Cumulative Incidence Of Myocardial Infarction Research Articles

Risk of Postoperative Ischemic Stroke and Myocardial Infarction in Patients Operated for Cancer.

Risk assessment for ischemic stroke (IS) and myocardial infarction (MI) is done routinely before surgery, but the increase in risks associated with surgery is not known. The aim of this study is to assess the risk of arterial ischemic events during the first year after oncological surgery. We used Swedish healthcare databases to identify 443,300 patients who underwent cancer surgery between 1987 and 2016 and 4,127,761 matched comparison subjects. We estimated odds ratios (ORs) for myocardial infarction and ischemic stroke during the hospitalization with logistic regression and calculated 1-year cumulative incidences and hazard ratios (HRs) with 95% confidence intervals (CIs) for the outcomes after discharge. The cumulative incidences of myocardial infarction and ischemic stroke during the first postoperative year were 1.33% and 1.25%, respectively. In the comparison cohort, the corresponding 1-year cumulative incidences were 1.04% and 1.00%. During the hospitalization, the OR for myocardial infarction was 8.81 (95% CI 8.24-9.42) and the OR for ischemic stroke was 6.71 (95% CI 6.22-7.23). After discharge, the average HR during follow-up for 365 days was 0.90 (95% CI 0.87-0.93) for myocardial infarction and 1.02 (95% CI 0.99-1.05) for ischemic stroke. We found an overall increased risk of IS and MI during the first year after cancer surgery that was attributable to events occurring during the hospitalization period. After discharge from the hospital, the overall risk of myocardial infarction was lower among the cancer surgery patients than among matched comparison subjects.

Impact of Hypomethylating Agents on Cardiovascular Disease Risk Among Patients with Myelodysplastic Syndromes

Introduction: The association between clonal hematopoiesis (CH) and cardiovascular disease (CVD) risk has drawn attention to cardiovascular outcomes in myelodysplastic syndromes (MDS). CVD accounts for 25% of deaths in MDS, potentially via CH-mediated accelerated atherosclerosis from inflammatory vascular responses. We previously demonstrated that MDS was independently associated with increased risk of CVD in older adults from SEER-Medicare. We subsequently hypothesized that treatment with hypomethylating agents (HMA) could reduce CVD risk by ameliorating CH clones and reducing the inflammation. In this study, we aimed to define the impact of HMA on incident cardiovascular events among older adults with MDS. Methods: We identified subjects ≥66 years diagnosed with MDS from 2007 to 2017 in SEER-Medicare. Exclusion criteria including lacking continuous Medicare parts A, B, and D, enrolled in HMO, or incomplete follow-up. Demographics included age, sex, race, rurality, socioeconomic quintile, marital status, and geographic region. Baseline CVD risk factors, defined from ICD-9/10 codes, included hypertension, hyperlipidemia, diabetes, atrial fibrillation, pre-existing cardiac disease, obesity, and smoking. MDS factors, defined using HCPCS codes, ICD-O-3 codes and prescription records, included MDS subtype and histologic risk stratification, transfusion dependence and treatment with hypomethylating agents (HMA), lenalidomide, or erythropoietin-stimulating agents (ESA) as time-varying variables. Incident CVD was defined as new myocardial infarction (MI) and/or ischemic stroke occurring after MDS diagnosis, using published ICD-9/10 algorithms. We controlled for confounding using 2 complementary analytic approaches. First, we assessed the association between HMA use and CVD using propensity score adjusted cause-specific competing risk Cox hazard models with death as competing risk, Second, we used a case-crossover design with conditional logistic regression, in which subjects with CVD served as their own controls, using a 3-month HMA treatment window and a control period 6 months prior to the incident event. Results: We identified a cohort of 15,227 eligible patients with MDS. Of these, 1,125 patients had an MI and/or ischemic stroke within 1 year before MDS diagnoses and were excluded. We analyzed 14,102 MDS patients, with median age 82 years (IQR 77 - 86), who were predominantly male (53.8%), non-Hispanic white (88.6%), and from urban/suburban areas (86.2%). MDS was of low, intermediate, and high histologic risk in 14.7%, 72.8%, and 12.5%, respectively, and 28.6% were transfusion dependent. Pre-existing CVD risk factors at time of MDS diagnosis were present in 12,538 patients, with baseline cardiovascular risk defined as low, intermediate, and high in 11.1%, 32.3%, and 56.6% of the cohort. The cumulative incidences of MI, ischemic stroke and composite CVD events were 11.3%, 10.6% and 20.4%, respectively. The propensity score (PS) conditional probability for being treated with HMA included demographic variables, CVD risk factors, MDS histology and transfusion dependence. Our PS model adequately predicted HMA treatment propensity (AUC 0.76). Cause-specific regression with death as competing risk, adjusted for PS and other MDS-specific treatments (ESA and lenalidomide), showed no significant effect of HMA on the risk of composite CVD events, MI, or ischemic stroke (Table 1). Conditional logistic regression in the case-crossover analysis of 1,907 patients with composite CVD events showed no significant effect of HMA. Results were similar for analysis of patients with MI and ischemic stroke (Table 2). Conclusions: No study has previously investigated the effect of HMA therapy on cardiovascular outcomes in patients with MDS. We demonstrate that HMA therapy is not associated with a significant risk reduction in cardiovascular events among patients with MDS patients from the SEER-Medicare database. These results show that HMA therapy is unlikely to reduce cardiovascular mortality and underscore the need for alternative therapeutic strategies targeting cardiovascular health patients with MDS.

Long-term cardiovascular events, graft failure, and mortality in kidney transplant recipients

BackgroundKidney transplant recipients are at increased risks of cardiovascular events, but contemporary risk estimates are sparse. Using the Danish nationwide administrative databases, we quantified 1- and 5-year risks of cardiovascular disease and kidney failure among all first-time kidney transplant recipients (2005-2018) and age- and sex-matched controls (1:10 ratio). MethodsCumulative 1- and 5-year incidence of cardiovascular events (myocardial infarction, stroke, or heart failure), kidney failure (re-transplantation or need for dialysis >30 days post-transplant), and mortality following transplantation were calculated until maximally Dec 31, 2018. ResultsA total of 2,565 kidney transplant recipients (median age 50.5 [25-75th percentile 40.2-60.7] years, 37 % females) and 25,650 controls were included. 1-year cumulative incidence of myocardial infarction, stroke, or heart failure was 2.6 % (95 % confidence interval 1.9 %-3.2 %) among kidney transplant recipients versus 0.5 % (0.4 %-0.5 %) in controls. Cumulative 5-year risk estimates for the same endpoints were 8.3 % (7.1 %-9.5 %) for the transplant patients, and 2.6 % (2.3 %-2.8 %) among controls, respectively. For the kidney transplant cohort, cumulative mortality was 2.2 % (1.7 %-2.8 %) and 10.3 % (9.0 %-11.6 %) at 1- and 5 years, respectively, versus 0.5 % (0.4 %-0.6 %) and 3.0 % (2.7 %-3.2 %) for controls. The cumulative incidence of dialysis and re-transplantation was 6.1 % (5.2 %-7.1 %) at 1 year and 16.3 % (14.7 %-17.9 %) at 5 years, respectively. ConclusionsDespite the benefits of transplantation, kidney transplant recipients continue to have significant long-term cardiovascular disease, end-stage kidney disease, and mortality risks even with contemporary medical management. Better cardiovascular preventive strategies are warranted to improve prognosis in this segment of patients.

Safety and cardiovascular effectiveness of olmesartan in combination therapy for advanced hypertension: an electronic health record-based cohort study.

Compared with placebo, olmesartan has been linked to numerical imbalances in cardiovascular mortality. There is a paucity of contemporary real-world evidence on this agent for different study populations. This study investigated the clinical outcomes of olmesartan and other antihypertensives in patients with advanced hypertension. This multicenter retrospective study used data from the Korea University Medical Center database, built from electronic health records. Patients prescribed at least two antihypertensive medications as a combined therapy were followed-up for 3 years. The primary outcome was a composite of all-cause mortality, myocardial infarction (MI), stroke, and hospitalization for heart failure. Adjusted outcomes were compared using propensity score (PS) matching. Among 24 806 patients, 4050 (16.3%) were olmesartan users between January 2017 and December 2018. The average patient age was 64 years, 45% were women, and 41% had diabetes. Olmesartan users were younger and less likely to have diabetes mellitus or chronic kidney disease. In PS-matched cohort, the 3-year cumulative incidences of the primary outcome were similar between the two groups (P = 0.91). The cumulative incidence of MI at 3 years was 1.4% in olmesartan users (4.8 per 1000 person-years) and 1.5% in active comparators (5.2 per 1000 person-years; P = 0.74). Olmesartan also showed similar safety profiles, including acute kidney injury and newly started dialysis. In real-world practice, olmesartan use in combination therapy resulted in similar cardiovascular outcomes when compared with those of active comparators, and our findings did not show any conclusive evidence that olmesartan is harmful in patients with hypertension.

Outcomes and Readmission in Patients With Retinal Artery Occlusion (from the Nationwide Readmission Database)

Retinal artery occlusion (RAO) is an ophthalmologic emergency, leading to sudden vision loss. Understanding its risk factors and garnering information on the incidence of adverse events can provide helpful information on the cost-effective evaluation of patients and secondary prevention. In this retrospective cohort study, we used the Nationwide Readmission Database from 2016 to 2018 and queried the database to identify patients with RAO. The clinical outcomes were cumulative incidence of myocardial infarction (MI), stroke, death (in-hospital and 6 months after discharge), resource utilization, all-cause readmission at 6 months, and reasons for all-cause readmission. We identified a total of 14,527 patients with RAO. The mean age of patients with RAO was 69 ± 13 years. Hypertension (11,839, 82%), hyperlipidemia (8,868, 61%), ischemic cardiomyopathy (4,826, 33%), smoking (4,772, 33%), and diabetes (4,588, 32%) were common co-morbidities in patients with RAO. Of 14,527 patients with RAO, 308 patients (2.1%) died, 1,577 (10.9%) developed stroke, and 615 (4.2%) developed MI within 6 months. A total of 2,841 patients (24.9%) were readmitted within 6 months of discharge. Carotid artery stenosis (386, 10.8%) was the most common cause of readmission. History of stroke or transient ischemic attack and Elixhauser co-morbidity index ≥3 were predictors of stroke. Female gender, ischemic cardiomyopathy, carotid artery disease, heart failure, chronic kidney disease, and cancer were predictors of MI. Cancer, chronic kidney disease, Elixhauser co-morbidity index ≥3, Medicare/Medicaid payer status, nonelective index admission, atrial fibrillation, and carotid artery disease were predictors of 6-month all-cause readmission. In conclusion, patients with RAO have a significant burden of co-morbidities, death, stroke, MI, and readmission. RAO may be used as a clinical marker of future stroke and MI, and should trigger screening for acute vascular ischemic events.

Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer: A Nationwide Registry-Based Study

BackgroundMyocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction. ObjectivesThe aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio). MethodsPatients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed. ResultsA total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant (P > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95; P < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84; P = 0.022). ConclusionsDespite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population.

Incidence of myocardial infarction, heart failure, and cardiovascular mortality in patients with peripheral artery disease: nationwide trends between 1997 and 2016

Abstract Background Over the past decades there has been a shift in cardiovascular (CV) risk factors with improved outcomes. Updated trends in incidence of myocardial infarction (MI) and heart failure (HF) in peripheral artery disease (PAD) are warranted. Purpose We aimed to investigate trends in the incidence of MI, HF, and CV mortality in PAD patients during the past two decades. Methods Nationwide registers were used to identify all patients aged ≥18 years, with first-time diagnosis of PAD between 1997 and 2016. Age-standardized incidence rates per 1,000 person-years (IR) were calculated to estimate trends of MI, HF, and CV mortality. Furthermore, risk of MI, HF, and CV mortality was estimated by 1-year cumulative-incidence with death as competing risk. Results A total of 136,746 patients with first-time diagnosis of PAD were included. Mean age was 70.01 [IQR 61–77 years], and 53.05% of the identified patients were male. The 1-year cumulative-incidence of MI in patients with PAD were 1.88% for year 1997–2000, 2.12% for year 2001–2005, 1.59% for year 2006–2010, and 1.32% for year 2011–2016, respectively. The 1-year cumulative-incidence of HF in patients with PAD were 1.71%, 1.48%, 1.25%, and 1.11% for the 1997–2000, 2001–2005, 2006–2010, and 2011–2016 year-groups, respectively. Furthermore the 1-year cumulative-incidence of CV mortality in patients with PAD were 12.0%, 9.41%, 8.75%, and 7.80% for the 1997–2000, 2001–2005, 2006–2010, and 2011–2016 year-groups, respectively. Likewise, the age-standardized incidence rates pr. 1,000 person-years showed increasing trends of MI up until 2002 with an estimated annual percent change (APC) of +0.6 (95% CI 3.3–16.1, p-value 0.2). After year 2002 the IR decreased significantly with an estimated APC of −5.0 (95% CI 3.7–6.3, p&amp;lt;0.0001). The age-standardized IR for HF decreased with an estimated APC of −3.3 (95% CI 2.0–4.6, p&amp;lt;0.0001), and similarly for CV death decreased by −3.5 (95% CI 3.0–4.0, p&amp;lt;0.0001). Conclusion The incidence of MI and HF in patients with PAD has significantly decreased over time together with a subsequent decline in CV mortality. This may suggest that the improvements in preventive strategies aimed at reducing CV risk are effective and contributes to lower incidence of MI and HF and thereby improved mortality rates in the past two decades. Funding Acknowledgement Type of funding sources: None.

Very long-term outcomes of older adults with stable coronary artery disease (from the CORONOR study).

There are limited data on stable coronary artery disease (CAD) in the very elderly. The present study aimed to investigate incident cardiovascular events and mortality in older adults (≥85 years) included in a multicenter registry on stable CAD. A long-term follow-up was performed in 198 patients ≥85 years with stable CAD, free from myocardial infarction (MI) or coronary revascularization within the year. The median age was 87 years. Clinical events during the follow-up period [death, MI, ischemic stroke, coronary revascularization and hospitalization for heart failure (HF)] were centrally adjudicated. There were 164 deaths during follow-up. The cumulative risk of all-cause death was 9.1% at 1 year, 53.9% at 5 years and 85.5% at 10 years. The cause of death was adjudicated as cardiovascular in 64 patients with death from HF in 36 patients. Male gender, previous hospitalization for HF and an estimated glomerular filtration rate <60 ml/min/1.73 m2 were independently associated with all-cause death. Ten-year cumulative incidences of MI, ischemic stroke and coronary revascularization were low (6.6, 7.7 and 6.6%, respectively). By contrast, the 10-year cumulative incidence of hospitalization for HF was high (27.8%). The 10-year mortality of elderly patients with stable CAD is very high. While ischemic events are relatively unfrequent, HF events are frequent and represent the most common cause of cardiovascular death in this population. Prevention and management of HF are important goals for physicians in charge of older adults with stable CAD.

Association between sepsis survivorship and long-term cardiovascular outcomes in adults: a systematic review and meta-analysis.

We aimed to determine the association between sepsis and long-term cardiovascular events. We conducted a systematic review of observational studies evaluating post-sepsis cardiovascular outcomes in adult sepsis survivors. MEDLINE, Embase, and the Cochrane Controlled Trials Register and Database of Systematic Reviews were searched from inception until April 21st, 2021. Two reviewers independently extracted individual study data and evaluated risk of bias. Random-effects models estimated the pooled crude cumulative incidence and adjusted hazard ratios (aHRs) of cardiovascular events compared to either non-septic hospital survivors or population controls. Primary outcomes included myocardial infarction, stroke, and congestive heart failure; outcomes were analysed at maximum reported follow-up (from 30days to beyond 5years post-discharge). Of 12,649 screened citations, 27 studies (25 cohort studies, 2 case-crossover studies) were included with a median of 4,289 (IQR 502-68,125) sepsis survivors and 18,399 (IQR 4,028-83,506) controls per study. The pooled cumulative incidence of myocardial infarction, stroke, and heart failure in sepsis survivors ranged from 3 to 9% at longest reported follow-up. Sepsis was associated with a higher long-term risk of myocardial infarction (aHR 1.77 [95% CI 1.26 to 2.48]; low certainty), stroke (aHR 1.67 [95% CI 1.37 to 2.05]; low certainty), and congestive heart failure (aHR 1.65 [95% CI 1.46 to 1.86]; very low certainty) compared to non-sepsis controls. Surviving sepsis may be associated with a long-term, excess hazard of late cardiovascular events which may persist for at least 5years following hospital discharge.

Application of the Modified High Bleeding Risk Criteria for Japanese Patients in an All-Comers Registry of Percutaneous Coronary Intervention - From the CREDO-Kyoto Registry Cohort-3.

The prevalence of and expected bleeding event rate in patients with the Japanese version of high bleeding risk (J-HBR) criteria are currently unknown in real-world percutaneous coronary intervention (PCI) practice.Methods and Results:We applied the J-HBR criteria in the multicenter CREDO-Kyoto registry cohort-3 that enrolled 13,258 consecutive patients who underwent first PCI. The J-HBR criteria included Japanese-specific major criteria such as heart failure, low body weight, peripheral artery disease and frailty in addition to the Academic Research Consortium (ARC)-HBR criteria. There were 8,496 patients with J-HBR, and 4,762 patients without J-HBR. The J-HBR criteria identified a greater proportion of patients with HBR than did ARC-HBR (64% and 48%, respectively). Cumulative incidence of the Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding was significantly higher in the J-HBR group than in the no-HBR group (14.0% vs. 4.1% at 1 year; 23.1% vs. 8.4% at 5 years, P<0.0001). Cumulative 5-year incidence of BARC 3/5 bleeding was 25.1% in patients with ARC-HBR, and 23.1% in patients with J-HBR. Cumulative incidence of myocardial infarction or ischemic stroke was also significantly higher in the J-HBR group than in the no-HBR group (6.9% vs. 3.6% at 1 year; 13.2% vs. 7.1% at 5 years, P<0.0001). The J-HBR criteria successfully identified those patients with very high bleeding risk after PCI, who represented 64% of patients in this all-comers registry.

Long-term outcomes after myocardial infarction in middle-aged and older patients with congenital heart disease-a nationwide study.

Aims We aimed to describe the risk of myocardial infarction (MI) in middle-aged and older patients with congenital heart disease (ACHD) and to evaluate the long-term outcomes after index MI in patients with ACHD compared with controls. Methods and results A search of the Swedish National Patient Register identified 17 189 patients with ACHD (52.2% male) and 180 131 age- and sex-matched controls randomly selected from the general population who were born from 1930 to 1970 and were alive at 40 years of age; all followed up until December 2017 (mean follow-up 23.2 ± 11.0 years). Patients with ACHD had a 1.6-fold higher risk of MI compared with controls [hazard ratio (HR) 1.6, 95% confidence interval (CI) 1.5–1.7, P < 0.001] and the cumulative incidence of MI by 65 years of age was 7.4% in patients with ACHD vs. 4.4% in controls. Patients with ACHD had a 1.4-fold increased risk of experiencing a composite event after the index MI compared with controls (HR 1.4, 95% CI 1.3–1.6, P < 0.001), driven largely by the occurrence of new-onset heart failure in 42.2% (n = 537) of patients with ACHD vs. 29.5% (n = 2526) of controls.Conclusion Patients with ACHD had an increased risk of developing MI and of recurrent MI, new-onset heart failure, or death after the index MI, compared with controls, mainly because of a higher incidence of newly diagnosed heart failure in patients with ACHD. Recognizing and managing the modifiable cardiovascular risk factors should be of importance to reduce morbidity and mortality in patients with ACHD.

Improved long-term survival with coronary artery bypass graft surgery compared to percutaneous coronary intervention in diabetics with multivessel disease

Abstract Background While randomized clinical trials have demonstrated the superiority of coronary artery bypass grafting (CABG) over percutaneous coronary intervention (PCI) in patients with diabetes and multivessel coronary artery disease (CAD), there remains a paucity of observational evidence comparing these two modalities. Methods Clinical and administrative databases for Canada's most populous province, Ontario, were linked to obtain records of all patients with angiographic evidence of multivessel CAD (defined as: 2-vessel and 3-vessel disease) treated with either isolated CABG or PCI from October 2008 to March 2017. Left main disease was excluded in the primary analysis. Baseline characteristics of patients undergoing CABG and PCI were compared and 1:1 propensity score matching was performed to account for baseline differences. 30-day mortality was compared in the matched groups. Late mortality and the composite of major cardiovascular and cerebrovascular events (MACCE, consisting of stroke, myocardial infarction (MI), repeat revascularization, and death) were compared between the matched groups using a stratified log rank test and Cox-proportional hazards model. The individual non-fatal components of MACCE were compared using the Fine-Gray model that accounted for death as a competing risk. A secondary analysis that included patients with left main disease was also performed for the outcome of late mortality. A sensitivity analysis that excluded patients with acute coronary syndrome was also conducted for late mortality. Results A total of 9,395 and 4,016 patients underwent CABG and PCI respectively. Prior to matching, CABG patients were younger (65.7 vs 68.5 years, p&amp;lt;0.001), more likely male (78% vs 73%, p&amp;lt;0.001) and with more severe CAD. Propensity score matching based on 24 baseline covariates yielded 3,782 well-balanced pairs. There was no difference in early mortality between CABG and PCI (2.3% vs 2.5%, p=0.65). The rate of all-cause mortality over 8-years was significantly higher with PCI compared to CABG (Figure- HR: 1.35, 95% CI: 1.23–1.50). The cumulative incidence of MI (HR 1.91, 95% CI: 1.66–2.20) and need for repeat revascularization (HR: 4.06, 95% CI: 3.54–4.66) were significantly higher with PCI over 8 years. There was no difference in late stroke between PCI and CABG (stroke (HR: 0.85, 95% CI: 0.68–1.07). Overall MACCE was higher in PCI compared to CABG (HR: 1.94, 95% CI: 1.80–2.09). In our secondary analysis that included patients with left main disease, findings were robust and late mortality remained higher with PCI compared to CABG (HR: 1.42, 95% CI: 1.30–1.54). In a sensitivity analysis where patients with acute coronary syndrome at the time of presentation were excluded, late mortality remained higher with PCI (HR: 1.30, 95% CI: 1.12–1.49) in 2,028 matched pairs. Conclusions In patients with multivessel CAD and diabetes we observed improved long-term mortality and freedom from MACCE at 8-years with CABG compared to PCI. Figure 1 Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Canadian Institutes of Health Research

Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease

Abstract Background Diabetes is considered a risk factor for myocardial infarction (MI). However, we have previously found that diabetes was not a short-term risk factor for MI in the absence of obstructive coronary artery disease (CAD). Purpose As long-term data are not available, we aimed to assess adverse cardiac events in patients with and without diabetes stratified by CAD up to 11 years after coronary angiography. Methods We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to the presence/absence of CAD and diabetes. Outcomes included MI, cardiac death, all-cause death, and coronary revascularization. Results A total of 86,202 patients were included (diabetes: n=12,652). Median follow-up was 8.8 years. Using patients with neither CAD nor diabetes as reference (cumulative MI incidence 2.6%), the risk of MI was similar for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% CI: 0.996–1.451), was increased for patients with CAD alone (9.3%; hazard ratio 2.75, 95% CI: 2.52–3.01), and was highest for patients with both CAD and diabetes (12.3%; hazard ratio 3.79, 95% CI: 3.43–4.20), see Figure. Similar associations were observed for cardiac death and coronary revascularization. Conclusions Diabetes patients without CAD by coronary angiography have a similar risk of MI compared to patients with neither CAD nor diabetes. In the presence of CAD, however, diabetes increases the risk of MI. Figure 1 Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): The Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark.

AHRR hypomethylation as an epigenetic marker of smoking history predicts risk of myocardial infarction in former smokers

Background and aimsSmoking causes cardiovascular disease. AHRR hypomethylation at the cg05575921 site is associated with active and former smoking status at baseline, and cumulative amount of tobacco smoked. We tested the hypothesis that AHRR cg05575921 hypomethylation as an epigenetic marker of smoking history predicts the risk of myocardial infarction in former smokers. MethodsWe included 10,510 individuals with methylation extent measurements and information on smoking status from the Copenhagen City Heart Study (CCHS), a prospective, cohort study of the general population carried out from 1991 to 2003. The endpoint myocardial infarction was retrieved from the national Danish Patient Registry and the national Danish Causes of Death Registry. ResultsFor individuals in the 1st (lowest) quartile of AHRR cg05575921 methylation (≤49% methylation extent), 99% were ever smokers at baseline (active and former smokers combined) compared to 42% in the 4th (highest) quartile (>62% methylation extent). For former smokers, the cumulative incidence of myocardial infarction was higher in the lowest methylation extent (1st-50th percentile) compared to the highest methylation extent (51st-100th percentile). Compared to never smokers, the multivariable adjusted subhazard ratio for myocardial infarction was 1.09 (95%CI:0.88–1.35) for former smokers with the highest methylation degree, 1.38 (1.06–1.80) for active smokers with the highest methylation extent, 1.39 (1.08–1.78) for former smokers with the lowest methylation extent, and 1.61 (1.35–1.92) for active smokers with the lowest methylation extent. ConclusionsAHRR cg05575921 hypomethylation as an epigenetic marker of smoking history predicts risk of myocardial infarction, particularly in former smokers. Further, AHRR hypomethylation, regardless of smoking status, was associated with increased risk of myocardial infarction.

Risk of Myocardial Infarction in Patients Without Angiographic Coronary Artery Disease Compared With the General Population

We examined the 10-year risk of myocardial infarction (MI) and death in patients without obstructive coronary artery disease (CAD) compared with the general population. We conducted a cohort study of every patient without obstructive CAD by coronary angiography (CAG) between 2003 and 2016 in Western Denmark. Patients were matched by gender and age with individuals from the general population of Western Denmark with no history of CAD. End points were MI and death. Ten-year risk differences in cumulative incidence proportions were computed, accounting for the competing risk of death in the case of MI. Unadjusted and adjusted incidence rate ratios (aIRRs) were estimated using conditional Poisson regression. We included 46,467 patients and 234,654 individuals from the general population. Median follow-up was 7.7 years. The 10-year cumulative incidence of MI was 2.40% (95% confidence interval [CI] 2.24 to 2.57) in patients without obstructive CAD in the CAG and 2.70% (95% CI 2.62 to 2.78) in the general population, with a reduced absolute 10-year risk (risk difference -0.30%, 95% CI -0.49 to -0.12) and a reduced aIRR (aIRR 0.70, 95% CI 0.63 to 0.77). Ten-year mortality was higher in patients without obstructive CAD in the CAG (21.44%, 95% CI 20.99 to 21.89) compared with the general population (17.25%, 95% CI 17.06 to 17.44). However, mortality rates were similar after adjustment (aIRR 1.00, 95% CI 0.96 to 1.02). In conclusion, the absence of obstructive CAD according to CAG is associated with a lower risk of MI than in the general population, and similar 10-year mortality.

Diabetes is not a risk factor for myocardial infarction in patients without coronary artery disease: A study from the Western Denmark Heart Registry.

Background:Diabetes is considered a risk factor for myocardial infarction. However, we have previously found that diabetes was not a short-term risk factor for myocardial infarction in the absence of obstructive coronary artery disease.Methods:We conducted a cohort study of patients undergoing coronary angiography from 2003 to 2012 and followed them by cross-linking Danish health registries. Patients were stratified according to coronary artery disease and diabetes. Endpoints included myocardial infarction, cardiac death, all-cause death and coronary revascularization.Results:86,202 patients were included in total (diabetes: n = 12,652). Median follow-up was 8.8 years. Using patients with neither coronary artery disease nor diabetes as reference (cumulative myocardial infarction incidence 2.6%), the risk of myocardial infarction was low and not substantially increased for patients with diabetes alone (3.2%; hazard ratio 1.202, 95% confidence interval 0.996−1.451), was increased for patients with coronary artery disease alone (9.3%; hazard ratio 2.75, 95% confidence interval 2.52−3.01) and was highest for patients with both coronary artery disease and diabetes (12.3%; hazard ratio 3.79, 95% confidence interval 3.43−4.20). Similar associations were observed for cardiac death and coronary revascularization.Conclusion:Diabetes patients without coronary artery disease by coronary angiography have a low risk of myocardial infarction, not substantially increased compared to patients with neither coronary artery disease nor diabetes. In the presence of coronary artery disease, however, diabetes increases the risk of myocardial infarction.

Impact of rheumatoid arthritis on major cardiovascular events in patients with and without coronary artery disease

IntroductionRheumatoid arthritis (RA) is a risk factor for cardiovascular disease. The clinical consequences of coincident RA and coronary artery disease (CAD) are unknown.ObjectiveWe aimed to estimate the impact of RA...

Long-Term Outcomes and Associations With Major Adverse Limb Events After Peripheral Artery Revascularization

BackgroundLong-term cardiovascular and limb outcomes after revascularization for peripheral artery disease and, in particular, prognosis after post-procedure major adverse limb events (MALE) are not well-studied. ObjectivesThis study sought to describe outcomes after peripheral revascularization and assess relationships between post-procedure MALE hospitalization and subsequent events. MethodsPatients undergoing peripheral artery revascularization between January 1, 2009, and September 30, 2015, in the Premier Healthcare Database were examined for the co-primary outcomes of interest, composite myocardial infarction (MI) or stroke and composite major amputation or peripheral revascularization. Multivariable adjusted Cox proportional hazards models with post-procedure MALE hospitalization included as a time-dependent covariate were developed to estimate hazard ratios for outcomes. ResultsAmong 393,017 revascularized patients followed for a median of 2.7 years (interquartile range: 1.3 to 4.4 years), the cumulative incidence of MI or stroke was 9.8% and that of major amputation or peripheral revascularization was 41.9%. A total of 50,750 patients (12.9%) had at least 1 post-procedure MALE hospitalization. In time-dependent covariate adjusted models, post-procedure MALE hospitalization was associated with greater risk of subsequent MI or stroke (hazard ratio: 1.34; 95% confidence interval: 1.28 to 1.40) and major amputation or peripheral revascularization (hazard ratio: 8.13; 95% confidence interval: 7.96 to 8.29). After peripheral revascularization with or without post-procedure MALE hospitalization, risk of limb events increased rapidly post-procedure and more slowly after the first year, whereas cardiac risk increased steadily during follow-up. ConclusionsRevascularized peripheral artery disease patients face earlier limb and later cardiovascular ischemic risk that is heightened among patients with post-procedure MALE hospitalization. Increased provider awareness of these long-term risks may guide efforts to improve post-procedural outcomes.

259Higher risk of myocardial infarction in the first year following 5-fluorouracil treatment

Abstract Abstract Background 5-fluorouracil (5-FU) is the third most commonly used chemotherapeutic agent in the treatment of solid malignancies across the world. The most common manifestation of cardiotoxicity associated with 5-FU is chest pain, presenting as atypical chest pain, angina on exertion or rest and acute coronary syndromes including myocardial infarction and in worse case even death. Nevertheless, a widespread appreciation of 5-FU related cardiotoxicity including myocardial infarction is poorly understood. Purpose This study aims to examine risk of myocardial infarction in patients treated with 5-FU compared to age- and sex-matched population controls. Methods and results Methods: Individuals treated with 5-FU between 2004 and 2014 in the Danish National Patient Register were identified and risk set matching was used to find background population controls matched on age and sex in a 1:5 ratio. Furthermore, two years follow-up time were added with total 13 years. Neither 5-FU patients nor controls had prior ischemic disease. Aalen-Johansen and Kaplan-Meier estimates were used to report the cumulative incidence of myocardial infarction and all-cause mortality, respectively. A multivariable Shared Frailty Cox regression analysis (adjusted for patient age, sex, hypertension, hypercholesterolemia, diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation as well as selected anti-anginal medications including nitrates, beta- and calcium-blockers) was used to determine the association between 5-FU treatment and the one-year risk of myocardial infarction. Results A total of 9,012 5-FU patients and 45,060 controls formed the study population. Differences in comorbid conditions (diabetes, chronic obstructive pulmonary disease, chronic kidney disease, heart failure and atrial fibrillation) and selected anti-anginal medications (nitrates, beta- and calcium-blockers) were non-significant (all P&gt;0.05). The one-year cumulative incidence of myocardial infarction is significantly higher for 5-FU patients at 0.8% versus 0.6% among population controls (Figure 1A), with a competing risk of death of 25.1% versus 1.2%. The risk diminishes beyond one year and becomes lower for 5-FU patients with time (Figure 1A), along with an increasing all-cause mortality (Figure 1B). The unadjusted and adjusted hazard ratio for the one-year risk of myocardial infarction were 1.38 [95% CI 1.07–1.78] and 1.54 [95% CI 1.19–1.99]. Conclusions Although the one-year risk of myocardial infarction is higher among 5-FU patients compared with population controls, the absolute risk is small and becomes insignificant beyond one year of follow-up.

462Impact of severe anemia (hemoglobin &lt;10 g/dl) in the ischemic-bleeding profile during treatment with dual antiplatelet therapy after hospital discharge for acute coronary syndrome

Abstract Introduction Anemia is strongly associated with increased risk of morbidity and mortality in patients after acute coronary syndromes (ACS). The aim of our study was to determine, after matching the baseline characteristics, the bleeding-ischemic risk profile during treatment with Dual Antiplatelet Therapy (DAPT) of patients with severe anemia (hemoglobin &lt;10 g/dL) after an ACS undergoing Percutaneous Coronary Intervention (PCI). Methods The data analyzed in this study were obtained from the fusion of 3 clinical registries of ACS patients: BleeMACS (2004–2013), CardioCHUVI/ARRITXACA (2010–2016) and RENAMI (2013–2016). All 3 registries include consecutive patients discharged after an ACS with DAPT and undergoing PCI. The merged data set contain 26,076 patients. A propensity-matched analysis was performed to match the baseline characteristics of patients according to presence or not of severe anemia (hemoglobin &lt;10 g/dL). The impact of severe anemia in the ischemic and bleeding risk was assessed by a competitive risk analysis, using a Fine and Gray regression model, with death being the competitive event. For ischemic risk we have considered a new acute myocardial infarction, whereas for bleeding risk we have considered major bleeding defined as bleeding requiring hospital admission. Follow-up time was censored by DAPT suspension/withdrawal. Results From the 26,076 ACS patients, 630 had severe anemia (2.4%). During a mean follow-up of 12.2±4.8 months, 964 patients died (3.7%), 640 had myocardial infarction (2.5%) and 685 had major bleeding (2.6%). After propensity-score matching, we obtained two matched groups (with hemoglobin &lt; and ≥10 g/dL) of 621 patients. In comparison with patients without severe anemia, patients with hemoglobin &lt;10 g/dL had similar risk of myocardial infarction (sHR 1.37, 95% CI 0.82–2.31, p=0.231) with higher risk of major bleeding (sHR 1.89, 95% CI 1.18–2.72, p=0.006). After propensity score matching, the cumulative incidence of myocardial infarction was 6 and 5 per 100 patients/year in patients with and without severe anemia, respectively, during DAPT. And the cumulative incidence of major bleeding was 12 and 6 per 100 patients/year in patients with and without severe anemia, respectively. The difference between myocardial infarction rate and major bleeding rate was −6 in patients with severe anemia (more bleeding than ischemic event rates; p&lt;0.05) and −1 in patients with hemoglobin ≥10 g/dL (similar bleeding and ischemic event rates; p&gt;0.05), per 100 patient-years (Figure). Conclusions After an ACS underwent PCI, during DAPT, the ischemic-bleeding balance of patients with severe anemia (hemoglobin &lt;10 g/dL) is not favorable. In those patients, a short-term DAPT (&lt;6 months) should be recommended.