Relative Risk Of Myocardial Infarction Research Articles

Myocardial infarction in a population-based cohort of patients with biopsy-confirmed giant cell arteritis in southern Sweden

ObjectivesTo determine the incidence rate (IR) of myocardial infarction (MI), relative risk of MI, and impact of incident MI on mortality in individuals with biopsy-confirmed giant cell arteritis (GCA).MethodsMIs in...

Sex-specific trends in incidence of first myocardial infarction among people with and without diabetes between 1985 and 2016 in a German region

BackgroundThe reduction of myocardial infarction (MI) and narrowing the gap between the populations with and without diabetes are important goals of diabetes care. We analyzed time trends for sex-specific incidence rates (IR) of first MI (both non-fatal MI and fatal MI) as well as separately for first non-fatal MI and fatal MI in the population with and without diabetes.MethodsUsing data from the KORA myocardial infarction registry (Augsburg, Germany), we estimated age-adjusted IR in people with and without diabetes, corresponding relative risks (RR), and time trends from 1985 to 2016 using Poisson regression.ResultsThere were 19,683 people with first MI (34% fatal MI, 71% men, 30% with diabetes) between 1985 and 2016. In the entire study population, the IR of first MI decreased from 359 (95% CI: 345–374) to 236 (226–245) per 100,000 person years. In men with diabetes, IR decreased only in 2013–2016. This was due to first non-fatal MI, where IR in men with diabetes increased until 2009–2012, and slightly decreased in 2013–2016. Overall, fatal MI declined stronger than first non-fatal MI corresponding to IRs. The RR of first MI substantially increased among men from 1.40 (1.22–1.61) in 1985–1988 to 2.60 (2.26–2.99) in 1997–2000 and moderately decreased in 2013–2016: RR: 1.75 (1.47–2.09). Among women no consistent time trend for RR was observed. Time trends for RR were similar regarding first non-fatal MI and fatal MI.ConclusionsOver the study period, we found a decreased incidence of first MI and fatal MI in the entire study population. The initial increase of first non-fatal MI in men with diabetes needs further research. The gap between populations with and without diabetes remained.

Long-term aspirin adherence following myocardial infarction and risk of cardiovascular events.

Aspirin is considered mandatory after myocardial infarction (MI). However, its long-term efficacy has been questioned. This study investigated the effectiveness of long-term aspirin after MI. Patients≥40 years with MI from 2004-2017 who were adherent to aspirin one year after MI were included from Danish nationwide registries. At 2, 4, 6, and 8 years after MI, continued adherence to aspirin was evaluated. Absolute and relative risks of MI, stroke, or death at 2 years from each timepoint were calculated using multivariable logistic regression analysis with average treatment effect modeling standardized for age, sex, and comorbidities. Subgroup analyses were stratified by sex and age>and≤65 years. Among 40114 individuals included, the risk of the composite endpoint was significantly higher for nonadherent patients at all timepoints. The absolute risk was highest at 2-4 years after MI for both adherent (8.34%, 95% confidence interval [CI]: 8.05-8.64%) and nonadherent patients (10.72%, 95% CI: 9.78-11.66%). The relative risk associated with nonadherence decreased from 4 years after index-MI and onwards: 1.41 (95% CI: 1.27-1.55) at 4-6 years and 1.21 (95% CI: 1.06-1.36) at 8-10 years (Ptrend=0.056). Aspirin nonadherence in women and individuals>65 years was not associated with increased risk. Pinteraction at each of the timepoints: Age-<0.001, <0.001, 0.002, 0.51; Sex-0.25, 0.02, 0.02, 0.82. Nonadherence to long-term aspirin was associated with increased risk of MI, stroke, or death, but not in women or individuals>65 years. The risk decreased from 4 years after MI with near statistical significance.

Risk of myocardial infarction following capecitabine treatment in patients with gastrointestinal cancer - a nationwide registry-based study

Abstract Background Myocardial infarction is a cardiac adverse event associated with fluoropyrimidines such as 5-fluorouracil and its orally available prodrug capecitabine. There are limited data on the incidence, risk, and prognosis of capecitabine associated myocardial infarction. Purpose The aim of this study was to examine the risk of myocardial infarction in patients with gastrointestinal (GI) cancer treated with capecitabine compared with age- and sex-matched population control subjects without cancer (1:2 ratio). Methods Patients with GI cancer treated with capecitabine between 2004-2016 were identified within the Danish National Patient Registry. Those with a history of ischemic heart disease were excluded. Absolute and relative risks of myocardial infarction at 6 months and 1 year were derived from multivariable Cox regression with average treatment effect modeling. Estimates were standardized to the distributions of age, sex, selected comorbidities, and pharmacotherapies of all included subjects. Results A total of 71,460 patients were included in the final analysis of whom 23,820 had GI cancer treated with capecitabine, and 47,640 were population control subjects without cancer. Differences in the prevalences of selected comorbid conditions, including diabetes, hypertension, and other risk factors for coronary artery disease and antianginal medications were not significant (P&amp;gt;0.05 for all). The 6-month absolute risk (AR) of myocardial infarction was significantly higher for capecitabine-treated patients at 0.6% [95% confidence interval (CI): 0.5%-0.7%] versus 0.3% [95% CI: 0.2%-0.3%] in population control subjects, corresponding to a relative risk (RR) of 2.00 [95% CI 1.53-2.48; P &amp;lt;0.001]. The corresponding 1-year ARs were 0.7% [95% CI: 0.6%-0.9%] versus 0.6% [95% CI: 0.5%-0.6%]; RR 1.28 [95% CI 1.03-1.52; P= 0.03]. Six-month and one-year all-cause mortality ARs for patients treated with capecitabine versus controls were 15.2% vs. 0.7% and 29.7% vs. 1.6% respectively. Conclusions The risk of myocardial infarction of capecitabine-treated patients both 6- and 12-month risks were significantly higher compared with population controls. Despite the absolute risk were low, the clinical significance of the differences appears limited in the context of the significant competing risk of death in this population.Risk of Myocardial InfarctionMortality

Serial high-sensitivity troponin-I and long-term risk of myocardial infarction and coronary revascularization in subjects with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity troponin-I (hsTnI) concentrations are associated with mortality in individuals with suspected acute coronary syndrome. However, their relation to myocardial infarction and revascularization events is unknown. Purpose To determine short- and long-term risks of myocardial infarction and revascularization (PCI or CABG) according to hsTnI concentrations and their changes from baseline, in patients with suspected acute coronary syndrome. Methods Through Danish national registries, we identified subjects who underwent two hsTnI measurements (Siemens TnI Flex® Reagent, 99th percentile upper reference limit, 45 ng/l) separated by 1-7 hours, during hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019. Individuals were stratified according to their hsTnI concentration pattern (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). We calculated standardized absolute and relative risks of myocardial infarction and coronary revascularization using multivariable logistic regression with average treatment effect modeling, a method that ensures equal distribution of factors that may affect the risk of outcomes across the various groups of interest. Results A total of 20,609 individuals were included of whom 22.4% were discharged with a diagnosis of myocardial infarction, 4.8% with unstable angina, and 72.8% with observation for suspected myocardial infarction or chest pain. Median age was 63.2 years, and 53.1% were male. Considering known cardiovascular disease, 21.3% had coronary artery disease, 7.0% had undergone prior PCI or CABG, 8.1% had heart failure, and 10.7% had atrial fibrillation or flutter. The standardized risk of being diagnosed with myocardial infarction was lowest in subjects with two normal hsTnI values and highest in those with persistently elevated concentrations. Within each main group, the likelihood of being diagnosed with myocardial infarction generally appeared to increase with more pronounced hsTnI changes. The standardized risk of undergoing coronary revascularization mimicked this pattern, although among persons with two elevated hsTnI levels, the long-term-risk was not influenced by relative concentration changes. The findings are summarized in the Figure. Conclusions Among individuals with suspected acute coronary syndrome, those with a persistently elevated hsTnI concentration consistently had the highest risk of being diagnosed with myocardial infarction and undergoing coronary revascularization. The risk of these outcomes was, for the most part, also positively associated with the magnitude of hsTnI change.Figure

Impact of Concomitant Use of Proton Pump Inhibitors and Clopidogrel on Recurrent Stroke and Myocardial Infarction.

Conflicting results have been reported regarding the interaction between proton pump inhibitors (PPIs) and clopidogrel. We investigated whether concomitant PPI use influenced the risk of recurrence in patients with stroke and myocardial infarction (MI). This study used two databases for two different designs, the Korean National Health Insurance Service (NHIS) database for a self-controlled case series design, and the national sample cohort of the NHIS data base converted to the Observational Medical Outcomes Partnership-Common Data Model version for a cohort study based on large-scale propensity score matching. In the PPI co-prescription group, recurrent hospitalization with stroke occurred in 17.6% of the 8201 patients with history of stroke, and recurrent MI occurred in 17.1% of the 1216 patients with history of MI within1 year. According to the self-controlled case series, the overall relative risk (RR) of recurrent stroke was 2.09 (95% confidence interval (CI); 1.83-2.38); the RR showed an increasing trend parallel to the time from the beginning of PPI co-prescription. In the cohort study, there was a higher incidence of recurrent stroke in the PPI co-prescription group (Hazard ratio (HR): 1.34, 95% CI: 1.01-1.76, p = 0.04). The overall RR of recurrent MI was 1.47 (95% CI; 1.02-2.11) in the self-controlled case series; however, there was no statistically significant difference in recurrent MI in the cohort study (HR:1.42, 95% CI:0.79-2.49, p = 0.23). The impact of individual PPIs on stroke and MI showed different patterns. A PPI co-prescription >4 weeks with clopidogrel was associated with hospitalization of recurrent stroke within 1 year of initial diagnosis; however, its association with recurrent MI remains inconclusive. The influence of individual PPIs should be clarified in the future.

Associations of MAFLD and MAFLD subtypes with the risk of the incident myocardial infarction and stroke

Metabolic dysfunction-associated fatty liver disease (MAFLD) is a condition characterized by liver fat accumulation and metabolic abnormalities. Given the potential impact of MAFLD on patient health, it is important to understand its association with major adverse cardiovascular events (MACE) such as myocardial infarction (MI) and stroke. In the prospective UK Biobank cohort, we sought to elucidate the association of MAFLD and its subtypes with incident MI and stroke. In this study, we analyzed the data of 325,129 participants in the UK Biobank and calculated relative risks for MI and stroke using Cox regression analysis. Among 325,129 participants over a median duration of 12.8 years follow-up, participants with MAFLD were significantly more likely to experience a MI (hazard ratio [HR] = 1.35, 95% confidence interval [CI: 1.29;1.41] P < 0.001) or a stroke (HR = 1.26 [1.18–1.33] P < 0.001) compared to those without MAFLD. In addition, diabetic, overweight with metabolic dysfunction (MD), and lean MAFLD subtypes were significantly associated with an increased risk for MI and stroke, whereas overweight without MD subtype did not appear to be associated with this risk. Our findings also revealed graded associations between liver fibrosis scores and risk of MI and stroke in MAFLD patients. However, only diabetic, and overweight patients with MD subtypes exhibited graded associations between liver fibrosis score and the risk of MI and stroke among the MAFLD subtypes. Furthermore, the risk alleles traits of fatty liver did not enhance the effect of MAFLD on the risk of MI and stroke. In conclusion, a diagnosis of MAFLD is associated with an increased risk of MI or stroke, and the assessment of MAFLD and its subtypes should be a component of the cardiovascular risk assessment.

Independent Causal Effect of Remnant Cholesterol on Atherosclerotic Cardiovascular Outcomes: A Mendelian Randomization Study.

Observational studies suggested that residual risk of cardiovascular events after LDL (low-density lipoprotein) cholesterol lowering may be linked to remnant cholesterol (RC). We conducted a large-scale Mendelian randomization study to investigate the causal role of RC to predict coronary artery disease (CAD), myocardial infarction (MI), and stroke risk. We extracted single-nucleotide polymorphisms for RC and LDL from large-scale genome-wide association databases. We estimated the genetic association with outcomes from the CARDIoGRAMplusC4D consortium (Coronary Artery Disease Genome-Wide Replication and Meta-Analysis Plus the Coronary Artery Disease Genetics), the Metastroke consortium, as well as the GLGC (Global Lipids Genetics Consortium). Genetic variants were used as instruments, thereby minimizing residual confounding and reverse causation biases of observational studies. By leveraging data from a combined sample of 958 434 participants, we found evidence for a significant causal effect of RC on the risk of CAD (odds ratio [OR], 1.51 per SD unit increase in RC [95% CI, 1.42-1.60]; P=5.3×10-5), MI (OR, 1.57 [95% CI, 1.21-2.05]; P=9.5×10-4), and stroke (OR, 1.23 [95% CI, 1.12-1.35]; P=3.72×10-6). There was no evidence of pleiotropy. The effect of RC on CAD and MI remained consistent after accounting for the effects of RC-associated genetic variants on LDL cholesterol: OR, 1.49 (95% CI, 1.37-1.61) for CAD and OR, 1.80 (95% CI, 1.70-19.1) for MI without a meaningful indirect effect exerted on these outcomes via the LDL cholesterol mediator. This large-scale Mendelian randomization study showed a robust genetic causal association between RC and cardiovascular outcomes. The effect on CAD and MI is independent of LDL cholesterol. Early screening for RC along with long-term inhibition of RC should be the focus of future therapeutic interventions.

Air pollution and myocardial infarction; effect modification by sociodemographic and environmental factors. A cohort study from Denmark

Air pollution is associated with increased risk of myocardial infarction (MI), but it is unresolved to what extent the association is modified by factors such as socioeconomic status, comorbidities, financial stress, residential green space, or road traffic noise. We formed a cohort of all (n = 1,964,702) Danes, aged 50–85 years, with 65,311 cases of MI during the followed-up period 2005–2017. For all participants we established residential five-year running average exposure to particulate matter <2.5 μm (PM2.5), ultrafine particles (UFP, <0.1 μm), elemental carbon (EC) and nitrogen dioxide (NO2). We evaluated risk in population strata, using Aalen additive hazards models to estimate absolute risk and Cox proportional hazards models to estimate relative risk of MI with 95% confidence intervals (CI).PM2.5 and the other pollutant were associated with MI. Lower education and lower income were associated with higher absolute risks of MI from air pollution, whereas no clear effect modification was apparent for relative risk estimates. For example, 5 μg/m3 higher PM2.5 was associated with HR for MI of 1.16 (95% CI: 1.10–1.22) among those with only mandatory education and 1.13 (95% CI: 1.03–1.24) among those with long education. The corresponding rate differences per 100,000 person years were 243 (95% CI: 216–271) and 358 (95% CI: 338–379), respectively. Higher level of comorbidity was consistently across all four pollutants associated with both higher absolute and relative risk of MI.In conclusion, people with comorbid conditions or of lower SES appeared more vulnerable to long-term exposure to air pollution and more cases of MI may be prevented by focused interventions in these groups.

Effect of bariatric surgery on long-term cardiovascular outcomes: a systematic review and meta-analysis of population-based cohort studies.

This meta-analysis aimed to compare the effects of bariatric surgery and nonsurgery on cardiovascular outcomes in patients with obesity. A systematic literature search of the Medline (via PubMed), Embase, and Cochrane Central Register of Controlled Trials databases was performed until August 18th, 2021. Population-based cohort studies comparing long-term cardiovascular outcomes for patients with obesity undergoing bariatric surgery or not were included. A meta-analysis of relative risks (RRs) was performed for all outcomes. We conducted subgroup analyses and meta-regression to explore sources of heterogeneity and the stability of the results. Twenty-one population-based cohort studies involving 2,857,016 participants were identified. The major adverse cardiovascular event (MACE) RR in the bariatric surgery group was .53 (95% confidence interval [CI] = .45-.62, P < .001) relative to the nonsurgical group. Relative to the nonsurgical group, the risk of myocardial infarction (MI) (RR= .40, 95% CI = .30-.52, P < .001), stroke (RR = .60, 95% CI = .46-.79, P < .001), cardiovascular death (RR = .43, 95% CI = .35-.54, P < .001), and all-cause death (RR = .44, 95% CI = .32-.59, P<.001) was significantly reduced for patients who underwent bariatric surgery. In subgroup analyses, as the proportion of patients with diabetes mellitus increased, lower RRs for MACE, MI, and stroke were observed in the surgery group relative to the nonsurgical group. The decreased risk of MACE was also observed in the subgroup with median follow-up duration ≥5 years.Bariatric surgery improves cardiovascular outcomes in patients with obesity, especially providing long-term benefits, and this effect is more pronounced in patients with comorbid diabetes.

Peripheral Artery Disease as a Risk Factor for Myocardial Infarction.

Introduction: Atherosclerosis contributes to the underlying pathophysiology for peripheral arterial disease (PAD), coronary artery disease (CAD), and cerebrovascular disease. Several studies have been conducted to demonstrate PAD as a major risk factor for cardiovascular (CV) events, however, the regional data are limited. This study aims to highlight PAD as a major risk factor in CV events in a local setting.Methods: In this longitudinal study, 400 hypertensive patients with a confirmed diagnosis of PAD were enrolled from the outpatient department of the cardiology unit. Diagnosis of PAD was made using the ankle brachial index (ABI). ABI less than 0.9 was labeled as participants with PAD. Another group of 400 without PAD was also enrolled as the control group from the outpatient department of cardiology unit. Patients were followed up for 12 months or for the development of myocardial infarction (MI).Result: Participants with PAD had a significant increased risk of total MI events with a relative risk (RR) of 1.67 (confidence interval, CI 95%: 1.05-2.66; p-value: 0.02). The RR for fatal MI was 2.62 (CI 95%: 0.94-7.29; p-value: 0.06) compared to the participants without PAD, however, it was not significant.Conclusion: This study has focused on the risk factors of PAD and has suggested that the patients who have any of the mentioned risk factors should be treated with caution under strict instructions given by doctors. A variety of treatment options is available, but the initial changes should be made in the lifestyle of these patients, making sure the risk factors are being treated.

Women With Polycystic Ovary Syndrome Have an Increased Risk of Major Cardiovascular Events: a Population Study.

ContextThe effects of polycystic ovary syndrome (PCOS) on cardiovascular morbidity and mortality are unclear.ObjectiveThis work aims to establish the relative risk of myocardial infarction (MI), stroke, angina, revascularization, and cardiovascular mortality for women with PCOS.MethodsData were extracted from the Clinical Practice Research Datalink Aurum database. Patients with PCOS were matched to controls (1:1) by age, body mass index (BMI) category, and primary care practice. The primary outcome was the time to major adverse cardiovascular event (MACE); a composite end point incorporating MI, stroke, angina, revascularization and cardiovascular mortality. Secondary outcomes were the individual MACE end points.ResultsOf 219 034 individuals with a diagnosis of PCOS, 174 660 (79.7%) met the eligibility criteria and were matched. Crude rates of the composite end point, MI, stroke, angina, revascularization, and cardiovascular mortality were respectively 82.7, 22.7, 27.4, 32.8, 10.5, and 6.97 per 100 000 patient-years for cases, and 64.3, 15.9, 25.7, 19.8, 7.13, and 7.75 per 100 000 patient-years for controls. In adjusted Cox proportional hazard models (CPHMs), the hazard ratios (HRs) were 1.26 (95% CI, 1.13-1.41), 1.38 (95% CI, 1.11-1.72), 1.60 (95% CI, 1.32-1.94), and 1.50 (95% CI, 1.08-2.07) for the composite outcome, MI, angina, and revascularization, respectively. In a time-dependent CPHM, weight gain (HR 1.01; 1.00-1.01), prior type 2 diabetes mellitus (T2DM) (HR 2.40; 1.76-3.30), and social deprivation (HR 1.53; 1.11-2.11) increased risk of progression to the composite end point.ConclusionThe risk of incident MI, angina, and revascularization is increased in young women with PCOS. Weight and T2DM are potentially modifiable risk factors amenable to intervention.

Physiologically increased total bilirubin is associated with reduced risk of first myocardial infarction: A meta-analysis and dose-response analysis

AimBilirubin has potential predictive and prognostic value for myocardial infarction (MI), but the clinical evidence remains controversial. We performed this meta-analysis to systematically quantify the relationships between circulating bilirubin levels and the incidence of MI and post–MI adverse events. Data synthesisWe searched the PubMed, Cochrane Library, Embase, and Web of Science databases for ad-hoc studies, published up to October 17, 2020, recording bilirubin before MI (predictive analyses) or adverse events (prognostic analyses). Relative risks (RR) were pooled by a random-effects model. The dose-response analysis was conducted by restricted cubic splines. In patients without previous MI, increased total bilirubin (TB) reduced the risk of long-term (>3 year) first MI by 22% (95% confidence interval [CI]: 0.69–0.88, n = 4). The dose-response analysis indicated that the RR for first MI decreased by 2.7% per each 2 μmol/L increment of TB (three studies, 95% CI: 1.3%–4.1%, P < 0.001), with a cut-off value of 12.60 μmol/L for RR > 1.00. Elevated bilirubin reduced the incidence of first and recurrent MI by 36% (95% CI: 0.42–0.98, n = 7). However, after suffering MI, higher TB concentrations could not decrease the risk of recurrent MI (RR: 1.02, 95% CI: 0.67–1.55, n = 5) and increased the incidence of short-term (<1 year) post–MI major adverse cardiovascular events, all-cause mortality, and cardiovascular mortality, but not long-term (≥1 year). ConclusionHigher TB levels within a physiological range reduced the incidence of long-term first MI, with a cut-off value of 12.60 μmol/L.

Association between the phenotype of metabolically healthy obesity and the risk of myocardial infarction

Abstract Aim This study aimed to investigate the associations between the metabolically healthy obesity (MHO) and the risk of myocardial infarction (MI) in a Russian population sample. Materials and methods A random population sample of men and women aged 45–69 years old at baseline was examined in 2003–2005 in a Russian city; after that the cohort was followed-up for 12 years on the average (2003–2016). A sub-cohort of subjects with body mass index (BMI) ≥30 kg/m2 at baseline was selected for present study (3157 individuals, 73.2% women); of those, 3008 subjects free from baseline history of MI/acute CHD was included for analysis. The data on incident myocardial infarction (MI) were ascertained from register of MI, two repeated examinations and repeated postal interviews during 12-year follow-up of the cohort. We used two definitions of MHO: by NCEP ATPIII, 2001 (the presence of 2 or less components of the metabolic syndrome) and by IDF 2005 (waist circumference (WC) ≥94 cm in men and ≥80 cm in women regardless of risk factors). Multivariable Cox regression was conducted using the SPSS package (V. 13.0). Results The prevalence of MHO at baseline ranged from 20% (by IDF) to 45% (by NCEPATPIII) in obese sub-cohort. Among subjects with MHO at baseline, about one half of subjects developed metabolically unhealthy obesity phenotype (MUO) during 12-years. Women were more likely to retain MHO (32%) and more frequent transited from MUO to MHO (14%) compared to men (22% and 6% by IDF criteria, correspondently) during 12 years. The relative risk of incident MI in subjects with MUO at baseline was 1.9 times higher than in those with MHO (HR 1.9, 95% CI 1.2–2.9) by NCEPATP III. Among men, the relative risk of MI in those with MUO (by NCEP ATP III) was 2 times higher than in a group with MHO (HR 2.1, 95% CI 1.1–4.0). Among women, the relative risk of MI in those with MUO (by NCEP ATP III) was 2.2 (95% CI 1.2- 4.2) compared to MHO group. Using the IDF criteria, the relative risk of MI in MUO vs. MHO was 2.2 (95% CI 0.9–5.7) in men and 2.2 (95% CI: 0.9–5.7) in women. Conclusions In this study population, men aged 45–69 have more frequent progression from metabolically healthy to metabolically unhealthy obesity during 12 years compared to women. The 12-year risk of incident MI in subjects with MUO was approximately twice higher compared to MHO and the excess risk was similar in men and women. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): Wellcom Trust

Diabetes, Glycated Hemoglobin, and the Risk of Myocardial Infarction in Women and Men: A Prospective Cohort Study of the UK Biobank.

Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated hemoglobin (HbA1c) with the risk of MI. Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HRs) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years. Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with an increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2.33 [95% CI 1.96; 2.78]) than men (1.81 [1.63; 2.02]), with a women-to-men ratio of HRs of 1.29 (1.05; 1.58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men. Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men.

Sex-specific associations between cardiovascular risk factors and myocardial infarction in patients with type 2 diabetes: The ADVANCE-ON study.

To examine possible sex differences in the excess risk of myocardial infarction (MI) consequent to a range of conventional risk factors in a large-scale international cohort of patients with diabetes, and to quantify these potential differences both on the relative and absolute scales. Eleven thousand and sixty-five participants (42% women) with type 2 diabetes in the ADVANCE trial and its post-trial follow-up study, ADVANCE-ON, were included. Cox regression models were used to estimate hazard ratios (HRs) for associations between risk factors and MI (fatal and non-fatal) by sex, and the women-to-men ratio of HRs (RHR). Over a median of 9.6 years of follow-up, 719 patients experienced MI. Smoking status, smoking intensity, higher systolic blood pressure (SBP), HbA1c, total and LDL cholesterol, duration of diabetes, triglycerides, body mass index (BMI) and lower HDL cholesterol were associated with an increased risk of MI in both sexes. Furthermore, some variables were associated with a greater relative risk of MI in women than men: RHRs were 1.75 (95% CI: 1.05-2.91) for current smoking, 1.53 (1.00-2.32) for former smoking, 1.18 (1.02-1.37) for SBP, and 1.13 (95% CI, 1.003-1.26) for duration of diabetes. Although incidence rates of MI were higher in men (9.3 per 1000 person-years) compared with women (5.8 per 1000 person-years), rate differences associated with risk factors were greater in women than men, except for HDL cholesterol and BMI. In patients with type 2 diabetes, smoking, higher SBP and longer duration of diabetes had a greater relative and absolute effect in women than men, highlighting the importance of routine sex-specific approaches and early interventions in women with diabetes.

The Roles of Lipoprotein in Psoriasis.

The association between psoriasis and cardiovascular disease risk has been supported by recent epidemiological data. Patients with psoriasis have an increased adjusted relative risk for myocardial infarction. As such, the cardiovascular risk conferred by severe psoriasis may be comparable to what is seen with other well-established risk factors, such as diabetes mellitus. Previous studies demonstrated that low-density lipoprotein (LDL) plays critical roles during atherogenesis. It may be caused by the accumulation of macrophages and lipoprotein in the vessel wall. Oxidized LDL (ox-LDL) stimulates the expression of adhesion molecules, such as ICAM-1 and VCAM-1, on endothelial cells and increases the attachment of mononuclear cells and the endothelium. Even though previous evidence demonstrated that psoriasis patients have tortuous and dilated blood vessels in the dermis, which results in the leakage of ox-LDL, the leaked ox-LDL may increase the expression of adhesion molecules and cytokines, and disturb the static balance of osmosis. Therefore, exploration of the relationship between hyperlipidemia and psoriasis may be another novel treatment option for psoriasis and may represent the most promising strategy.

Direct Anticoagulants and Risk of Myocardial Infarction, a Multiple Treatment Network Meta-Analysis.

We assessed the cardiovascular safety of long-term direct-acting oral anticoagulant (DOAC) treatment. A search of the medical literature was performed from inception until May 31, 2019. Inclusion criteria were (1) randomized trial that assessed the clinical efficacy and/or safety of 1 or more DOAC, (2) control group including oral anticoagulation and/or antiplatelet and/or placebo treatment, and (3) the incidence of acute coronary syndrome during follow-up was reported. Fixed-effect and random-effects models were applied. The analyzed outcomes were myocardial infarction (MI), major bleeding, and mortality. Twenty-eight randomized clinical trials (196 761 patients) were included. Rivaroxaban was associated with a 21% reduction in the relative risk of MI when compared to placebo (relative risk [RR]: 0.79 [95% credible interval, CrI: 0.65-0.94]) and a 31% reduction (RR: 0.70 [95% CrI: 0.53-0.89]) when compared to dabigatran. Apixaban resulted in 24% (RR: 0.76 [95% CrI: 0.58-0.99]) and vitamin K antagonists anticoagulation resulted in 19% (RR: 0.81 [95% CrI: 0.65-0.98]) risk reduction compared to dabigatran. The computed probability of being the first best choice of treatment was 61.8% for rivaroxaban. Cardiovascular safety shows considerable heterogeneity among oral anticoagulants. Treatment with rivaroxaban is associated with reduced rate of MI.

Cardiovascular Adverse Events Associated With BRAF and MEK Inhibitors

Cardiovascular adverse events (CVAEs) after treatment with BRAF and MEK inhibitors in patients with melanoma remain incompletely characterized. To determine the association of BRAF and MEK inhibitor treatment with CVAEs in patients with melanoma compared with BRAF inhibitor monotherapy. PubMed, Cochrane, and Web of Science were systematically searched for keywords vemurafenib, dabrafenib, encorafenib, trametinib, binimetinib, and cobinimetinib from database inception through November 30, 2018. Randomized clinical trials reporting on CVAEs in patients with melanoma being treated with BRAF and MEK inhibitors compared with patients with melanoma being treated with BRAF inhibitor monotherapy were selected. Data assessment followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. Pooled relative risks (RRs) and 95% CIs were determined using random-effects and fixed-effects analyses. Subgroup analyses were conducted to assess study-level characteristics associated with CVAEs. The selected end points were pulmonary embolism, a decrease in left ventricular ejection fraction, arterial hypertension, myocardial infarction, atrial fibrillation, and QTc interval prolongation. All-grade and high-grade (≥3) CVAEs were recorded. Overall, 5 randomized clinical trials including 2317 patients with melanoma were selected. Treatment with BRAF and MEK inhibitors was associated with an increased risk of pulmonary embolism (RR, 4.36; 95% CI, 1.23-15.44; P = .02), a decrease in left ventricular ejection fraction (RR, 3.72; 95% CI, 1.74-7.94; P < .001), and arterial hypertension (RR, 1.49; 95% CI, 1.12-1.97; P = .005) compared with BRAF inhibitor monotherapy. The RRs for myocardial infarction, atrial fibrillation, and QTc prolongation were similar between the groups. These results were consistent when assessing high-grade CVAEs (left ventricular ejection fraction: RR, 2.79; 95% CI, 1.36-5.73; P = .005; I2 = 29%; high-grade arterial hypertension: RR, 1.54; 95% CI, 1.14-2.08; P = .005; I2 = 0%), but RRs for high-grade pulmonary embolism were similar between groups. A higher risk of a decrease in left ventricular ejection fraction was associated with patients with a mean age younger than 55 years (RR, 26.50; 95% CI, 3.58-196.10; P = .001), and the associated risk of pulmonary embolism was higher for patients with a mean follow-up time longer than 15 months (RR, 7.70; 95% CI, 1.40-42.12; P = .02). Therapy with BRAF and MEK inhibitors was associated with a higher risk of CVAEs compared with BRAF inhibitor monotherapy. The findings may help to balance between beneficial melanoma treatment and cardiovascular morbidity and mortality.

1269-P: Assessing the Performance of the UKPDS 82 Risk Equations to Predict Cardiovascular Events in the DECLARE-TIMI 58 Trial Population

Risk equations (RE) from the UK Prospective Diabetes Study (UKPDS) remain the most commonly used within economic models of type 2 diabetes mellitus (T2DM). However, clinical practice has evolved since UKPDS reported and the applicability of these RE to contemporary T2DM patients is uncertain. The Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial assessed cardiovascular (CV) outcomes in a broad T2DM population treated with dapagliflozin (DAPA) versus placebo (PLA). This study aimed to assess the performance of the UKPDS 82 RE in the DECLARE-TIMI 58 population. RE for myocardial infarction (MI), heart failure (HF) and stroke were applied to baseline characteristics and 12-month effects of DAPA versus PLA on HbA1c, weight and blood pressure from DECLARE-TIMI 58. Predicted annual probabilities were converted to event rates per 1,000-person years and associated relative risks (RR) for DAPA versus PLA derived for comparison to trial outcomes. Due to misalignment of the UKPDS and DECLARE-TIMI 58 endpoints, predictions of congestive heart failure were compared to observed incidence of hospitalization for HF and stroke to ischemic stroke, respectively. Predicted (study reported) rates per 1,000 person years for MI, HF and stroke were 8.15 (11.7), 2.47 (6.20) and 3.28 (6.90) for DAPA, and 8.53 (13.2), 2.59 (8.50) and 3.46 (6.80) for PLA. Predicted RR of MI, HF and stroke for DAPA versus PLA were 0.96, 0.95, 0.95, respectively, compared to reported hazard ratios of 0.89 (95% CI: 0.77, 1.01), 0.73 (0.61, 0.88) and 1.01 (0.84, 1.21) in DECLARE-TIMI 58. UKPDS 82 RE did not predict the reduction in CV events demonstrated for DAPA versus PLA based on risk factor improvements observed in DECLARE-TIMI 58. These findings add to a growing body of evidence that suggests the CV effects of sodium-glucose co-transporter inhibitors such as DAPA cannot be fully described via treatment-induced changes in conventional prognostic factors. Disclosure P. McEwan: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. V. Foos: Employee; Self; Health Economics and Outcomes Research Ltd., IQVIA. H. Bennett: Consultant; Self; AstraZeneca. Employee; Self; Health Economics and Outcomes Research Ltd. B. Kartman: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca. C. Edmonds: Employee; Self; AstraZeneca. I.A. Gause-Nilsson: Employee; Self; AstraZeneca. Funding AstraZeneca