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Patients with kidney failure have a high risk for cardiovascular events. We aimed to evaluate the prognostic importance of selected biomarkers related to haemostasis, endothelial function, and vascular regulation in patients with acute coronary syndrome (ACS), and to study whether this association differed in patients with renal dysfunction.Plasma was collected in 1370 ACS patients included between 2008 and 2015. Biomarkers were analysed using a Proximity Extension Assay and a Multiple Reaction Monitoring mass spectrometry assay. To reduce multiplicity, biomarkers correlating with eGFR were selected a priori among 36 plasma biomarkers reflecting endothelial and vascular function, and haemostasis. Adjusted Cox regression were used to study their association with the composite outcome of myocardial infarction, ischemic stroke, heart failure or death. Interaction with eGFR strata above or below 60 mL/min/1.73 mTissue factor, proteinase-activated receptor, soluble urokinase plasminogen activator surface receptor (suPAR), thrombomodulin, adrenomedullin, renin, and angiotensinogen correlated inversely with eGFR and were selected for the Cox regression. Mean follow-up was 5.2 years during which 428 events occurred. Adrenomedullin, suPAR, and renin were independently associated with the composite outcome. Adrenomedullin showed interaction with eGFR strata (p = 0.010) and was associated with increased risk (HR 1.88; CI 1.44-2.45) only in patients with eGFR ≥60 mL/min/ 1.73 mAdrenomedullin, suPAR, and renin were associated with the composite outcome in all. Adrenomedullin, involved in endothelial protection, showed a significant interaction with renal function and outcome, and was associated with the composite outcome only in patients with preserved kidney function.

Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades, but there are concerns regarding their cardiovascular safety.To provide an updated synthesis of evidence on whether ADHD medications are associated with the risk of a broad range of cardiovascular diseases (CVDs).PubMed, Embase, PsycINFO, and Web of Science up to May 1, 2022.Observational studies investigating the association between ADHD medications (including stimulants and nonstimulants) and risk of CVD.Independent reviewers extracted data and assessed study quality using the Good Research for Comparative Effectiveness (GRACE) checklist. Data were pooled using random-effects models. This study is reported according to the Meta-analyses of Observational Studies in Epidemiology guideline.The outcome was any type of cardiovascular event, including hypertension, ischemic heart disease, cerebrovascular disease, heart failure, venous thromboembolism, tachyarrhythmias, and cardiac arrest.Nineteen studies (with 3 931 532 participants including children, adolescents, and adults; 60.9% male), of which 14 were cohort studies, from 6 countries or regions were included in the meta-analysis. Median follow-up time ranged from 0.25 to 9.5 years (median, 1.5 years). Pooled adjusted relative risk (RR) did not show a statistically significant association between ADHD medication use and any CVD among children and adolescents (RR, 1.18; 95% CI, 0.91-1.53), young or middle-aged adults (RR, 1.04; 95% CI, 0.43-2.48), or older adults (RR, 1.59; 95% CI, 0.62-4.05). No significant associations for stimulants (RR, 1.24; 95% CI, 0.84-1.83) or nonstimulants (RR, 1.22; 95% CI, 0.25-5.97) were observed. For specific cardiovascular outcomes, no statistically significant association was found in relation to cardiac arrest or arrhythmias (RR, 1.60; 95% CI, 0.94-2.72), cerebrovascular diseases (RR, 0.91; 95% CI, 0.72-1.15), or myocardial infarction (RR, 1.06; 95% CI, 0.68-1.65). There was no associations with any CVD in female patients (RR, 1.88; 95% CI, 0.43-8.24) and in those with preexisting CVD (RR, 1.31; 95% CI, 0.80-2.16). Heterogeneity between studies was high and significant except for the analysis on cerebrovascular diseases.This meta-analysis suggests no statistically significant association between ADHD medications and the risk of CVD across age groups, although a modest risk increase could not be ruled out, especially for the risk of cardiac arrest or tachyarrhythmias. Further investigation is warranted for the cardiovascular risk in female patients and patients with preexisting CVD as well as long-term risks associated with ADHD medication use.

Background: Persons with bipolar disorder (BD) have a higher cardiovascular mortality compared to the general population, partially explained by the increased burden of cardiovascular risk factors. Research regarding outcomes following acute coronary syndrome (ACS) in this population remains scarce. Design: This Danish register-based study included patients diagnosed with BD and ACS in the period between January 1st, 1995, to December 31st, 2013. Study participants were matched 1:2 to patients without BD on sex, date of birth, time of ACS diagnosis and comorbidities. The primary outcome of interest was major adverse cardiovascular events (MACE) a composite of all-cause mortality, reinfarction or stroke. MACE and its individual components were compared between patients with and without BD. Results: 796 patients with BD were compared to 1592 patients without BD, both groups had a mean age of first ACS of 66.5 years. MACE was 38% increased (HR 1.38 95% CI 1.25–1.54), all-cause mortality was 71% increased (HR 1.71 95% CI 1.52–1.92), stroke was 94% increased (HR 1.94 95% CI 1.56–2.41) and reinfarction rates were 17% lower (HR 0.83 95% CI 0.69–1.00) in the BD population compared to the population without BD. We also found higher prevalences of heart failure (9.1% vs. 6.5%), valve disease (5.3% vs. 3.5%), anemia (8.7% vs. 5.8%), chronic obstructive pulmonary disease (13.4% vs. 9.3%) and stroke (11.8% vs. 7.8%) in the population with BD at baseline, all p-values

Patients with acute coronary syndrome (ACS) are at risk for recurrent adverse events, and multiple reports suggest that this risk is increased in patients with concomitant diabetes mellitus (DM) and peripheral artery disease (PAD). The aim of this article was to investigate cardiovascular outcomes in patients with DM presenting with ACS, stratified by PAD status. Data were derived from 4 randomized post-ACS trials (PLATO [Platelet Inhibition and Patient Outcomes], APPRAISE-2 p Apixaban for Prevention of Acute Ischemic Events 2], TRILOGY [Targeted Platelet Inhibition to Clarify the Optimal Strategy to Medically Manage], and TRACER [Thrombin Receptor Agonist for Clinical Event Reduction in Acute Coronary Syndrome]). Using Cox regression analysis, we investigated major adverse cardiovascular events (MACEs), a composite of cardiovascular mortality, myocardial infarction (MI), or stroke and the individual components of MACE and all-cause mortality in patients with DM, presenting with ACS, stratified by PAD status as the risk modifier. This study included 15,387 patients with a diagnosis of DM and ACS, of whom 1,751 had an additional diagnosis of PAD. PAD was associated with more than doubled rates of MACE (hazard ratio [HR] 2.03, 95% confidence interval [CI] 1.81 to 2.27), all-cause mortality (HR 2.48, 95% CI 2.14 to 2.87), cardiovascular mortality (HR 2.42, 95% CI 2.04 to 2.86), and MI (HR 2.07, 95% CI 1.79 to 2.38). Patients with both PAD and DM were also more optimally treated with antihypertensive, antidiabetic, and statin medication at baseline. In conclusion, this analysis of 4 major post-ACS trials showed that patients with DM and PAD had a substantially higher risk of MACE, cardiovascular mortality, all-cause mortality, and MI despite being optimally treated with guideline-based therapies.

Background Aortic stenosis (AS) is the most common valvular heart disease in developed countries, confers high mortality in advanced cases, but can effectively be reversed using endovascular or open-heart surgery. We evaluated the association between AS and neighborhood socioeconomic status (NSES). Methods We used Swedish population-based nationwide registers and an echocardiography screening cohort during the study period 1997–2014. NSES was determined by an established neighborhood deprivation index composed of education, income, unemployment, and receipt of social welfare. Multilevel adjusted logistic regression models determined the association between NSES and incident AS (according to ICD-10 diagnostic codes). Results The study population of men and women (n=6,641,905) was divided into individuals living in high (n = 1,608,815 [24%]), moderate (n = 3,857,367 [58%]) and low (n = 1,175,723 [18%]) SES neighborhoods. There were 63,227 AS cases in total. Low NSES (versus high) was associated with a slightly increased risk of AS (OR 1.06 [95% CI 1.03–1.08]) in the nationwide study population. In the echocardiography screening cohort (n = 1586), the association between low NSES and AS was markedly stronger (OR: 2.73 [1.05–7.12]). There were more previously undiagnosed AS cases in low compared to high SES neighborhoods (3.1% versus 1.0%). Conclusions In this nationwide Swedish register study, low NSES was associated with a slightly increased risk of incident AS. However, the association was markedly stronger in the echocardiography screening cohort, which revealed an almost three-fold increase of AS among individuals living in low SES neighborhoods, possibly indicating an underdiagnosis of AS among these individuals.

Background: Patients with chronic kidney disease (CKD) have poor outcomes following myocardial infarction (MI). We performed an untargeted examination of 175 biomarkers to identify those with the strongest association with CKD and to examine the association of those biomarkers with long-term outcomes. Methods: A total of 175 different biomarkers from MI patients enrolled in the Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies (SWEDEHEART) registry were analysed either by a multiple reaction monitoring mass spectrometry assay or by a multiplex assay (proximity extension assay). Random forests statistical models were used to assess the predictor importance of biomarkers, CKD and outcomes. Results: A total of 1098 MI patients with a median estimated glomerular filtration rate of 85 mL min−1/1.73 m2 were followed for a median of 3.2 years. The random forests analyses, without and with adjustment for differences in demography, comorbidities and severity of disease, identified six biomarkers (adrenomedullin, TNF receptor-1, adipocyte fatty acid-binding protein-4, TNF-related apoptosis-inducing ligand receptor 2, growth differentiation factor-15 and TNF receptor-2) to be strongly associated with CKD. All six biomarkers were also amongst the 15 strongest predictors for death, and four of them were amongst the strongest predictors of subsequent MI and heart failure hospitalization. Conclusion: In patients with MI, a proteomic approach could identify six biomarkers that best predicted CKD. These biomarkers were also amongst the most important predictors of long-term outcomes. Thus, these biomarkers indicate underlying mechanisms that may contribute to the poor prognosis seen in patients with MI and CKD. (Less)

Olanzapine and quetiapine are routinely used off-label at lower doses, though it remains unclear whether treatment is associated with mortality. Here, we examined the associations between low-dose olanzapine/quetiapine, defined as 5 mg/day of olanzapine equivalents (OE) with cardiometabolic mortality in a population-based, longitudinal cohort of individuals who sought specialized psychiatric services. Through cross-linked Swedish registries, 428,525 individuals without psychotic, bipolar, or cardiometabolic disorders, or previous treatment with antipsychotics or cardiometabolic-related drugs were followed for up to 10.5 years. Extended stratified Cox proportional hazards regressions were employed to estimate the hazard ratios (HR) of cardiometabolic mortality as a function of cumulative OE exposures, adjusted for age, sex, inpatient care, and time-dependent psychiatric diagnoses and treatments. Individuals were followed for a total of 2.1 million person-years. Treatment with olanzapine/quetiapine occurred in 18,317 of the cohort. In total, 2606 cardiometabolic-related deaths occurred. Treatment status (treated vs. untreated) was not significantly associated with cardiometabolic mortality (adjusted HR 0.86, 95% CI 0.64-1.15, P = 0.307). However, compared to no treatment, treatment for

Background: People living with HIV (PLHIV) on antiretroviral treatment (ART) may have unfavourable cardiovascular outcomes compared to people without HIV. A potential explanation could be differences in acute treatment and in-hospital management. This study aimed to compare patients with and without HIV experiencing an acute myocardial infarction (MI) in relation to baseline characteristics, treatment, and cardiovascular outcomes. Methods: Two Swedish disease registry cohorts were used to identify patients with and without HIV experiencing MI. The primary outcome was the occurrence of a combined composite endpoint of major adverse cardiovascular events (MACE: reinfarction, stroke, or all-cause mortality) within 5 years in PLHIV versus patients without HIV presenting with MI. Cox regression models were used to compare populations. Findings: We identified all PLHIV (n=191; 89% male) and people without HIV (n=324,635; 64% male) who experienced a MI during 1996–2017 in Sweden. PLHIV presented with MI more than 15 years earlier (median age 55 vs 72 years), had a higher prevalence of smoking, and a lower prevalence of hypertension. PLHIV with MI had higher risks of MACE (adjusted hazard ratio (aHR) 2·01 [1·56-2·58]), reinfarction (aHR 2·06 [1·46–2·91]), stroke (aHR 2·00 [1·11–3·62]), and all-cause mortality (aHR 2·07 [1·45–2·94]) at 5 years. Interpretation: HIV was independently associated with higher risk of MACE and more than doubled the risk of all-cause mortality at 5 years after MI. This study indicates that HIV is an independent risk factor for worse outcomes following MI. Funding Information: This work was supported by a Gilead Science Fellowship and the Public Health Agency of Sweden to GM. Declaration of Interests: Dr. Jernberg reports grants from MSD, grants from Novartis, and that his employer has received reimbursement from Astra Zeneca, Bayer, MSD, Novartis and Sanofi for lecturing. Dr. Elvstam reports grants from Pfizer, outside the submitted work. The other authors declare that there is no conflict of interest. Ethics Approval Statement: The study is ethically approved by the ethical review board of Stockholm, Sweden (reference number: 2018/1957-32). The ethical review board waived the need for consent for this study.

Background To investigate the optimal periprocedural antithrombotic strategy in patients on oral anticoagulants (OAC) who undergoing unplanned percutaneous coronary intervention (PCI). Methods Using data from the SWEDEHEART registry, we identified all patients on OAC who underwent an unplanned PCI, from 2005 to 2017. We compared uninterrupted OAC (U-OAC) vs interrupted OAC (I-OAC) therapy, defined as any discontinuation of OAC at least 24 hours prior to PCI. Outcomes were major adverse cardiac and cerebrovascular events (MACCE), including death, MI or stroke and net adverse cardiac and cerebrovascular events (NACCE), including MACCE or major bleeds, up to 120 days after the index procedure. Results We included 6485 patients, 3163 in U-OAC and 3322 in I-OAC group. The U-OAC strategy increased over time, by 13% per year. Almost 80% of patients in both groups had an acute coronary syndrome. We found no major differences in terms of medical history, clinical characteristics and the CRUSADE bleeding score on admission. The proportion of patients on warfarin was higher in the I-OAC group (85 vs 81%). Patients in the I-OAC were more likely to receive low-molecular weight heparin (29 vs 12%) and glycoprotein IIb/IIIa inhibitors (6 vs 3%) during the index hospitalisation. In the I-OAC group, dual antiplatelet therapy without OAC was more often prescribed (22 vs 8%) and OAC plus single antiplatelet therapy was less often prescribed (8 vs 22%) at discharge. At 120 days, the cumulative rate of MACCE was 8.2 vs 8.2% and the rate of NACCE was 12.6 vs 12.9% in I-OAC vs U-OAC, respectively. We found no significant difference in the risk for MACCE and NACCE between the two groups (table). The risk for major or minor in-hospital bleeds was similar. I-OAC was associated with significantly longer time-delay to PCI and length of hospitalisation (table). Conclusion Uninterrupted OAC was safe and was associated with significantly shorter length of hospitalisation. Our data support U-OAC as the preferable strategy in patients on OAC undergoing PCI. Funding Acknowledgement Type of funding source: None

Background People living with HIV (PLHIV) on antiretroviral therapy (ART) have a higher risk of developing cardiovascular diseases (CVD) at a younger age due to chronic inflammation, higher prevalence of traditional cardiovascular risk factors and side-effects of ART – although the last is controversial. Moreover, recent studies have shown that PLHIV have unfavorable CVD outcomes compared to HIV-negative people. A potential explanation could be differences in acute treatment and in-hospital management. Purpose This study is aimed at investigating patients with and without HIV experiencing an acute myocardial infarction (AMI) in relation to baseline characteristics, in-hospital management and short-term outcomes. Methods The nationwide SWEDEHEART (The Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry and Swedish National HIV Registry (InfCareHIV) were used to identify patients with and without HIV experiencing AMI. Primary outcome was the occurrence of a combined composite endpoint of major adverse cardiovascular events (MACE: all-cause mortality, new myocardial infarction or stroke) at 1 year in PLHIV versus HIV-negative people presenting with acute MI. Secondary outcomes were the occurrence of any of the individual components of the above composite endpoint. Kaplan-Meier survival curves and multivariable Cox regression models were used to compare the populations. Results We identified all PLHIV (n=319; 85% male) and HIV-negative people (n=711,506; 59% male) who experienced an AMI during 1996–2017 in Sweden. PLHIV presented with AMI more than ten years younger (median age 54.7 vs 67.1 years), had a higher prevalence of smoking and chewing tobacco use and a lower prevalence of hypertension. PLHIV with AMI had higher risks of MACE (adjusted hazard ratio (adjHR) for age, sex, traditional risk factors, comorbidities, in-hospital treatment and discharge medication = 1.60, 95% confidence interval (CI) 0.98–2.61) and mortality (adjHR = 2.37, 95% CI 1.34–4.16) at 1 year compared to HIV-negative people with AMI. Conclusion PLHIV suffer AMI more than 10 years earlier than HIV-negative people. HIV was independently associated with higher risk of MACE and more than doubled all-cause mortality at 1 year after AMI. Improved primary and secondary prevention (e.g. smoking cessation) may improve outcomes. Funding Acknowledgement Type of funding source: Private grant(s) and/or Sponsorship. Main funding source(s): Fellowship Gilead Science, Public Health Agency of Sweden

Objectives This study sought to compare interrupted and uninterrupted oral anticoagulant therapy (I-OAC vs. U-OAC) in patients on OAC undergoing percutaneous coronary intervention. Background There is a paucity of data regarding the optimal peri-procedural management of OAC-treated patients. Methods In the SWEDEHEART registry, all patients on OAC who were admitted acutely and underwent percutaneous coronary intervention or coronary angiography with a diagnostic procedure, from 2005 to 2017, were included. Outcomes were major adverse cardiac and cerebrovascular events (MACCE; death, myocardial infarction, or stroke) and bleeds at 120 days. Propensity score was used to adjust for the nonrandomized treatment selection. Results The study included 6,485 patients: 3,322 in the I-OAC group and 3,163 in the U-OAC group. The cumulative incidence of MACCE was 8.2% (269 events) versus 8.2% (254 events) in the I-OAC and the U-OAC groups, respectively. The adjusted risk for MACCE did not differ between the groups (I-OAC vs. U-OAC hazard ratio: 0.89; 95% confidence interval: 0.71 to 1.12). Similarly, no difference was found in the risk for MACCE or bleeds (12.6% vs. 12.9%, adjusted hazard ratio: 0.87; 95% confidence interval: 0.70 to 1.07). The risk for major or minor in-hospital bleeds did not differ between the groups. However, U-OAC was associated with a significantly shorter duration of hospitalization: 4 (3 to 7) days versus 5 (3 to 8) days; p Conclusions I-OAC and U-OAC were associated with equivalent risk for MACCE and bleeding complications. An U-OAC strategy was associated with shorter length of hospitalization. These data support U-OAC as the preferable strategy in patients on OAC undergoing coronary intervention.

Objectives The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). Background iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking. Methods The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements. Results In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p Conclusions Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated.

OBJECTIVES: Patients with chronic obstructive pulmonary disease (COPD) who also have acute coronary syndromes are a high-risk population with a high mortality rate. Little is known about these patients following coronary artery bypass grafting (CABG). METHODS: Patients presenting with acute coronary syndromes between 2006 and 2014 with an angiogram showing 3-vessel disease or left main coronary artery involvement who were treated with CABG or percutaneous coronary intervention (PCI) only were included from the nationwide SWEDEHEART registry. Patients were stratified according to COPD status and compared with regard to outcome. The primary end-point was the 5-year mortality rate; secondary outcomes were the 30-day mortality rate and in-hospital complications after CABG. RESULTS: We identified 6985 patients in the population who had CABG (COPD prevalence = 8.0%) and 14 209 who had PCI only (COPD = 8.2%). Patients with COPD were older and had more comorbidities than patients without COPD. The 5-year mortality rate was nearly doubled in patients with COPD versus patients without COPD (CABG: 27.2% vs 14.5%, P < 0.001; PCI only: 50.1% vs 29.1%, P < 0.001). After adjusting for age, sex and comorbidities, patients with COPD in both CABG-treated [hazard ratio = 1.52 (1.25-1.86), P < 0.001] and PCI-treated populations still had a significantly higher 5-year mortality rate. COPD was also independently associated with significantly more postoperative infections in need of antibiotics [odds ratio = 1.48 (1.07-2.04), P = 0.017] and pneumonia [odds ratio = 2.21 (1.39-3.52), P = 0.001]. CONCLUSIONS: Patients with COPD presenting with acute coronary syndromes and severe coronary artery disease are a high-risk population following CABG or PCI only, with higher risk of long-term and short-term death and postoperative infections. Preventive measures, including careful monitoring for signs of infection and prompt antibiotic treatment when indicated, should be considered. (Less)

Aims The aim of this study is to investigate the association between adherence to beta‐blocker treatment after a first acute myocardial infarction (AMI) and long‐term risk of heart failure (HF) and death. Methods and results All patients admitted for a first AMI included in the nationwide Swedish web‐system for enhancement and development of evidence‐based care in heart disease evaluated according to recommended therapies register between 2005 and 2010 were eligible (n = 71 638). After exclusion of patients who died in‐hospital, patients with previous HF, patients with unknown left ventricular ejection fraction (EF), and patients who died during the first year after the index event, 38 608 patients remained in the final analysis. Adherence to prescribed beta‐blockers was determined for 1 year after the index event using the national registry for prescribed drugs and was measured as proportion of days covered, the ratio between the numbers of days covered by the dispensed prescriptions and number of days in the period. As customary, a threshold level for proportion of days covered ≥80% was used to classify patients as adherent or non‐adherent. At discharge 90.6% (n = 36 869) of all patients were prescribed a beta‐blocker. Among 38 608 1 year survivors, 31.1% (n = 12 013) were non‐adherent to beta‐blockers. Patients with reduced EF with and without HF were more likely to remain adherent to beta‐blockers at 1‐year compared with patients with normal EF without HF (NEF). Being married/cohabiting and having higher income level, hypertension, ST‐elevation MI, and percutaneous coronary intervention were associated with better adherence. Adherence was independently associated with lower all‐cause mortality [hazard ratio (HR) 0.77, 95% confidence interval [CI] 0.71–0.84] and a lower risk for the composite of HF readmission/death, (HR 0.83, 95% CI 0.78–0.89, P value

Background It remains unclear whether heritable factors can contribute to risk stratification for ischemic stroke in patients with atrial fibrillation (AF). We examined whether having a sibling with ischemic stroke was associated with increased risk of ischemic stroke and mortality in patients with AF . Methods and Results In this nationwide study of the Swedish population, patients with AF and their siblings were identified from the Swedish patient registers and the Swedish MGR (Multi‐Generation Register). Ischemic stroke events were retrieved from the Swedish patient registers and CDR (Cause of Death Register). Risk of ischemic stroke was compared between patients with AF with and without a sibling affected by ischemic stroke, AF , or both ischemic stroke and AF . The total study population comprised 113 988 subjects (mean age, 60±12 years) diagnosed with AF between 1989 and 2012. In total, 11 709 of them were diagnosed with a first ischemic stroke and 20 097 died during a mean follow‐up time of 5.5 years for ischemic stroke and 5.9 years for mortality. After adjustment for covariates having a sibling with ischemic stroke, or both ischemic stroke and AF , was associated with increased risk of ischemic stroke (hazard ratio, 1.31; 95% CI, 1.23–1.40 or hazard ratio, 1.36; 95% CI , 1.24–1.49, respectively). Furthermore, ischemic stroke in a sibling was associated with all‐cause mortality (hazard ratio, 1.09; 95% CI , 1.05–1.14). In contrast, the risk of stroke was only marginally increased for patients with AF with a spouse affected by ischemic stroke. Conclusions Having a sibling affected by ischemic stroke confers an increased risk of ischemic stroke and death independently of traditional risk factors in patients with AF.

Background The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction (AMI). Patients with chronic obstructive pulmonary disease (COPD) may both benefit and be harmed by supplemental oxygen. Thus, we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic COPD patients with suspected AMI. Methods and results A total of 6629 patients with suspected AMI were randomized in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group (n=3311) and the ambient air group (n=3318), 155 and 141 patients, respectively, had COPD (prevalence of 4.5%). Patients with COPD were older, had more comorbid conditions and experienced a two-fold higher risk of death at one year (COPD: 32/296 [10.8%] vs. non-COPD 302/6333 [4.8%]). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (COPD: all-cause mortality HR 0.99 [95% CI 0.50–1.99, interaction-p=0.96]; cardiovascular death HR 0.80 [0.32–2.04, interaction-p=0.59]; rehospitalization with AMI or death HR 1.27 [0.71–2.28, interaction-p=0.46]; hospitalization for heart failure or death HR 1.08 [0.61–1.91, interaction-p=0.77]); there were no significant treatment-by-COPD interactions. Outcome Conclusions Although COPD patients had twice the mortality rate compared to non-COPD patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic COPD patients with suspected AMI revealed no evidence for benefit of routine oxygen therapy consistent with the main trial's findings.

ObjectiveTo assess the risk of future death and cardiac events following percutaneous coronary intervention (PCI) in patients using smokeless tobacco, snus, compared with patients not using snus at admission for a first PCI.MethodsThe Swedish Coronary Angiography and Angioplasty Registry is a prospective registry on coronary diagnostic procedures and interventions. A total of 74 958 patients admitted for a first PCI were enrolled between 2009 and 2018, 6790 snus users and 68 168 not using snus. We used Cox proportional hazards regression for statistical modelling on imputed datasets as well as complete-case datasets.ResultsPatients using snus were younger (mean (SD) age 61.0 (±10.2) years) than patients not using snus (67.6 (±11.1), pConclusionsSnus use at admission for a first PCI was not associated with a higher occurrence of all-cause mortality, new revascularisation or heart failure hospitalisation. Discontinuing snus after a first PCI was associated with a significantly longer duration to a subsequent PCI.

Background Patients with schizophrenia are a high-risk population due to a high prevalence of cardiovascular risk factors that translates into increased cardiovascular morbidity and mortality. Purpose To describe the characteristics of patients with schizophrenia experiencing a myocardial infarction (MI) and to analyse the 1-year major adverse cardiac events (MACE: all-cause mortality, reinfarction, stroke and heart failure) and prescriptions of guideline-recommended secondary preventive treatments at hospital discharge. Methods All patients with schizophrenia who experienced a MI in the period between 2000–2017 were identified and included from the SWEDEHEART registry and compared to patients without schizophrenia. Uni- and multivariable Cox proportional hazards and Kaplan-Meier survival models were used to compare the populations. Results The main results are shown in Table 1. Compared to the general population (n=285,325), patients with schizophrenia (n=1,008) were younger (63 vs 71 years), had a higher smoking burden and prevalence's of diabetes, heart failure, chronic obstructive pulmonary disorder and major bleeding (all p-values Table 1. Clinical endpoints at 5-years for patients with schizophrenia following a MI compared to patients without schizophrenia End-points Unadjusted HR (95% CI) Adjusted HR (95% CI) Model 1 Model 2 Model 3 MACE 1.35 (1.23–1.47)* 2.44 (2.23–2.67)* 2.20 (1.79–2.72)* 2.05 (1.63–2.58)* Mortality 1.44 (1.31–1.59)* 2.99 (2.72–3.29)* 2.53 (2.00–3.21)* 2.38 (1.84–3.09)* Reinfarction 1.00 (0.82–1.24) 1.53 (1.25–1.89)* 1.41 (0.86–2.30) 1.29 (0.77–2.13) Stroke 1.03 (0.80–1.34) 1.67 (1.29–2.17)* 1.72 (1.00–2.97) 1.72 (1.00–2.98) Heart failure 1.25 (1.10–1.42)* 2.14 (1.88–2.42)* 1.49 (1.13–1.98)* 1.39 (1.04–1.86)* *p Conclusion Patients with schizophrenia remain a high-risk population who experience a MI almost 10 years earlier than patients without schizophrenia and have worse outcome. Improved primary and secondary preventive measures are urgently warranted.

Aim: Schizophrenia is associated with high cardiovascular mortality predominantly as a result of acute coronary syndrome (ACS). The aim of this study is to analyze time trends of coronary procedures, guideline-based therapy, and all-cause mortality in patients diagnosed with schizophrenia. Methods and Results: This Danish nationwide register-based study analyzed 734 patients with a baseline diagnosis of schizophrenia and an incident diagnosis of ACS in the period between January 1, 1996, and December 31, 2015. The 734 patients with schizophrenia were matched to 2,202 psychiatric healthy controls (PHC). No change over time was seen in the relative difference between the population with schizophrenia and the PHC in the use of coronary angiography, percutaneous coronary intervention, and coronary bypass grafting, nor in 1-year mortality or guideline-based therapy following ACS. Patients with schizophrenia had higher prevalence rates of diabetes, chronic obstructive pulmonary disease, and stroke, and a lower prevalence of hypertension (p < 0.05). Conclusion: The gap in the use of coronary procedures, guideline-based therapy, and all-cause mortality following ACS in patients with schizophrenia compared to those without has remained constant over the past 2 decades.

Background The impact of baseline anemia in a contemporary acute coronary syndrome ( ACS ) population undergoing percutaneous coronary intervention in the era of predominant radial artery access, potent P2Y12 inhibition, and rare use of glycoprotein II b/ III a inhibitors has not been adequately studied. Methods and Results ACS patients who underwent percutaneous coronary intervention between 2014 and 2016 in the VALIDATE ‐ SWEDEHEART (Bivalirudin Versus Heparin in ST ‐Segment and Non– ST ‐Segment Elevation Myocardial Infarction in Patients on Modern Antiplatelet Therapy in the Swedish Web System for Enhancement and Development of Evidence‐Based Care in Heart Disease Evaluated According to Recommended Therapies Registry) trial without missing values for hemoglobin were included (n=5482). Mortality, myocardial reinfarction, and major bleeding at 180 days were assessed using Cox regression models and propensity score matching. All studied comorbidities were more common in ACS patients who had anemia (n=792). ACS patients with anemia had higher rates of 180‐day mortality (6.9% versus 2.1%; hazard ratio, 1.9; 95% CI , 1.3–2.7; P CI , 1.1–2.7; P =0.013), and major bleeding (13.4% versus 8.2%; hazard ratio, 1.3; 95% CI , 1.0–1.6; P =0.041). The results were most evident in patients with a hemoglobin value Conclusions Baseline anemia in ACS patients undergoing percutaneous coronary intervention, treated according to current practice including routine radial artery access, constitutes a high‐risk feature for both ischemic events, bleeding events, and mortality. A multidisciplinary approach is warranted to maximize benefit and minimize patient risk. Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT02311231.

Background: The DETermination of the role of Oxygen in suspected Acute Myocardial Infarction (DETO2X-AMI) trial did not find any benefit of oxygen therapy compared to ambient air in normoxemic patients with suspected acute myocardial infarction. Patients with chronic obstructive pulmonary disease may both benefit and be harmed by supplemental oxygen. Thus we evaluated the effect of routine oxygen therapy compared to ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction. Methods and results: A total of 6629 patients with suspected acute myocardial infarction were randomly assigned in the DETO2X-AMI trial to oxygen or ambient air. In the oxygen group (n=3311) and the ambient air group (n=3318), 155 and 141 patients, respectively, had chronic obstructive pulmonary disease (prevalence of 4.5%). Patients with chronic obstructive pulmonary disease were older, had more comorbid conditions and experienced a twofold higher risk of death at one year (chronic obstructive pulmonary disease: 32/296 (10.8%) vs. non-chronic obstructive pulmonary disease: 302/6333 (4.8%)). Oxygen therapy compared to ambient air was not associated with improved outcomes at 365 days (chronic obstructive pulmonary disease: all-cause mortality hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.50–1.99, Pinteraction=0.96); cardiovascular death HR 0.80, 95% CI 0.32–2.04, Pinteraction=0.59); rehospitalisation with acute myocardial infarction or death HR 1.27, 95% CI 0.71–2.28, Pinteraction=0.46); hospitalisation for heart failure or death HR 1.08, 95% CI 0.61–1.91, Pinteraction=0.77]); there were no significant treatment-by-chronic obstructive pulmonary disease interactions. Conclusions: Although chronic obstructive pulmonary disease patients had twice the mortality rate compared to non-chronic obstructive pulmonary disease patients, this prespecified subgroup analysis from the DETO2X-AMI trial on oxygen therapy versus ambient air in normoxemic chronic obstructive pulmonary disease patients with suspected acute myocardial infarction revealed no evidence for benefit of routine oxygen therapy consistent with the main trial’s findings. Clinical Trials Registration: NCT02290080

AIMS: We aimed to investigate major adverse cardiac events (MACE: defined as all-cause mortality, re-infarction, and stroke), length of hospital stays (LOS), and comorbidities following acute coronary syndrome (ACS) in a population with schizophrenia.METHODS AND RESULTS: This Danish register study included patients diagnosed with ACS in the period between 1995 and 2013 with a preceding diagnosis of schizophrenia (n = 726). Each patient was matched to a psychiatric healthy control 1:2 on sex, age, year of ACS diagnosis, and number of comorbidities (total n = 2178). After performing Cox regression and Kaplan-Meier analyses, we found that patients with schizophrenia had an increased risk of MACE [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.45-1.81], all-cause mortality (HR 2.54, 95% CI 2.22-2.90), and stroke (HR 1.51, 95% CI 1.15-1.99). No differences were found in the re-infarction rates and LOS between the populations. Patients with schizophrenia had higher prevalence's diabetes, anaemia, heart failure, cardiomyopathy, chronic obstructive lung disease, and stroke. Nonetheless, we found lower prevalence's of hypertension and hyperlipidaemia.CONCLUSION: Schizophrenia is associated with an increased risk of MACE despite a lower prevalence of some diagnosed traditional cardiac risk factors which may indicate underdiagnosing of these. Awareness of treatment bias may improve this increased risk. (Less)

ObjectivesThe objectives of this study were to investigate if findings by intracoronary near-infrared spectroscopy (NIRS) and intravascular ultrasound (IVUS) are associated with future cardiovascular events and if NIRS can differentiate culprit from non-culprit segments in patients with coronary artery disease.MethodsThe study included 144 patients with coronary artery disease undergoing percutaneous coronary intervention and combined NIRS-IVUS imaging at two Swedish hospitals. The NIRS-derived lipid core burden index (LCBI), the 4 mm segment with maximum LCBI (MaxLCBI4mm) and the IVUS-derived maximum plaque burden (MaxPB) were analysed within the culprit segment and continuous 10 mm non-culprit segments of the index culprit vessels. The association with future major adverse cardiovascular and cerebrovascular events (MACCE), defined as all-cause mortality, acute coronary syndrome requiring revascularisation and cerebrovascular events during follow-up was evaluated using multivariable Cox regressions. A receiver operating characteristic (ROC) analysis was performed to test the ability of NIRS to discriminate culprit against non-culprit segments.ResultsA non-culprit maxLCBI4mm ≥400 (HR: 3.67, 95% CI 1.46 to 9.23, p=0.006) and a non-culprit LCBI ≥ median (HR: 3.08, 95% CI 1.11 to 8.56, p=0.031) were both significantly associated with MACCE, whereas a non-culprit MaxPB ≥70% (HR: 0.61, 95% CI 0.08 to 4.59, p=0.63) was not. The culprit segments had larger lipid cores compared with non-culprit segments (MaxLCBI4mm 425 vs 74, pConclusionA maxLCBI4mm ≥400 and LCBI ≥ median, assessed by NIRS in non-culprit segments of a culprit artery, were significantly associated with patient-level MACCE. NIRS furthermore adequately discriminated culprit against non-culprit segments in patients with coronary disease.

Background Acquired loss of the largest von Willebrand factor multimers is a common hemostatic disturbance in patients with aortic valve stenosis (AS), resulting in impaired platelet adhesion and increased bleeding risk. AS is also associated with atherosclerosis and myocardial infarction (MI). Our aim was to study the clinical outcomes associated with AS in MI patients treated with dual antiplatelet therapy (DAPT) in a nationwide hospital-based register study. Methods Based on nationwide hospital discharge registers from Sweden (2005–2010) and Denmark (2005–2015), we calculated 1-year incidence rates and hazard ratios of bleeding, recurrent MI, and all-cause mortality in MI patients with and without AS treated with DAPT. Results from both countries were also combined in a meta-analysis. Results We included 50,460 MI patients from Sweden and 50,307 MI patients from Denmark, of which 3% had AS. The bleeding rates (per 100 person-years) in Sweden and Denmark were 3.2 and 3.3 among patients without AS vs. 9.2 and 8.3 among patients with AS. All-cause mortality rates were 7.1 vs. 28.7 in Sweden and 5.8 vs. 30.7 in Denmark among patients without and with AS, respectively. Patients with AS had an increased risk of bleeding, recurrent MI and all-cause mortality. Combined results from both countries were similar for bleeding (hazard ratio 1.59 [0.98–2.59]), recurrent MI (1.78 [1.25–2.54]), and all-cause mortality (1.76 [1.26–2.47]). Conclusion AS was associated with an increased risk of bleeding, recurrent MI and mortality after MI when treated with DAPT. Individualized selection of antiplatelet therapy may be warranted in this high-risk population.

The authors sought to compare reclassification of treatment strategy following instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR).iFR was noninferior to FFR in 2 large randomized controlled trials in guiding coronary revascularization. Reclassification of treatment strategy by FFR is well-studied, but similar reports on iFR are lacking.The iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome Trial) study randomized 2,037 participants with stable angina or acute coronary syndrome to treatment guided by iFR or FFR. Interventionalists entered the preferred treatment (optimal medical therapy [OMT], percutaneous coronary intervention [PCI], or coronary artery bypass grafting [CABG]) on the basis of coronary angiograms, and the final treatment decision was mandated by the iFR/FFR measurements.In the iFR/FFR (n = 1,009/n = 1,004) populations, angiogram-based treatment approaches were similar (p = 0.50) with respect to OMT (38%/35%), PCI of 1 (37%/39%), 2 (15%/16%), and 3 vessels (2%/2%) and CABG (8%/8%). iFR and FFR reclassified 40% and 41% of patients, respectively (p = 0.78). The majority of reclassifications were conversion of PCI to OMT in both the iFR/FFR groups (31.4%/29.0%). Reclassification increased with increasing number of lesions evaluated (odds ratio per evaluated lesion for FFR: 1.46 [95% confidence interval: 1.22 to 1.76] vs. iFR 1.37 [95% confidence interval: 1.18 to 1.59]). Reclassification rates for patients with 1, 2, and 3 assessed vessels were 36%, 52%, and 53% (p 0.01).Reclassification of treatment strategy of intermediate lesions was common and occurred in 40% of patients with iFR or FFR. The most frequent reclassification was conversion from PCI to OMT regardless of physiology modality. Irrespective of the physiological index reclassification of angiogram-based treatment strategy increased with the number of lesions evaluated.

BackgroundST-elevation myocardial infarction (STEMI) occurs as a result of rupture of an atherosclerotic plaque in the coronary arteries. Limited data exist regarding the impact of culprit coronary vessel on hard clinical event rates. This study investigated the impact of culprit vessel on outcomes after primary percutaneous coronary intervention (PCI) of STEMI.MethodsA total of 29 832 previously cardiac healthy patients who underwent primary PCI between 2003 and 2014 were prospectively included from the Swedish Coronary Angiography and Angioplasty Registry and the Registry of Information and Knowledge about Swedish Heart Intensive care Admissions. Patients were stratified into three groups based on culprit vessel (right coronary artery (RCA), left anterior descending artery (LAD) and left circumflex artery (LCx)). The primary outcome was 1-year mortality. The secondary outcomes included 30-day and 5-year mortality, as well as heart failure, stroke, bleeding and myocardial reinfarction at 30 days, 1 year and 5 years. Univariable and multivariable analyses were done using Cox regression models.ResultsOne-year analyses revealed that LAD infarctions had the highest increased risk of death, heart failure and stroke compared with RCA infarctions, which had the lowest risk. Sensitivity analyses revealed that reduced left ventricular ejection fraction on discharge partially explained this increased relative risk in mortality. Furthermore, landmark analyses revealed that culprit vessel had no significant influence on 1-year mortality if a patient survived 30 days after myocardial infarction. Subgroup analyses revealed female sex and multivessel disease (MVD) as significant high-risk groups with respect to 1-year mortality.ConclusionsLAD and LCx infarctions had a relatively higher adjusted mortality rate compared with RCA infarctions, with LAD infarctions in particular being associated with an increased risk of heart failure, stroke and death. Culprit vessel had limited influence on mortality after 1 month. High-risk patient groups include LAD infarctions in women or with concomitant MVD.

Background— Familial aggregation has been described for primary mitral regurgitation (MR) caused by mitral valve prolapse. We hypothesized that heritability of MR exists across different MR subtypes including nonprimary MR. Methods and Results— Study participants were FHS (Framingham Heart Study) Generation 3 (Gen 3) and Gen 2 cohort participants and all adult Swedish siblings born after 1932 identified in 1997 and followed through 2010. MR was defined as ≥ mild regurgitation on color Doppler in FHS and from International Classification of Diseases codes in Sweden. We estimated the association of sibling MR with MR in Gen 2/Gen 3/Swedish siblings. We also estimated heritability of MR in 539 FHS pedigrees (7580 individuals). Among 5132 FHS Gen 2/Gen 3 participants with sibling information, 1062 had MR. Of siblings with sibling MR, 28% (500/1797) had MR compared with 17% (562/3335) without sibling MR (multivariable-adjusted odds ratio, 1.20; 95% confidence interval [CI], 1.01–1.43; P =0.04). When we combined parental and sibling data in FHS pedigrees, heritability of MR was estimated at 0.15 (95% CI, 0.07–0.23), 0.12 (95% CI, 0.04–0.20) excluding mitral valve prolapse, and 0.44 (95% CI, 0.15–0.73) for ≥ moderate MR only (all P P Conclusions— Familial clustering of MR exists in the community, supporting a genetic susceptibility common to primary and nonprimary MR. Further studies are needed to elucidate the common regulatory pathways that may lead to MR irrespective of its cause.

Background: Pre-treatment with unfractionated heparin is common in ST-segment elevation myocardial infarction (STEMI) protocols, but the effect on intracoronary thrombus burden is unknown. We studied the effect of heparin pre-treatment on intracoronary thrombus burden and Thrombolysis in Myocardial Infarction (TIMI) flow prior to percutaneous coronary intervention in patients with STEMI. Methods: The Thrombus Aspiration in ST-Elevation Myocardial Infarction in Scandinavia (TASTE) trial angiographically assessed intracoronary thrombus burden and TIMI flow, prior to percutaneous coronary intervention, in patients with STEMI. In this observational sub-study, patients pre-treated with heparin were compared with patients not pre-treated with heparin. Primary end points were a visible intracoronary thrombus and total vessel occlusion prior to percutaneous coronary intervention. Secondary end points were in-hospital bleeding, in-hospital stroke and 30-day all-cause mortality. Results: Heparin pre-treatment was administered in 2898 out of 7144 patients (41.0%). Patients pre-treated with heparin less often presented with an intracoronary thrombus (61.3% vs. 66.0%, pConclusions: Heparin pre-treatment was independently associated with a lower risk of intracoronary thrombus and total vessel occlusion before percutaneous coronary intervention in patients with STEMI, without evident safety concerns, in this large multi-centre observational study.

Background— Small observational studies have indicated better outcome with intravascular ultrasound (IVUS) guidance when performing unprotected left main coronary artery (LMCA) percutaneous coronary intervention (PCI), but the overall picture remains inconclusive and warrants further investigation. We studied the impact of IVUS guidance on outcome in patients undergoing unprotected LMCA PCI in a Swedish nationwide observational study. Methods and Results— Patients who underwent unprotected LMCA PCI between 2005 and 2014 because of stable coronary artery disease or acute coronary syndrome were included from the nationwide SCAAR (Swedish Coronary Angiography and Angioplasty Registry). Of 2468 patients, IVUS guidance was used in 621 (25.2%). The IVUS group was younger (median age, 70 versus 75 years) and had fewer comorbidities but more complex lesions. IVUS was associated with larger stent diameters (median, 4 mm versus 3.5 mm). After adjusting for potential confounders, IVUS was associated with significantly lower occurrence of the primary composite end point of all-cause mortality, restenosis, or definite stent thrombosis (hazard ratio, 0.65; 95% confidence interval, 0.50–0.84) and all-cause mortality alone (hazard ratio, 0.62; 95% confidence interval, 0.47–0.82). In 340 propensity score–matched pairs, IVUS was also associated with significantly lower occurrence of the primary end point (hazard ratio, 0.54; 95% confidence interval, 0.37–0.80). Conclusions— IVUS was associated with an independent and significant outcome benefit when performing unprotected LMCA PCI. Potential mediators of this benefit include larger and more appropriately sized stents, perhaps translating into lower risk of subsequent stent thrombosis. Although residual confounding cannot be ruled out, our findings indicate a possible hazard when performing unprotected LMCA PCI without IVUS guidance.

Our aim was to investigate the impact of intravenous (IV) beta-blocker therapy on short-term mortality and other in-hospital events in patients with ST-segment elevation myocardial infarction (STEMI) treated with dual antiplatelet therapy (DAPT) and primary percutaneous coronary intervention (PCI).Using the nationwide Swedish Web-system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) registry, we identified all patients with STEMI undergoing PCI between 2006 and 2013. Patients with cardiogenic shock and cardiac arrest at presentation were excluded. The primary endpoint was mortality within 30 days. Secondary endpoints were in-hospital events (mortality, cardiogenic shock and left ventricular ejection fraction [LVEF]40% at discharge). We adjusted for confounders with a multivariable model and propensity score matching. Out of 16,909 patients, 2,876 (17.0%) were treated with an IV beta-blocker. After adjusting for confounders, the IV beta-blocker group had higher 30-day all-cause mortality (HR: 1.44, 95% CI: 1.14-1.83), more in-hospital cardiogenic shock (OR: 1.53, 95% CI: 1.09-2.16) and were more often discharged with an LVEF40% (OR: 1.70, 95% CI: 1.51-1.92).In this large nationwide observational study, the use of IV beta-blockers in patients with STEMI treated with primary PCI was associated with higher short-term mortality, lower LVEF at discharge, as well as a higher risk of in-hospital cardiogenic shock.

Background— Aortic valvular stenosis (AS) is the most common cause of cardiac valvular replacement surgery. During the last century, the pathogenesis of AS has undergone transitions in developed countries, from rheumatic heart disease to a degenerative calcific pathogenesis. Although a familial component has been described for a subset of cases with a bicuspid valve, data are limited on the overall familial aggregation of this disease. Methods and Results— Contemporary information on 6 117 263 Swedish siblings, of which 13 442 had a clinical diagnosis of AS, was collected from the nationwide Swedish Multi-Generation Register and the National Patient Register. A total of 4.8% of AS cases had a sibling history of AS. Having at least 1 sibling with AS was associated with a hazard ratio of 3.41 (95% confidence interval, 2.23–5.21) to be diagnosed with AS in an adjusted model. Individuals with >1 sibling with AS had an exceptionally high risk (hazard ratio, 32.84) but were uncommon (34 siblings from 11 sibships). In contrast, spouses of subjects with AS were only slightly more likely to be diagnosed with AS compared with subjects without spousal AS (hazard ratio 1.16 for husbands and 1.18 for wives). Conclusions— A sibling history of clinically diagnosed AS was associated with increased risk of AS. Spouses of patients with AS only had a modest risk increase, suggesting that shared adult environmental factors contribute less to the development of AS than genetic factors.

Background Treatment with renin‐angiotensin system ( RAS ) inhibitors might restrain the structural/electrical remodeling associated with atrial fibrillation (AF). Limited evidence exists regarding the potential benefits of RAS inhibition post‐acute myocardial infarction (AMI) in patients with AF. This study sought to assess the association between RAS inhibition and all‐cause mortality and new‐onset AF in patients with/without congestive heart failure ( CHF ) post‐AMI. Methods and Results Patients hospitalized for AMI between 2006 and 2012 were identified in Swedish registries. Patients were stratified in 4 subgroups; patients with CHF and AF (n=11 489); patients with CHF without AF (n=31 676); patients with AF without CHF (n=10 066); and patients without both CHF and AF (n=59 417). Patients exposed to RAS inhibition were compared to nontreated. Three‐year risk of all‐cause mortality and new‐onset AF was assessed using adjusted Cox regression analyses. At discharge, 83 291 (73.9%) patients received RAS inhibition. RAS inhibition was associated with lower 3‐year risk of all‐cause mortality in CHF patients with AF, adjusted hazard ratio ( HR ) with 95% CI 0.75 (0.70–0.81), CHF patients without AF, HR 0.65 (0.60–0.69), AF patients without CHF , HR 0.82 (0.75–0.90), and in patients without CHF and AF, HR 0.76 (0.72–0.81), respectively. RAS inhibition was not associated with lower 3‐year risk of new‐onset AF in patients without AF but with/without CHF ; HR 0.96 (0.84–1.10) and 1.12 (1.02–1.22), respectively. Conclusions RAS inhibition post‐AMI was associated with lower risk of all‐cause mortality. In patients with/without CHF , RAS inhibition was not associated with lower incidence of new‐onset AF.

Objective Transitions in the spectrum of valvular heart diseases (VHDs) in developed countries over the 20th century have been reported from clinical case series, but large, contemporary population-based studies are lacking. Methods We used nationwide registers to identify all patients with a first diagnosis of VHD at Swedish hospitals between 2003 and 2010. Age-stratified and sex-stratified incidence of each VHD and adjusted comorbidity profiles were assessed. Results In the Swedish population (n=10 164 211), the incidence of VHD was 63.9 per 100 000 person-years, with aortic stenosis (AS; 47.2%), mitral regurgitation (MR; 24.2%) and aortic regurgitation (AR; 18.0%) contributing most of the VHD diagnoses. The majority of VHDs were diagnosed in the elderly (68.9% in subjects aged ≥65 years), but pulmonary valve disease incidence peaked in newborns. Incidences of AR, AS and MR were higher in men who were also more frequently diagnosed at an earlier age. Mitral stenosis (MS) incidence was higher in women. Rheumatic fever was rare. Half of AS cases had concomitant atherosclerotic vascular disease (48.4%), whereas concomitant heart failure and atrial fibrillation were common in mitral valve disease and tricuspid regurgitation. Other common comorbidities were thoracic aortic aneurysms in AR (10.3%), autoimmune disorders in MS (24.5%) and abdominal hernias or prolapse in MR (10.7%) and TR (10.3%). Conclusions Clinically diagnosed VHD was primarily a disease of the elderly. Rheumatic fever was rare in Sweden, but specific VHDs showed a range of different comorbidity profiles . Pronounced sex-specific patterns were observed for AR and MS, for which the mechanisms remain incompletely understood.

Aims Non-ST-elevation acute coronary syndrome (NSTE-ACS) is present in about 60-70% of patients admitted with acute coronary syndromes in clinical practice. This study provides a 'real-life' overview of NSTE-ACS patient characteristics, dual antiplatelet therapy clinical practice, and outcomes at both the time of discharge from hospital and up to 1-year post-discharge. Methods and results A total of 10 registries (documenting 84 054 NSTE-ACS patients) provided data in a systematic manner on patient characteristics and outcomes for NSTE-ACS in general, and 6 of these (with 52 173 NSTE-ACS patients) also provided more specific data according to P2Y12 receptor inhibitor used. Unadjusted analyses were performed at the study level, and no formal meta-analysis was performed due to large heterogeneity between studies in the settings, patient characteristics, and outcome definitions. All-cause death rates across registries ranged from 0.76 to 4.79% in-hospital, from 1.61 to 6.65% at 30 days, from 3.66 to 7.16% at 180 days, and from 3.14 to 9.73% at 1 year. Major bleeding events were reported in up to 2.77% of patients while in hospital (in seven registries), up to 1.08% at 30 days (data from one registry only), and 2.06% at 1 year (one registry). Conclusions There were substantial differences in the use of and patient selection for clopidogrel, prasugrel, and ticagrelor, which were associated with differences in short-and long-term ischaemic and bleeding events. In future registries, data collection should be performed in a more standardized way with respect to endpoints, definitions, and time points.

Aims Among acute coronary syndromes (ACS), ST-segment elevation myocardial infarction (STEMI) has the most severe early clinical course. We aimed to describe the effectiveness and safety of P2Y12 receptor inhibitors in patients with STEMI based on the data from contemporary European ACS registries. Methods and results Twelve registries provided data in a systematic manner on outcomes in STEMI patients overall, and seven of these also provided data for P2Y12 receptor inhibitor-based dual antiplatelet therapy. The registries were heterogeneous in terms of site, patient, and treatment selection, as well as in definition of endpoints (e.g. bleeding events). All-cause death rates based on the data from 84 299 patients (9612 patients on prasugrel, 11 492 on ticagrelor, and 27 824 on clopidogrel) ranged between 0.49 and 6.68% in-hospital, between 3.07 and 7.95% at 30 days (reported in 6 registries), between 8.15 and 9.13% at 180 days, and between 2.41 and 9.58% at 1 year (5 registries). Major bleeding rates were 0.09-3.55% in hospital (8 registries), 0.09-1.65% at 30 days, and 1.96% at 1 year (only 1 registry). Fatal/life-threatening bleeding was rare occurring between 0.08 and 0.13% in-hospital (4 registries) and 1.96% at 1 year (1 registry). Conclusions Real-world evidence from European contemporary registries shows that death, ischaemic events, and bleeding rates are lower than those reported in Phase III studies of P2Y12 inhibitors. Regarding individual P2Y12 inhibitors, patients on prasugrel, and, to a lesser degree, ticagrelor, had fewer ischaemic and bleeding events at all time points than clopidogrel-treated patients. These findings are partly related to the fact that the newer agents are used in younger and less ill patients.