Impact of proton pump inhibitor treatment on gastrointestinal bleeding associated with non-steroidal anti-inflammatory drug use among post-myocardial infarction patients taking antithrombotics: nationwide study

Study question What is the effect of proton pump inhibitors (PPIs) on the risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with non-steroidal anti-inflammatory drugs (NSAIDs)? Methods This was a nationwide cohort study based on linked administrative registry data from all hospitals in Denmark between 1997 and 2011. The study included patients aged 30 years and over admitted with a first myocardial infarction who survived at least 30 days after discharge. The association between PPIs and risk of gastrointestinal bleeding according to NSAID plus antithrombotic therapy was estimated using adjusted time dependent Cox regression models. Study answer and limitations The use of PPIs was independently associated with decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and treated with NSAIDs. Of 82 955 post-myocardial infarction patients (mean age 67.4 years, 64% (n=53 070) men), all of whom were taking single or dual antithrombotic therapy, 42.5% (n=35 233) filled at least one prescription for NSAIDs and 45.5% (n=37 771) received PPIs. Over a mean follow-up of 5.1 years, 3229 gastrointestinal bleeds occurred. The crude incidence rates of bleeding (events/100 person years) on NSAID plus antithrombotic therapy were 1.8 for patients taking PPIs and 2.1 for those not taking PPIs. The adjusted risk of bleeding was lower with PPI use (hazard ratio 0.72, 95% confidence interval 0.54 to 0.95) regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. The main limitation of the study is its observational non-randomised design. The results suggest that PPI treatment probably has a beneficial effect regardless of underlying gastrointestinal risk and that when NSAIDs cannot be avoided in post-myocardial infarction patients, physicians might prescribe a PPI as well. The study does not clarify whether PPIs might be safely omitted in specific subgroups of patients with a low risk of gastrointestinal bleeding. What this study adds In post-myocardial infarction patients, bleeding complications have been associated with both antithrombotic and NSAID treatment. Concurrent use of PPIs was independently associated with a decreased risk of gastrointestinal bleeding in post-myocardial infarction patients taking antithrombotics and NSAID, regardless of antithrombotic treatment regimen, type of NSAID, and type of PPI used. Funding, competing interests, data sharing AMSO has received a grant from the Danish Council of Independent Research (grant 12-132760). GHG is supported by an unrestricted research scholarship from the Novo Nordisk Foundation

Metabolic Syndrome and Early-Onset Coronary Artery Disease Is the Whole Greater Than Its Parts?

ObjectivesWe sought to examine the association between the metabolic syndrome (MetS) (defined both by the 2001 National Cholesterol Educational Program Adult Treatment Panel III [ATP-III] definition and the American Heart Association/National Heart, Lung and Blood Institute [AHA/NHLBI] revision incorporating the lower threshold for impaired fasting glucose [IFG]) and early-onset coronary artery disease (CAD).BackgroundThe impact of MetS on premature CAD has not been studied extensively. Lowering the threshold to define the IFG component (from 110 to 100 mg/dl) and the value of the syndrome as a whole versus its individual components are subjects of intense debate.MethodsWe performed a case-control study with 393 early-onset CAD subjects (acute myocardial infarction, angina with ≥50% stenosis, or coronary revascularization) in men under age 46 years or women under age 56 years and 393 control subjects individually matched for gender, age, and race/ethnicity.ResultsBy conditional logistic regression, presence of ATP-III MetS without diabetes (adjusted odds ratio [adj-OR] 4.9; 95% confidence interval [CI] 3.4 to 8.0) and with diabetes (adj-OR 8.0, 95% CI 4.39 to 14.6) was a strong independent determinant of early-onset CAD. Using the AHA/NHLBI revision, these ORs became slightly stronger. However, neither definition of MetS remained significantly associated with early-onset CAD in multivariate models adjusting for individual components.ConclusionsThe presence of MetS imparts a high risk of early-onset clinical CAD, but the prognostic information associated with the syndrome is not greater than the sum of its parts

Peroxisome Proliferator-Activated Receptor Gamma Polymorphisms and Coronary Heart Disease

Single nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor γ (PPARG) gene have been associated with cardiovascular risk factors, particularly obesity and diabetes. We assessed the relationship between 4 PPARG SNPs (C-681G, C-689T, Pro12Ala, and C1431T) and coronary heart disease (CHD) in the PRIME (249 cases/494 controls, only men) and ADVANCE (1,076 cases/805 controls, men or women) studies. In PRIME, homozygote individuals for the minor allele of the PPARG C-689T, Pro12Ala, and C1431T SNPs tended to have a higher risk of CHD than homozygote individuals for the frequent allele (adjusted OR [95% CI] = 3.43 [0.96–12.27], P = .058, 3.41 [0.95–12.22], P = .060 and 5.10 [0.99–26.37], P = .050, resp.). No such association could be detected in ADVANCE. Haplotype distributions were similar in cases and control in both studies. A meta-analysis on the Pro12Ala SNP, based on our data and 11 other published association studies (6,898 CHD cases/11,287 controls), revealed that there was no evidence for a significant association under the dominant model (OR = 0.99 [0.92–1.07], P = .82). However, there was a borderline association under the recessive model (OR = 1.29 [0.99–1.67], P = .06) that became significant when considering men only (OR = 1.73 [1.20–2.48], P = .003). In conclusion, the PPARG Ala12Ala genotype might be associated with a higher CHD risk in men but further confirmation studies are needed

A Guided Workbook Intervention (WorkPlan) to Support Work-Related Goals Among Cancer Survivors: Protocol of a Feasibility Randomized Controlled Trial

Background: Returning to and staying at work following illness is associated with better physical and psychological functioning. Not working has been shown to be associated with reduced self-esteem, lowered self-efficacy, and decreased belief in one's ability to return to the workplace. Although there is a growing body of research looking at what predicts return to work following cancer treatment, there are fewer studies examining interventions targeting return to work. Objective: The primary objective is to assess the feasibility and acceptability of a theoretically led workbook intervention designed to support cancer patients in returning to work to inform a fully powered randomized controlled trial (RCT). Methods: This is a multicenter feasibility RCT where the main analysis uses a qualitative approach. Sixty participants (aged 18-65 years) who have received a diagnosis of cancer and who intend to return to work will be randomized to either the WorkPlan intervention group or a usual care group (ratio 1:1). Participants in the intervention group will receive a guided workbook intervention (which contains activities aimed at eliciting thoughts and beliefs, identifying targets and actions, and concrete steps to achieve goals) and will receive telephone support over a 4-week period. The primary outcome measure is time taken to return to work (in days), and secondary outcome measures include mood, quality of life, illness perceptions, and job satisfaction. Data will be collected through postal questionnaires administered immediately postintervention and at 6- and 12-month follow-ups. In addition, interviews will be undertaken immediately postintervention (to explore acceptability of the intervention and materials) and at 12-month follow-up (to explore perceptions of participation in the trial and experiences of returning to work). Results: Enrollment for the study will be completed in May 2016. Data analysis will commence in April 2017, and the first results are expected to be submitted for publication in late 2017. Conclusions: Currently no standardized return-to-work intervention based on targeting cancer patient beliefs is in existence. If the intervention is shown to be feasible and acceptable, the results of this study will inform a future full RCT with the potential to provide a valuable and cost-efficient tool in supporting cancer survivors in the return-to-work process

Right coronary wall cmr in the older asymptomatic advance cohort: positive remodeling and associations with type 2 diabetes and coronary calcium

<p>Abstract</p> <p>Background</p> <p>Coronary wall cardiovascular magnetic resonance (CMR) is a promising noninvasive approach to assess subclinical atherosclerosis, but data are limited in subjects over 60 years old, who are at increased risk. The purpose of the study was to evaluate coronary wall CMR in an asymptomatic older cohort.</p> <p>Results</p> <p>Cross-sectional images of the proximal right coronary artery (RCA) were acquired using spiral black-blood coronary CMR (0.7 mm resolution) in 223 older, community-based patients without a history of cardiovascular disease (age 60-72 years old, 38% female). Coronary measurements (total vessel area, lumen area, wall area, and wall thickness) had small intra- and inter-observer variabilities (r = 0.93~0.99, all p < 0.0001), though one-third of these older subjects had suboptimal image quality. Increased coronary wall thickness correlated with increased coronary vessel area (p < 0.0001), consistent with positive remodeling. On multivariate analysis, type 2 diabetes was the only risk factor associated with increased coronary wall area and thickness (p = 0.03 and p = 0.007, respectively). Coronary wall CMR measures were also associated with coronary calcification (p = 0.01-0.03).</p> <p>Conclusions</p> <p>Right coronary wall CMR in asymptomatic older subjects showed increased coronary atherosclerosis in subjects with type 2 diabetes as well as coronary calcification. Coronary wall CMR may contribute to the noninvasive assessment of subclinical coronary atherosclerosis in older, at-risk patient groups.</p

Failure to replicate an association of SNPs in the oxidized LDL receptor gene (OLR1) with CAD

Abstract Background The lectin-like oxidized LDL receptor LOX-1 (encoded by OLR1) is believed to play a key role in atherogenesis and some reports suggest an association of OLR1 polymorphisms with myocardial infarction (MI). We tested whether single nucleotide polymorphisms (SNPs) in OLR1 are associated with clinically significant CAD in the Atherosclerotic Disease, VAscular FuNction, & Geneti C Epidemiology (ADVANCE) study. Methods ADVANCE is a population-based case-control study of subjects receiving care within Kaiser Permanente of Northern California including a subset of participants of the Coronary Artery Risk Development in Young Adults (CARDIA) study. We first resequenced the promoter, exonic, and splice site regions of OLR1 and then genotyped four single nucleotide polymorphisms (SNPs), including a non-synonymous SNP (rs11053646, Lys167Asn) as well as an intronic SNP (rs3736232) previously associated with CAD. Results In 1,809 cases with clinical CAD and 1,734 controls, the minor allele of the coding SNP was nominally associated with a lower odds ratio (OR) of CAD across all ethnic groups studied (minimally adjusted OR 0.8, P = 0.007; fully adjusted OR 0.8, P = 0.01). The intronic SNP was nominally associated with an increased risk of CAD (minimally adjusted OR 1.12, p = 0.03; fully adjusted OR 1.13, P = 0.03). However, these associations were not replicated in over 13,200 individuals (including 1,470 cases) in the Atherosclerosis Risk in Communities (ARIC) study. Conclusion Our results do not support the presence of an association between selected common SNPs in OLR1 and the risk of clinical CAD.http://deepblue.lib.umich.edu/bitstream/2027.42/112726/1/12881_2008_Article_317.pd

Evaluating the Quality of Research into a Single Prognostic Biomarker: A Systematic Review and Meta-analysis of 83 Studies of C-Reactive Protein in Stable Coronary Artery Disease

Background Systematic evaluations of the quality of research on a single prognostic biomarker are rare. We sought to evaluate the quality of prognostic research evidence for the association of C-reactive protein (CRP) with fatal and nonfatal events among patients with stable coronary disease. Methods and Findings We searched MEDLINE (1966 to 2009) and EMBASE (1980 to 2009) and selected prospective studies of patients with stable coronary disease, reporting a relative risk for the association of CRP with death and nonfatal cardiovascular events. We included 83 studies, reporting 61,684 patients and 6,485 outcome events. No study reported a prespecified statistical analysis protocol; only two studies reported the time elapsed (in months or years) between initial presentation of symptomatic coronary disease and inclusion in the study. Studies reported a median of seven items (of 17) from the REMARK reporting guidelines, with no evidence of change over time. The pooled relative risk for the top versus bottom third of CRP distribution was 1.97 (95% confidence interval [CI] 1.78–2.17), with substantial heterogeneity (I2 = 79.5). Only 13 studies adjusted for conventional risk factors (age, sex, smoking, obesity, diabetes, and low-density lipoprotein [LDL] cholesterol) and these had a relative risk of 1.65 (95% CI 1.39–1.96), I2 = 33.7. Studies reported ten different ways of comparing CRP values, with weaker relative risks for those based on continuous measures. Adjusting for publication bias (for which there was strong evidence, Egger's p<0.001) using a validated method reduced the relative risk to 1.19 (95% CI 1.13–1.25). Only two studies reported a measure of discrimination (c-statistic). In 20 studies the detection rate for subsequent events could be calculated and was 31% for a 10% false positive rate, and the calculated pooled c-statistic was 0.61 (0.57–0.66). Conclusion Multiple types of reporting bias, and publication bias, make the magnitude of any independent association between CRP and prognosis among patients with stable coronary disease sufficiently uncertain that no clinical practice recommendations can be made. Publication of prespecified statistical analytic protocols and prospective registration of studies, among other measures, might help improve the quality of prognostic biomarker research