Cardiovascular disease in pregnancy: Prevalence and obstetric outcomes in a Swedish population-based cohort study between 2000 and 2019.

INTRODUCTION: The prevalence of cardiovascular disease during pregnancy (cardiovascular disease diagnosed before, during or up to 6 months after childbirth) and the risk of adverse outcomes associated with it have not been previously described in Sweden. This study examined trends in prevalence of cardiovascular disease and its association with maternal and perinatal outcomes, overall and by timing of diagnosis in relation to pregnancy. MATERIAL AND METHODS: This population-based observational retrospective cohort study consisted of women aged 15-49 years who were registered in the Swedish Medical Birth Register 2000-2019. Prevalence was defined as annual diagnosis of cardiovascular disease per pregnant woman as numerator and all pregnant women per year as denominator. Adverse maternal and perinatal outcomes were analyzed using time-dependent Cox regression and Poisson regression models. Outcomes were obtained during and after childbirth up to 1 year postpartum, depending on the outcome. RESULTS: There were 2 069 107 births to 1 186 137 women (911 101 primiparous). The prevalence of cardiovascular disease among pregnant women in Sweden during 2000-2019 increased from 0.31% to 1.34%, for non-congenital cardiovascular disease, this was primarily driven by arrythmia (0.11%-0.58%). Primiparous women with cardiovascular disease had a higher risk of eclampsia over-all (aHR 4.50, 95% CI 2.01-10.05) and when diagnosed during pregnancy (aHR 3.22, 95% CI 1.21-8.61); admission to psychiatric ward overall (aHR 2.51, 95% CI 1.30-4.83), and when diagnosed during pregnancy (aHR 2.54, 95% CI 1.21-5.34); and one-year mortality when diagnosed before pregnancy (aHR 1.67, 95% CI 1.16-2.42) and when diagnosed postpartum (aHR 6.59, 95% CI 3.38-12.84), compared to those without cardiovascular disease. Children born to women with cardiovascular disease diagnosed both overall and in relation to timing of diagnosis had an increased risk of being born preterm and small for gestational age. CONCLUSIONS: Cardiovascular disease prevalence among pregnant women in Sweden increased during 2000-2019, primarily driven by arrhythmias. In primiparous women, the timing of diagnosis of cardiovascular disease is important for maternal and perinatal outcomes, including when diagnosed postpartum. This calls for awareness among all staff when planning pregnancy and monitoring women with cardiovascular disease throughout pregnancy and in the postpartum period.

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.

Body Weight in Adolescent Men in Sweden and Risk of an Early Acute Coronary Event: A Prospective Population-Based Study.

Background Coronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and Results This was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m2), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m2 had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. Conclusions An increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.

Ten year age- and sex-specific temporal trends in incidence and prevalence of heart failure in Västra Götaland, Sweden.

AIM: Heart failure (HF) is predominantly a disorder of the elderly. During the last decades, cardiovascular primary and secondary prevention and life expectancy have improved. Accordingly, trends in incidence and prevalence of HF are dynamic and may differ over time by age and gender. We aim to investigate the overall and age-specific and sex-specific trends, in incidence, prevalence, and the proportion with co-morbidities of HF over a 10 year period in Region Västra Götaland, Sweden. METHODS AND RESULTS: The VEGA database is an administrative database of all patients managed in hospital and/or in primary care (private and public) living in Region Västra Götaland. All patients with a main or contributory diagnosis of HF (I50) aged 18 years or older between 2008 and 2017 were included. Incidence and prevalence of HF were calculated based on the entire adult population of Region Västra Götaland. The adult population in Region Västra Götaland increased by 8% from 2008 (n = 1 234 609) to 2017 (n = 1 338 906). Half the population was female and 69% < 60 years of age, both constant over time. In total, 62 228 incident cases of HF were identified. In 2008, we identified 6464 cases, mean age 78.7 (11.5) years, and 49.8% (n = 3222) men, while in 2017, 5727 cases were identified, mean age 78.3 (11.8) years, and 52.5% (n = 3006) men. The overall yearly incidence rate of HF decreased by 3%, RR 0.97 (95% CI 0.96-0.97) per year, P < 0.0001, mainly driven by the age categories >75 years. A constantly higher incidence of HF was seen for men compared with women in all age categories, RR 1.46 (95% CI 1.44-1.49), P < 0.0001. During the same period, we observed a steady increase in overall prevalence from 1.8% for women and 2.0% for men in 2008, to 2.4% in women and 2.8% in men in 2017, particularly in those >85 years of age who had a prevalence of 16.5% (men) and 14.6% (women) in 2008 and 23.5% (men) and 21.5% (women) in 2017. The overall 1 year mortality rate was 22.7%. When adjusted for age, women had a lower risk for death by 13% compared with men [hazard ratio 0.87 (95% CI 0.84-0.90, P < 0.0001)]. CONCLUSION: We saw a decrease in overall incidence, but incidence of HF remains high, particularly in the oldest age groups. Prevalence of HF keeps increasing particularly in those aged >85 years. Our findings emphasize the need for implementation of effective preventive strategies for HF.

Factors associated with excess female mortality in obstructive hypertrophic cardiomyopathy.

BACKGROUND: Several studies have reported excess female mortality in patients with hypertrophic cardiomyopathy, but the cause is unknown. AIMS: To compare risk-factors for disease-related death in both sexes in a geographical cohort of patients with obstructive hypertrophic cardiomyopathy (oHCM). METHODS AND RESULTS: Data-bases in all ten hospitals within West Götaland Region yielded 250 oHCM-patients (123 females, 127 males). Mean follow-up was 18.1 y. Risk-factors for disease-related death were evaluated by Cox-hazard regression and Kaplan-Meier survival-curves, with sex-comparisons of distribution of risk-factors and therapy in total and age-matched (n = 166) groups. At diagnosis females were older, median 62 y vs. 51 y, (P < 0.001), but not different in outflow-gradients and median NYHA-class. However, septal hypertrophy was more advanced: 10.6 [IQR = 3.2] vs. 9.6 [2.5] mm/m2 BSA; P = 0.002. Females had higher disease-related mortality than males (P = <0.001), with annual mortality 2.9% vs. 1.5% in age-matched groups (P = 0.010 log-rank). For each risk-category identified (NYHA-class ≥ III, outflow-gradient ≥50 mmHg), a higher proportion of females died (P = 0.0004; P = 0.001). Calcium-blocker therapy was a risk-factor (P = 0.005) and was used more frequently in females (P = 0.034). A beta-blocker dose above cohort-median reduced risk for disease-related death in both males (HR = 0.32; P = 0.0040) and in females (HR = 0.49; P = 0.020). Excess female deaths occurred in chronic heart-failure (P = 0.001) and acute myocardial infarctions (P = 0.015). Fewer females received beta-blocker therapy after diagnosis (64% vs. 78%, P = 0.018), in a smaller dose (P = 0.007), and less frequently combined with disopyramide (7% vs. 16%, P = 0.048). CONCLUSION: Addressing sex-disparities in the timing of diagnosis and pharmacological therapy has the potential to improve the care of females with oHCM.

Patient-level comparison of heart failure patients in clinical phenotype and prognosis from China and Sweden.

BACKGROUND: Clinical phenotype and prognosis of heart failure (HF) may be variable among different racial populations. Therefore, a patient-level comparison of hospitalized HF patients in two university hospitals from China and Sweden was performed. METHODS AND RESULTS: This study was a pooled data analysis of the patients prospectively enrolled in two single-center studies in China (n = 949) and Sweden (n = 1639) from 2011 to 2015. Clinical characteristics and 6-month all-cause mortality were collected. Higher systolic blood pressure (126.1 ± 20.3 vs. 114.2 ± 15.4 mmHg, p < 0.001) and NT-proBNP level (4540 vs. 3251 pg/mL, p = 0.013) were found in the Swedish cohort, also more patients with ischemic heart disease (32.0% vs. 19.2%), hypertension (64.2% vs. 36.8%), valvular heart disease (40.9% vs.31.6%) and atrial fibrillation (55.3% vs. 39.6%) (all p < 0.001). The use of ACEIs/ARBs (48.8% vs. 80.8%) or beta-blockers (58.8% vs. 86.5%) (both p < 0.001) was lower in Chinese cohort. Given younger age in Chinese cohort (61.6 vs. 76.4 years, p < 0.001), age-stratified analyses were conducted, as there were similar patient numbers in 50-74 years in Chinese (n = 550) and Swedish (n = 554) cohorts, therefore baseline characteristics and prognosis were further compared. The age- and sex-adjusted outcome (HR 0.80 [95% CI 0.55-1.19], p = 0.273) was comparable between the two populations. The NT-proBNP and eGFR independently predicted 6-month mortality in both Chinese (HR [95% CI] 1.006 [1.003-1.008], 0.986 [0.976-0.999]) and Swedish cohort (1.003 [1.000-1.007], 0.988 [0.976-0.999]). CONCLUSIONS: Patient-level comparison of real-world HF populations from China and Sweden demonstrated different clinical phenotypes and therapy but similar prognosis and their predictors.

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.

Trends in survival of Swedish men and women with heart failure from 1987 to 2014: a population-based case-control study.

AIMS: To compare trends in short-term and long-term survival of patients with heart failure (HF) compared with controls from the general population. METHODS AND RESULTS: We used data from the Swedish National Inpatient Registry to identify all patients aged ≥18 years with a first recorded diagnosis of HF between 1 January 1987 and 31 December 2014 and compared them with controls matched on age and sex from the Total Population Register. We included 702 485 patients with HF and 1 306 183 controls. In patients with HF aged 18-64 years, short-term (29 days to 6 months) and long-term mortality (>11 years) decreased from 166 and 76.6 per 1000 person-years in 1987 to 2000 to 99.6 and 49.4 per 1000 person-years, respectively, in 2001 to 2014. During the same period, mortality improved marginally, in those aged ≥65 years: short-time mortality from 368.8 to 326.2 per 1000 person-years and long-term mortality from 219.6 to 193.9 per 1000 person-years. In 1987-2000, patients aged <65 years had more than three times higher risk of dying at 29 days to 6 months, with an hazard ratio (HR) of 3.66 [95% confidence interval (CI) 3.46-3.87], compared with controls (P < 0.0001) but substantially higher in 2001-2014 with an HR of 11.3 (95% CI 9.99-12.7, P < 0.0001). HRs for long-term mortality (6-10 and >11 years) increased moderately from 2.49 (95% CI 2.41-2.57) and 3.16 (95% CI 3.07-3.24) in 1987-2000 to 4.35 (95% CI 4.09-4.63) and 4.11 (95% CI 3.49-4.85) in 2001-2014, largely because survival among controls improved more than that among patients with HF (P < 0.0001). CONCLUSIONS: Absolute survival improved in HF patients aged <65 years, but only marginally so in those aged ≥65 years. Compared with controls, both short-term and long-term relative risk of dying increased, especially in younger patients with HF.

Increasing home-time after a first diagnosis of heart failure in Sweden, 20 years trends.

AIMS: This study was performed to compare trends in home-time for patients with heart failure (HF) between those of working age and those of retirement age in Sweden from 1992 to 2012. METHODS AND RESULTS: The National Inpatient Register (IPR) was used to identify all patients aged 18 to 84 years with a first hospitalization for HF in Sweden from 1992 to 2012. Information on date of death, comorbidities, and sociodemographic factors were collected from the Swedish National Register on Cause of Death, the IPR, and the longitudinal integration database for health insurance and labour market studies, respectively. The patients were divided into two groups according to their age: working age (<65 years) and retirement age (≥65 years). Follow-up was 4 years. In total, following exclusions, 388 775 patients aged 18 to 84 years who were alive 1 day after discharge from a first hospitalization for HF were included in the study. The working age group comprised 62 428 (16%) patients with a median age of 58 (interquartile range, 53-62) years and 31.2% women, and the retirement age group comprised 326 347 (84%) patients with a median age of 77 (interquartile range, 73-81) years and 47.4% women. Patients of working age had more home-time than patients of retirement age (83.8% vs. 68.2%, respectively), mainly because of their lower 4 year mortality rate (14.2% vs. 29.7%, respectively). Home-time increased over the study period for both age groups, but the increase levelled off for older women after 2007, most likely because of less reduction in mortality in older women than in the other groups. CONCLUSIONS: This nationwide study showed increasing home-time over the study period except for women of retirement age and older for whom the increase stalled after 2007, mainly because of a lower mortality reduction in this group. Efforts to improve patient-related outcome measures specifically targeted to this group may be warranted.

Hospital readmissions of patients with heart failure from real world: timing and associated risk factors.

AIMS: This study aims to investigate hospital readmissions and timing, as well as risk factors in a real world heart failure (HF) population. METHODS AND RESULTS: All patients discharged alive in 2016 from Sahlgrenska University Hospital/Östra, Gothenburg, Sweden, with a primary diagnosis of HF were consecutively included. Patient characteristics, type of HF, treatment, and follow-up were registered. Time to first all-cause or HF readmission, as well as number of 1 year readmissions from discharge were recorded. In total, 448 patients were included: 273 patients (mean age 78 ± 11.8 years) were readmitted for any cause within 1 year (readmission rate of 60.9%), and 175 patients (mean age 76.6 ± 13.7) were never readmitted. Among readmissions, 60.1% occurred during the first quarter after index hospitalization, giving a 3 month all-cause readmission rate of 36.6%. HF-related 1 year readmission rate was 38.4%. Patients who were readmitted had significantly more renal dysfunction (52.4% vs. 36.6%, P = 0.001), pulmonary disease (25.6% vs. 15.4%, P = 0.010), and psychiatric illness (24.9% vs. 12.0%, P = 0.001). Number of co-morbidities and readmissions were significantly associated (P < 0.001 for all cause readmission rate and P = 0.012 for 1 year HF readmission rate). Worsening HF constituted 63% of all-cause readmissions. Psychiatric disease was an independent risk factor for 1 month and 1 year all-cause readmissions. Poor compliance to medication was an independent risk factor for 1 month and 1 year HF readmission. CONCLUSIONS: In our real world cohort of HF patients, frequent hospital readmissions occurred in the early post-discharge period and were mainly driven by worsening HF. Co-morbidity was one of the most important factors for readmission.

Increased arterial stiffness and reduced left ventricular long-axis function in patients recovered from peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is idiopathic pregnancy-associated heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We aimed to assess arterial stiffness and left ventricular (LV) function in women recovered from PPCM compared with controls. METHODS: Twenty-two PPCM patients were compared with 15 age-matched controls with previous uncomplicated pregnancies. Eleven of the patients were at inclusion in the study recovered and off medication since at least 6 months and still free from cardiovascular symptoms with normal LVEF and normal NT-proBNP. All underwent echocardiography, including LV strain, left atrial (LA) reservoir strain and tissue Doppler early diastolic velocity (e´) and non-invasive assessment for arterial stiffness and central aortic systolic blood pressure (AoBP) at rest and immediately postexercise. RESULTS: The patients off medication showed alterations compared with controls. AoBP was higher (120 ± 9 mm Hg vs. 104 ± 13 mm Hg; p = .001), a difference which persisted postexercise. The arterial elastance was higher (1.9 ± 0.4 mm Hg/ml vs. 1.3 ± 0.2 mm Hg/ml; p < .001), while there were lower e´ septal (8.9 ± 1.7 cm/s vs. 11.0 ± 1.1 cm/s; p = 0. 002), LV global strain (18.7 ± 3.9% vs. 23.1 ± 1.6%; p = .004) and LA reservoir strain (24.8 ± 9.1% vs. 37.7 ± 6.3%; p = .002). CONCLUSIONS: Compared with healthy controls, PPCM patients considered recovered and off medication had increased arterial stiffness, decreased LV longitudinal function and reduced LA function.

Risk of stroke in patients with heart failure and sinus rhythm: data from the Swedish Heart Failure Registry.

AIMS: We investigated the 2 year rate of ischaemic stroke/transient ischaemic attack (IS) in patients with heart failure (HF) who were in sinus rhythm (HF-SR) and aimed to develop a score for stratifying risk of IS in this population. METHODS AND RESULTS: A total of 15 425 patients (mean age 71.5 years, 39% women) with HF-SR enrolled in the Swedish Heart Failure Register were included; 28 815 age-matched and sex-matched controls, without a registered diagnosis of HF, were selected from the Swedish Population Register. The 2 year rate of IS was 3.0% in patients and 1.4% in controls. In the patient group, a risk score including age (1p for 65-74 years; 2p for 75-84 years; 3p for ≥85 years), previous IS (2p), ischaemic heart disease, diabetes, hypertension, kidney dysfunction, and New York Heart Association III/IV class (1p each) was generated. Over a mean follow-up of 20.1 (SD 7.5) months, the cumulative incidences (per 1000 person-years) of IS in patients with score 0 to ≥7 were 2.2, 5.3, 8.9, 13.2, 15.7, 20.4, 26.4, and 33.0, with hazard ratios for score 1 to ≥7 (with 0 as reference): 2.4, 4.1, 6.1, 7.2, 9.4, 12.2, and 15.3. The risk score performed modestly (area under the curve 63.7%; P = 0.4711 for lack of fit with a logistic model; P = 0.7062 with Poisson, scaled by deviance). CONCLUSIONS: In terms of absolute risk, only 27.6% of patients had an annual IS incidence of ≤1%. To which extent this would be amenable to anticoagulant treatment remains conjectural. A score compiling age and specific co-morbidities identified HF-SR patients with increased risk of IS with modest discriminative ability.

Clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy: an ESC EORP registry.

AIMS: We sought to describe the clinical presentation, management, and 6-month outcomes in women with peripartum cardiomyopathy (PPCM) globally. METHODS AND RESULTS: In 2011, >100 national and affiliated member cardiac societies of the European Society of Cardiology (ESC) were contacted to contribute to a global registry on PPCM, under the auspices of the ESC EURObservational Research Programme. These societies were tasked with identifying centres who could participate in this registry. In low-income countries, e.g. Mozambique or Burkina Faso, where there are no national societies due to a shortage of cardiologists, we identified potential participants through abstracts and publications and encouraged participation into the study. Seven hundred and thirty-nine women were enrolled in 49 countries in Europe (33%), Africa (29%), Asia-Pacific (15%), and the Middle East (22%). Mean age was 31 ± 6 years, mean left ventricular ejection fraction (LVEF) was 31 ± 10%, and 10% had a previous pregnancy complicated by PPCM. Symptom-onset occurred most often within 1 month of delivery (44%). At diagnosis, 67% of patients had severe (NYHA III/IV) symptoms and 67% had a LVEF ≤35%. Fifteen percent received bromocriptine with significant regional variation (Europe 15%, Africa 26%, Asia-Pacific 8%, the Middle East 4%, P < 0.001). Follow-up was available for 598 (81%) women. Six-month mortality was 6% overall, lowest in Europe (4%), and highest in the Middle East (10%). Most deaths were due to heart failure (42%) or sudden (30%). Re-admission for any reason occurred in 10% (with just over half of these for heart failure) and thromboembolic events in 7%. Myocardial recovery (LVEF > 50%) occurred only in 46%, most commonly in Asia-Pacific (62%), and least commonly in the Middle East (25%). Neonatal death occurred in 5% with marked regional variation (Europe 2%, the Middle East 9%). CONCLUSION: Peripartum cardiomyopathy is a global disease, but clinical presentation and outcomes vary by region. Just under half of women experience myocardial recovery. Peripartum cardiomyopathy is a disease with substantial maternal and neonatal morbidity and mortality.

Young patients with heart failure: clinical characteristics and outcomes. Data from the Swedish Heart Failure, National Patient, Population and Cause of Death Registers.

AIMS: The prevalence and hospitalizations of patients with heart failure (HF) aged <55 years have increased in Sweden during the last decades. We aimed to compare characteristics of younger and older patients with HF, and examine survival in patients <55 years compared with matched controls. METHODS AND RESULTS: All patients ≥18 years in the Swedish Heart Failure Register from 2003 to 2014 were included. Data were merged with National Patient and Cause of Death Registers. Among 60 962 patients, 3752 (6.2%) were <55 years, and were compared with 7425 controls from the Population Register. Compared with patients ≥55 years, patients <55 years more frequently had registered diagnoses of obesity, dilated cardiomyopathy, congenital heart disease, and an ejection fraction <40% (9.8% vs. 4.7%, 27.2% vs. 5.5%, 3.7% vs. 0.8%, 67.9% vs. 45.1%, respectively; all P < 0.001). One-year all-cause mortality was 21.2%, 4.2%, and 0.3% in patients ≥55 years, patients <55 years, and controls <55 years, respectively (all P < 0.001). Patients <55 years had a five times higher mortality risk compared with controls [hazard ratio (HR) 5.48, 95% confidence interval (CI) 4.45-6.74]; the highest HR was in patients 18-34 years (HR 38.3, 95% CI 8.70-169; both P < 0.001). At the age of 20, the estimated life-years lost was up to 36 years for 50% of patients, with declining estimates with increasing age. CONCLUSION: Patients with HF <55 years had different comorbidities than patients ≥55 years. The highest mortality risk relative to that of controls was among the youngest patients.

Elevated resting heart rate in adolescent men and risk of heart failure and cardiomyopathy.

AIMS: This study aims to investigate the association of resting heart rate (RHR) measured in late adolescence with long-term risk of cause-specific heart failure (HF) and subtypes of cardiomyopathy (CM), with special attention to cardiorespiratory fitness. METHODS AND RESULTS: We performed a nation-wide, register-based cohort study of all Swedish men enrolled for conscription in 1968-2005 (n = 1 008 363; mean age = 18.3 years). RHR and arterial blood pressure were measured together with anthropometrics as part of the enlistment protocol. HF and its concomitant diagnoses, as well as all CM diagnoses, were collected from the national inpatient, outpatient, and cause of death registries. Risk estimates were calculated by Cox-proportional hazards models while adjusting for potential confounders. During follow-up, there were 8400 cases of first hospitalization for HF and 3377 for CM. Comparing the first and fifth quintiles of the RHR distribution, the hazard ratio (HR) for HF associated with coronary heart disease, diabetes, or hypertension was 1.25 [95% confidence interval (CI) = 1.13-1.38] after adjustment for body mass index, blood pressure, and cardiorespiratory fitness. The corresponding HR was 1.43 (CI = 1.08-1.90) for HF associated with CM and 1.34 (CI = 1.16-1.54) for HF without concomitant diagnosis. There was an association between RHR and dilated CM [HR = 1.47 (CI = 1.27-1.71)] but not hypertrophic, alcohol/drug-induced, or other cardiomyopathies. CONCLUSIONS: Adolescent RHR is associated with future risk of HF, regardless of associated aetiological condition. The association was strongest for HF associated with CM, driven by the association with dilated CM. These findings indicate a causal pathway between elevated RHR and myocardial dysfunction that warrants further investigation.

Body Mass Index in Young Women and Risk of Cardiomyopathy: A Long-Term Follow-Up Study in Sweden.

BACKGROUND: Incidence rates of cardiomyopathies, which are a common cause of heart failure in young people, have increased during the last decades. An association between body weight in adolescence and future cardiomyopathy among men was recently identified. Whether or not this holds true also for women is unknown. The aim was therefore to determine whether for young women being overweight or obese is associated with a higher risk of developing cardiomyopathy. METHODS: This was a registry-based national prospective cohort study with data collected from the Swedish Medical Birth Register, 1982 to 2014, with up to 33 years of follow-up. Included women were of childbearing age (18-45 years) during the initial antenatal visit in their first or second pregnancy (n=1 393 346). We obtained baseline data on body mass index (BMI), smoking, education, and previous disorders. After exclusions, mainly because of previous disorders, the final sample was composed of 1 388 571 women. Cardiomyopathy cases were identified by linking the Medical Birth Register to the National Patient and Cause of Death registers. RESULTS: In total, we identified 1699 cases of cardiomyopathy (mean age at diagnosis, 46.2 [SD 9.1] years) during the follow-up with an incidence rate of 5.9 per 100 000 observation years. Of these, 481 were diagnosed with dilated cardiomyopathy, 246 had hypertrophic cardiomyopathy, 61 had alcohol/drug-induced cardiomyopathy, and 509 had other forms. The lowest risk for being diagnosed with a cardiomyopathy was detected at a BMI of 21 kg/m2, with a gradual increase in risk with higher BMI, particularly for dilated cardiomyopathy, where a hazard ratio of 4.71 (95% CI, 2.81-7.89) was found for severely obese subjects (BMI ≥35 kg/m2), as compared with BMI 20 to <22.5. CONCLUSIONS: Elevated BMI among young women was associated with an increased risk of being diagnosed with a subsequent cardiomyopathy, especially dilated cardiomyopathy, starting already at mildly elevated body weight, whereas severe obesity entailed an almost 5-fold increase in risk. With the increasing numbers of persons who are overweight or obese, higher rates of cardiomyopathy can be expected in the future, along with an altered disease burden related to adiposity.

The eligible population of the PARADIGM-HF trial in a real-world outpatient clinic and its cardiovascular risk between 2005 and 2016.

BACKGROUND: The PARADIGM-HF trial showed that sacubitril-valsartan - an angiotensin receptor-neprilysin inhibitor (ARNI) - is more effective than enalapril for some patients with heart failure. However, the eligibility of the PARADIGM-HF study to a real-world heart failure population was not well established. METHODS: We made secondary analysis of patients (n = 4872) with heart failure prospectively enrolled in the Swedish Heart Failure Registry from Sahlgrenska University Hospital/Östra Hospital, Sweden during 2005-2016. The eligibility of the PARADIGM-HF trial in the real world was studied based on patients whether they were either fully or partially compatible with the PARADIGM-HF population. Patients were judged to be fully eligible for the PARADIGM-HF trial if they completely met the inclusion and exclusion criteria, and partially eligible if they did not stay on target dose of angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB), despite their having been treated with ACEI/ARB for at least 6 months. RESULTS: Among patients who had heart failure with reduced left ventricular ejection fraction (≤40%) (HFrEF) (n = 2165), 653 (30%) and 958 (44%) patients were fully and partially compatible with PARADIGM-HF criteria, respectively. In both fully and partially eligible groups, patients were more male. Despite those fully eligible patients being younger (77.6 ±â€Š12.7 vs. 84.0 ±â€Š13.7 years) than noneligible patients, they were much older than in the PARADIGM-HF trial. Moreover, those fully eligible patients had lower all-cause mortality compared with both partially and noneligible patients. However, both fully and partially eligible patients had higher all-cause mortality than that in the PARADIGM-HF trial. CONCLUSION: In a real-world outpatient clinical setting, around 1/3-1/2 of HFrEF were eligible for treatment of Sac/Val except that they are older, sicker, and carry higher risk for all-cause mortality than the PARADIGM-HF trial population.

Body mass index in women aged 18 to 45 and subsequent risk of heart failure.

BACKGROUND: The incidence of heart failure (HF) is decreasing in older ages, but increasing rates have been observed among younger persons in Sweden. Therefore, we investigated the relationship between risk of hospitalization for HF and body mass index (BMI). METHODS: This was a prospective registry-based cohort study. We included 1,374,031 women aged 18-45 years (mean age 27.9 years) who gave birth during 1982-2014, and were registered in the Medical Birth Register. Information on hospitalization because of HF was collected through linkage to the National Inpatient Register. RESULTS: Compared to women with a BMI of 20-<22.5 kg/m2, women with a BMI of 22.5-<25.0 had a hazard ratio (HR) of 1.24 (95% confidence interval (CI), 1.10-1.39) for HF after adjustment for age, year, parity, baseline disorders, smoking, and education. The HR (95% CI) increased to 1.56 (1.36-1.78), 2.39 (2.05-2.78), 2.82 (2.43-3.28), and 4.51 (3.63-5.61) in women with a BMI of 25-<27.5, 27.5-<30, 30-<35, and ≥35 kg/m2, respectively. The multiple-adjusted HRs (95% CI) associated with risk of HF per one-unit increase in BMI in women with a BMI ≥ 22.5 kg/m2 ranged from 1.01 (0.97-1.06) for HF related to valvular disease to 1.14 (1.12-1.15) for coronary heart disease, diabetes, or hypertension. CONCLUSION: Increasing body weight was strongly associated with the risk of early HF in women. Compared with lean women, the risk for HF started to increase at high-normal BMI levels, and was nearly five-fold in women with a BMI ≥ 35 kg/m2.