Myocardial Infarction Odds Ratio Research Articles

Risk factors for acute myocardial infarction in patients with alcohol-related cirrhosis - a Danish nested case-control study

Background & Aims Alcohol-related cirrhosis (ALD cirrhosis) has a weaker effect on acute myocardial infarction (MI) than on other arterial or venous thromboses, and the reasons for this pattern are unclear. This study aimed to identify risk factors of MI amongst patients with ALD cirrhosis. Methods This nationwide register-based nested case-control study was conducted within a cohort of all Danish patients diagnosed with ALD cirrhosis from 2000-2019. Patients with first-time MI after diagnosis of ALD cirrhosis were identified as cases, and matching cohort members (10:1) with no history of MI, using risk-set sampling. We selected candidate risk factors a priori and used conditional logistic regression to study the association between them and the adjusted odds ratio of MI. Results and conclusions We included 373 cases and 3,730 controls. We identified the following risk factors for MI: hospitalization for infection (adjusted odds ratio 2.26 [95% CI 1.38-3.71]), recent surgery (adjusted odds ratio 1.82 [95% CI 1.18-2.81]), history of atherosclerosis (adjusted odds ratio 1.89 [95% CI 1.39-2.57]), cardiac ischemia (adjusted odds ratio 6.23 [95% CI 4.30-9.04]), heart failure (adjusted odds ratio 2.83 [95% CI 1.90-4.22]) or chronic obstructive pulmonary disease (COPD) (adjusted odds ratio 2.26 [95% CI 1.62-3.17]). Use of anticoagulants had a protective effect (adjusted odds ratio 0.47 [95% CI 0.25–0.91]). Our findings contribute to the understanding of risk factors for MI in patients with ALD cirrhosis. They may have clinical implications e.g. for the decision to offer thromboprophylaxis.

Lithium and zinc levels along with oxidative status in myocardial infarction: A case-control study

BackgroundCoronary artery disease (CAD) and myocardial infarction (MI) are the most prevalent diseases globally. While several risk factors for MI are well assessed, the influence of trace elements on MI has not been thoroughly studied. This study aimed to evaluate lithium (Li) and zinc (Zn) levels in MI patients and healthy control and assess their relationship with oxidative stress (OS) parameters, such as nitric oxide (NO) and total antioxidant capacity (TAC). MethodsThis case-control study was performed on 182 patients with MI and 83 healthy subjects at Shafa Hospital in Kerman, Iran. MI patients were divided into two groups based on the angiography results: those with coronary artery block above 50 % (CAB >50 %, n = 92) and those with coronary artery block below 50 % (CAB <50 %, n = 90). A flame atomic absorption spectrometer was used to detect Li and Zn levels, and biochemical indices were measured by an autoanalyzer. Also, ferric reducing antioxidant power assay and the Griess method were used to measure the amounts of NO and TAC. ResultsThe levels of TAC and Li were significantly higher in the control group than in the patient groups (in both CAB >50 % and CAB <50 % groups). Furthermore, in the CAB <50 % group, TAC and Li levels were significantly higher than in the CAB >50 % group. In the Zn levels evaluation, higher concentration was seen in the CAB >50 % group compared to the CAB <50 % group (P < 0.05). Moreover, Zn and NO levels were significantly higher in both CAB groups compared to controls. In continue, Li levels had a positive association with TAC and ejection fraction percentage (EF%) as well as a negative association with NO levels and Zn levels had a significant positive association with NO and a negative association with TAC. In logistic regression analysis, Li, TAC, and high-density lipoprotein-cholesterol significantly decreased the odds ratio (OR) of MI, whereas Zn, NO, total cholesterol, triglyceride, low-density lipoprotein-cholesterol, and high-sensitivity C-reactive protein (hs-CRP) significantly increased the OR of MI. Furthermore, the area under the curve (AUC) analysis indicated that Li had the highest AUC for the diagnosis of CAB >50 % (Li < 167 ng/mL), and Zn ≥ 1810 μg/mL increased disease severity. ConclusionOur investigation revealed that Li had a protective effect against CAD by decreasing OS and increasing EF%. However, Zn at concentrations higher than 1810 μg/mL was found to be cytotoxic and increased the risk of MI through increased OS. Taken togather, it could be concluded that Li supplementation may decrease the risk of CAD.

Risk of myocardial infarction in Parkinson's disease: A systematic review and meta-analysis.

Previous studies investigating cardiovascular disorders in patients with Parkinson's disease (PD) showed heterogeneous results regarding whether there is a higher or lower risk of myocardial infarction (MI) in these patients compared to the general population. Because of the inconsistency in findings, herein the aim was to perform a systematic review and meta-analysis to investigate the risk of MI in patients with PD. A comprehensive literature search was performed using four databases, PubMed, Web of Science, Scopus and Embase, in June 2022. Peer-reviewed observational studies comprising case-controls, cohort, cross-sectional and longitudinal studies that reported MI in the PD population were included. After the screening, 20 studies with a total of 80,441 patients with PD and 802,857 controls were included in our qualitative and quantitative synthesis. The pooled estimated odds ratio for MI in PD patients compared to controls was 0.80 (95% confidence interval [CI] 0.56-1.05) which indicates that there is no association. The pooled prevalence of MI was 5% (95% CI 3%-7%) with a range of 1%-20% amongst patients with PD. The men (6%, 95% CI 1%-13%) and women (6%, 95% CI 1%-14%, Q = 29.27, I2 = 98.50%, p < 0.001) had similar MI prevalence. This comprehensive systematic review and meta-analysis provide compelling evidence that PD is associated with a reduced risk of MI. Whilst the exact mechanism underlying this association remains to be fully elucidated, it is clear that certain risk factors for cardiac events appear to be less present in PD patients, which may serve as a protective factor. However, given the reports of increased risk for cerebrovascular events in PD patients, it is possible that the major risk factors for MI and cardiovascular accidents in this population differ. These findings have important implications for clinical management and further research in this area is warranted.

Relationship Between Gender Differences and Clinical Outcome in Patients With the Antiphospholipid Syndrome.

Antiphospholipid syndrome (APS), characterized by artherial and/or venous thrombosis, pregnancy morbidity and “antiphospholipid” antibodies (aPLs), is more common in women than in men, with a female to male ratio of about 3.5:1. Only few studies have investigated the clinical differences between male and female patients with APS. Therefore, this study was aimed to analyze the differences of clinical manifestations and laboratory tests, at diagnosis, between female and male APS patients and the clinical outcome. We enrolled 191 consecutive APS patients (125 with primary APS, PAPS, and 66 with secondary APS, SAPS) with a female predominant ratio of approximately 3:1 (142 vs 49). The prevalence of PAPS was higher in males than females (p<0.001). The analysis of aPL profile revealed that high IgM anti-cardiolipin (aCL) and high-medium IgG aCL titers were more frequent in males. In thrombotic APS peripheral arterial thrombosis was more common in male than female patients (p=0.049), as well as myocardial infarction (p=0.031). Multivariate analysis to correct for cardiovascular risk factors, high titer of aPLs and triple positivity for aPLs, revealed that the odds ratio for myocardial infarction in male was 3.77. Thus, APS may be considered as a disease in which serological (IgM titer) and clinical profiles are influenced by gender.

Raised Glycated Hemoglobin (HbA1c) Level as a Risk Factor for Myocardial Infarction in Diabetic Patients: A Hospital-Based, Cross-Sectional Study in Peshawar

BackgroundDiabetes is a rapidly rising chronic illness in developing countries. The main objective of this research is to compare the frequency of myocardial infarction (MI) in controlled and uncontrolled diabetics in Pakistan, especially in the underprivileged district of Peshawar, and to determine raised blood glucose as a risk factor for MI.MethodologyThis cross-sectional study involving 237 diabetic patients aged 30-80 years was conducted in three major tertiary care hospitals in Peshawar, Pakistan. The inclusion criteria were diabetic patients with glycated hemoglobin (HbA1C) levels of less than 7% considered to be “controlled diabetics” and above 7% considered to be “uncontrolled diabetics.” Data were collected using structured questionnaires, past medical records, and patient history and were analyzed using SPSS software (IBM Corp., Armonk, NY, USA). The study was concluded in March 2022.ResultsThe highest number of MIs occurred in diabetics with HbA1c levels of 8-9% (47.9% of all MIs). There was a significant association between increasing HbA1c levels and the incidence of MI (p = 0.002). The adjusted prevalence odds ratio for MI in uncontrolled diabetics was 6.105 (95% confidence interval = 2.42-15.43), that is, six times increased incidence of MI in patients with HbA1c of more than 7%. Furthermore, with a 1% increase in HbA1c, there was a 10% increase in the proportion of MIs.ConclusionsFrom this study, it is clear that HbA1c levels of 8-9% were most significantly associated with the risk of MI in uncontrolled diabetics, and with rising levels of HbA1c, the risk of MI increased significantly. Thus, this study highlights the importance of HbA1c control in diabetic patients to prevent a heart attack.

Is myocardial infarction a surrogate endpoint for all-cause mortality? A trial-level meta-analysis of 144 randomized controlled trials enrolling 1.2 million patients from 1972–2020

Abstract Background Nonfatal myocardial infarction (MI) is commonly included as an endpoint in studies of treatment or prevention of coronary artery disease driven by the assumption that MI is a surrogate for downstream mortality and that preventing MI will reduce mortality. Though biologically plausible and frequently associated in epidemiological studies, the validity of MI as a surrogate marker for all-cause mortality in randomized controlled trials (RCTs) has not been previously demonstrated with trial-level meta-analytic evidence. Purpose To assess MI as a surrogate endpoint for all-cause mortality in RCTs Methods In December 2020, PubMed was searched for all RCTs reporting all-cause mortality and MI published in the New England Journal of Medicine, the Lancet, or the Journal of the American Medical Association. RCTs with a minimum sample size of 1000 patients and 24 months of follow up were included. Trial-level correlation between MI and all-cause mortality was then assessed for surrogacy using the coefficient of determination (R2) between the natural logarithm of the odds ratios for MI and mortality using a weighted linear regression where each study was weighted by the number of observations. Criteria for surrogacy was set at 0.8. Prespecified subgroup analyses based on era of trial enrollment (before 2000, 2000–2009, 2010+), duration of follow up (2–3.9, 4–5.9, or 6+ years), and study subject (revascularization, primary prevention, secondary prevention, mixed primary/secondary prevention) were also assessed. Results 1025 RCTs were retrieved and reviewed with 144 articles representing 1,211,897 patients ultimately meeting criteria for inclusion in the meta-analysis. Overall, MI had no correlation with all-cause mortality (R2=0.02, 95% CI: 0.00–0.08) (figure 1). In terms of era of trial enrollment, before year 2000 MI had low correlation with all-cause mortality (R2=0.22, 95% CI: 0.08–0.36) and had no correlation for the periods 2000–2009 (R2=0.02, 95% CI: 0.00–0.17) and 2010 and beyond (R2=0.01, 95% CI: 0.00–0.09). By follow-up period, MI had low correlation with all-cause mortality at 6+ years (R2=0.30, 95% CI: 0.01–0.55) and had no correlation with mortality at 2–3.9 years (R2=0.004, 95% CI: 0.00–0.08) or 4–5.9 years (R2=0.06, 95% CI: 0.001–0.16). MI had low correlation with all-cause mortality in revascularization trials (R2=0.21, 95% CI: 0.002–0.50) and no correlation with mortality in primary (R2=0.10, 95% CI: 0.001–0.26), secondary (R2=0.03, 95% CI: 0.00–0.20), and mixed primary/secondary prevention trials (R2=0.001, 95% CI: 0.00–0.08). Conclusions MI cannot be validated as a surrogate endpoint for all-cause mortality in RCTs of treatments for or to prevent CAD. Thus, treatments that reduce MI cannot be assumed to reduce mortality. Inclusion of MI as an endpoint in RCTs may still be justified based upon its association with impaired quality of life and increased utilization of health care resources but not based on its surrogacy for mortality. Funding Acknowledgement Type of funding sources: None. Figure 1. Overall analysis of 144 trials

Association of Psychological Distress and Cardiovascular Disease among Adult USA Population

Background: Cardiovascular disease (CVD) is the major cause of mortality and morbidity among the adult USA population. Major cardiovascular risk factors include age, obesity, hypertension, hypercholesterolemia, diabetes, and chronic kidney disease (CKD) with both diabetes and CKD being considered CVD risk equivalent. Psychological distress is known to be associated with diverse health outcomes. We aim to assess the relationship between psychological distress and cardiovascular disease among adult USA population. Materials & Methods: Data was analyzed from National Health Interview Survey (NHIS) administered by the CDC’s National Center for Health Statistics (NCHS). The NHIS samples non-institutionalized American civilians by household following a multi-stage area probability design. The survey included Kessler 6, a standardized psychological distress scale. SPSS® version 26 was used for analysis which included utilizing both the t-test and ANOVA for continuous variables and the Chi-squared analysis for categorical variables. A logistic regression model was developed to estimate the odds ratio and the strength of association between psychological distress and cardiovascular risk factors, coronary heart disease and stroke. Data is presented as the mean value ±SEM unless otherwise specified. Results: The analysis included 284,497 respondents with 3.6% of the US representative sample reporting psychological distress with a mean age of 48.09 ±0.16. Psychological distress was more common among age group 45-64 years, women, Hispanics and Blacks, alcoholic drinkers, those without a high school diploma, and those below the poverty level. The unadjusted odds ratio for myocardial infarction among those with psychological distress was 2.6 (2.45-2.83 95% CI), p<0.01. The unadjusted odds ratio for stroke among those with psychological distress was 3.1 (2.88-3.34 95% CI), p<0.01. After adjusting for age, BMI, diabetes, hypertension, hypercholesterolemia, smoking and chronic kidney disease, the odds ratio of myocardial infarction among the psychologically distressed was 1.96 (1.66-2.31 95% CI), p<0.01. The adjusted odds ratio for stroke was 2.56 (2.18-3.01 95% CI) p<0.01. Conclusion: Psychological distress is associated with a substantially higher risk of myocardial infarction and stroke independent of the traditional cardiovascular disease risk factors and is highly prevalent among ethnic minorities and disadvantaged socioeconomic groups. Further research is needed to develop effective interventions to manage psychological distress and decrease the disproportionately higher rates of cardiovascular disease among vulnerable populations.

Prevalence of Myocardial Infarction in Patients With Chronic Pancreatitis.

We conducted this study to ascertain whether chronic inflammation secondary to chronic pancreatitis (CP) has any association with myocardial infarction(MI). Data were collected from a commercial database (Explorys, Inc, IBM Watson, Ohio). Adults with the diagnosis of "chronic pancreatitis," based on Systematized Nomenclature of Medicine-Clinical Terms, were included in the CP group, and the rest of the patients were included in the non-CP group. The prevalence of MI was compared in both groups, and statistical multivariate model was performed. A total of 28,842,210 patients were included in the study. The overall prevalence of MI was 14.22% in the CP group as compared with 3.23% in the non-CP group (P < 0.0001). In the multivariate analysis, the odds ratio (OR) for MI in CP group was 1.453 (95% confidence interval, 1.418-1.488, P < 0.0001). Hypertension was a strong predictor for MI in the CP group with an OR of 3.2 (95% confidence interval, 3.0-3.5), followed by chronic kidney disease, older than 65 years, dyslipidemia, diabetes mellitus, obesity, alcohol abuse, smoking, White race, and male sex. This study showed that CP is associated with comorbidities, which can increase the prevalence and OR of MI.

Evaluating the relationship between alcohol consumption, tobacco use, and cardiovascular disease: A multivariable Mendelian randomization study.

BackgroundAlcohol consumption and smoking, 2 major risk factors for cardiovascular disease (CVD), often occur together. The objective of this study is to use a wide range of CVD risk factors and outcomes to evaluate potential total and direct causal roles of alcohol and tobacco use on CVD risk factors and events.Methods and findingsUsing large publicly available genome-wide association studies (GWASs) (results from more than 1.2 million combined study participants) of predominantly European ancestry, we conducted 2-sample single-variable Mendelian randomization (SVMR) and multivariable Mendelian randomization (MVMR) to simultaneously assess the independent impact of alcohol consumption and smoking on a wide range of CVD risk factors and outcomes. Multiple sensitivity analyses, including complementary Mendelian randomization (MR) methods, and secondary alcohol consumption and smoking datasets were used. SVMR showed genetic predisposition for alcohol consumption to be associated with CVD risk factors, including high-density lipoprotein cholesterol (HDL-C) (beta 0.40, 95% confidence interval (CI), 0.04–0.47, P value = 1.72 × 10−28), triglycerides (TRG) (beta −0.23, 95% CI, −0.30, −0.15, P value = 4.69 × 10−10), automated systolic blood pressure (BP) measurement (beta 0.11, 95% CI, 0.03–0.18, P value = 4.72 × 10−3), and automated diastolic BP measurement (beta 0.09, 95% CI, 0.03–0.16, P value = 5.24 × 10−3). Conversely, genetically predicted smoking was associated with increased TRG (beta 0.097, 95% CI, 0.014–0.027, P value = 6.59 × 10−12). Alcohol consumption was also associated with increased myocardial infarction (MI) and coronary heart disease (CHD) risks (MI odds ratio (OR) = 1.24, 95% CI, 1.03–1.50, P value = 0.02; CHD OR = 1.21, 95% CI, 1.01–1.45, P value = 0.04); however, its impact was attenuated in MVMR adjusting for smoking. Conversely, alcohol maintained an association with coronary atherosclerosis (OR 1.02, 95% CI, 1.01–1.03, P value = 5.56 × 10−4). In comparison, after adjusting for alcohol consumption, smoking retained its association with several CVD outcomes including MI (OR = 1.84, 95% CI, 1.43, 2.37, P value = 2.0 × 10−6), CHD (OR = 1.64, 95% CI, 1.28–2.09, P value = 8.07 × 10−5), heart failure (HF) (OR = 1.61, 95% CI, 1.32–1.95, P value = 1.9 × 10−6), and large artery atherosclerosis (OR = 2.4, 95% CI, 1.41–4.07, P value = 0.003). Notably, using the FinnGen cohort data, we were able to replicate the association between smoking and several CVD outcomes including MI (OR = 1.77, 95% CI, 1.10–2.84, P value = 0.02), HF (OR = 1.67, 95% CI, 1.14–2.46, P value = 0.008), and peripheral artery disease (PAD) (OR = 2.35, 95% CI, 1.38–4.01, P value = 0.002). The main limitations of this study include possible bias from unmeasured confounders, inability of summary-level MR to investigate a potentially nonlinear relationship between alcohol consumption and CVD risk, and the generalizability of the UK Biobank (UKB) to other populations.ConclusionsEvaluating the widest range of CVD risk factors and outcomes of any alcohol consumption or smoking MR study to date, we failed to find a cardioprotective impact of genetically predicted alcohol consumption on CVD outcomes. However, alcohol was associated with and increased HDL-C, decreased TRG, and increased BP, which may indicate pathways through impact CVD risk, warranting further study. We found smoking to be a risk factor for many CVDs even after adjusting for alcohol. While future studies incorporating alcohol consumption patterns are necessary, our data suggest causal inference between alcohol, smoking, and CVD risk, further supporting that lifestyle modifications might be able to reduce overall CVD risk.

Non-alcoholic steatohepatitis and the risk of myocardial infarction: A population-based national study.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is a systemic disease with bidirectional relationships with cardiovascular disease (CVD). Non-alcoholic steatohepatitis (NASH) is a more severe subtype of NAFLD. Patients with NASH exhibit more intra and extrahepatic inflammation, procoagulant imbalances and proatherogenic lipid profiles. Whether NASH increases the risk of ischemic heart disease is currently unclear.AIMTo investigate the relationship between acute myocardial infarction (MI) and NASH in a large cohort of subjects in the United States.METHODSWe reviewed data from a large commercial database (Explorys IBM) that aggregates electronic health records from 26 large nationwide healthcare systems. Using systemized nomenclature of clinical medical terms (SNOMED CT), we identified adult with the diagnosis of NASH from 1999-2019. We included patients with the diagnosis of acute MI from 2018-2019. Comorbidities known to be associated with NASH and MI such as obesity, diabetes mellitus, hyperlipidemia, smoking, male gender, and hypertension were collected. Univariable and multivariable analyses were performed to investigate whether NASH is independently associated with the risk of MI.RESULTSOut of 55099280 patients, 43170 were diagnosed with NASH (0.08%) and 107000 (0.194%) had a MI within 2018-2019. After adjusting for traditional risk factors, NASH conferred greater odds of MI odds ratio (OR) 1.5 [95% confidence interval (CI): 1.40-1.62]. Hyperlipidemia had the strongest association with MI OR 8.39 (95%CI: 8.21-8.58) followed by hypertension OR 3.11 (95%CI: 3.05-3.17) and smoking OR 2.83 (95%CI: 2.79-2.87). NASH had a similar association with MI as the following traditional risk factors like age above 65 years OR 1.47 (95%CI: 1.45-1.49), male gender OR 1.53 (95%CI: 1.51-1.55) diabetes mellitus OR 1.89 (95%CI: 1.86-1.91).CONCLUSIONMI appears to be a prevalent disease in NASH. Patients with NASH may need early identification and aggressive cardiovascular risk modification.

Increased Prevalence, Complications, and Costs of Smokers Undergoing Total Knee Arthroplasty.

Given a national push toward bundled payment models, the purpose of this study was to examine the prevalence as well as the effect of smoking on early inpatient complications and cost following elective total knee arthroplasty (TKA) in the United States across multiple years. Using the nationwide inpatient sample, all primary elective TKA admissions were identified from 2012 to 2014. Patients were stratified by smoking status through a secondary diagnosis of "tobacco use disorder." Patient characteristics as well as prevalence, costs, and incidence of complications were compared. There was a significant increase in the rate of smoking in TKA from 17.9% in 2012 to 19.2% in 2014 (p < 0.0001). The highest rate was seen in patients < 45 years of age (27.3%). Hospital resource usage was significantly higher for smokers, with a length of stay of 3.3 versus 2.9 days (p < 0.0001), and hospital costs of $16,752 versus $15,653 (p < 0.0001). A multivariable logistic model adjusting for age, gender, and comorbidities showed that smokers had an increased odds ratio for myocardial infarction (5.72), cardiac arrest (4.59), stroke (4.42), inpatient mortality (4.21), pneumonia (4.01), acute renal failure (2.95), deep vein thrombosis (2.74), urinary tract infection (2.43), transfusion (1.38) and sepsis (0.65) (all p < 0.0001). Smoking is common among patients undergoing elective TKA, and its prevalence continues to rise. Smoking is associated with higher hospital costs as well as higher rates of immediate inpatient complications. These findings are critical for risk stratification, improving of bundled payment models as well as patient education, and optimization prior to surgery to reduce costs and complications.

Updating insights into rosiglitazone and cardiovascular risk through shared data: individual patient and summary level meta-analyses

ObjectivesTo conduct a systematic review and meta-analysis of the effects of rosiglitazone treatment on cardiovascular risk and mortality using multiple data sources and varying analytical approaches with three aims in...

Myocardial infarction and death findings from a 22-year follow-up of a cohort of 980 employed Swedish men

ObjectivesIn this article, we present death and myocardial infarction (MI) incidences over 22 years in relation to possible risk factors and their explanatory value. Study designIn 1993, 980 middle-aged Swedish men in an automotive industry were surveyed at a health checkup as part of the Renault-Volvo Coeur project. The Swedish cohort was revisited in 2015. MethodsIn 2015, incident MIs were identified using postal questionnaires, hospital records, and the Swedish national MI and death registers. The statistical results were given as odds ratios (ORs) and pseudo-R2 (PR2), showing the proportion of variation in risk explained by logistic models. ResultsOne hundred and four deaths (4.6 per 1000 person-years) and 89 first MIs (4.2 per 1000 person-years) were identified. The Framingham risk index showed the strongest association with MI (OR = 23; 95% confidence interval [CI] = 5.42, 96.9), comparing the fifth quintile with the first. The all-cause death showed an OR of 3.2 (95% CI = 1.65, 6.08), with a suggested U-shape over quintiles. The percentages of PR2 for MI and death were 8.8% and 6.6%, respectively. All risk factors together explained 22% of the variation in risk of MI. Comparing mortality in men living alone with those married yielded an OR of 3.78, which was found to be statistically significant. The corresponding OR for MI was not significant. ConclusionsTraditional risk factors were confirmed but explained a modest proportion of the risk variation.

Sex-specific Mendelian randomization study of genetically predicted insulin and cardiovascular events in the UK Biobank

Insulin drives growth and reproduction which trade-off against longevity. Genetically predicted insulin, i.e., insulin proxied by genetic variants, is positively associated with ischemic heart disease, but sex differences are unclear, despite different disease rates and reproductive strategies by sex. We used Mendelian randomization in 392,010 white British from the UK Biobank to assess the sex-specific role of genetically predicted insulin in myocardial infarction (MI) (14,442 cases, 77% men), angina (21,939 cases, 65% men) and heart failure (5537 cases, 71% men). Genetically predicted insulin was associated with MI (odds ratio (OR) 4.27 per pmol/L higher insulin, 95% confidence interval (CI) 1.60 to 11.3) and angina (OR 2.93, 1.27 to 6.73) in men, but not women (MI OR 0.80, 95% CI 0.23 to 2.84, angina OR 1.10, 95% CI 0.38 to 3.18). Patterns were similar for insulin resistance and heart failure. Mitigating the effects of insulin might address sexual disparities in health.

Associations of Genetically Predicted Insulin and Insulin Resistance with Myocardial Infarction, Angina and Heart Failure: A Mendelian Randomization Study in the UK Biobank

Background: Evolutionary biology suggests growth and reproduction trade-off against longevity. Genetically predicted insulin, a promotor of both growth and reproduction, is positively associated with ischemic heart disease. Here, we further investigate the role of genetically predicted insulin and insulin resistance in cardiovascular disease sub-types (myocardial infarction (MI), angina, and heart failure) and its risk factors by sex, given drivers of reproduction have sexspecific effects. Methods: Two-sample Mendelian randomization was used to obtain unconfounded estimates. Genetic variants strongly (p-value<5x10-8) associated with insulin, insulin adjusted for body mass index, and a validated insulin resistance genetic score, obtained from 108,557 Europeans without diabetes in MAGIC, were applied to 392,010 white British in the UK Biobank, with 14,442 MI cases (77% men), 21,939 angina cases (65% men), and 5,537 heart failure cases (71% men). The role in cardiovascular risk factors (low density lipoprotein (LDL)-cholesterol, apolipoprotein B, blood pressure, and reticulocyte count) was similarly examined. Findings: Genetically predicted insulin was associated with MI (odds ratio (OR) 4·27 per pmol/L higher insulin, 95% confidence interval (CI) 1·60 to 11·3) and angina (OR 2·93, 1·27 to 6·73) in men, but not women (OR for MI 0·80, 95% CI 0·23 to 2·84; angina 1·10, 95% CI 0·38 to 3·18), as was insulin resistance. The pattern was similar for heart failure. Interpretation: As suggested by evolutionary biology, genetically predicted insulin and insulin resistance were associated with MI and angina in a sex-specific way. Clarifying the underlying pathways could provide new insights into prevention and treatment strategies. Funding Statement: The authors received no specific funding for this work. Declaration of Interests: The authors declare: None. Ethics Approval Statement: The UK Biobank has already received ethical approval from the Research Ethics Committee and participants provided written informed consent. The analysis of other publicly available data or summary statistics does not require additional ethical approval.

The large sample coverage probability of confidence intervals in general regression models after a preliminary hypothesis test

AbstractWe derive a computationally convenient formula for the large sample coverage probability of a confidence interval for a scalar parameter of interest following a preliminary hypothesis test that a specified vector parameter takes a given value in a general regression model. Previously, this large sample coverage probability could only be estimated by simulation. Our formula only requires the evaluation, by numerical integration, of either a double or a triple integral, irrespective of the dimension of this specified vector parameter. We illustrate the application of this formula to a confidence interval for the odds ratio of myocardial infarction when the exposure is recent oral contraceptive use, following a preliminary test where two specified interactions in a logistic regression model are zero. For this real‐life data, we compare this large sample coverage probability with the actual coverage probability of this confidence interval, obtained by simulation.

Meloxicam and risk of myocardial infarction: a population-based nested case-control study.

Certain non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with an increased risk of myocardial infarction (MI), a risk linked to cyclo-oxygenase-2 inhibition. There are limited studies assessing the risk of MI associated with meloxicam, an increasingly popular drug with COX-2 inhibiting properties. A nested matched case-control study using The Health Improvement Network, a UK population-based database was conducted. NSAID users between 35 and 89years of age with at least 1 year enrollment in the cohort were included. Incident MI cases were matched on age, sex, practice and event date with up to 4 controls. NSAID exposure was categorized as remote (between 60days and 1year), recent (between 1 and 60days) or current relative to the event date. Current users were further classified as naproxen (negative control), diclofenac (positive control), meloxicam or other NSAID users. Multivariable conditional logistic regression was conducted to determine the risk of MI for each NSAID use categories compared with that of remote users. 9291 MI cases were matched with 30,676 controls. The cases had a higher prevalence of traditional cardiac risk factors, chronic kidney disease and inflammatory arthritis and cardioprotective drug utilization. The adjusted odds ratio of MI for current user compared to remote users were: meloxicam 1.38 (1.17-1.63), naproxen 1.12 (0.96-1.30) and diclofenac 1.37 (1.25-1.50). In this large population-based study, meloxicam increased the risk of MI by 38%. This study warrants cautious use of this increasingly popular drug.

Association of Helicobacter Pylori with Presence of Myocardial Infarction in Iran: A Systematic Review and Meta-Analysis.

Over the past decade, cardiovascular diseases have been recognized as the leading cause of mortality worldwide. Myocardial infarction (MI) is one of the most prevalent types of cardiovascular diseases that is caused by the closure of coronary arteries and ischemic heart muscle. Numerous studies have analyzed the role of H. pylori as a possible risk factor for coronary artery diseases, in most of which the role of infection in coronary artery disease is not statistically significant. These contradictory findings made us conduct a systematic review to analyze all relevant studies in Iran through a meta-analysis and report a comprehensive and integrated result. All published studies from September 2000 until September 2016 were considered. Using reliable Latin databases like PubMed, Google Scholar, Google search, Scopus, Science Direct and Persian databases like SID, Irandoc, Iran Mede and Magiran. After quality control, these studies were entered into a meta-analysis by using the random effects model. After evaluating the studies, 11 papers were finally selected and assessed. A total of 2517 participants had been evaluated in these studies, including 1253 cases and 1264 controls. Based on the results of meta-analysis and using random effects model, an overall estimate of OR Helicobacter Pylori with Presence of Myocardial Infarction in Iran was OR=2.53 (CI=1.37-4.67). The results of this review study show that H. pylori are associated with the incidence of MI so that the odds ratio of MI in the patients with helicobacter pylori is twice greater than that of the people without H. pylori. Future studies are recommended to evaluate the mechanisms associated with relation of H. pylori with MI as well as its association with time.

Age and Cardiovascular Risk Attributable to Apolipoprotein B, Low-Density Lipoprotein Cholesterol or Non-High-Density Lipoprotein Cholesterol.

BackgroundHigher concentrations of the apolipoprotein B (apoB) lipoproteins increase the risk of cardiovascular disease. However, whether the risk associated with apoB lipoproteins varies with age has not been well examined.Methods and ResultsWe determined the associations for total cholesterol, low‐density lipoprotein (LDL)‐cholesterol (LDL‐C), non‐high‐density lipoprotein‐cholesterol (non‐HDL‐C), apoB, apolipoprotein A‐I (apoA‐I), and HDL‐cholesterol (HDL‐C) with myocardial infarction at different ages in 11 760 controls and 8998 myocardial infarction cases of the INTERHEART Study. Logistic regression was used to compute the odds ratio of myocardial infarction for 1 SD change in each lipid marker by decade from <40 to >70 years of age. Except for those >70, plasma levels of total cholesterol, LDL‐C, and non‐HDL‐C and apoB were greater in cases than controls. However, the average levels of these markers decreased significantly as age increased. By contrast, levels of apoA‐I and HDL‐C were significantly greater in controls than cases but increased significantly as age increased. The cardiovascular risk associated with the atherogenic lipid markers differed at different ages. Most notably, there was a significant decline in the odds ratio for total cholesterol, LDL‐C, and non‐HDL‐C, and apoB with increases in age whereas the odds ratios associated with apoA‐I and HDL‐C were consistent across the age groups.ConclusionsThese data indicate that the risk of cardiovascular events associated with apoB particles is greater in younger compared to older individuals. This finding is consistent with greater relative benefit from LDL‐lowering therapy in younger compared to older individuals and so argues for therapy in younger individuals with elevated lipids.

Risk of Bias in Systematic Reviews of Non-Randomized Studies of Adverse Cardiovascular Effects of Thiazolidinediones and Cyclooxygenase-2 Inhibitors: Application of a New Cochrane Risk of Bias Tool.

BackgroundSystematic reviews of the effects of healthcare interventions frequently include non-randomized studies. These are subject to confounding and a range of other biases that are seldom considered in detail when synthesizing and interpreting the results. Our aims were to assess the reliability and usability of a new Cochrane risk of bias (RoB) tool for non-randomized studies of interventions and to determine whether restricting analysis to studies with low or moderate RoB made a material difference to the results of the reviews.Methods and FindingsWe selected two systematic reviews of population-based, controlled non-randomized studies of the relationship between the use of thiazolidinediones (TZDs) and cyclooxygenase-2 (COX-2) inhibitors and major cardiovascular events. Two epidemiologists applied the Cochrane RoB tool and made assessments across the seven specified domains of bias for each of 37 component studies. Inter-rater agreement was measured using the weighted Kappa statistic. We grouped studies according to overall RoB and performed statistical pooling for (a) all studies and (b) only studies with low or moderate RoB. Kappa scores across the seven bias domains ranged from 0.50 to 1.0. In the COX-2 inhibitor review, two studies had low overall RoB, 14 had moderate RoB, and five had serious RoB. In the TZD review, six studies had low RoB, four had moderate RoB, four had serious RoB, and two had critical RoB. The pooled odds ratios for myocardial infarction, heart failure, and death for rosiglitazone versus pioglitazone remained significantly elevated when analyses were confined to studies with low or moderate RoB. However, the estimate for myocardial infarction declined from 1.14 (95% CI 1.07–1.24) to 1.06 (95% CI 0.99–1.13) when analysis was confined to studies with low RoB. Estimates of pooled relative risks of cardiovascular events with COX-2 inhibitors compared with no nonsteroidal anti-inflammatory drug changed little when analyses were confined to studies with low or moderate RoB. The exception was a rise in the relative risk associated with ibuprofen from 1.07 (95% CI 0.97–1.18) to 1.14 (95% CI 1.03–1.26). The main limitation of our study was testing the instrument on a narrow range of pharmacoepidemiological studies; we cannot assume our findings extend to a broader range of interventions and settings.ConclusionsThe Cochrane RoB tool highlighted a wide range of risks of bias in studies included in two widely cited reviews and had the potential to change the conclusions of the reviews. Systematic reviews that incorporate non-randomized studies of medical interventions should include a detailed assessment of RoB for each included study.