON-1 activity (6.39 U/L, p = 0.02) whereas this was not observed in the atorvastatin arm (1.84 U/L, p = 0.77). The difference between groups did not reach significance (p = 0.11). Both rosuvastatin and atorvastatin resulted in significant (p = 0.0001) and similar increases in HDL-C after 6 weeks [0.06 mmol/L (2.32 mg/dL) vs. 0.05 mmol/L (1.93 mg/dL)] and after 18 weeks [0.10 mmol/L (3.87 mg/dL) vs. 0.10 mmol/L (3.87 mg/dL)]. CONCLUSIONS: Rosuvastatin treatment resulted in a significant increment of serum PON-1 activity with increasing dose while this was not observed with atorvastatin. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To explore the prognostic value of signs of prior myocardial infarction (MI) and atrial fibrillation (AF) on routine electrocardiograms (ECGs) at the age of 85 with respect to mortality and changes in functional status. DESIGN: Observational, prospective cohort study with complete 6-year follow-up. SETTING: General population. PARTICIPANTS: A population-based sample of 566 85-year-old participants (377 women, 189 men), without exclusion criteria. MEASUREMENTS: Annual ECG recording and evaluation using automated Minnesota Coding; annual assessment of functional status using validated questionnaires and tests; complete mortality data from civic and national registries. RESULTS: Participants with prior MI at the age of 85 (prevalence 9%) showed greater all-cause mortality (relative risk (RR)=1.7, 95% confidence interval (CI)=1.2-2.2) and cardiovascular mortality (RR=2.5, 95% CI=1.6-3.8) but no accelerated decline in functional status during follow-up. Participants with AF at the age of 85 (prevalence 10%) showed greater all-cause (RR=1.5, 95% CI=1.2-2.0) and cardiovascular (RR=2.0, 95% CI=1.3-3.0) mortality, as well as an accelerated decline in functional status during follow-up. CONCLUSION: Very elderly people with prior MI or AF on a routine ECG have markedly greater (cardiovascular) mortality risks. In addition, AF, but not prior MI, is associated with accelerated decline in functional status. These findings suggest that older patients with occasional findings of prior MI or AF on a routine ECG should receive optimal secondary preventive therapy. Furthermore, programmatic ECG recording could be of significant value for cardiovascular risk stratification in old age and needs further exploration. [ABSTRACT FROM AUTHOR]

There is increased recognition that determinants of health should be investigated in a life-course perspective. Retirement is a major transition in the life course and offers opportunities for changes in physical activity that may improve health in the aging population. The authors examined the effect of retirement on changes in physical activity in the GLOBE Study, a prospective cohort study known by the Dutch acronym for 'Health and Living Conditions of the Population of Eindhoven and surroundings,' 1991-2004. They followed respondents (n = 971) by postal questionnaire who were employed and aged 40-65 years in 1991 for 13 years, after which they were still employed (n = 287) or had retired (n = 684). Physical activity included 1) work-related transportation, 2) sports participation, and 3) nonsports leisure-time physical activity. Multinomial logistic regression analyses indicated that retirement was associated with a significantly higher odds for a decline in physical activity from work-related transportation (odds ratio (OR) = 3.03, 95% confidence interval (CI): 1.97, 4.65), adjusted for sex, age, marital status, chronic diseases, and education, compared with remaining employed. Retirement was not associated with an increase in sports participation (OR = 1.12, 95% CI: 0.71, 1.75) or nonsports leisure-time physical activity (OR = 0.80, 95% CI: 0.54, 1.19). In conclusion, retirement introduces a reduction in physical activity from work-related transportation that is not compensated for by an increase in sports participation or an increase in nonsports leisure-time physical activity. [ABSTRACT FROM AUTHOR]

Background: An elevated apolipoprotein B-apolipoprotein A-I (apo B-apo A-I) ratio is a risk factor for future coronary artery disease (CAD). It is not known whether this ratio is better than traditional lipid values for risk assessment and prediction and whether it adds predictive value to the Framingham risk score.Objective: To evaluate whether the apo B-apo A-I ratio is associated with future CAD events independent of traditional lipid measurements and the Framingham risk score and to evaluate the ability of this ratio to predict occurrence of future CAD.Design: Prospective, nested case-control study.Setting: Norfolk, United Kingdom.Participants: Apparently healthy men and women (45 to 79 years of age) in the European Prospective Investigation into Cancer and Nutrition-Norfolk. Cases (n = 869) were persons who developed fatal or nonfatal CAD. Controls (n = 1511) were persons without CAD who were matched for age, sex, and enrollment period.Measurements: Total cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, apolipoprotein, and C-reactive protein levels were measured directly. Low-density lipoprotein (LDL) cholesterol values were calculated by using the Friedewald formula.Results: The apo B-apo A-I ratio was associated with future CAD events, independent of traditional lipid values (adjusted odds ratio, 1.85 [95% CI, 1.15 to 2.98]), including the total cholesterol-HDL cholesterol ratio, and independent of the Framingham risk score (adjusted odds ratio, 1.77 [CI, 1.31 to 2.39]). However, it did no better than lipid values at discriminating between CAD cases and controls (area under the receiver-operating characteristic curve, 0.670 for total cholesterol-HDL cholesterol ratio vs. 0.673 for apo B-apo A-I ratio [P = 0.38]) and added little to the predictive value of the Framingham risk score (area under the receiver-operating characteristic curve, 0.594 for Framingham risk score alone vs. 0.613 for Framingham risk score plus apo B-apo A-I ratio [P < 0.001]). In addition, it incorrectly classified 41.1% of cases and 50.4% of controls.Limitations: No participant was taking lipid-lowering medication, and diabetes was uncommon.Conclusions: The apo B-apo A-I ratio is independently associated with, but adds little to, existing measures for CAD risk assessment and discrimination in the general population. Other characteristics of the test, such as the ability to perform it on nonfasting samples, may still make it useful in some settings. [ABSTRACT FROM AUTHOR]

Objective: To clarify the association of circulating levels of leptin with risk for cardiovascular disease (CVD) events and new-onset diabetes in men and women.Research Design and Methods: We related baseline leptin levels to CVD events (n = 864) and incident diabetes (n = 289) in an elderly population (n = 5,672) over 3.2 years of follow-up.Results: In treatment-, age-, and country-adjusted models, leptin was not associated with risk of CVD in men (hazard ratio 1.02 [95% CI 0.90-1.16] per unit log-leptin increase) or women (1.05 [0.91-1.20]) but was associated with risk of diabetes in men (2.75 [2.14-3.52]) and women (1.54 [1.22-1.94]). After adjusting for classic risk factors and BMI, C-reactive protein, and glucose, the diabetes association retained significance in men (1.85 [1.30-2.63]) but not in women (0.89 [0.64-1.26]).Conclusions: Leptin, similar to other markers of adiposity in general, is more strongly related to risk of diabetes than CVD in the elderly. [ABSTRACT FROM AUTHOR]

Background: Circulating inflammatory markers may more strongly relate to risk of fatal versus nonfatal cardiovascular disease (CVD) events, but robust prospective evidence is lacking. We tested whether interleukin (IL)-6, C-reactive protein (CRP), and fibrinogen more strongly associate with fatal compared to nonfatal myocardial infarction (MI) and stroke.Methods and Findings: In the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER), baseline inflammatory markers in up to 5,680 men and women aged 70-82 y were related to risk for endpoints; nonfatal CVD (i.e., nonfatal MI and nonfatal stroke [n = 672]), fatal CVD (n = 190), death from other CV causes (n = 38), and non-CVD mortality (n = 300), over 3.2-y follow-up. Elevations in baseline IL-6 levels were significantly (p = 0.0009; competing risks model analysis) more strongly associated with fatal CVD (hazard ratio [HR] for 1 log unit increase in IL-6 1.75, 95% confidence interval [CI] 1.44-2.12) than with risk of nonfatal CVD (1.17, 95% CI 1.04-1.31), in analyses adjusted for treatment allocation. The findings were consistent in a fully adjusted model. These broad trends were similar for CRP and, to a lesser extent, for fibrinogen. The results were also similar in placebo and statin recipients (i.e., no interaction). The C-statistic for fatal CVD using traditional risk factors was significantly (+0.017; p<0.0001) improved by inclusion of IL-6 but not so for nonfatal CVD events (p = 0.20).Conclusions: In PROSPER, inflammatory markers, in particular IL-6 and CRP, are more strongly associated with risk of fatal vascular events than nonfatal vascular events. These novel observations may have important implications for better understanding aetiology of CVD mortality, and have potential clinical relevance. [ABSTRACT FROM AUTHOR]

A considerable number of patients with an acute coronary syndrome (ACS) who present with a 0 or low calcium score (CS) still demonstrate coronary artery disease (CAD) and significant stenosis. The aim of the present study was to evaluate the relation between the CS and the degree and character of atherosclerosis in patients with suspected ACS versus patients with stable CAD obtained by computed tomography angiography and virtual histology intravascular ultrasound (VH IVUS). Overall 112 patients were studied, 53 with ACS and 59 with stable CAD. Calcium scoring and computed tomography angiography were performed and followed by VH IVUS. On computed tomography angiography each segment was evaluated for plaque and classified as noncalcified, mixed, or calcified. Vulnerable plaque characteristics on VH IVUS were defined by percent necrotic core and presence of thin-cap fibroatheroma. If the CS was 0, patients with ACS had a higher mean number of plaques (5.0 ± 2.0 vs 2.0 ± 1.9, p <0.05) and noncalcified plaques (4.6 ± 3.5 vs 1.3 ± 1.9, p <0.05) on computed tomography angiography than those with stable CAD. If the CS was 0, VH IVUS demonstrated that patients with ACS had a larger amount of necrotic core area (0.58 ± 0.73 vs 0.22 ± 0.43 mm(2), p <0.05) and a higher mean number of thin-cap fibroatheromas (0.6 ± 0.7 vs 0.1 ± 0.3, p <0.05) than patients with stable CAD. In conclusion, even in the presence of a 0 CS, patients with ACS have increased plaque burden and increased vulnerability compared to patients with stable CAD. Therefore, absence of coronary calcification does not exclude the presence of clinically relevant and potentially vulnerable atherosclerotic plaque burden in patients with ACS. [ABSTRACT FROM AUTHOR]

Multislice computed tomographic coronary angiography (MSCT) can accurately detect the presence of atherosclerosis noninvasively. However, a discrepancy has been observed between MSCT and noninvasive functional imaging. The purpose of the present study was to evaluate the correlation between MSCT and invasive fractional flow reserve (FFR) in men with known coronary artery disease. Thirty-three patients (mean age 57 +/- 11 years) clinically referred for coronary angiography underwent MSCT and FFR analysis. Coronary angiography and MSCT were evaluated for nonsignificant (30% to 50% luminal narrowing) and significant (>50% luminal narrowing) stenosis. Abnormal FFR was defined as < or =0.75. A total of 36 vessels were evaluated for FFR, with 8 (22%) showing reduced FFR. Results on MSCT were normal (completely normal or <30% luminal narrowing in 11 vessesl [31%], nonsignificant lesions in 13 vessels [36%], and significant stenoses in 12 vessels [33%]). Abnormal FFR was observed in only 58% of vessels with lesions >50% on MSCT. Nevertheless, the agreement between normal results on MSCT and normal FFR was excellent; FFR was normal in all 11 vessels with normal results on MSCT. In conclusion, significant stenoses on MSCT frequently do not result in reduced FFR. Normal results on MSCT, however, can accurately rule out the presence of hemodynamically significant lesions in men with known coronary artery disease. [ABSTRACT FROM AUTHOR]

Objectives: Our purpose was to evaluate the efficacy and safety of drug-eluting stents in the setting of primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). Background: There is inconsistent and limited evidence about the efficacy and safety of drug-eluting stents in STEMI patients. Methods: A single-blind, single-center, randomized study was performed to compare bare-metal stents (BMS) with sirolimus-eluting stents (SES) in 310 STEMI patients. The primary end point was in-segment late luminal loss (LLL) at 9 months. Secondary end points included late stent malapposition (LSM) at 9 months as determined by intravascular ultrasound imaging and clinical events at 12 months. Results: In-segment LLL was 0.68 +/- 0.57 mm in the BMS group and 0.12 +/- 0.43 mm in the SES group with a mean difference of 0.56 mm, 95% confidence interval 0.43 to 0.68 mm (p < 0.001). Late stent malapposition at 9 months was present in 12.5% BMS patients and in 37.5% SES patients (p < 0.001). Event-free survival at 12 months was 73.6% in BMS patients and 86.0% in SES patients (p = 0.01). The target-vessel-failure-free survival was 84.7% in the BMS group and 93.0% in the SES group (p = 0.02), mainly because of a higher target lesion revascularization rate in BMS patients (11.3% vs. 3.2%; p = 0.006). Rates of death, myocardial infarction, and stent thrombosis were not different. Conclusions: Sirolimus-eluting stent implantation in STEMI patients is associated with a favorable midterm clinical and angiographic outcome compared with treatment with BMS. However, LSM raises concern about the long-term safety of SES in STEMI patients. [ABSTRACT FROM AUTHOR]

Objectives: We sought to conduct a randomized trial with folic acid 0.5 mg/day in a patient population with stable coronary artery disease (CAD).Background: Folic acid has favorable effects on vascular endothelium and lowers plasma homocysteine levels. In addition, homocysteine appears to be an independent risk factor for atherosclerotic disease. However, the value of folic acid in secondary prevention had seldom been tested.Methods: In this open-label study, 593 patients were included; 300 were randomized to folic acid and 293 served as controls. Mean follow-up time was 24 months. At baseline all patients had been on statin therapy for a mean of 3.2 years.Results: In patients treated with folic acid, plasma homocysteine levels decreased by 18%, from 12.0 +/- 4.8 to 9.4 +/- 3.5 micromol/l, whereas these levels remained unaffected in the control group (p < 0.001 between groups). The primary end point (all-cause mortality and a composite of vascular events) was encountered in 31 (10.3%) patients in the folic acid group and in 28 (9.6%) patients in the control group (relative risk 1.05; 95% confidence interval: 0.63 to 1.75). In a multifactorial survival model with adjustments for clinical factors, the most predictive laboratory parameters were, in order of significance, levels of creatinine clearance, plasma fibrinogen, and homocysteine.Conclusions: Within two years, folic acid does not seem to reduce clinical end points in patients with stable coronary artery disease (CAD) while on statin treatment. Homocysteine might therefore merely be a modifiable marker of disease. Thus, low-dose folic acid supplementation should be treated with reservation, until more trial outcomes become available. [ABSTRACT FROM AUTHOR]

Background: Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke.Methods: We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat.Findings: Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability.Interpretation: Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people. [ABSTRACT FROM AUTHOR]