Effects of pre-existing type 1 diabetes mellitus on survival outcome following out-of-hospital cardiac arrest: a registry-based observational study in Sweden.

BACKGROUND: It has been estimated that 80% of cases of out-of-hospital cardiac arrest (OHCA) are due to cardiac causes. It is well-documented that diabetes is a risk factor for conditions associated with sudden cardiac arrest. Type 1 diabetes (T1D) displays a threefold to fivefold increased risk of cardiovascular disease and death compared with the general population. OBJECTIVE: This study aims to assess the characteristics and survival outcomes of individuals with and without T1D who experienced an OHCA. Design: A registry-based nationwide observational study with two cohorts, patients with T1D and patients without T1D. Setting: All emergency medical services and hospitals in Sweden were included in the study. PARTICIPANTS: Using the Swedish Cardiopulmonary Resuscitation Registry, we enrolled 54 568 cases of OHCA where cardiopulmonary resuscitation was attempted between 2010 and 2020. Among them, 448 patients with T1D were identified using International Classification of Diseases-code: E10. METHODS: Survival analysis was performed using Kaplan-Meier and logistic regression. Multiple regression was adjusted for age, sex, cause of arrest, prevalence of T1D and time to cardiopulmonary resuscitation. MAIN OUTCOME MEASURES: The outcomes were discharge status (alive vs dead), 30 days survival and neurological outcome at discharge. RESULTS: There were no significant differences in patients discharged alive with T1D 37.3% versus, 46% among cases without T1D. There was also no difference in neurological outcome. Kaplan-Meier curves yielded no significant difference in long-term survival. Multiple regression showed no significant association with survival after accounting for covariates, OR 0.99 (95% CI 0.96 to 1.02), p value=0.7. Baseline characteristics indicate that patients with T1D were 5 years younger at OHCA occurrence and had proportionally fewer cases of heart disease as the cause of arrest (57.6% vs 62.7%). CONCLUSION: We conclude, with the current sample size, that there is no statistically significant difference in long-term or short-term survival between patients with and without T1D following OHCA.

Heart disease in pregnancy and risk of pre-eclampsia: a Swedish register-based study.

BACKGROUND AND AIMS: Pre-eclampsia complicates 3-5% of pregnancies worldwide and is associated with adverse outcomes for the mother and the offspring. Pre-eclampsia and heart failure have common risk factors, including hypertension, obesity and diabetes. It is not known whether heart failure increases the risk of pre-eclampsia. This study examines whether pregestational heart failure increases the risk of pre-eclampsia. METHODS: In a registry-based case-cohort study that included all pregnancies in Sweden (n=3 125 527) between 1990 and 2019, all pregnancies with pre-eclampsia (n=90 354) were identified and up to five control pregnancies (n=451 466) for each case were chosen, matched on the mother's birth year. Multiple logistic regression analysis was used to evaluate the impact of heart failure on the risk of pre-eclampsia, with adjustment for established risk factors and other cardiovascular diseases. RESULTS: Women with heart failure had no increased risk for pre-eclampsia, OR 1.02 (95% CI 0.69 to 1.50). Women with valvular heart disease had an increased OR of preterm pre-eclampsia, with an adjusted OR of 1.78 (95% CI 1.04 to 3.06). Hypertension and diabetes were independent risk factors for pre-eclampsia. Obesity, multifetal pregnancies, in vitro fertilisation, older age, Nordic origin and nulliparity were more common among women who developed pre-eclampsia compared with controls. CONCLUSION: Women with heart failure do not have an increased risk of pre-eclampsia. However, women with valvular heart disease prior to pregnancy have an increased risk of developing preterm pre-eclampsia independent of other known risk factors.

Risk of uterine rupture in multiparous women after induction of labor with prostaglandin: A national population-based cohort study.

OBJECTIVE: To assess whether, after induction of labor with prostaglandin, multiparous (≥2 para) women have an increased risk of uterine rupture compared with nulliparous or uniparous women. METHODS: This was a retrospective population-based cohort study including women who underwent induction with prostaglandin in all maternity wards in Sweden between May 1996 and December 2019 (n = 56 784). The study cohort was obtained by using data from the Swedish Medical Birth Register, which contains information from maternity and delivery records. The main outcome measure was uterine rupture. RESULTS: Overall, multiparous women induced with prostaglandin had an increased risk of uterine rupture compared with nulliparous women (adjusted odds ratio [OR], 3.33 [95% confidence interval (CI), 1.38-8.04]; P < 0.007). Multiparous women with no previous cesarean section (CS) induced with prostaglandin had more than three times higher risk of uterine rupture (crude OR, 3.55 [95% Cl, 1.48-8.53]; P = 0.005) compared with nulliparous women and four times higher risk compared with uniparous women (OR, 4.10 [95% CI, 1.12-15.00]; P < 0.033). Multiparous women with previous CS had a decreased risk of uterine rupture compared with uniparous women with one previous CS (crude OR, 0.41 [95% Cl, 0.21-0.78]; P = 0.007). CONCLUSION: Our study implies that multiparity in women with no previous CS is a risk factor for uterine rupture when induced with prostaglandin. This should be taken into consideration when deciding on the appropriate method of induction.

Adherence to CPAP Treatment and the Risk of Recurrent Cardiovascular Events: A Meta-Analysis.

Importance: The effect of continuous positive airway pressure (CPAP) on secondary cardiovascular disease prevention is highly debated. Objective: To assess the effect of CPAP treatment for obstructive sleep apnea (OSA) on the risk of adverse cardiovascular events in randomized clinical trials. Data Sources: PubMed (MEDLINE), EMBASE, Current Controlled Trials: metaRegister of Controlled Trials, ISRCTN Registry, European Union clinical trials database, CENTRAL (Cochrane Central Register of Controlled Trials), and ClinicalTrials.gov databases were systematically searched through June 22, 2023. Study Selection: For qualitative and individual participant data (IPD) meta-analysis, randomized clinical trials addressing the therapeutic effect of CPAP on cardiovascular outcomes and mortality in adults with cardiovascular disease and OSA were included. Data Extraction and Synthesis: Two reviewers independently screened records, evaluated potentially eligible primary studies in full text, extracted data, and cross-checked errors. IPD were requested from authors of the selected studies (SAVE [NCT00738179], ISAACC [NCT01335087], and RICCADSA [NCT00519597]). Main Outcomes and Measures: One-stage and 2-stage IPD meta-analyses were completed to estimate the effect of CPAP treatment on risk of recurrent major adverse cardiac and cerebrovascular events (MACCEs) using mixed-effect Cox regression models. Additionally, an on-treatment analysis with marginal structural Cox models using inverse probability of treatment weighting was fitted to assess the effect of good adherence to CPAP (≥4 hours per day). Results: A total of 4186 individual participants were evaluated (82.1% men; mean [SD] body mass index, 28.9 [4.5]; mean [SD] age, 61.2 [8.7] years; mean [SD] apnea-hypopnea index, 31.2 [17] events per hour; 71% with hypertension; 50.1% receiving CPAP [mean {SD} adherence, 3.1 {2.4} hours per day]; 49.9% not receiving CPAP [usual care], mean [SD] follow-up, 3.25 [1.8] years). The main outcome was defined as the first MACCE, which was similar for the CPAP and no CPAP groups (hazard ratio, 1.01 [95% CI, 0.87-1.17]). However, an on-treatment analysis by marginal structural model revealed a reduced risk of MACCEs associated with good adherence to CPAP (hazard ratio, 0.69 [95% CI, 0.52-0.92]). Conclusions and Relevance: Adherence to CPAP was associated with a reduced MACCE recurrence risk, suggesting that treatment adherence is a key factor in secondary cardiovascular prevention in patients with OSA.

Obstructive sleep apnea severity and prevalent atrial fibrillation in a sleep clinic cohort with versus without excessive daytime sleepiness.

BACKGROUND: Obstructive sleep apnea (OSA) is associated with atrial fibrillation (AF) in cardiac cohorts. Less is known regarding the magnitude of this association in a sleep clinic cohort with vs. without excessive daytime sleepiness (EDS). OBJECTIVES: To explore the association of OSA severity with AF in a sleep clinic cohort stratified by EDS. PATIENTS AND METHODS: All consecutive adults (n = 3814) admitted to the Skaraborg Hospital, Sweden between Jan 2005 and December 2011 were registered in a local database, and the follow-up ended in December 2018. OSA was defined as an apnea-hypopnea index (AHI) ≥5 events/h. Mild OSA was defined as AHI ≥5 & AHI<15 events/h; moderate OSA as AHI ≥15 & AHI<30 events/h; and severe OSA as AHI ≥30 events/h. EDS was defined as an Epworth Sleepiness Scale score ≥11. We conducted cross-sectional analyzes of the prevalent AF across the OSA severity categories and logistic regression analyzes stratified by EDS. RESULTS: In all, 202 patients (5.3%) had AF at baseline, 1.6% in no-OSA, 3.9% in mild OSA, 5.2% in moderate OSA, and 7.6% in severe OSA, respectively (p < 0.001). The stratified analyzes revealed that patients with severe OSA without EDS had an increased risk for prevalent AF (OR 2.54, 95% CI 1.05-6.16; p = 0.039) independent of the confounding factors. CONCLUSIONS: There was an independent dose-response relationship between OSA and prevalent AF among the non-sleepy phenotype in this sleep clinic cohort. Since adherence to OSA treatment is challenging in the absence of EDS, these patients may have increased risk for adverse cardiovascular outcomes.

Cardiovascular Outcomes in Adults with Coronary Artery Disease and Obstructive Sleep Apnea with versus without Excessive Daytime Sleepiness in the RICCADSA Cinical Trial.

Rationale: Recent randomized controlled trials did not show cardiovascular benefits of continuous positive airway pressure (CPAP) in adults with coronary artery disease (CAD) and obstructive sleep apnea (OSA) in intention-to-treat analyses. It has been argued that exclusion of patients with OSA with excessive daytime sleepiness (EDS), who may be most likely to benefit from CPAP treatment, may be a reason for the null results. Objectives: We addressed 1) the effect of concomitant EDS on adverse outcomes in patients with CAD and OSA; and 2) whether the cardiovascular benefit of CPAP adherence differs between individuals with versus without EDS. Methods: This was a secondary analysis of the RICCADSA (Randomized Intervention with CPAP in CAD and Obstructive Sleep Apnea) trial, conducted in Sweden between 2005 and 2013. Data were analyzed from 155 patients with CAD with OSA (apnea-hypopnea index ⩾ 15/h) and EDS (Epworth Sleepiness Scale score ⩾ 10), who were allocated to CPAP and 244 patients without EDS (ESS < 10), who were randomized to CPAP or no CPAP. Patients who were allocated to no CPAP or were nonadherent (CPAP usage < 4 h/night) were compared with adherent patients (CPAP usage ⩾ 4 h/night) at 1-year follow-up. Inverse probability of treatment weighting was applied to mimic randomization of EDS. The primary endpoint was the first event of repeat revascularization, myocardial infarction, stroke, or cardiovascular mortality. Results: The median follow-up was 52.2 months. The incidence of the primary endpoint did not differ significantly between the EDS versus no-EDS groups in the entire cohort. Within the adherent group, patients without EDS had a significantly decreased risk compared with patients with EDS (adjusted hazard ratio, 0.41; 95% confidence interval, 0.20-0.85; P = 0.02). Conclusions: Adverse cardiovascular outcomes did not differ by degrees of EDS for patients with CAD with OSA who were untreated or nonadherent to treatment. CPAP use, at least 4 h/night, was associated with reduced adverse outcomes in participants without EDS. Clinical trial registered with www.clinicaltrials.gov (NCT00519597).

Association Between History of Adverse Pregnancy Outcomes and Coronary Artery Disease Assessed by Coronary Computed Tomography Angiography.

Importance: Adverse pregnancy outcomes are recognized risk enhancers for cardiovascular disease, but the prevalence of subclinical coronary atherosclerosis after these conditions is unknown. Objective: To assess associations between history of adverse pregnancy outcomes and coronary artery disease assessed by coronary computed tomography angiography screening. Design, Setting, and Participants: Cross-sectional study of a population-based cohort of women in Sweden (n = 10 528) with 1 or more deliveries in 1973 or later, ascertained via the Swedish National Medical Birth Register, who subsequently participated in the Swedish Cardiopulmonary Bioimage Study at age 50 to 65 (median, 57.3) years in 2013-2018. Delivery data were prospectively collected. Exposures: Adverse pregnancy outcomes, including preeclampsia, gestational hypertension, preterm delivery, small-for-gestational-age infant, and gestational diabetes. The reference category included women with no history of these exposures. Main Outcomes and Measures: Coronary computed tomography angiography indexes, including any coronary atherosclerosis, significant stenosis, noncalcified plaque, segment involvement score of 4 or greater, and coronary artery calcium score greater than 100. Results: A median 29.6 (IQR, 25.0-34.9) years after first registered delivery, 18.9% of women had a history of adverse pregnancy outcomes, with specific pregnancy histories ranging from 1.4% (gestational diabetes) to 9.5% (preterm delivery). The prevalence of any coronary atherosclerosis in women with a history of any adverse pregnancy outcome was 32.1% (95% CI, 30.0%-34.2%), which was significantly higher (prevalence difference, 3.8% [95% CI, 1.6%-6.1%]; prevalence ratio, 1.14 [95% CI, 1.06-1.22]) compared with reference women. History of gestational hypertension and preeclampsia were both significantly associated with higher and similar prevalence of all outcome indexes. For preeclampsia, the highest prevalence difference was observed for any coronary atherosclerosis (prevalence difference, 8.0% [95% CI, 3.7%-12.3%]; prevalence ratio, 1.28 [95% CI, 1.14-1.45]), and the highest prevalence ratio was observed for significant stenosis (prevalence difference, 3.1% [95% CI, 1.1%-5.1%]; prevalence ratio, 2.46 [95% CI, 1.65-3.67]). In adjusted models, odds ratios for preeclampsia ranged from 1.31 (95% CI, 1.07-1.61) for any coronary atherosclerosis to 2.21 (95% CI, 1.42-3.44) for significant stenosis. Similar associations were observed for history of preeclampsia or gestational hypertension among women with low predicted cardiovascular risk. Conclusions and Relevance: Among Swedish women undergoing coronary computed tomography angiography screening, there was a statistically significant association between history of adverse pregnancy outcomes and image-identified coronary artery disease, including among women estimated to be at low cardiovascular disease risk. Further research is needed to understand the clinical importance of these associations.

Hyperkalaemia as a cause of undertreatment with mineralocorticoid receptor antagonists in heart failure.

AIMS: To determine the incidence of hyperkalaemia in patients with heart failure with reduced ejection fraction (HFrEF) during up-titration of guideline-directed medical therapy (GDMT) in real-world settings. METHODS: A retrospective review of medical records of all patients hospitalized for newly onset HFrEF at Sahlgrenska University Hospital, Sweden, between 1 January 2016 and 31 December 2019. Based on mineralocorticoid receptor antagonist (MRA) treatment within the first 6 months, patients were divided into four groups: (i) never received MRA, (ii) needed MRA dose reduction, (iii) needed discontinuation of MRA, and (iv) stable MRA treatment. Potassium levels were assessed at baseline and has the highest potassium level during the 6 months of up-titration. RESULTS: Of 3456 patients hospitalized for heart failure, 630 (18%) were eligible (68.4% men, 66.8 years, mean EF of 29.4%). After up-titration of GDMT 48.4% of patients received MRAs. Patients without MRA treatment were older (P < 0.0001), had lower EF (P = 0.022), had higher NTproBNP (P = 0.017), had lower eGFR (P = 0.001), and were more often treated with angiotensin receptor inhibitors/angiotensin receptor blockers/angiotensin receptor neprilysin inhibitors (all P < 0.0001). In overall study population, hyperkalaemia increased from 5.9 to 24.4% after 6 months of up-titration of GDMT (P < 0.0001). Among four groups, the incidence of hyperkalaemia throughout up-titration of GDMT increased from 6.8 to 54.5% in patients with dose reduction of MRA, from 8.8 to 50.9% in those with discontinuation of MRA, from 5 to 10% in patients with stable MRA treatment, and from 6 to 28% in patients who were MRA naive (all P < 0.0001). In the MRA-naive group, normokalaemia/hypokalaemia occurred in 87.5% at baseline, and after 6 months of up-titration of GDMT, normokalaemia/hypokalaemia remained in 47.8%, whereas mild, moderate, and severe hyperkalaemia occurred in 22.4%, 5.7%, and 0.9%, respectively. CONCLUSIONS: Hyperkalaemia increased significantly during up-titration of GDMT but with varying magnitudes in different clinical phenotypes, which might explain why physicians refrain from prescribing MRAs to patients with HFrEF.

Aortic size predicts aortic dissection in Turner syndrome - A 25-year prospective cohort study.

BACKGROUND: Women with Turner syndrome (TS) have an increased risk of aortic dissection. The current recommended cutoff to prevent aortic dissection in TS is an aortic size index (ASI) of ≥2.5 cm/m2. This study estimated which aortic size had the best predictive value for the risk of aortic dissection, and whether adjusting for body size improved risk prediction. METHODS: A prospective, observational study in Sweden, of women with TS, n = 400, all evaluated with echocardiography of the aorta and data on medical history for up to 25 years. Receiver operating characteristic (ROC) curves, sensitivity and specificity were calculated for the absolute ascending aortic diameter (AAD), ascending ASI and TS specific z-score. RESULTS: There were 12 patients (3%) with aortic dissection. ROC curves demonstrated that absolute AAD and TS specific z-score were superior to ascending ASI in predicting aortic dissection. The best cutoff for absolute AAD was 3.3 cm and 2.12 for the TS specific z-score, respectively, with a sensitivity of 92% for both. The ascending ASI cutoff of 2.5 cm/m2 had a sensitivity of 17% only. Subgroup analyses in women with an aortic diameter ≥ 3.3 cm could not demonstrate any association between karyotype, aortic coarctation, bicuspid aortic valve, BMI, antihypertensive medication, previous growth hormone therapy or ongoing estrogen replacement treatment and aortic dissection. All models failed to predict a dissection in a pregnant woman. CONCLUSIONS: In Turner syndrome, absolute AAD and TS-specific z-score were more reliable predictors for aortic dissection than ASI. Care should be taken before and during pregnancy.

Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists.

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.

Postoperative Atrial Fibrillation in Adults with Obstructive Sleep Apnea Undergoing Coronary Artery Bypass Grafting in the RICCADSA Cohort.

Postoperative atrial fibrillation (POAF) occurs in 20−50% of patients with coronary artery disease (CAD) after coronary artery bypass grafting (CABG). Obstructive sleep apnea (OSA) is also common in adults with CAD, and may contribute to POAF as well to the reoccurrence of AF in patients at long-term. In the current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure (CPAP) in Coronary Artery Disease and Obstructive Sleep Apnea (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT 00519597), we included 147 patients with CABG, who underwent a home sleep apnea testing, in average 73 ± 30 days after the surgical intervention. POAF was defined as a new-onset AF occurring within the 30 days following the CABG. POAF was observed among 48 (32.7%) patients, occurring within the first week among 45 of those cases. The distribution of the apnea-hypopnea-index (AHI) categories < 5.0 events/h (no-OSA); 5.0−14.9 events/h (mild OSA); 15.0−29.9 events/h (moderate OSA); and ≥30 events/h (severe OSA), was 4.2%, 14.6%, 35.4%, and 45.8%, in the POAF group, and 16.2%, 17.2%, 39.4%, and 27.3%, respectively, in the no-POAF group. In a multivariate logistic regression model, there was a significant risk increase for POAF across the AHI categories, with the highest odds ratio (OR) for severe OSA (OR 6.82, 95% confidence interval 1.31−35.50; p = 0.023) vs. no-OSA, independent of age, sex, and body-mass-index. In the entire cohort, 90% were on ß-blockers according to the clinical routines, they all had sinus rhythm on the electrocardiogram at baseline before the study start, and 28 out of 40 patients with moderate to severe OSA (70%) were allocated to CPAP. During a median follow-up period of 67 months, two patients (none with POAF) were hospitalized due to AF. To conclude, severe OSA was significantly associated with POAF in patients with CAD undergoing CABG. However, none of those individuals had an AF-reoccurrence at long term, and whether CPAP should be considered as an add-on treatment to ß-blockers in secondary prevention models for OSA patients presenting POAF after CABG requires further studies in larger cohorts.

Body iron stores had no impact on coronary heart disease outcomes: a middle-aged male cohort from the general population with 21-year follow-up.

BACKGROUND: Body iron stores (BISs) have been proposed to be related to the development of cardiovascular diseases. However, results from epidemiological studies are conflicting. Knowledge on the long-term impact of BIS on cardiovascular outcomes in the general population is lacking. PURPOSE: The aim of this study was to explore the relationship between BIS and coronary heart disease (CHD) including death due to CHD. METHODS: This investigation is part of 'The Study of Men Born in 1943', a longitudinal prospective study of men living in the city of Gothenburg, Sweden. This random population sample was examined in 1993 (all at 50 years of age at baseline). A medical examination was performed, and questionnaires were used to evaluate lifestyle factors. Biomarkers for iron stores (serum ferritin and serum transferrin receptor) was analysed from frozen blood samples in 2014. All hospital admissions were registered through national registers during the entire follow-up from 1993 to 2014. HRs were estimated by Cox proportional-hazard regression analyses. RESULTS: During the 21 years follow-up period, 120 participants (15.2%) developed CHD and 16 patients (2%) died due to CHD. The all-cause mortality was 15.2% (n=120) including 40 cardiovascular deaths (5.1%). In a multivariable Cox regression analysis, the daily smoking, hypertension and the increased resting heart rate was independent predictors of CHD, while no significant association was found between BIS and risk of CHD. CONCLUSIONS: In a cohort of middle-aged men from the general population with well validated and prospectively collected data, we did not find any association between serum ferritin or serum transferrin receptor as markers of BIS and CHD events after 21 years of follow-up. TRAIL REGISTRATION NUMBER: NCT03138122.

Cumulative incidence and predictors of acquired aortic stenosis in a large population of men followed for up to 43 years.

BACKGROUND: Acquired aortic stenosis (AS) increases with age and has high mortality without intervention. Factors predicting its development are unclear, although atherosclerotic factors are assumed to be involved. Our aim in this study is to estimate the lifetime cumulative incidence and predictors of AS in middle-aged men. METHODS: We included a random sample of men (n = 9998) born 1915-1925 in Gothenburg, Sweden. From them, 7,494 were examined and followed until a diagnosis of AS or death (maximum follow-up time 42.8 years). We identified AS diagnosis from the Swedish National Patient Registry and deaths from the Swedish Cause of Death Registry by using International Classification of Disease (ICD) diagnostic criteria. To study time-dependent relationships between AS and risk factors with death as the competing risk, we divided the cohort into three overlapping follow-up groups: 25-43, 30-43 and 35-43 years. We used age-adjusted Cox proportional hazards model to identify predictors of AS. RESULTS: The lifelong cumulative incidence of AS was 3.2%. At baseline, participants in the third group had a healthier lifestyle, lower body mass index (BMI), blood pressure, and serum cholesterol levels. Higher BMI, obesity, cholesterol, hypertension, atrial fibrillation, smoking and heredity for stroke were associated with AS. With BMI of 20-22.5 as a reference, hazard ratios of being diagnosed with AS for men with a baseline BMI of 25-27.5 kg/m2, 27.5-30 kg/m2 and > 30 kg/m2 were 1.99 (95% CI 1.12-3.55), 2.98 (95% CI 1.65-5.40) and 3.55 (95% CI 1.84-6.87), respectively. CONCLUSIONS: The lifetime cumulative incidence of AS in middle-aged male population was 3.2%. Multiple atherosclerotic risk factors, particularly high BMI might be associated with a higher risk of developing AS.

Trends in myocarditis incidence, complications and mortality in Sweden from 2000 to 2014.

Investigate trends in myocarditis incidence and prognosis in Sweden during 2000-2014. Little data exist concerning population-trends in incidence of hospitalizations for myocarditis and subsequent prognosis. Linking Swedish National Patient and Cause of Death Registers, we identified individuals ≥ 16 years with first-time diagnosis of myocarditis during 2000-2014. Reference population, matched for age and birth year (n = 16,622) was selected from Swedish Total Population Register. Among the 8 679 cases (75% men, 64% < 50 years), incidence rate/100,000 inhabitants rose from 6.3 to 8.6 per 100,000, mostly in men and those < 50 years. Incident heart failure/dilated cardiomyopathy occurred in 6.2% within 1 year after index hospitalization and in 10.2% during 2000-2014, predominantly in those ≥ 50 years (12.1% within 1 year, 20.8% during 2000-2014). In all 8.1% died within 1 year, 0.9% (< 50 years) and 20.8% (≥ 50 years). Hazard ratios (adjusted for age, sex) for 1-year mortality comparing cases and controls were 4.00 (95% confidence interval 1.37-11.70), 4.48 (2.57-7.82), 4.57 (3.31-6.31) and 3.93 (3.39-4.57) for individuals aged < 30, 30 to < 50, 50 to < 70, and ≥ 70 years, respectively. The incidence of myocarditis during 2000-2014 increased, predominantly in men < 50 years. One-year mortality was low, but fourfold higher compared with reference population.

Mid-life extrapyramidal symptoms predict cognitive impairment 23 years later.

OBJECTIVES: The prevalence of dementia is growing rapidly worldwide. The early identification and treatment of cognitive decline could reduce the burden on the health care system. Our objective was to investigate whether factors measured at an examination at age 50 predict cognitive impairment (CI) 23 years later. MATERIALS & METHODS: In 1993 we enrolled a randomly selected sample of 798 men, 50 years of age, from the general population. They all underwent a physical examination, provided blood samples and filled out questionnaires addressing lifestyle and psychosocial factors. Cognitive testing was offered to all participants still alive in 2016, at age 73. RESULTS: A total of 333 men participated in the cognitive study, of which 80 (24.0%) performed at a level corresponding to mild cognitive impairment, and four (1.2%) at a level consistent with severe cognitive impairment. After the first step in the multivariable analysis, hypertension, heavy smoking, high intake of alcohol, financial stress, difficulty falling asleep, and cogwheel rigidity were associated with cognitive impairment. After further adjustment, only wide waist circumference measured in cm (OR 1.04, 95% CI 1.00-1.08, p = .04), leg pendulousness (OR 41.97, 95% CI 3.27-538.62, p = .004) and self-assessed hidden irritability (OR 2.18, 95% CI 1.10-4.32, p = .03) at baseline, remained as being associated with cognitive impairment 23 years later. CONCLUSIONS: Extrapyramidal symptoms such as leg pendulousness, at the age of 50, may be an indicator for very early identification of future cognitive decline.

Association of TNF-α (-308G/A) Gene Polymorphism with Circulating TNF-α Levels and Excessive Daytime Sleepiness in Adults with Coronary Artery Disease and Concomitant Obstructive Sleep Apnea.

Obstructive sleep apnea (OSA) is common in patients with coronary artery disease (CAD), in which inflammatory activity has a crucial role. The manifestation of OSA varies significantly between individuals in clinical cohorts; not all adults with OSA demonstrate the same set of symptoms; i.e., excessive daytime sleepiness (EDS) and/or increased levels of inflammatory biomarkers. The further exploration of the molecular basis of these differences is therefore essential for a better understanding of the OSA phenotypes in cardiac patients. In this current secondary analysis of the Randomized Intervention with Continuous Positive Airway Pressure in CAD and OSA (RICCADSA) trial (Trial Registry: ClinicalTrials.gov; No: NCT00519597), we aimed to address the association of tumor necrosis factor alpha (TNF-α)-308G/A gene polymorphism with circulating TNF-α levels and EDS among 326 participants. CAD patients with OSA (apnea-hypopnea-index (AHI) ≥ 15 events/h; n = 256) were categorized as having EDS (n = 100) or no-EDS (n = 156) based on the Epworth Sleepiness Scale score with a cut-off of 10. CAD patients with no-OSA (AHI < 5 events/h; n = 70) were included as a control group. The results demonstrated no significant differences regarding the distribution of the TNF-α alleles and genotypes between CAD patients with vs. without OSA. In a multivariate analysis, the oxygen desaturation index and TNF-α genotypes from GG to GA and GA to AA as well as the TNF-α-308A allele carriage were significantly associated with the circulating TNF-α levels. Moreover, the TNF-α-308A allele was associated with a decreased risk for EDS (odds ratio 0.64, 95% confidence interval 0.41-0.99; p = 0.043) independent of age, sex, obesity, OSA severity and the circulating TNF-α levels. We conclude that the TNF-α-308A allele appears to modulate circulatory TNF-α levels and mitigate EDS in adults with CAD and concomitant OSA.

Incremental changes in QRS duration as predictor for cardiovascular disease: a 21-year follow-up of a randomly selected general population.

The QRS complex has been shown to be a prognostic marker in coronary artery disease. However, the changes in QRS duration over time, and its predictive value for cardiovascular disease in the general population is poorly studied. So we aimed to explore if increased QRS duration from the age of 50-60 is associated with increased risk of major cardiovascular events during a further follow-up to age 71. A random population sample of 798 men born in 1943 were examined in 1993 at 50 years of age, and re-examined in 2003 at age 60 and 2014 at age 71. Participants who developed cardiovascular disease before the re-examination in 2003 (n = 86) or missing value of QRS duration in 2003 (n = 127) were excluded. ΔQRS was defined as increase in QRS duration from age 50 to 60. Participants were divided into three groups: group 1: ΔQRS < 4 ms, group 2: 4 ms ≤ ΔQRS < 8 ms, group 3: ΔQRS ≥ 8 ms. Endpoints were major cardiovascular events. And we found compared with men in group 1 (ΔQRS < 4 ms), men with ΔQRS ≥ 8 ms had a 56% increased risk of MACE during follow-up to 71 years of age after adjusted for BMI, systolic blood pressure, smoking, hyperlipidemia, diabetes and heart rate in a multivariable Cox regression analysis (HR 1.56, 95% CI:1.07-2.27, P = 0.022). In conclusion, in this longitudinal follow-up over a decade QRS duration increased in almost two out of three men between age 50 and 60 and the increased QRS duration in middle age is an independent predictor of major cardiovascular events.

Prognosis and outcome determinants after heart failure diagnosis in patients who underwent aortic valvular intervention.

AIMS: To study clinical phenotype, prognosis for all-cause and cardiovascular (CV) mortality and predictive factors in patients with incident heart failure (HF) after aortic valvular intervention (AVI) for aortic stenosis (AS). METHODS AND RESULTS: In this retrospective, observational study we included patients from the Swedish Heart Failure Registry (SwedeHF) recorded 2003-2016, with AS diagnosis and AVI before HF diagnosis. The AS diagnosis was established according to International Classification of Diseases 10th revision (ICD-10) codes, thus without information concerning clinical or echocardiographical data on the aortic valve disease. The patients were divided into two subgroups: left ventricular ejection fraction (LVEF) ≥ 50% (AS-HFpEF) and <50% (AS-HFrEF). We individually matched three controls with HF from the SwedeHF without AS (control group) for each patient. Baseline characteristics, co-morbidities, survival status and outcomes were obtained by linking the SwedeHF with two other Swedish registries. We used Kaplan-Meier curves to present time to all-cause mortality, cumulative incidence function for time to CV mortality and Cox proportional hazards model to evaluate the relative difference between AS-HFrEF and AS-HFpEF and AS-HF and controls. The crude all-cause mortality was 49.0%, CV mortality 27.9% in AS-HF patients, respectively 44.7% and 26.6% in matched controls. The adjusted risk for all-cause mortality and CV mortality was similar in HF, regardless of LVEF vs. controls. No significant difference in factors predicting higher all-cause mortality was observed in AS-HFrEF vs. AS-HFpEF, except for diabetes (only in AS-HFrEF), with statistically significant interaction predicting death between the two groups. CONCLUSIONS: In this nationwide SwedeHF study, we characterized incident HF population after AVI. We found no significant differences in all-cause and CV mortality compared with general HF population. They had virtually the same predictors for mortality, regardless of LVEF.

Multi-modality biomarkers in the early prediction of ischaemic heart disease in middle-aged men during a 21-year follow-up.

BACKGROUND: Ischaemic heart disease (IHD) often develops after decades of preceding subclinical coronary atherosclerosis. Biomarkers are useful prognostic predictors of IHD, but their long-term predictive value in a general population has not been adequately studied. PURPOSE: To investigate the early predictive value of multi-modality biomarkers in addition to clinical risk factors in incident IHD in a random male general population sample followed from 50 to 71 years of age. METHOD: "The Study of Men Born in 1943" is a longitudinal cohort study during follow-up. All the men underwent a baseline examination in 1993, where a panel of biomarkers were analysed and incident IHD was registered during 21-year follow-ups. RESULTS: Of 739 participants, 97 men (13.1%) developed an IHD event. For time to first occurrence of IHD, univariable analyses showed that elevated levels of high sensitivity troponin T (hs-TNT), high sensitivity-C reactive protein (hs-CRP) and interleukin-6 (IL-6) were significant predictors of IHD. In addition, a high number of biomarkers with elevated levels (hs-TNT > 10 ng/L, hs-CRP > 1 mg/L, IL-6 > 8 ng/L and N-terminal pro b-type natriuretic peptide (NT-proBNP) > 100 pg/mL) increased predictive ability. In univariable and multivariable analysis high-density lipoprotein-cholesterol (HDL-C) had the highest predictive ability. Hs-TNT provided better predictive ability than smoking, body mass index and glucose, and was an independent significant predictor when adjusted for HDL-C, total cholesterol and hypertension. Addition of biomarkers on top of clinical risk factors provided significantly better prediction as tested by likelihood ratio test (p = 0.033), but did not significantly enhance the model's discriminative ability However, it appeared contributing to higher sensitivity in the late phase of follow-up. CONCLUSION: In this random, middle-aged male population sample, the addition of biomarker hs-TNT was an independent significant predictor of IHD and significantly improved prediction, indicating the probability of a better prediction of long-term risk of IHD in a low-risk population. TRIAL REGISTRATION: The study is registered at Clinical Trials.gov Identifier number: NCT03138122.