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Importance: Family caregiving after critical illness has been associated with several adverse health outcomes, including various aspects of mental health, but research focusing specifically on family members of stroke survivors is limited., Objectives: To examine the associations of stroke in a partner or parent with the risk of depression, substance use disorders, anxiety disorders, and self-harm or suicide., Design, Setting, and Participants: This nationwide, population-based cohort study used data from Danish nationwide administrative and clinical registries (2004-2021). Participants included partners and adult children of survivors of stroke. Data analysis was performed from March to December 2023., Exposure: Having a partner or parent who survived stroke., Main Outcomes and Measures: The Aalen-Johansen estimator was used to compute propensity score-weighted 3-year absolute risks, risk differences, and risk ratios for depression, substance use disorders, anxiety disorders, and self-harm or suicide among partners or children of survivors of stroke compared with partners or children of survivors of myocardial infarction (MI) and matched individuals from the general population., Results: The study included a total of 1 923 732 individuals: 70 917 partners of stroke survivors (median [IQR] age, 68 [59-76] years; 46 369 women [65%]), 70 664 partners of MI survivors (median [IQR] age, 65 [55-73] years; 51 849 women [73%]), 354 570 partners of individuals from the general population (median [IQR] age, 68 [59-76] years; 231 833 women [65%]), 207 386 adult children of stroke survivors (median [IQR] age, 45 [36-52] years; 99 382 women [48%]), 183 309 adult children of MI survivors (median [IQR] age, 42 [33-49] years; 88 078 women [48%]), and 1 036 886 adult children of individuals from the general population (median [IQR] age, 45 [36-52] years; 496 875 women [48%]). Baseline characteristics were well balanced across cohorts after propensity score weighting. Among partners of stroke survivors, the 3-year absolute risk was 1.0% for depression, 0.7% for substance use disorders, 0.3% for anxiety disorders, and 0.04% for self-harm or suicide. Risk ratio point estimates for the assessed outcomes ranged from 1.14 to 1.42 compared with the general population and from 1.04 to 1.09 compared with partners of MI survivors. The elevated risk of depression in partners of stroke survivors was more pronounced after severe or moderate stroke than after mild stroke. Among adult children of stroke survivors, the 3-year absolute risk was 0.6% for depression, 0.6% for substance use disorders, 0.2% for anxiety disorders, and 0.05% for self-harm or suicide. Both absolute risks and risk ratios for adult children of stroke survivors were smaller than those reported in the partner analyses., Conclusions and Relevance: In this cohort study of partners and adult children of stroke survivors, risks of several mental health conditions and self-harm or suicide were moderately higher compared with the general population and, to a lesser extent, partners and adult children of MI survivors. These findings highlight the potential consequences of stroke among family members, particularly partners, and its findings may possibly serve as a quantitative foundation for the development of future stroke rehabilitation services.

Background and Objectives: Migraine and pregnancy-induced hypertension (PIH) are known to increase cardiovascular risk on their own. However, evidence is limited on the combined impact of migraine and PIH on risk of cardiovascular disease. The aim of this study was to examine the combined impact of migraine and PIH on risk of premature (age 60 years and younger) major adverse cardiovascular and cerebrovascular events (MACCE), a composite end point consisting of myocardial infarction, stroke, or death due to one of these diseases., Methods: We conducted a population-based cohort study in Denmark (1996-2018) among women who had delivered at least one child. This population was stratified into 4 cohorts: women with neither migraine nor PIH, women with migraine, women with PIH, and women with both migraine and PIH. As a measure of absolute risk, we computed the 20-year cumulative incidence of premature MACCE, treating death by other causes than myocardial infarction and stroke as a competing risk. We used Cox regression to compute 20-year adjusted hazard ratios (HRs) of premature MACCE. Women with neither migraine nor PIH served as the comparison cohort., Results: The 20-year absolute risk of premature MACCE was 1.3% (95% CI 1.2%; 1.3%) for women without migraine and without PIH (n = 1,288,541), 2.2% (95% CI 2.0%; 2.4%) for women with migraine (n = 54,827), 2.8% (95% CI 2.6%; 3.1%) for women with PIH (n = 49,008), and 3.1% (95% CI 2.1%; 4.4%) for women with both migraine and PIH (n = 3,140). The adjusted HR of premature MACCE was 1.66 (95% confidence interval [CI] 1.50-1.84) for women with migraine, 2.76 (95% CI 2.52-3.03) for women with PIH, and 2.41 (95% CI 1.61-3.61) for women with both migraine and PIH., Discussion: Migraine and PIH separately increased the risk of premature MACCE. The risk of premature MACCE among women who had both migraine and PIH was similar to that among women with PIH only.

Background: Women's reproductive health is associated with cardiovascular morbidity. However, an association of vaginal bleeding (VB) in pregnancy with diabetes and cardiovascular outcomes has scarcely been investigated., Methods: We conducted a population-based cohort study in Denmark (1994-2018). Using nationwide registries, among 903 327 women we identified 1 901 725 pregnancies: 39 265 ended in childbirth and were affected by VB; 1 389 285 ended in childbirth and were unaffected by VB; 333 785 ended in a termination, and 139 390 ended in a miscarriage. The outcomes were diabetes types 1 and 2, hypertension, ischaemic heart disease including myocardial infarction, atrial fibrillation or flutter, heart failure and ischaemic and haemorrhagic stroke. We computed incidence rates and hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for age, calendar year of pregnancy end, morbidities and reproductive and socioeconomic factors, using inverse probability of treatment-weighted Cox proportional hazards regression., Results: In analyses of VB-affected vs VB-unaffected pregnancies, aHRs were 1.15 (1.03-1.28) for diabetes type 1, 1.19 (1.13-1.26) for diabetes type 2, 1.19 (1.14-1.25) for hypertension, 1.26 (1.16-1.37) for ischaemic heart disease, 1.21 (1.03-1.42) for myocardial infarction, 1.32 (1.14-1.51) for atrial fibrillation or flutter and 1.23 (0.99-1.52) for heart failure. aHRs were 1.41 (1.26-1.57) and 1.46 (1.23-1.72) for ischaemic and haemorrhagic stroke, respectively. When contrasting VB-affected pregnancies with terminations, aHRs were up to 1.3-fold increased for diabetes and hypertension; however, when contrasting VB-affected pregnancies with miscarriages, estimates were below or close to the null value., Conclusions: Women's risks of diabetes and cardiovascular outcomes later in life were increased following VB-affected vs VB-unaffected pregnancy or termination, but not following VB-affected pregnancy vs miscarriage., (© The Author(s) 2023; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Objective: Non-steroidal anti-inflammatory drugs (NSAIDs) should be used cautiously in patients with type 2 diabetes. We examined whether the cardiovascular risks associated with NSAID use depended on HbA1c level in patients with type 2 diabetes., Methods: We conducted a population-based cohort study of all adult Danes with a first-time HbA1c measurement ≥48 mmol/mol during 2012-2020 (n = 103 308). We used information on sex, age, comorbidity burden, and drug use to calculate time-varying inverse probability of treatment weights. After applying these weights in a pooled logistic regression, we estimated hazard ratios (HRs) of the association between use of NSAIDs (ibuprofen, naproxen, or diclofenac) and cardiovascular events (a composite of myocardial infarction, ischemic stroke, congestive heart failure, atrial fibrillation or flutter, and all-cause death). We stratified all analyses by HbA1c level (<53 or ≥53 mmol/mol)., Results: For ibuprofen use, the HR of a cardiovascular event was 1.53 (95% confidence interval [CI]: 1.34-1.75) in patients with HbA1c <53 and 1.24 (95% CI: 1.00-1.53) in patients with HbA1c ≥53 mmol/mol. For naproxen use, the HR was 1.14 (95% CI: 0.59-2.21) in patients with HbA1c <53 and 1.30 (95% CI: 0.49-3.49) in patients with HbA1c ≥53 mmol/mol. For diclofenac use, the HR was 2.40 (95% CI: 1.62-3.56) in patients with HbA1c <53 and 2.89 (95% CI: 1.65-5.04) in patients with HbA1c ≥53 mmol/mol., Conclusions: In patients with type 2 diabetes, glycemic dysregulation did not affect the cardiovascular risk associated with NSAID use., (© 2023 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: Comparison of the danish comorbidity index for acute myocardial infarction (DANCAMI), the charlson comorbidity index (CCI), the elixhauser comorbidity index (ECI), and the CHA 2 DS 2 -VASc score to predict ischemic stroke, cardiovascular mortality, and all-cause mortality after atrial fibrillation/flutter., Materials and Methods: A population-based cohort study of all Danish patients with incident atrial fibrillation/flutter during 2000-2020 (n=361,901). C-Statistics were used to evaluate the discriminatory performance for predicting 1 and 5-year risks of the outcomes for a baseline model (including age and sex) +/- the individual indices., Results: For the DANCAMI, the 5-year risk did not increase with comorbidity burden for ischemic stroke (5.9% for low vs. 5.6% for severe) but did increase for cardiovascular mortality (10% for low vs. 16% for severe) and all-cause mortality (33% for low vs. 61% for severe). C-Statistics for predicting 5-year ischemic stroke risk were similar for all models (0.64). C-Statistics for predicting 5-year cardiovascular mortality risk were also similar for the baseline (0.76), the DANCAMI (0.77), the CCI (0.76), the ECI (0.76), and the CHA 2 DS 2 -VASc (0.76) models. C-Statistics for predicting 5-year all-cause mortality risk were lower for the baseline (0.71) and the CHA 2 DS 2 -VASc (0.71) models than for the DANCAMI (0.75), the CCI (0.74), and the ECI (0.74) models. The 1-year C-Statistics were comparable., Conclusion: The DANCAMI predicted ischemic stroke and cardiovascular mortality risks similar to the CCI, the ECI, and the CHA 2 DS 2 -VASc. The DANCAMI predicted all-cause mortality risk similar to the CCI and the ECI, but better than the baseline and the CHA 2 DS 2 -VASc., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Elevated triglyceride levels are a clinically useful marker of remnant cholesterol. It is unknown whether triglycerides are associated with residual cardiovascular risk in CVD-naïve patients with newly diagnosed type 2 diabetes mellitus (T2DM), who are already on statin therapy. We aimed to assess the association between triglyceride levels and risk of major cardiovascular events (MACE) in statin-treated patients with newly diagnosed T2DM managed in routine clinical care., Methods: This cohort study included newly diagnosed T2DM patients without a previous diagnosis of cardiovascular disease in Northern Denmark during 2005-2017. Individual triglyceride levels while on statin treatment were assessed within 1 year after T2DM diagnosis. The primary outcome was a composite of myocardial infarction, ischemic stroke, or cardiac death (MACE). Patients were followed from one year after T2DM diagnosis until 30 April 2021, MACE, emigration, or death. We used Cox regression to compute hazard ratios (HRs) controlling for confounding factors., Results: Among 27,080 statin-treated patients with T2DM (median age 63 years; 53% males), triglyceride levels were < 1.0 mmol/L in 17%, 1.0-1.9 mmol/L in 52%, 2.0-2.9 mmol/L in 20%, and ≥ 3.0 mmol/L in 11%. During follow-up, 1,957 incident MACE events occurred (11.0 per 1000 person-years). Compared with triglyceride levels < 1.0 mmol/L, confounder-adjusted HRs for incident MACE were 1.14 (95% CI 1.00-1.29) for levels between 1.0 and 1.9 mmol/L, 1.30 (95% CI 1.12-1.51) for levels between 2.0 and 2.9 mmol/L, and 1.44 (95% CI 1.20-1.73) for levels ≥ 3.0 mmol/L. This association was primarily driven by higher rates of myocardial infarction and cardiac death and attenuated only slightly after additional adjustment for LDL cholesterol. Spline analyses confirmed a linearly increasing risk of MACE with higher triglyceride levels. Stratified analyses showed that the associations between triglyceride levels and MACE were stronger among women., Conclusions: In statin-treated patients with newly diagnosed T2DM, triglyceride levels are associated with MACE already from 1.0 mmol/L. This suggests that high triglyceride levels are a predictor of residual cardiovascular risk in early T2DM and could be used to guide allocation of additional lipid-lowering therapies for CVD prevention., (© 2023. The Author(s).)

Background: Migraine carries risk of myocardial infarction (MI) and stroke. The risk of premature MI (i.e., among young adults) and stroke differs between men and women; previous studies indicate that migraine is mainly associated with an increased risk of stroke among young women. The aim of this study was to examine impact of migraine on the risk of premature (age ≤60 years) MI and ischemic/hemorrhagic stroke among men and women., Methods and Findings: Using Danish medical registries, we conducted a nationwide population-based cohort study (1996 to 2018). Redeemed prescriptions for migraine-specific medication were used to identify women with migraine (n = 179,680) and men with migraine (n = 40,757). These individuals were matched on sex, index year, and birth year 1:5 with a random sample of the general population who did not use migraine-specific medication. All individuals were required to be between 18 and 60 years old. Median age was 41.5 years for women and 40.3 years for men. The main outcome measures to assess impact of migraine were absolute risk differences (RDs) and hazard ratios (HRs) with 95% confidence intervals (CIs) of premature MI, ischemic, and hemorrhagic stroke, comparing individuals with migraine to migraine-free individuals of the same sex. HRs were adjusted for age, index year, and comorbidities. The RD of premature MI for those with migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.3% (95% CI [-0.1%, 0.6%]; p = 0.061) for men. The adjusted HR was 1.22 (95% CI [1.14, 1.31]; p < 0.001) for women and 1.07 (95% CI [0.97, 1.17]; p = 0.164) for men. The RD of premature ischemic stroke for migraine versus no migraine was 0.3% (95% CI [0.2%, 0.4%]; p < 0.001) for women and 0.5% (95% CI [0.1%, 0.8%]; p < 0.001) for men. The adjusted HR was 1.21 (95% CI [1.13, 1.30]; p < 0.001) for women and 1.23 (95% CI [1.10, 1.38]; p < 0.001) for men. The RD of premature hemorrhagic stroke for migraine versus no migraine was 0.1% (95% CI [0.0%, 0.2%]; p = 0.011) for women and -0.1% (95% CI [-0.3%, 0.0%]; p = 0.176) for men. The adjusted HR was 1.13 (95% CI [1.02, 1.24]; p = 0.014) for women and 0.85 (95% CI [0.69, 1.05]; p = 0.131) for men. The main limitation of this study was the risk of misclassification of migraine, which could lead to underestimation of the impact of migraine on each outcome., Conclusions: In this study, we observed that migraine was associated with similarly increased risk of premature ischemic stroke among men and women. For premature MI and hemorrhagic stroke, there may be an increased risk associated with migraine only among women., Competing Interests: CHF owns stock in Novo Nordisk. MS is supported by the Novo Nordisk Foundation (grant NNF19OC0054908). The Department of Clinical Epidemiology, Aarhus University, receives funding for other studies in the form of institutional research grants to (and administered by) Aarhus University. None of these studies has any relation to the present study., (Copyright: © 2023 Hvitfeldt Fuglsang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: It is unknown whether the cardiovascular risks associated with non-steroidal anti-inflammatory drug (NSAID) use differ according to lifestyle and socioeconomic position., Objective: We examined the association between NSAID use and major adverse cardiovascular events (MACE) within subgroups defined by lifestyle and socioeconomic position., Methods: We conducted a case-crossover study of all adult first-time respondents to the Danish National Health Surveys of 2010, 2013, or 2017, without previous cardiovascular disease, who experienced a MACE from survey completion through 2020. We used a Mantel-Haenszel method to obtain odds ratios (ORs) of the association between NSAID use (ibuprofen, naproxen, or diclofenac) and MACE (myocardial infarction, ischemic stroke, heart failure, or all-cause death). We identified NSAID use and MACE via nationwide Danish health registries. We stratified the analyses by body mass index, smoking status, alcohol consumption, physical activity level, marital status, education, income, and employment., Results: Compared with non-use, the OR of MACE was 1.34 (95% confidence interval: 1.23-1.46) for ibuprofen, 1.48 (1.04-2.43) for naproxen, and 2.18 (1.72-2.78) for diclofenac. When comparing NSAID use with non-use or the individual NSAIDs with each other, we observed no notable heterogeneity in the ORs within subgroups of lifestyle and socioeconomic position for any NSAID. Compared with ibuprofen, diclofenac was associated with increased risk of MACE in several subgroups with high cardiovascular risk, e.g., individuals with overweight (OR 1.52, 1.01-2.39) and smokers (OR 1.54, 0.96-2.46)., Conclusions: The relative increase in cardiovascular risk associated with NSAID use was not modified by lifestyle or socioeconomic position., (© 2023. The Author(s).)

Objective: We investigated the relationship between hs-CRP, a marker of low-grade inflammation, alone or in combination with C-peptide, a marker of hyperinsulinemia/insulin resistance, and risk for cardiovascular events (CVEs) and mortality in patients recently diagnosed with type 2 diabetes (T2D)., Research Design and Methods: In patients with recent-onset T2D, we measured serum hs-CRP (n = 7,301) and C-peptide (n = 5,765) in the prospective Danish Centre for Strategic Research in Type 2 Diabetes cohort study. Patients with no prior CVE (n = 6,407) were followed until first myocardial infarction, stroke, coronary revascularization, or cardiovascular death, and all patients (n = 7,301) were followed for all-cause mortality. We computed adjusted hazard ratios (aHRs) by Cox regression and tested for the interaction between hs-CRP and C-peptide., Results: During follow-up (median 4.8 years), high (>3 mg/L) versus low (<1 mg/L) hs-CRP was associated with increased CVE risk (aHR 1.45 [95% CI 1.07-1.96]) and with even greater risk of all-cause mortality (2.47 [1.88-3.25]). Compared with patients with low hs-CRP (≤3 mg/L) and low C-peptide (<1,470 pmol/L), those with high levels of both biomarkers had the highest CVE (1.61 [1.10-2.34]) and all-cause mortality risk (2.36 [1.73-3.21]). Among patients with high C-peptide, risk of CVEs did not differ by low or high hs-CRP, whereas risk of all-cause mortality did., Conclusions: The finding of high hs-CRP as a stronger prognostic biomarker of all-cause mortality than of CVEs may facilitate improved early detection and prevention of deadly diseases besides CVEs. Conversely, elevated C-peptide as a strong CVE biomarker supports the need to target hyperinsulinemia/insulin resistance in T2D CVE prevention., (© 2023 by the American Diabetes Association.)

Background Opioid use has been linked to an increased risk of myocardial infarction and cardiovascular mortality, but the prognostic impact of opioid use before an incident myocardial infarction is largely unknown. Methods and Results We conducted a nationwide population-based cohort study including all patients hospitalized for an incident myocardial infarction in Denmark (1997-2016). Based on their last redeemed opioid prescription before admission, patients were categorized as current users (0-30 days), recent users (31-365 days), former users (>365 days), and nonusers. One-year all-cause mortality was calculated using the Kaplan-Meier method. Hazard ratios (HRs) were computed using Cox proportional hazards regression analyses, adjusting for age, sex, comorbidity, any preceding surgery within 6 months before the myocardial infarction admission, and medication use before the myocardial infarction admission. We identified 162 861 patients with an incident myocardial infarction. Of these, 8% were current opioid users, 10% were recent opioid users, 24% were former opioid users, and 58% were nonusers of opioids. One-year mortality was highest among current users (42.5% [95% CI, 41.7%-43.3%]) and lowest among nonusers (20.5% [95% CI, 20.2%-20.7%]). Compared with nonusers, current users had an elevated 1-year all-cause mortality risk (adjusted HR, 1.26 [95% CI, 1.22-1.30]). Following adjustment, neither recent users nor former users of opioids were at elevated risk. Conclusions Preadmission opioid use was associated with an increased 1-year all-cause mortality risk following an incident myocardial infarction. Opioid users thus represent a high-risk subgroup of patients with myocardial infarction.

Background: Accurate estimates of risks of poststroke outcomes from large population-based studies can provide a basis for public health policy decisions. We examined the absolute and relative risks of a spectrum of incident mental disorders following ischemic stroke and intracerebral hemorrhage., Methods: During 2004 to 2018, we used Danish registries to identify patients (≥18 years and with no hospital history of mental disorders), with a first-time ischemic stroke (n=76 767) or intracerebral hemorrhage (n=9344), as well as age-,sex-, and calendar year-matched general population (n=464 840) and myocardial infarction (n=92 968) comparators. We computed risk differences, considering death a competing event, and hazard ratios adjusted for income, occupation, education, and history of cardiovascular and noncardiovascular comorbidity., Results: Compared with the general population, following ischemic stroke, the 1-year risk difference was 7.3% (95% CI, 7.0-7.5) for mood disorders (driven by depression), 1.4% (95% CI, 1.3-1.5) for organic brain disorders (driven by dementia and delirium), 0.8% (95% CI, 0.7-0.8) for substance abuse disorders (driven by alcohol and tobacco abuse), and 0.5% (95% CI, 0.4-0.5) for neurotic disorders (driven by anxiety and stress disorders). For suicide, risk differences were near null. Hazard ratios were particularly elevated in the first year of follow-up, ranging from a 2- to a 4-fold increased hazard, decreasing thereafter. Compared with myocardial infarction patients, the 1-year risk difference was 4.9% (95% CI, 4.6 to 5.3) for mood disorders, 1.0% (95% CI, 0.8 to 1.1) for organic brain disorders, 0.1% (95% CI, 0.0 to 0.2) for substance abuse disorders, but -0.2% (95% CI, -0.2 to -0.1) for neurotic disorders. Hazard ratios during the first year of follow-up were elevated 1.1- to 1.8-fold for mood, organic brain, and neurotic disorders, while decreased 0.8-fold for neurotic disorders., Conclusions: The considerably greater risks of mental disorders following a stroke, particularly mood disorders, underline the importance of mental health evaluation after stroke.

Background: Perioperative myocardial infarction is a serious cardiovascular complication of noncardiac surgery. The clinical course of perioperative myocardial infarction, other than all-cause mortality, is largely unknown. We examined long-term fatal and nonfatal outcomes of perioperative myocardial infarction compared with nonoperative myocardial infarction., Methods: We conducted a population-based cohort study of first-time myocardial infarction in Denmark from 2000 to 2016. We calculated cumulative incidence of all-cause mortality, cardiac mortality, recurrent myocardial infarction, heart failure, stroke, venous thromboembolism, acute kidney injury, and kidney failure with replacement therapy. We computed 5-year risk ratios adjusted for age, sex, year of diagnosis, educational level, and comorbidities., Results: We identified 5068 patients with perioperative myocardial infarction and 137 862 patients with nonoperative myocardial infarction. The 5-year risk of all-cause mortality was 67.5% (95% CI, 66.1%-69.0%) for perioperative myocardial infarction patients and 38.0% (95% CI, 37.7%-38.3%) for nonoperative myocardial infarction patients. The adjusted risk ratio of all-cause mortality was 1.13 (95% CI, 1.11-1.16) at 5 years. After adjustment, we found no association between patients with perioperative myocardial infarction and 5-year cardiac mortality, recurrent myocardial infarction, heart failure, stroke, or kidney failure with replacement therapy when compared with nonoperative myocardial infarction patients. Perioperative myocardial infarction patients had a higher relative risk of venous thromboembolism (5-year risk ratio, 1.21 [95% CI, 1.01-1.46]) and acute kidney injury (5-year risk ratio, 1.37 [95% CI, 1.22-1.53])., Conclusions: Compared with nonoperative myocardial infarction patients, perioperative myocardial infarction patients had elevated risk of all-cause mortality, venous thromboembolism, and acute kidney failure. In addition to the myocardial infarction component of perioperative myocardial infarction, this poor prognosis seemed associated with the surgery or underlying comorbidities. These findings warrant further research on strategies to reduce the risk of perioperative myocardial infarction and on strategies to manage perioperative myocardial infarction.

Aims: To examine combined and sex-specific temporal changes in risks of adverse cardiovascular events and coronary revascularization in patients with chronic coronary syndrome undergoing coronary angiography., Methods and Results: We included all patients with stable angina pectoris and coronary artery disease examined by coronary angiography in Western Denmark from 2004 to 2016. Patients were stratified by examination year interval: 2004-2006, 2007-2009, 2010-2012, and 2013-2016. Outcomes were 2-year risk of myocardial infarction, ischaemic stroke, cardiac death, and all-cause death estimated by adjusted incidence rate ratios using patients examined in 2004-2006 as reference. A total of 29 471 patients were included, of whom 70% were men. The 2-year risk of myocardial infarction [2.8% vs. 1.9%, adjusted incidence rate ratio 0.65, 95% confidence interval (CI) 0.53-0.81], ischaemic stroke (1.8% vs. 1.1%, adjusted incidence rate ratio 0.48, 95% CI 0.37-0.64), cardiac death (2.1% vs. 0.9%, adjusted incidence rate ratio 0.38, 95% CI 0.29-0.51), and all-cause death (5.0% vs. 3.6%, adjusted incidence rate ratio 0.65, 95% CI 0.55-0.76) decreased from the first examination interval (2004-2006) to the last examination interval (2013-2016). Coronary revascularizations also decreased (percutaneous coronary intervention: 51.6% vs. 42.5%; coronary artery bypass grafting: 24.6% vs. 17.5%). Risk reductions were observed in both men and women, however, women had a lower absolute risk., Conclusion: The risk for adverse cardiovascular events decreased substantially in both men and women with chronic coronary syndrome from 2004 to 2016. These results most likely reflect the cumulative effect of improvements in the management of chronic coronary artery disease., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Importance: Long-term risks of neurologic and psychiatric disease after cardiac arrest are largely unknown., Objective: To examine the short-term and long-term risks of common neurologic outcomes (stroke, epilepsy, Parkinson disease, and dementia) and psychiatric outcomes (depression and anxiety) in patients after hospitalization for cardiac arrest., Design, Setting, and Participants: This nationwide population-based cohort study with 21 years of follow-up included data on 250 838 adults from all Danish hospitals between January 1, 1996, and December 31, 2016. Danish medical registries were used to identify all patients with a first-time diagnosis of cardiac arrest and 2 matched comparison cohorts. The first comparison cohort included patients with a first-time diagnosis of myocardial infarction; the second comprised people from the general population. Data analysis was performed from November 1, 2020, to June 30, 2021., Exposures: In-hospital or out-of-hospital cardiac arrest., Main Outcomes and Measures: Neurologic and psychiatric outcomes after hospital discharge were ascertained using medical registries. Twenty-one-year hazard ratios (HRs) and 95% CIs were computed based on Cox regression analysis, controlled for matching factors, and adjusted for comorbidity and socioeconomic status., Results: Among the 250 838 individuals included in this study (median age, 67 years [IQR, 57-76 years]; 173 946 [69.3%] male), 3 groups were identified: 12 046 patients with cardiac arrest, 118 332 patients with myocardial infarction, and 120 460 people from the general population. Compared with patients with myocardial infarction, patients with cardiac arrest had an increased rate of ischemic stroke (10 per 1000 persons; HR, 1.30; 95% CI, 1.02-1.64) and hemorrhagic stroke (2 per 1000 persons; HR, 2.03; 95% CI, 1.12-3.67) in the first year after discharge. During the full follow-up period, rates were as follows: for epilepsy, 28 per 1000 persons (HR, 2.01; 95% CI, 1.66-2.44); for dementia, 73 per 1000 persons (HR, 1.23; 95% CI, 1.09-1.38); for mood disorders including depression, 270 per 1000 persons (HR, 1.78; 95% CI, 1.68-1.89); and for anxiety, 187 per 1000 persons (HR, 1.98; 95% CI, 1.85-2.12). The rate of Parkinson disease was similar in the 2 cohorts (8 per 1000 persons; HR, 0.96; 95% CI, 0.65-1.42). The rates of the aforementioned outcomes were highest during the first year after cardiac arrest and then declined over time. Comparisons between the cohort of patients with cardiac arrest and the general population cohort showed higher rates of epilepsy, dementia, depression, and anxiety in the cardiac arrest group., Conclusions and Relevance: In this cohort study, patients discharged after cardiac arrest had an increased rate of subsequent stroke, epilepsy, dementia, depression, and anxiety compared with patients with myocardial infarction and people from the general population, with declining rates over time. These findings suggest the need for preventive strategies and close follow-up of cardiac arrest survivors.

Introduction: The Danish Comorbidity Index for Acute Myocardial Infarction (DANCAMI) was developed to predict one-year mortality after myocardial infarction. We validated DANCAMI in predicting one-year mortality after venous thromboembolism (VTE)., Materials and Methods: We identified all first-time VTE patients in Denmark during 2000-2015. Using Cox regression, we assessed the performance of DANCAMI to predict one-year all-cause mortality using Nagelkerke's R 2 , Harrell's C-Statistic, the net reclassification index (NRI), and the integrated discrimination improvement (IDI). We compared the performance of DANCAMI with the Charlson Comorbidity Index (CCI) and the Elixhauser Comorbidity Index (ECI) and evaluated whether DANCAMI comorbidities not included in the CCI predicted one-year mortality. We stratified the analyses by type (deep vein thrombosis [DVT] and pulmonary embolism [PE]) and presence of provoking risk factors., Results: We identified 108,824 VTE patients of whom 20,649 (19%) died within one year. The R 2 , C-Statistic, NRI, and IDI for DANCAMI were 0.35, 0.76, 0.63, and 0.098 for VTE overall; 0.43, 0.80, 0.70, and 0.105 for DVT; and 0.24, 0.71, 0.54, and 0.083 for PE. The R 2 and C-Statistic for VTE overall were 0.35 and 0.76 for CCI and 0.33 and 0.75 for ECI. After adjusting for age, sex, and all CCI comorbidities, seven DANCAMI comorbidities, not included in the CCI, predicted increased mortality. DANCAMI performed better than the CCI and ECI in predicting mortality after provoked VTE, including provoked DVT and PE., Conclusion: DANCAMI performed comparable to existing comorbidity indices in predicting one-year mortality after first-time VTE overall, but better after provoked VTE., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background In addition to primary neurodegenerative processes, vascular disorders, such as stroke, can lead to parkinsonism. However, some cardiovascular risk factors, such as smoking and elevated cholesterol levels, are associated with reduced risk of Parkinson disease. We examined the risk of Parkinson disease and secondary parkinsonism in 1-year survivors of myocardial infarction (MI). Methods and Results We conducted a nationwide population-based matched cohort study using Danish medical registries from 1995 to 2016. We identified all patients with a first-time MI diagnosis and sampled a sex-, age-, and calendar year-matched general population comparison cohort without MI. Cox regression analysis was used to compute adjusted hazard ratios (aHRs) for Parkinson disease and secondary parkinsonism, controlled for matching factors and adjusted for relevant comorbidities and socioeconomic factors. We identified 181 994 patients with MI and 909 970 matched comparison cohort members (median age, 71 years; 62% men). After 21 years of follow-up, the cumulative incidence was 0.9% for Parkinson disease and 0.1% for secondary parkinsonism in the MI cohort. Compared with the general population cohort, MI was associated with a decreased risk of Parkinson disease (aHR, 0.80; 95% CI, 0.73-0.87) and secondary parkinsonism (aHR, 0.72; 95% CI, 0.54-0.94). Conclusions MI was associated with a 20% decreased risk of Parkinson disease and 28% decreased risk of secondary parkinsonism. Reduced risk may reflect an inverse relationship between cardiovascular risk factors and Parkinson disease.

The aim of this study was to examine whether myocardial infarction (MI) incidence rate continues to decrease and to determine whether the relative magnitude of a potentially decreasing incidence rate has surpassed increasing survival, demasking a breaking point in trends of MI prevalence proportion. This was a nationwide population-based cohort study using medical registries covering all hospitals in Denmark (1994 to 2016). We identified 193,870 persons with a first-time hospitalization for MI. Age-standardized incidence rates (per 100,000 persons) decreased from 154 (95% confidence interval [CI] 149 to 159) in 1994 to 90 (95% CI 86 to 93) in 2016 for females, and from 335 (95% CI 326 to 344) in 1994 to 205 (95% CI 199 to 211) in 2016 for males. Age-standardized prevalence proportion increased overall from 1994 to 2004 with a subsequent plateau. From 2006 to 2016, age-standardized prevalence proportion decreased by 0.09% (95% CI 0.07% to 0.11%) for females (from 1.07% to 0.98%) and by 0.20% (95% CI 0.17% to 0.23%) for males (from 2.85% to 2.65%). The age-standardized prevalence proportion decreased solely among persons aged 55 to 84 years. It remained stable among persons aged <55 years and increased among persons aged ≥85 years until 2012 with subsequent stable trends. We conclude that the continuous decreasing age-standardized incidence rate of MI over decades has, although with increasing survival, led to an overall breaking point toward a decreasing age-standardized prevalence proportion of MI since 2006., Competing Interests: Disclosures The Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University, but none of these studies have relation to the submitted work. Dr. Schmidt is supported by the Novo Nordisk Foundation outside of the submitted work., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

This study aimed to examine the 30-day risk of myocardial infarction (MI) and death in patients who underwent noncardiac surgery within 1 year after coronary drug-eluting stent implantation for acute coronary syndrome (ACS) or stable angina pectoris (SAP) and to compare it with the risk in surgical patients without known coronary artery disease. Patients with drug-eluting stent implantation for ACS (n = 2,291) or SAP (n = 1,804) who underwent noncardiac surgery were compared with a cohort from the general population without known coronary artery disease matched on the surgical procedure, hospital contact type, gender, and age. In patients with ACS, the 30-day MI risk was markedly increased when surgery was performed within 1 month after stenting (10% vs 0.8%; adjusted odds ratio [OR adj ] 20.1, 95% confidence interval [CI] 8.85 to 45.6), whereas mortality was comparable (10% vs 8%, OR adj 1.17, 95% CI 0.76 to 1.79). When surgery was performed between 1 and 12 months after stenting, the 30-day absolute risk for MI was low but higher than in the comparison cohort (0.6% vs 0.2%, OR adj 2.18, 95% CI 0.89 to 5.38), whereas the mortality risks were similar (2.0% vs 1.8%, OR adj 1.03, 95% CI 0.69 to 1.55). In patients with SAP, the 30-day MI risk was low but higher than in the comparison cohort (0.4% vs 0.2%, OR adj 1.90, 95% CI 0.70 to 5.14), whereas the mortality risks were similar (2.2% vs 2.1%, OR adj 0.91, 95% CI 0.61 to 1.37). In conclusion, patients with ACS and SAP who underwent surgery between 1 and 12 months after stent implantation had a risk for MI and death that was similar to the risk observed in surgical patients without coronary artery disease., Competing Interests: Disclosures The authors have no conflicts of interest to disclose., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: The incidence of cardiovascular events among cancer patients with bone metastases is poorly understood. We examined rates of cardiovascular events among cancer patients with bone metastases and mortality following such events., Methods: Using Danish health registries, we identified all Danish cancer patients diagnosed with bone metastases (1994-2013) and followed them from bone metastasis diagnosis. We computed incidence rates (IR) per 100 person-years and cumulative incidence for first-time inpatient hospitalization or outpatient clinic visit for cardiovascular events, defined as myocardial infarction, ischemic stroke, or venous thromboembolism (VTE). We also analyzed all-cause mortality rates including cardiovascular events as time-varying exposure with adjustment for age, sex, and Charlson Comorbidity Index score. All analyses were performed overall and stratified by cancer type (prostate, breast, lung, and other)., Results: We included 23,113 cancer patients with bone metastases. The cumulative incidence of cardiovascular events was 1.3% at 30 days, 3.7% at 1 year, and 5.2% at 5 years of follow-up. The highest IR was observed for VTE, followed by ischemic stroke and myocardial infarction, both overall and by cancer types. Lung cancer patients with bone metastases had the highest incidence of cardiovascular events followed by prostate and breast cancer. Occurrence of any cardiovascular event was a strong predictor of death (5 years following the event, the adjusted hazard ratio was 1.8 [95% confidence interval: 1.7-1.9])., Conclusion: Cancer patients with bone metastases had a substantial risk of developing cardiovascular events, and these events were associated with a subsequent increased mortality. Our findings underscore the importance of continuous optimized prevention of and care for cardiovascular disease among cancer patients with bone metastases., (© 2021 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

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., Competing Interests: Disclosures The authors declare that they have no known competing financial interests or personal relations that could have appeared to influence the work reported in this study., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Myocardial infarction (MI) is a risk factor for venous thromboembolism (VTE). Although comorbidities affect MI prognosis, it is unclear whether they affect VTE risk after MI., Objectives: We examined the impact of comorbidity on VTE risk after MI., Methods: We used nationwide population-based registries to identify first-time hospitalizations for MI and subsequent occurrence of VTE in Denmark (1995-2013). We included a comparison cohort from the general population matched 5:1 with MI patients by sex, age, and comorbidities. We computed 30-day and 1- to 12-month cumulative risks, rates, and hazard ratios of VTE. We also assessed the interaction between MI and comorbidity, defined as excess VTE risk in patients with both MI and comorbidity, by computing interaction contrasts and attributable fractions relating to the interaction., Results: Thirty-day and 1- to 12-month VTE risks were 0.6% and 0.5% in the MI cohort (n = 160 338) and 0.03% and 0.3% in the comparison cohort (n = 792 384). The 30-day hazard ratio for VTE in the MI cohort was 23 (95% confidence interval, 20-27), which decreased during 1-year follow-up. Thirty days after MI, interactions between MI and comorbidity accounted for 16% and 39% of VTE rates in MI patients with low-to-moderate and high comorbidity, respectively. The interactions were driven primarily by hemiplegia and cancer., Conclusions: Thirty-day VTE risk was substantially increased after MI compared with the general population. Although the absolute VTE risk was low, comorbidity substantially increased this risk, especially hemiplegia and cancer. VTE prophylaxis might be indicated in such high-risk patients but warrants further investigation., (© 2020 International Society on Thrombosis and Haemostasis.)

Background: Whether the prognostic impact of comorbidity on myocardial infarction (MI) mortality is due to comorbidity alone or/and its interaction effect is unknown., Methods: We used Danish medical registries to conduct a nationwide cohort study of all first-time MIs during 1995-2016 (n = 179,515) and a comparison cohort matched on age, sex, and individual comorbidities (n = 880,347). We calculated age-standardized 5-year all-cause mortality rates. Interaction was examined on an additive scale by calculating interaction contrasts (difference in rate differences)., Results: Among individuals without comorbidity, the 30-day mortality rate per 1000 person-years was 1851 (95% CI: 1818-1884) for MI patients and 22 (21-24) for comparison cohort members (rate difference = 1829). For individuals with low comorbidity, corresponding baseline mortality rates were 2498 (2436-2560) in the MI and 54 (50-57) in the comparison cohort (rate difference = 2444). The interaction contrast (616) indicated that the interaction accounted for 25% (616/2498) of the total 30-day mortality rate in MI patients with low comorbidity. This percentage increased further for moderate (35%) and severe (45%) comorbidity levels. Absolute and relative interaction effects were largest within the first 30 days and younger individuals. Dose-response patterns were also observed during 31-365 days and 1-5 years of follow-up (p-values for trends<0.002). The interaction differed substantially between individual types of cardiac and non-cardiac comorbidities., Conclusion: Cardiac and non-cardiac comorbidities interact with MI to increase short- and long-term mortality beyond that explained by their additive effects. The interaction had a dose-response relation with comorbidity burden and a magnitude of clinical importance., Competing Interests: Declaration of competing interest The authors report no conflicts of interest in this work. None of the authors has received any fees, honoraria, grants or consultancies that would constitute a conflict of interest with the current study. The Department of Clinical Epidemiology, Aarhus University Hospital, receives funding for other studies from companies in the form of research grants to (and administered by) Aarhus University. None of those studies has any relation to the present study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months., Methods: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed., Findings: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed., Interpretation: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI., Funding: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden., (Copyright © 2019 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Objective: We examined the risk of myocardial infarction associated with glucose-lowering therapy among diabetes patients with and without obstructive coronary artery disease., Methods: A cohort of patients with type 1 or type 2 diabetes (n = 12,030), who underwent coronary angiography from 2004 to 2012, were stratified by presence of obstructive (any stenosis ⩾50%) coronary artery disease and by type of diabetes treatment: diet, non-insulin treatment and insulin (±oral anti-diabetics). The primary endpoint was myocardial infarction. Adjusted hazard ratios were calculated using diet-treated patients without coronary artery disease as reference., Results: In patients without coronary artery disease, risk of myocardial infarction was similar in patients treated with non-insulin medication (adjusted hazard ratio 0.70, 95% confidence interval 0.27-1.81) and insulin (adjusted hazard ratio 0.76, 95% confidence interval 0.27-2.08) as compared to diet only. In patients with coronary artery disease, the risk of myocardial infarction was higher than in the reference group and an incremental risk was observed being lowest in patients treated with diet (adjusted hazard ratio 3.79, 95% confidence interval 1.61-8.88), followed by non-insulin medication (adjusted hazard ratio 5.42, 95% confidence interval 2.40-12.22), and highest in insulin-treated patients (adjusted hazard ratio 7.91, 95% confidence interval 3.51-17.82)., Conclusion: The presence of obstructive coronary artery disease defines the risk of myocardial infarction in diabetes patients. Glucose-lowering therapy, in particular insulin, was associated with risk of myocardial infarction only in the presence of coronary artery disease.

Background: The occurrence of myocardial infarction (MI), ischemic stroke, and hemorrhagic stroke has decreased in recent years, but trends in seasonal occurrence remain unclear., Methods: Using Danish healthcare databases, we identified all patients with a first-time MI, ischemic stroke, or hemorrhagic stroke during the study period (1977-2016). We summarized monthly cases for each disease separately and computed the peak-to-trough ratio as a measure of seasonal occurrence of one cycle. To examine trends over time in seasonal occurrence, we computed the peak-to-trough ratio for each of the 40 years. We also quantified the amount of bias arising from random error in peak-to-trough ratios., Results: Before consideration of bias, the peak-to-trough ratio of summarized monthly cases was 1.11 (95% confidence interval [CI] = 1.10, 1.12) for MI, 1.08 (95% CI = 1.07, 1.09) for ischemic stroke, and 1.12 (95% CI = 1.10, 1.14) for hemorrhagic stroke. The peak-to-trough ratio of MI occurrence increased from 1.09 (95% CI = 1.04, 1.15) in 1977 to 1.16 (95% CI = 1.09, 1.23) in 1999. The trend then remained stable. The peak-to-trough ratio of ischemic stroke occurrence declined continuously during the study period, dropping from 1.12 (95% CI = 1.02, 1.24) in 1977 to 1.06 (95% CI = 1.00, 1.12) in 2016. The peak-to-trough ratio of hemorrhagic stroke occurrence remained stable over time. However, after adjusting for potential bias, time trends in peak-to-trough ratios were almost flat., Conclusions: We found no substantial seasonality for MI, ischemic stroke, or hemorrhagic stroke occurrence during 1977-2016. Modest peak-to-trough ratios should be interpreted after considering bias induced by random variation.

Background: Increased risk of dementia after myocardial infarction (MI) may be mediated by shared risk factors (eg, atherosclerosis) and post-MI stroke. We examined risk of dementia in 1-year survivors of MI., Methods: Using Danish medical registries, we conducted a nationwide population-based cohort study of all patients with first-time MI and a sex-, birth year-, and calendar year-matched general population comparison cohort without MI (1980-2012). Cox regression analysis was used to compute 1- to 35-year adjusted hazard ratios (aHRs) for dementia, controlled for matching factors and adjusted for comorbidities and socioeconomic status., Results: We identified 314 911 patients with MI and 1 573 193 matched comparison cohort members randomly sampled from the general population (median age, 70 years; 63% male). After 35 years of follow-up, the cumulative incidence of all-cause dementia in the MI cohort was 9% (2.8% for Alzheimer disease, 1.6% for vascular dementia, and 4.5% for other dementias). Compared with the general population cohort, MI was not associated with all-cause dementia (aHR, 1.01; 95% confidence interval [CI], 0.98-1.03). Risk of Alzheimer disease (aHR, 0.92; 95% CI, 0.88-0.95) and other dementias (aHR, 0.98; 95% CI, 0.95-1.01) also approximated unity. However, MI was associated with higher risk of vascular dementia (aHR, 1.35; 95% CI, 1.28-1.43), which was substantially strengthened for patients experiencing stroke after MI (aHR, 4.48; 95% CI, 3.29-6.12)., Conclusions: MI was associated with higher risk of vascular dementia throughout follow-up, and this association was stronger in patients with stroke. The risk of Alzheimer disease and other dementias was not higher in patients with MI., (© 2017 American Heart Association, Inc.)

We evaluated risks of MI and stroke in elderly patients with hip fracture compared with the general population. We also examined the interaction between hip fracture and comorbidity with respect to risks of MI or stroke, defined as excess of risk explained by combining risks of hip fracture and comorbidity. We conducted a population-based cohort study using Danish health registries, in 1995 to 2015 including 110,563 hip fracture patients and 552,774 members of the comparison cohort from the general population. Thirty-day cumulative incidences of MI were 1.15% among patients with hip fracture and 0.09% in the general population (adjusted hazard ratio [aHR] = 12.97; 95% confidence interval [CI], 11.56 to 14.55). Thirty-day cumulative incidences of stroke were 2.16% for hip fracture patients and 0.21% in the general population (aHR = 9.42; 95% CI, 8.71 to 10.19). During the 31 to 365 days following hip fracture, the aHR for MI was 1.05 (95% CI, 0.97 to 1.14) and remained at this level during the remainder of follow-up (maximum of 20 years). The aHR for stroke was 1.29 (95% CI, 1.22 to 1.35) during the 31 to 365 days following hip fracture, remained elevated for up to 10 years, and then decreased to the general population level. The aHRs for MI and stroke were increased for both men and women, and in all age and comorbidity groups. During the first 30 days, up to 76% of MI and stroke risk was attributable to interaction between hip fracture and comorbidity. Patients with hip fracture are at increased risk of both MI and stroke up to 1 year following the fracture. Risk of stroke, but not of MI, was elevated during up to 10 years postfracture. Although the absolute risks were low, our finding underscores the importance of targeting multimorbidity, including prevention and adequate treatment, to improve the prognosis of hip fracture patients. © 2017 American Society for Bone and Mineral Research., (© 2017 American Society for Bone and Mineral Research.)

Objective: The risk of myocardial infarction (MI) in patients with diabetes is greater than for patients without diabetes. Consequently, prophylactic treatment is recommended for patients with diabetes and risk factors for ischemic heart disease. We aimed to estimate the risk of adverse cardiac events in patients with and without diabetes with and without coronary artery disease (CAD) after coronary angiography (CAG)., Research Design and Methods: A population-based cohort of patients registered in the Western Denmark Heart Registry who underwent CAG between 1 January 2003 and 31 December 2012 was stratified according to the presence or absence of obstructive CAD and diabetes. End points were death, cardiac death, and MI. Unadjusted and adjusted rate ratios (RRs) were calculated by using patients without diabetes and without CAD as the reference group., Results: We included 93,866 patients of whom 12,544 (13.4%) had diabetes at the time of CAG. Median follow-up was 4.1 years. Patients with and without diabetes without obstructive CAD had the same adjusted risk of death (RR 1.03 [95% CI 0.92-1.15]), cardiac death (RR 1.21 [95% CI 0.90-1.64]), and MI (RR 0.88 [95% CI 0.65-1.17]). Patients with diabetes without CAD were more often treated with statins (75.3% vs. 46.0%) and aspirin (65.7% vs. 52.7%) than patients without diabetes and CAD., Conclusions: In a real-world population, patients with diabetes with high rates of statin and aspirin treatment had the same risk of cardiovascular events as patients without diabetes in the absence of angiographically significant CAD., (© 2017 by the American Diabetes Association.)

Background The prognostic impact of previous depression on myocardial infarction survival remains poorly understood. Aims To examine the association between depression and all-cause mortality following myocardial infarction. Method Using Danish medical registries, we conducted a nationwide population-based cohort study. We included all patients with first-time myocardial infarction (1995-2014) and identified previous depression as either a depression diagnosis or use of antidepressants. We used Cox regression to compute adjusted mortality rate ratios (aMRRs) with 95% confidence intervals. Results We identified 170 771 patients with first-time myocardial infarction. Patients with myocardial infarction and a previous depression diagnosis had higher 19-year mortality risks (87% v. 78%). The overall aMRR was 1.11 (95% CI 1.07-1.15) increasing to 1.22 (95% CI 1.17-1.27) when including use of antidepressants in the depression definition. Conclusions A history of depression was associated with a moderately increased all-cause mortality following myocardial infarction., Competing Interests: Declaration of interestNone., (© The Royal College of Psychiatrists 2017.)

Design: Valid data on acromegaly incidence, complications and mortality are scarce. The Danish Health Care System enables nationwide studies with complete follow-up and linkage among health-related databases to assess acromegaly incidence, prevalence, complications and mortality in a population-based cohort study., Method: All incident cases of acromegaly in Denmark (1991-2010) were identified from health registries and validated by chart review. We estimated the annual incidence rate of acromegaly per 10(6) person-years (py) with 95% confidence intervals (95% CIs). For every patient, 10 persons were sampled from the general population as a comparison cohort. Cox regression and hazard ratios (HRs) with 95% confidence intervals (95% CIs) were used., Results: Mean age at diagnosis (48.7 years (CI: 95%: 47.2-50.1)) and annual incidence rate (3.8 cases/10(6) persons (95% CI: 3.6-4.1)) among the 405 cases remained stable. The prevalence in 2010 was 85 cases/10(6) persons. The patients were at increased risk of diabetes mellitus (HR: 4.0 (95% CI: 2.7-5.8)), heart failure (HR: 2.5 (95% CI: 1.4-4.5)), venous thromboembolism (HR: 2.3 (95% CI: 1.1-5.0)), sleep apnoea (HR: 11.7 (95% CI: 7.0-19.4)) and arthropathy (HR: 2.1 (95% CI: 1.6-2.6)). The complication risk was also increased before the diagnosis of acromegaly. Overall mortality risk was elevated (HR: 1.3 (95% CI: 1.0-1.7)) but uninfluenced by treatment modality., Conclusion: (i) The incidence rate and age at diagnosis of acromegaly have been stable over decades, and the prevalence is higher than previously reported. (ii) The risk of complications is very high even before the diagnosis. (iii) Mortality risk remains elevated but uninfluenced by mode of treatment., (© 2016 European Society of Endocrinology.)

Background: The long-term prognosis for young myocardial infarction (MI) survivors remains poorly understood., Methods and Results: We conducted a nationwide population-based cohort study using prospectively collected medical data from all hospitals in Denmark during 1980 to 2009. We examined 30-year cause-specific death rates among 21 693 MI patients <50 years versus 216 930 sex- and age-matched people from the general population. We calculated mortality rate ratios (MRRs) based on Cox regression. Between 1980 to 1989 and 2000 to 2009, MI mortality declined from 12.5% to 3.2% within 30 days, 5.1% to 1.6% within 31 to 365 days, and 24.2% to 8.9% within 1 to 10 years. Compared with the general population, the MRR adjusted for sex, age, and cardiovascular and noncardiovascular comorbidity decreased 4.5-fold within 30 days (from 468 to 97), 3-fold within 31 to 365 days (from 11.32 to 3.70), and 2.5-fold within 1 to 10 years (from 4.77 to 1.89). The remaining 1.89-fold increased mortality rate among 1-year survivors in 2000 to 2009 corresponded to 6 additional deaths each year per 1000 patients compared with the general population. Long-term causes of death were primarily because of cardiovascular and chronic pulmonary diseases. The excess 10-year MRR among 1-year survivors was consistent within MI subtypes, did not differ substantially between comorbidity categories, but was higher for women than men (3-fold versus 1.7-fold)., Conclusions: The long-term mortality rate after MI before age 50 has decreased remarkably over the last 3 decades, but remains increased relative to the general population, mainly because of deaths from ischemic heart disease and other smoking-related diseases., (© 2016 American Heart Association, Inc.)

Background and Purpose: Improved survival after myocardial infarction (MI) has increased the number of patients at risk of post-MI stroke. We examined risks of ischemic stroke, intracerebral hemorrhage (ICH), and subarachnoid hemorrhage (SAH) in patients with MI compared with the general population., Methods: We conducted a nationwide population-based cohort study using Danish medical registries. During 1980 to 2009, we identified all patients with a first-time inpatient diagnosis of MI and formed a sex- and age-matched comparison cohort. We computed cumulative stroke risks and adjusted stroke rate ratios with 95% confidence intervals (CIs)., Results: We identified 258 806 patients with an MI and 1 244 773 individuals from the general population. For patients with MI, the cumulative stroke risks after 1 to 30 years were 12.6% for ischemic stroke, 1.2% for ICH, and 0.24% for SAH. During the first 30 days after MI, the adjusted stroke rate ratio was 30-fold increased for ischemic stroke (31.9; 95% CI, 28.4-35.8), 20-fold for ICH (21.8; 95% CI, 16.6-28.5), and 15-fold for SAH (16.6; 95% CI, 8.7-32.0). The adjusted stroke rate ratio remained increased during 31 to 365 days (3-fold for ischemic stroke, 2-fold for ICH, and 1.5-fold for SAH). During the ensuing 1 to 30 years, the risks remained increased for ischemic stroke (1.6; 95% CI, 1.6-1.6) but decreased to near unity for ICH (1.1; 95% CI, 1.0-1.2) and SAH (1.1; 95% CI, 0.94-1.2)., Conclusions: MI was a risk factor for all stroke subtypes during the first year of follow-up, but only for ischemic stroke thereafter., (© 2016 American Heart Association, Inc.)

Mycosis fungoides (MF) and parapsoriasis display increased inflammation, which may be associated with increased risk of arterial cardiovascular events. The aim of this Danish nationwide population-based cohort study was to assess the relative risk (RR) of acute myocardial infarction (AMI) or stroke in patients with MF and parapsoriasis. In patients with MF, the RR of AMI or stroke was 1.0 (95% confidence interval (95% CI) 0.7-1.3). In the second half of the study period, the RR was 1.8 (95% CI 1.1-2.9) during the first 5 years of follow-up. In men with parapsoriasis, the RR of AMI or stroke was 1.7 (95% CI 1.1-2.7) within the first 5 years of follow-up, whereas the RR of AMI during the first 5 years of follow-up was 2.0 (95% CI 1.2-3.4). In conclusion, patients with MF and parapsoriasis have an increased RR of AMI or stroke within the first 5 years of follow-up.

Background: Myocardial infarction-related cardiogenic shock is frequently complicated by acute kidney injury. We examined the influence of acute kidney injury treated with renal replacement therapy (AKI-RRT) on risk of chronic dialysis and mortality, and assessed the role of comorbidity in patients with cardiogenic shock., Methods: In this Danish cohort study conducted during 2005-2012, we used population-based medical registries to identify patients diagnosed with first-time myocardial infarction-related cardiogenic shock and assessed their AKI-RRT status. We computed the in-hospital mortality risk and adjusted relative risk. For hospital survivors, we computed 5-year cumulative risk of chronic dialysis accounting for competing risk of death. Mortality after discharge was computed with use of Kaplan-Meier methods. We computed 5-year hazard ratios for chronic dialysis and death after discharge, comparing AKI-RRT with non-AKI-RRT patients using a propensity score-adjusted Cox regression model., Results: We identified 5079 patients with cardiogenic shock, among whom 13% had AKI-RRT. The in-hospital mortality was 62% for AKI-RRT patients, and 36% for non-AKI-RRT patients. AKI-RRT remained associated with increased in-hospital mortality after adjustment for confounders (relative risk=1.70, 95% confidence interval (CI): 1.59-1.81). Among the 3059 hospital survivors, the 5-year risk of chronic dialysis was 11% (95% CI: 8-16%) for AKI-RRT patients, and 1% (95% CI: 0.5-1%) for non-AKI-RRT patients (adjusted hazard ratio: 15.9 (95% CI: 8.7-29.3). The 5-year mortality was 43% (95% CI: 37-53%) for AKI-RRT patients compared with 29% (95% CI: 29-31%) for non-AKI-RRT patients. The adjusted 5-year hazard ratio for death was 1.55 (95% CI: 1.22-1.96) for AKI-RRT patients compared with non-AKI-RRT patients. In patients with comorbidity, absolute mortality increased while relative impact of AKI-RRT on mortality decreased., Conclusion: AKI-RRT following myocardial infarction-related cardiogenic shock predicted elevated short-term mortality and long-term risk of chronic dialysis and mortality. The impact of AKI-RRT declined with increasing comorbidity suggesting that intensive treatment of AKI-RRT should be accompanied with optimized treatment of comorbidity when possible.

Objectives: Post-traumatic stress disorder (PTSD) is a well-documented risk factor for cardiovascular disease (CVD). However, it is unknown whether another common stress disorder-adjustment disorder--is also associated with an increased risk of CVD and whether gender modifies these associations. The aim of this study was to examine the overall and gender-stratified associations between PTSD and adjustment disorder and 4 CVD events., Design: Prospective cohort study utilising Danish national registry data., Setting: The general population of Denmark., Participants: PTSD (n=4724) and adjustment disorder (n=64,855) cohorts compared with the general population of Denmark from 1995 to 2011., Primary Outcome Measures: CVD events including myocardial infarction (MI), stroke, ischaemic stroke and venous thromboembolism (VTE). Standardised incidence rates and 95% CIs were calculated., Results: Associations were found between PTSD and all 4 CVD events ranging from 1.5 (95% CI 1.1 to 1.9) for MI to 2.1 (95% CI 1.7 to 2.7) for VTE. Associations that were similar in magnitude were also found for adjustment disorder and all 4 CVD events: 1.5 (95% CI 1.4 to 1.6) for MI to 1.9 (95% CI 1.8 to 2.0) for VTE. No gender differences were noted., Conclusions: By expanding beyond PTSD and examining a second stress disorder-adjustment disorder-this study provides evidence that stress-related psychopathology is associated with CVD events. Further, limited evidence of gender differences in associations for either of the stress disorders and CVD was found., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

The rationale and study design for the multicentre, randomized, controlled CONDI2/ERIC-PPCI study are discussed.

Background: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PCI) is the preferred treatment. In primary PCI patients with multivessel disease, it is unclear whether culprit vessel PCI only is the preferred treatment. We compared mortality among (1) STEMI patients with single-vessel disease and those with multivessel disease and (2) multivessel disease patients with and without additional revascularization of nonculprit lesions within 2 months after the index PCI., Methods: From January 2002 to June 2009, all patients presenting with STEMI and treated with primary PCI were identified from the Western Denmark Heart Registry, which covers a population of 3.0 million. The hazard ratio (HR) for death was estimated using a Cox regression model, controlling for potential confounding., Results: The study cohort consisted of 8,822 patients: 4,770 (54.1%) had single-vessel disease and 4,052 (45.9%) had multivessel disease. Overall, 1-year cumulative mortality was 7.6%, and 7-year cumulative mortality was 24.0%. Multivessel disease was associated with higher 7-year mortality (adjusted HR 1.45 [95% CI 1.30-1.62], P < .001). Among patients with multivessel disease, lack of additional revascularization beyond the culprit lesion was associated with higher 7-year mortality (adjusted HR 1.50 [95% CI 1.25-1.80], P < .001). In patients with multivessel disease who underwent additional revascularization, 7-year mortality (adjusted HR 1.01 [95% CI 0.84-1.22], P = .89) was similar compared to patients with single-vessel disease., Conclusion: In STEMI patients, multivessel disease was associated with a higher mortality compared to single-vessel disease. In multivessel disease patients, additional revascularization was associated with a higher survival compared with culprit vessel PCI only., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objectives: Remote ischaemic conditioning (RIC) promotes cardioprotection in patients undergoing primary percutaneous coronary intervention (pPCI) for ST-elevation myocardial infarction (STEMI). The effect of RIC may be modified by cardiovascular risk factors and their medications. We examined whether cardiovascular risk factors, lipid and glucose levels, and medication use influenced the efficacy of RIC in patients with STEMI treated with pPCI., Design: Post hoc subgroup analysis of a single-centre randomised controlled trial., Participants: A total of 139 patients with STEMI, randomised during ambulance transport to hospital for pPCI with (n=71) or without (n=68) RIC, met the trial criteria and achieved data for a myocardial salvage index (MSI)., Interventions: RIC was administered through intermittent arm ischaemia with four cycles of 5 min inflation and 5 min deflation of a blood pressure cuff., Primary Outcome Measures: MSI, estimated by single-photon emission CT. We evaluated the efficacy of RIC on the MSI in patient subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use., Results: We found no significant difference in the efficacy of RIC in subgroups of cardiovascular risk factors, lipid and glucose levels, and medication use. However, point estimates indicated a reduced effect of RIC among smokers (median difference in MSI between RIC and control groups: -0.02 (95% CI -0.32 to 0.28) in smokers vs 0.25 (95% CI 0.08 to 0.42) in non-smokers, p value for interaction=0.13) and an increased effect of RIC in statin users (median difference in MSI between RIC and control groups: 0.34 (95% CI 0.03 to 0.65) in statin users vs 0.09 (95% CI -0.11 to 0.29) in non-statin users, p value for interaction=0.19)., Conclusions: RIC as an adjunct to pPCI seems to improve MSI in our trial population of patients with STEMI regardless of most cardiovascular risk factors and their medications. Our post hoc finding on a limited sample size calls for further investigation in large-scale multicentre trials., Trial Registration Number: NCT00435266., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Introduction: Patients with acute myocardial infarction or stroke are at high risk of venous thromboembolism, which is traditionally considered a complication rather than a marker of occult cancer. We examined the association between venous thromboembolism and cancer in patients with acute myocardial infarction or stroke., Methods: We used medical databases to conduct a population-based cohort study including all patients with a first-time venous thromboembolism from 1978 through 2011 who also had a diagnosis of acute myocardial infarction (n=2,878) or stroke (n=1,971) recorded on the same day or within the previous 90days. We followed patients until a first-time cancer diagnosis, emigration, death, or December 31, 2011, whichever came first. We computed 1-year absolute risks and standardised incidence ratios for cancer based on national incidence rates., Results: The 1-year absolute cancer risk was 2.7% in the acute myocardial infarction cohort and 3.7% in the stroke cohort. The corresponding standardised incidence ratios were 3.22 (95% confidence interval [CI]: 2.54-4.03) and 3.76 (95% CI: 2.95-4.74), respectively. For cancers diagnosed in the first year, the estimated number of venous thromboembolism patients needed to examine to detect one excess cancer was 25 in the acute myocardial infarction cohort and 19 in the stroke cohort., Conclusion: Among acute myocardial infarction and stroke patients, venous thromboembolism can be a marker of occult cancer. We suggest that current guidelines for cancer screening in patients with unprovoked venous thromboembolism could be applied to this group of patients., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Background: As proxies for local and remote ischemic preconditioning, we examined whether preinfarction angina pectoris and intermittent claudication influenced mortality following myocardial infarction., Methods: Using medical registries, we conducted a nationwide population-based cohort study of all first-time myocardial infarction patients in Denmark during 2004-2012 (n=70,458). We computed all-cause and coronary mortality rate ratios (MRRs). We categorized time between angina/claudication presentation and subsequent myocardial infarction as 0-14, 15-30, 31-90, and > 90 days. We adjusted for age, sex, coronary intervention, comorbidities, and medication use., Results: Among all myocardial infarction patients, 18.4% had prior angina and 3.8% had prior intermittent claudication. Compared to patients without prior angina, the adjusted 30-day coronary MRR was 0.85 (95% confidence interval (CI): 0.80-0.92) for stable and 0.68 (95% CI: 0.58-0.79) for unstable angina patients. The mortality reduction increased when angina presented close to myocardial infarction and was higher for unstable than for stable angina. Thus, the 30-day coronary MRR was 0.72 (95% CI: 0.51-1.02) for stable angina and 0.35 (95% CI: 0.17-0.73) for unstable angina presenting within 14 days before MI. The results were robust for all-cause mortality and in numerous subgroups, including women, diabetics, patients treated with PCI, and patients treated with and without cardioprotective drugs. Preinfarction intermittent claudication was associated with higher short- and long-term mortality compared to patients without intermittent claudication., Conclusions: Preinfarction angina reduced 30-day mortality, particularly when unstable angina closely preceded MI. Preinfarction intermittent claudication was associated with increased short- and long-term mortality., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

The impact of co-morbidity on the cardiovascular risk after single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI) remains unclear. We examined the association between a normal versus abnormal SPECT MPI scan on 10-year risk of myocardial infarction, stroke, and all-cause death, overall and according to co-morbidity level. We identified all patients without previous myocardial infarction or cerebrovascular disease, who had an SPECT MPI performed at Aarhus University Hospital Skejby during 1999 to 2011. We categorized the SPECT MPI scan as normal (no defects) or abnormal (reversible and/or fixed defects). Using nationwide medical registries, we obtained information on co-morbidity level (using Charlson co-morbidity index) and outcomes. We used Cox regression to compute hazard ratios with 95% confidence intervals (CIs), adjusting for gender, age, and co-morbidity level. Among 7,040 patients, 4,962 (70%) had normal scans and 2,078 (30%) abnormal scans. Patients with a normal versus abnormal scan had a 10-year risk of 5.7% versus 10.9% for myocardial infarction, 6.0% versus 7.8% for stroke, and 16.5% versus 29.0% for all-cause death. After adjustment, an abnormal scan was associated with increased risk of myocardial infarction (adjusted hazard ratio 1.73, 95% CI 1.37 to 2.18) and all-cause death (1.42, 95% CI 1.23 to 1.65) but not stroke (1.12, 95% CI 0.86 to 1.45). Co-morbidity level did not affect substantially the association between the scan result and the outcomes. In conclusion, independently of co-morbidity level, an abnormal SPECT MPI scan was associated with an increased 10-year risk of myocardial infarction and all-cause death but not stroke., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Aims: Remote ischaemic conditioning as an adjunct to primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction increases myocardial salvage. We investigated the effect of remote ischaemic conditioning on long-term clinical outcome., Methods and Results: From February 2007 to November 2008, 333 patients with a suspected first acute ST-elevation myocardial infarction were randomized to receive primary percutaneous coronary intervention with (n = 166) or without (n = 167) remote ischaemic conditioning (intermittent arm ischaemia through four cycles of 5-min inflation followed by 5-min deflation of a blood-pressure cuff). Patient follow-up extended from the randomization date until an outcome, emigration or January 2012 (median follow-up = 3.8 years). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE)-a composite of all-cause mortality, myocardial infarction, readmission for heart failure, and ischaemic stroke/transient ischaemic attack. The individual components of the primary endpoint comprised the secondary endpoints. Outcomes were obtained from Danish nationwide medical registries and validated by medical record review and contact to patients' general practitioner. In the per-protocol analysis of 251 patient fulfilling trial criteria, MACCE occurred for 17 (13.5%) patients in the intervention group compared with 32 (25.6%) patients in the control group, yielding a hazard ratio (HR) of 0.49 (95% confidence interval: 0.27-0.89, P = 0.018). The HR for all-cause mortality was 0.32 (95% confidence interval: 0.12-0.88, P = 0.027). Although lower precision, the HRs were also directionally lower for all other secondary endpoints., Conclusion: Remote ischaemic conditioning before primary percutaneous coronary intervention seemed to improve long-term clinical outcomes in patients with ST-elevation myocardial infarction.

Objectives: This study examined the association between prenatal exposure to pandemic influenza and cardiovascular events in adulthood., Design: Using Danish surveillance data to identify months when influenza activity was highest during three previous pandemics (1918, 1957, and 1968), persons were defined as exposed/unexposed based on whether they were in utero during peak months of one of the pandemics. Episodes of acute myocardial infarction (MI) and stroke were identified in the Danish National Registry of Patients covering all Danish hospitals since 1977., Setting/sample: Information from Danish national registries on all persons with a Civil Personal Registry number and birthdates in 1915 through 1922, 1954 through 1960, and 1966 through 1972 was collected., Main Outcome Measures: Crude incidence rate ratios (IRRs) were calculated per pandemic. Generalized linear models were fit to estimate IRRs adjusted for sex., Results: For acute MI, sex-adjusted IRRs for persons in utero during peaks of the 1918, 1957, and 1968 pandemics, compared with those born afterward, were 1·02 (95% confidence interval (CI): 0·99, 1·05), 0·96 (95% CI: 0·87, 1·05), and 1·18 (95% CI: 0·96, 1·45), respectively. For stroke, the corresponding IRRs were 0·99 (95% CI: 0·97, 1·02), 0·99 (95% CI: 0·92, 1·05), and 0·85 (95% CI: 0·77, 0·94), respectively., Conclusions: There was generally no evidence of an association between prenatal influenza exposure and acute MI or stroke in adulthood. However, survivor bias and left truncation of outcomes for the 1918 pandemic are possible, and the current young ages of persons included in the analyses for the 1957 and 1968 pandemics may warrant later re-evaluation., (© 2013 The Authors. Influenza and Other Respiratory Viruses Published by John Wiley & Sons Ltd.)

Background: An association between colorectal cancer and acute myocardial infarction (AMI) and stroke has been suggested, but evidence is conflicting., Method: We conducted a population-based cohort study (1978-2010) of the association between AMI/stroke and colorectal cancer by linking nationwide Danish registries. We calculated standardized incidence ratios (SIR) of colorectal cancer after AMI/stroke as the ratios of observed to expected incidence., Results: A total of 297,523 patients with AMI (median age, 69.4 years; 64% men) were followed for a median of 3.1 years (range, 0-33 years) and 4,387 developed colorectal cancer [SIR, 1.08; 95% confidence interval (CI), 1.05-1.11; P < 0.001]. In the first year of follow-up, the SIR was 1.85 (95% CI, 1.73-1.98; P < 0.001), whereas it was 0.98 (95% CI, 0.95-1.02; P = 0.318) in the second and subsequent years. We followed 246,998 patients with stroke (median age, 72.4 years; 52% men) for a median of 2.9 years (range, 0-33 years) and 3,035 developed colorectal cancer (SIR, 1.04; 95% CI, 1.00-1.07; P = 0.053). In the first year of follow-up, the SIR was 1.42 (95% CI, 1.31-1.53; P < 0.001), whereas it was 0.96 (95% CI, 0.93-1.00; P = 0.072) thereafter. We found no difference between the SIRs for ischemic and hemorrhagic stroke. The increased one-year relative risks for AMI and stroke corresponded to a 0.3% absolute risk., Conclusions: Our findings reflect detection of occult cancer at the time of the vascular event. The lack of increased risk after one year suggests that an association based on shared risk factors or chronic inflammation is unlikely., Impact: In patients with AMI/stroke, the diagnostic workup including screening for colorectal cancer should follow that of the general population., (©2013 AACR.)

Aims: In patients with ST-segment elevation myocardial infarction (STEMI), timely reperfusion with primary percutaneous coronary intervention (PPCI) is the preferred treatment. However, it remains unclear whether the optimal strategy is complete revascularisation or culprit vessel PPCI only., Methods and Results: From January 2002 to June 2009 all patients treated with PPCI were identified from the Western Denmark Heart Registry. We examined mortality according to timing of multivessel PCI: acute procedure, staged procedure during the index hospitalisation, or staged procedure performed within 60 days. The hazard ratio (HR) for death was estimated using a time-dependent Cox regression model, with time of PCI for the non-culprit lesion as the time-dependent variable. The study cohort consisted of 5,944 patients, of whom 4,770 (80%) had single-vessel disease and 1,174 (20%) had multivessel PCI within 60 days. Among 354 (30.2%) patients with acute multivessel PCI, 194 (16.5%) patients with multivessel PCI during the index hospitalisation, and 626 (53.3%) patients with multivessel PCI within 60 days after the index hospitalisation, the adjusted HRs for one-year mortality were 1.53 (95% confidence interval (CI): 1.07-2.18), 0.60 (95% CI: 0.28-1.26), and 0.28 (95% CI: 0.14-0.54), respectively, compared to patients with single vessel disease., Conclusions: Acute multivessel PCI in patients with STEMI was associated with increased mortality.

Patients with diabetes mellitus (DM) have a worse outcome after percutaneous coronary intervention (PCI) than nondiabetic patients. The purpose of this study was to compare rates of stent thrombosis, myocardial infarction (MI), target lesion revascularization (TLR), and death in diabetic and nondiabetic patients treated with primary PCI for ST-segment elevation MI (STEMI) in Western Denmark. From January 2002 through June 2005, 3,655 consecutive patients with STEMI treated with primary PCI and stent implantation (316 patients with DM, 8.6%; 3,339 patients without DM, 91.4%) were recorded in the Western Denmark Heart Registry. All patients were followed for 3 years. Cox regression analysis was used to compute hazard ratios (HRs), controlling for potential confounding. Three-year rates of definite stent thrombosis were 1.6% in the DM group and 1.5% in the non-DM group (adjusted HR 1.15, 95% confidence interval [CI] 0.50 to 2.67). The rate of MI was 12.3% in the DM group versus 5.6% in the non-DM group (adjusted HR 2.56, 95% CI 1.81 to 3.61). Rates of TLR were 12.1% in the DM group and 8.7% in the non-DM group (adjusted HR 1.55, 95% CI 1.14 to 2.11). All-cause mortality was 23.7% in patients with DM versus 12.7% in patients without DM (adjusted HR 2.03, 95% CI 1.59 to 2.59). In conclusion, stent thrombosis rate was similar in patients with and without DM and STEMI treated with primary PCI, whereas the presence of DM increased the risk of MI, TLR, and death., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objectives: To examine 25 year trends in first time hospitalisation for acute myocardial infarction in Denmark, subsequent short and long term mortality, and the prognostic impact of sex and comorbidity., Design: Nationwide population based cohort study using medical registries., Setting: All hospitals in Denmark., Subjects: 234,331 patients with a first time hospitalisation for myocardial infarction from 1984 through 2008., Main Outcome Measures: Standardised incidence rate of myocardial infarction and 30 day and 31-365 day mortality by sex. Comorbidity categories were defined as normal, moderate, severe, and very severe according to the Charlson comorbidity index, and were compared by means of mortality rate ratios based on Cox regression., Results: The standardised incidence rate per 100,000 people decreased in the 25 year period by 37% for women (from 209 to 131) and by 48% for men (from 410 to 213). The 30 day, 31-365 day, and one year mortality declined from 31.4%, 15.6%, and 42.1% in 1984-8 to 14.8%, 11.1%, and 24.2% in 2004-8, respectively. After adjustment for age at time of myocardial infarction, men and women had the same one year risk of dying. The mortality reduction was independent of comorbidity category. Comparing patients with very severe versus normal comorbidity during 2004-8, the mortality rate ratio, adjusted for age and sex, was 1.96 (95% CI 1.83 to 2.11) within 30 days and 3.89 (3.58 to 4.24) within 31-365 days., Conclusions: The rate of first time hospitalisation for myocardial infarction and subsequent short term mortality both declined by nearly half between 1984 and 2008. The reduction in mortality occurred for all patients, independent of sex and comorbidity. However, comorbidity burden was a strong prognostic factor for short and long term mortality, while sex was not.

Background: Cytochrome P450 inhibition by proton pump inhibitors (PPIs) may attenuate the effectiveness of clopidogrel., Aim: To examine whether PPI use modifies the association between clopidogrel use and major adverse cardiovascular events (MACE) after percutaneous coronary intervention (PCI) with stent implantation, using time-varying drug exposure ascertainment., Methods: We conducted this population-based cohort study in Western Denmark (population 3 million) using medical databases. We identified all 13,001 patients with coronary stent implantation between 2002 and 2005 and ascertained their reported comorbidities. During the recommended 12-month postintervention treatment period, we tracked use of clopidogrel and PPI and the rate of MACE. We used Cox regression to compute hazard ratios (HRs), controlling for potential confounders., Results: During follow-up, one or more prescriptions were redeemed by 91% of patients for clopidogrel and by 21% of patients for PPIs. Of the patients, 15% experienced a MACE. The adjusted HR for MACE comparing clopidogrel use with non-use was 0.57 [95% confidence interval (CI): 0.44-0.74] among PPI users and 0.47 (95% CI: 0.42-0.53) among PPI non-users, yielding an interaction effect (i.e. relative rate increase) of 1.20 (95% CI: 0.91-1.58). PPI users treated from before PCI had a 25% increased rate of MACE compared to PPI non-users, independent of clopidogrel use [adjusted HR = 1.24 (95% CI: 0.97-1.58) for clopidogrel users and 1.26 (95% CI: 0.97-1.63) for clopidogrel non-users]., Conclusions: The use of PPIs as a class did not modify the protective effect of clopidogrel, but its use was associated with major adverse cardiovascular events itself, particularly among patients having used PPIs before percutaneous coronary intervention., (© 2011 Blackwell Publishing Ltd.)

Introduction: Chronic diseases and their complications may increase breast cancer risk through known or still unknown mechanisms, or by shared causes. The association between morbidities and breast cancer risk has not been studied in depth., Methods: Data on all Danish women aged 45 to 85 years, diagnosed with breast cancer between 1994 and 2008 and data on preceding morbidities were retrieved from nationwide medical registries. Odds ratios (OR) and 95% confidence intervals (CI) were estimated using conditional logistic regression associating the Charlson comorbidity score (measured using both the original and an updated Charlson Comorbidity Index (CCI)) with incident breast cancer. Furthermore, we estimated associations between 202 morbidity categories and incident breast cancer, adjusting for multiple comparisons using empirical Bayes (EB) methods., Results: The study included 46,324 cases and 463,240 population controls. Increasing CCI score, up to a score of six, was associated with slightly increased breast cancer risk. Among the Charlson diseases, preceding moderate to severe renal disease (OR = 1.25, 95% CI: 1.06, 1.48), any tumor (OR = 1.17, 95% CI: 1.10, 1.25), moderate to severe liver disease (OR = 1.86, 95% CI: 1.32, 2.62), and metastatic solid tumors (OR = 1.49, 95% CI: 1.17, 1.89), were most strongly associated with subsequent breast cancer. Preceding myocardial infarction (OR = 0.89, 95% CI: 0.81, 0.99), connective tissue disease (OR = 0.87, 95% CI: 0.80, 0.94), and ulcer disease (OR = 0.91, 95% CI: 0.83, 0.99) were most strongly inversely associated with subsequent breast cancer. A history of breast disorders was associated with breast cancer after EB adjustment. Anemias were inversely associated with breast cancer, but the association was near null after EB adjustment., Conclusions: There was no substantial association between morbidity measured with the CCI and breast cancer risk.

Patients ≥ 80 years old with coronary artery disease constitute a particular risk group in relation to percutaneous coronary intervention (PCI). From 2002 through 2008 we examined the annual proportion of patients ≥ 80 years old undergoing PCI in western Denmark, their indications for PCI, and prognosis. From 2002 through 2009 all elderly patients treated with PCI were identified in a population of 3.0 million based on the Western Denmark Heart Registry. Cox regression analysis was used to compare mortality rates according to clinical indications controlling for potential confounding. In total 3,792 elderly patients (≥ 80 years old) were treated with PCI and the annual proportion increased from 224 (5.4%) in 2002 to 588 (10.2%) in 2009. The clinical indication was stable angina pectoris (SAP) in 30.2%, ST-segment elevation myocardial infarction (STEMI) in 35.0%, UAP/non-STEMI in 29.7%, and "ventricular arrhythmia or congestive heart failure" in 5.1%. Overall 30-day and 1-year mortality rates were 9.2% and 18.1%, respectively. Compared to patients with SAP the adjusted 1-year mortality risk was significantly higher for patients presenting with STEMI (hazard ratio 3.86, 95% confidence interval 3.08 to 4.85), UAP/non-STEMI (hazard ratio 1.95, 95% confidence interval 1.53 to 2.50), and ventricular arrhythmia or congestive heart failure (hazard ratio 2.75, 95% confidence interval 1.92 to 3.92). In patients with SAP target vessel revascularization decreased from 7.1% in 2002 to 2.5% in 2008. In conclusion, the proportion of patients ≥ 80 years old treated with PCI increased significantly over an 8-year period. Patients with SAP had the lowest mortality rates and rates of clinically driven target vessel revascularization decreased over time., (Copyright © 2011 Elsevier Inc. All rights reserved.)