The incidence and risk factors for new onset atrial fibrillation in the PROSPER study

Aims Atrial fibrillation/flutter (AF) is the most common arrhythmia in older people. It associates with reduced exercise capacity, increased risk of stroke, and mortality. We aimed to determine retrospectively whether pravastatin reduces the incidence of AF and whether any electrocardiographic measures or clinical conditions might be risk factors for its development. Methods and results The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) was a randomized, double-blind controlled trial that recruited 5804 individuals aged 70-82 years with a history of, or risk factors for, vascular disease. A total of 2891 were allocated to pravastatin and 2913 to placebo; mean follow-up was 3.2 years. Electrocardiograms (ECGs), which were recorded at baseline, annually thereafter, and at run-out, were processed by computer and reviewed manually. In all, 264 of 2912 (9.1%) of the placebo group and 283 of 2888 (9.8%) of the pravastatin-treated group developed AF [hazard ratio 1.08 (0.92,1.28), P = 0.35)]. Multivariate analysis showed that PR and QTc intervals, age, left ventricular hypertrophy, and ST-T abnormalities were related to development of AF after adjustment for many variables including alcohol consumption, which itself was univariately predictive of developing AF. Previous myocardial infarction on the ECG was not a risk factor. A history of vascular disease was strongly linked with developing AF but not diabetes and hypertension. Conclusion Pravastatin does not reduce the incidence of AF in older people at risk of vascular disease, at least in the short-medium term. Risk factors for AF include older age, prolongation of PR or QTc intervals, left ventricular hypertrophy, and ST-T abnormalities on the EC

Homocysteine levels and treatment effect in the prospective study of pravastatin in the elderly at risk

Objectives: To assess the effect of preventive pravastatin treatment on coronary heart disease (CHD) morbidity and mortality in older persons at risk for cardiovascular disease (CVD), stratified according to plasma levels of homocysteine.<p></p> Design: A post hoc subanalysis in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER), started in 1997, which is a double-blind, randomized, placebo-controlled trial with a mean follow-up of 3.2 years.<p></p> Setting: Primary care setting in two of the three PROSPER study sites (Netherlands and Scotland).<p></p> Participants: Individuals (n = 3,522, aged 70–82, 1,765 male) with a history of or risk factors for CVD were ranked in three groups depending on baseline homocysteine level, sex, and study site.<p></p> Intervention: Pravastatin (40 mg) versus placebo.<p></p> Measurements: Fatal and nonfatal CHD and mortality.<p></p> Results: In the placebo group, participants with a high homocysteine level (n = 588) had a 1.8 higher risk (95% confidence interval (CI) = 1.2–2.5, P = .001) of fatal and nonfatal CHD than those with a low homocysteine level (n = 597). The absolute risk reduction in fatal and nonfatal CHD with pravastatin treatment was 1.6% (95% CI = −1.6 to 4.7%) in the low homocysteine group and 6.7% (95% CI = 2.7–10.7%) in the high homocysteine group (difference 5.2%, 95% CI = 0.11–10.3, P = .046). Therefore, the number needed to treat (NNT) with pravastatin for 3.2 years for benefit related to fatal and nonfatal CHD events was 14.8 (95% CI = 9.3–36.6) for high homocysteine and 64.5 (95% CI = 21.4–∞) for low homocysteine.<p></p> Conclusion: In older persons at risk of CVD, those with high homocysteine are at highest risk for fatal and nonfatal CHD. With pravastatin treatment, this group has the highest absolute risk reduction and the lowest NNT to prevent fatal and nonfatal CHD.<p></p&gt

Reduction of radiation dose using 80 kV tube voltage: a feasible strategy?

Cardiolog

IVUS detects more coronary calcifications than MSCT; matter of both resolution and cross-sectional assessment?

Vascular Biology and Interventio

Increased Carotid Intima-Media Thickness as a Predictor of the Presence and Extent of Abnormal Myocardial Perfusion in Type 2 Diabetes

OBJECTIVE - identification of asymptomatic patients with type 2 diabetes at increased risk for coronary artery disease (CAD) remains a challenge. We evaluated the Potential of carotid intima-media thickness (CIMT) for prediction of abnormal myocardial perfusion in this population. RESEARCH DESIGN AND METHODS- CIMT and SPECT myocardial perfusion imaging were assessed in 98 asymptomatic patients with type 2 diabetes. An increased CIMT was defined as >= 75th percentile of reference values. RESULTS - increased CIMT was an independent predictor of the extent of abnormal perfusion (P < 0.001). In patients with increased CIMT as compared with patients with normal CIMT, abnormal perfusion (75 vs. 9%) and severely abnormal perfusion (28 vs. 3%) were observed more frequently. CONCLUSIONS - increased CIMT was significantly related to the presence and extent of abnormal myocardial perfusion. Assessment of CIMT may be useful to identify asymptomatic patients with type 2 diabetes at higher risk for CAD.Diabetes mellitus: pathophysiological changes and therap

PPARγ Variant Influences Angiographic Outcome and 10-Year Cardiovascular Risk in Male Symptomatic Coronary Artery Disease Patients

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 ris

Ventricular repolarization is associated with cognitive function, but not with cognitive decline and brain Magnetic Resonance Imaging (MRI) measurements in older adults

We aimed to investigate the cross-sectional and longitudinal associations of electrocardiogram (ECG)-based QT, QTc, JT, JTc, and QRS intervals with cognitive function and brain magnetic resonance imaging (MRI) measurements in a cohort of older individuals at increased risk for cardiovascular disease, but free of known arrhythmias. We studied 4627 participants (54% female, mean age 75 years) enrolled in the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). Ten-second ECGs were conducted at baseline. Cognitive function was tested at baseline and repeated during a mean follow-up time of 3.2 years. Structural MRIs were conducted in a subgroup of 535 participants. Analyses were performed with multivariable (repeated) linear regression models and adjusted for cardiovascular risk-factors, co-morbidities, and cardiovascular drug use. At baseline, longer QT, JT, JTc—but not QTc and QRS intervals—were associated with a worse cognitive performance. Most notably, on the Stroop Test, participants performed 3.02 (95% CI 0.31; 5.73) seconds worse per standard deviation higher QT interval, independent of cardiovascular risk factors and medication use. There was no association between longer ventricular de- or repolarization and structural brain measurements. Therefore, specifically ventricular repolarization was associated with worse cognitive performance in older individuals at baseline but not during follow-up

Relation of overall and abdominal adiposity with electrocardiogram parameters of subclinical cardiovascular disease in individuals aged 45 to 65 years (from the Netherlands Epidemiology of Obesity Study)

Overall and abdominal obesity are well-established risk factors for cardiometabolic disease. However, associations of overall and abdominal adiposity with electrocardiographic (ECG) markers of subclinical cardiovascular disease (CVD) have not yet been fully elucidated. Therefore, we investigated these associations in a population without preexisting CVD. We performed cross-sectional analyses in the Netherlands Epidemiology of Obesity Study. Body mass index (BMI), total body fat, and waist circumference were assessed in all participants, and abdominal subcutaneous adipose tissue and visceral adipose tissue (by magnetic resonance imaging) were assessed in a random subgroup. ECG parameters were determined using 12-lead electrocardiograms. We performed linear regression analyses, adjusting for potential confounding factors and, when investigating abdominal adiposity, additionally for total body fat. After exclusion of participants with preexisting CVD (n = 654), 5,939 individuals (42% men) were analyzed, with a mean (SD) age of 55 (6) years and BMI of 26.3 (4.4) kg/m2. Measures of both overall and abdominal adiposity were associated with ECG parameters but none of these measures was more strongly associated than the others. For example, heart rate (beats/min) increased per SD higher BMI (2.2; 95% confidence interval 1.9,2.5), total body fat (2.9; 2.4,3.4), subcutaneous adipose tissue (2.3;1.7,2.9), waist circumference (2.1; 1.4,2.8), and visceral adipose tissue (1.7; 0.8,2.5). In subgroup analyses based on gender and cardiovascular risk factors, no consistent interactions were observed. In conclusion, in a middle-aged population without preexisting CVD, measures of both overall and abdominal adiposity were associated with ECG parameters. Future studies should evaluate the added value of adiposity measures in electrocardiography-based diagnoses and the prognostic value of adding adiposity measures to risk prediction tools

Estimating effects of rare haplotypes on failure time using a penalized Cox proportional hazards regression model

BACKGROUND: This paper describes a likelihood approach to model the relation between failure time and haplotypes in studies with unrelated individuals where haplotype phase is unknown, while dealing with the problem of unstable estimates due to rare haplotypes by considering a penalized log-likelihood. RESULTS: The Cox model presented here incorporates the uncertainty related to the unknown phase of multiple heterozygous individuals as weights. Estimation is performed with an EM algorithm. In the E-step the weights are estimated, and in the M-step the parameter estimates are estimated by maximizing the expectation of the joint log-likelihood, and the baseline hazard function and haplotype frequencies are calculated. These steps are iterated until the parameter estimates converge. Two penalty functions are considered, namely the ridge penalty and a difference penalty, which is based on the assumption that similar haplotypes show similar effects. Simulations were conducted to investigate properties of the method, and the association between IL10 haplotypes and risk of target vessel revascularization was investigated in 2653 patients from the GENDER study. CONCLUSION: Results from simulations and real data show that the penalized log-likelihood approach produces valid results, indicating that this method is of interest when studying the association between rare haplotypes and failure time in studies of unrelated individuals