Age and sex differences in cause-specific excess mortality and years of life lost associated with COVID-19 infection in the Swedish population.

BACKGROUND: Estimating excess mortality and years of life lost (YLL) attributed to coronavirus disease 19 (COVID-19) infection provides a comprehensive picture of the mortality burden on society. We aimed to estimate the impact of the COVID-19 pandemic on age- and sex-specific excess mortality and YLL in Sweden during the first 17 months of the pandemic. METHODS: In this population-based observational study, we calculated age- and sex-specific excess all-cause mortality and excess YLL during 2020 and the first 5 months of 2021 and cause-specific death [deaths from cardiovascular disease (CVD), cancer, other causes and deaths excluding COVID-19] in 2020 compared with an average baseline for 2017-19 in the whole Swedish population. RESULTS: COVID-19 deaths contributed 9.9% of total deaths (98 441 deaths, 960 305 YLL) in 2020, accounting for 75 151 YLL (7.7 YLL/death). There were 2672 (5.7%) and 1408 (3.0%) excess deaths, and 19 141 (3.8%) and 3596 (0.8%) excess YLL in men and women, respectively. Men aged 65-110 years and women aged 75-110 years were the greatest contributors. Fewer deaths and YLL from CVD, cancer and other causes were observed in 2020 compared with the baseline adjusted to the population size in 2020. CONCLUSIONS: Compared with the baseline, excess mortality and YLL from all causes were experienced in Sweden during 2020, with a higher excess observed in men than in women, indicating that more men died at a younger age while more women died at older ages than expected. A notable reduction in deaths and YLL due to CVD suggests a displacement effect from CVD to COVID-19.

Risk factors and treatment of oxygenator high-pressure excursions during cardiopulmonary bypass.

INTRODUCTION: A high-pressure excursion (HPE) is a sudden increase in oxygenator inlet pressure during cardiopulmonary bypass (CPB). The aims of this study were to identify factors associated with HPE, to describe a treatment protocol utilizing epoprostenol in severe cases, and to assess early outcome in HPE patients. METHODS: Patients who underwent cardiac surgery with cardiopulmonary bypass at Sahlgrenska University Hospital 2016-2018 were included in a retrospective observational study. Pre- and post-operative data collected from electronic health records, local databases, and registries were compared between HPE and non-HPE patients. Factors associated with HPE were identified with logistic regression models. RESULTS: In total, 2024 patients were analyzed, and 37 (1.8%) developed HPE. Large body surface area (adjusted Odds Ratio (aOR): 1.43 per 0.1 m2; 95% confidence interval (CI): 1.16-1.76, p < 0.001), higher hematocrit during CPB (aOR: 1.20 per 1%; (1.09-1.33), p < 0.001), acute surgery (aOR: 2.98; (1.26-6.62), p = 0.018), and previous stroke (aOR: 2.93; (1.03-7.20), p = 0.027) were independently associated with HPE. HPE was treated with hemodilution (n = 29, 78.4%), and/or extra heparin (n = 23, 62.2%), and/or epoprostenol (n = 12, 32.4%). No oxygenator change-out was necessary. While there was no significant difference in 30-day mortality (2.7% vs 3.2%, p = 1.0), HPE was associated with a higher perioperative stroke rate (8.1% vs 1.8%, aOR 5.09 (1.17-15.57), p = 0.011). CONCLUSIONS: Large body surface area, high hematocrit during CPB, previous stroke and acute surgery were independently associated with HPE. A treatment protocol including epoprostenol appears to be a safe option. Perioperative stroke rate was increased in HPE patients.

Severe COVID-19 in people 55 and older during the first year of the pandemic in Sweden.

BACKGROUND: Exposure to many contacts is the main risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, while risk of serious disease and death is chiefly determined by old age and comorbidities. Relative and population-attributable fractions (PAFs) of multiple medical and social exposures for COVID-19 outcomes have not been evaluated among older adults. OBJECTIVES: We describe the effect of multiple exposures on the odds of testing positive for the virus and of severe disease (hospital care or death) and PAFs in Swedish citizens aged 55 years and above. METHODS: We used national registers to follow all citizens aged 55 years and above with respect to (1) testing positive, (2) hospitalization, and (3) death between 31 January 2020 and 1 February 2021. RESULTS: Of 3,410,241 persons, 156,017 (4.6%, mean age 68.3 years) tested positive for SARS-CoV-2, while 35,999 (1.1%, mean age 76.7 years) were hospitalized or died (12,384 deaths, 0.4%, mean age 84.0 years). Among the total cohort, the proportion living without home care or long-term care was 98.8% among persons aged 55-64 and 22.1% of those aged 95 and above. After multiple adjustment, home care and long-term care were associated with odds ratios of 7.9 (95% confidence interval [CI] 6.8-9.1) and 22.5 (95% CI 19.6-25.7) for mortality, with PAFs of 21.9% (95% CI 20.9-22.9) and 33.3% (95% CI 32.4-34.3), respectively. CONCLUSION: Among Swedish residents aged 55 years and above, those with home care or long-term care had markedly increased risk for COVID-19 death during the first year of the pandemic, with over 50% of deaths attributable to these factors.

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 risk of dementia after coronary artery bypass grafting in relation to age and sex.

INTRODUCTION: We examined the long-term risk of dementia after coronary artery bypass grafting (CABG) in relation to age and sex. METHODS: All CABG patients in Sweden 1992-2015 (n = 111,335), and matched controls (n = 222,396) were included in a population-based study. Adjusted hazard ratios (aHR) for all-cause dementia, vascular dementia, and Alzheimer's disease were calculated. RESULTS: There was no difference in the risk for all-cause dementia between CABG patients and control subjects (aHR 0.98 [95% confidence interval 0.95 to 1.02]). CABG patients <65 years and 65 to 74 years had higher risk (aHR 1.29 [1.17-1.42] and 1.08 [1.02-1.13], respectively), and patients ≥75 years had lower risk (aHR 0.76 [0.71-0.81]). The highest risk was observed in women <65 years (aHR 1.64 [1.31-2.05]). DISCUSSION: Overall, the long-term risk for all-cause dementia does not differ between CABG patients and the general population. Younger patients have a higher risk, while older patients have a lower risk, compared to controls.

Higher Body Mass Index in Adolescence Predicts Cardiomyopathy Risk in Midlife.

BACKGROUND: Modifiable lifestyle factors in relation to risk for cardiomyopathy, a common and increasing cause of heart failure in the young, have not been widely studied. We sought to investigate a potential link between obesity, a recognized predictor of early heart failure, in adolescence and being diagnosed with cardiomyopathy in adulthood. METHODS: This was a nationwide register-based prospective cohort study of 1 668 893 adolescent men (mean age, 18.3 years; SD, 0.7 years) who enlisted for compulsory military service from 1969 to 2005. At baseline, body mass index (BMI), blood pressure, and medical disorders were registered, along with test results for fitness and muscle strength. Cardiomyopathy diagnoses were identified from the National Hospital Register and Cause of Death Register during an up to 46-year follow-up and divided into categories: dilated, hypertrophic, alcohol/drug-induced, and other. Hazard ratios were calculated with Cox proportional hazards models. RESULTS: During follow-up (median, 27 years; Q1-Q3, 19-35 years), 4477 cases of cardiomyopathy were identified, of which 2631 (59%) were dilated, 673 (15%) were hypertrophic, and 480 (11%) were alcohol/drug-induced. Increasing BMI was strongly associated with elevated risk of cardiomyopathy, especially dilated, starting at levels considered normal (BMI, 22.5-<25 kg/m2; hazard ratio, 1.38 [95% CI, 1.22-1.57]), adjusted for age, year, center, and baseline comorbidities, and with a >8-fold increased risk at BMI ≥35 kg/m2 compared with BMI of 18.5 to <20 kg/m2. For each 1-unit increase in BMI, similarly adjusted hazard ratios were 1.15 (95% CI, 1.14-1.17) for dilated cardiomyopathy, 1.09 (95% CI, 1.06-1.12) for hypertrophic cardiomyopathy, and 1.10 (1.06-1.13) for alcohol/drug-induced cardiomyopathy. CONCLUSIONS: Even mildly elevated body weight in late adolescence may contribute to being diagnosed with cardiomyopathy in adulthood. The already marked importance of weight control in youth is further strengthened by these findings, as well as greater evidence for obesity as a potential important cause of adverse cardiac remodeling that is independent of clinically evident ischemic heart disease.

Body mass index and fitness in late adolescence and risk of cardiovascular disease, respiratory disease, and overall death after COVID-19.

Objective: Since obesity and poor fitness appear to be unfavorable for both cardiovascular health and coping with viral infections such as COVID-19, they are of specific interest in light of the increased risk of cardiovascular and respiratory events now seen after infection with SARS-CoV-2. Therefore, the aim of the present study was to investigate how body mass index (BMI) and cardiorespiratory fitness (CRF) in late adolescence are associated with the risk of cardiovascular disease (CVD), respiratory disease, and mortality after COVID-19. Methods: In this study, 1.5 million 18-year-old Swedish men with BMI and CRF measured during enlistment for military service 1968-2005 were included. Hospitalized and non-hospitalized COVID-19 cases were identified through the Patient Register or positive polymerase chain reaction tests, and age-matched with non-infected controls. CVD, respiratory disease, and mortality after COVID-19 were divided into <60days, 60-180days, >180days post-infection. Cox regression models were used. Results: Hospitalized COVID-19 cases (n = 9839), compared to controls, had >10-fold, 50 to 70-fold, and >70-fold hazards of CVD, respiratory disease, and mortality over the initial 60 days post-infection with little variation across BMI or CRF categories. The elevated risks persisted at declining levels >180 days. For non-hospitalized COVID-19 cases (n = 181,822), there was a 4- to 7-fold increased acute mortality risk, and high CRF was associated with lower risk of post-infectious respiratory disease. Conclusions: The high hazards of adverse outcomes during the first two months after COVID-19 hospitalization, and across BMI and CRF categories, declined rapidly but were still elevated after six months. Adolescent CRF was associated with respiratory disease after COVID-19 without hospitalization, which gives further support to the health benefits of physical activity.

Postdischarge major bleeding, myocardial infarction, and mortality risk after coronary artery bypass grafting.

OBJECTIVE: To investigate the incidence and mortality risk associated with postdischarge major bleeding after coronary artery bypass grafting (CABG), and relate this to the incidence of, and mortality risk from, postdischarge myocardial infarction. METHODS: All patients undergoing first-time isolated CABG in Sweden in 2006-2017 and surviving 14 days after hospital discharge were included in a cohort study. Individual patient data from the SWEDEHEART Registry and five other mandatory nationwide registries were merged. Piecewise Cox proportional hazards models were used to investigate associations between major bleeding, defined as hospitalisation for bleeding, with subsequent mortality risk. Similar Cox proportional hazards models were used to investigate the association between postdischarge myocardial infarction and mortality risk. RESULTS: Among 36 633 patients, 2429 (6.6%) had a major bleeding event and 2231 (6.1%) had a myocardial infarction. Median follow-up was 6.0 (range 0-11) years. Major bleeding was associated with higher mortality risk <30 days (adjusted HR (aHR)=20.2 (95% CI 17.3 to 23.5)), 30-365 days (aHR=3.8 (95% CI 3.4 to 4.3)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. Myocardial infarction was associated with higher mortality risk <30 days (aHR=20.0 (95% CI 16.7 to 23.8)), 30-365 days (aHR=4.1 (95% CI 3.6 to 4.8)) and >365 days (aHR=1.8 (95% CI 1.7 to 2.0)) after the event. CONCLUSIONS: The increase in mortality risk associated with a postdischarge major bleeding after CABG is substantial and is similar to the mortality risk associated with a postdischarge myocardial infarction.

Aerobic exercise and strength training effects on cardiovascular sympathetic function in healthy adults: a randomized controlled trial.

OBJECTIVE: Exercise has widely documented cardioprotective effects, but the mechanisms underlying these effects are not entirely known. Previously, we demonstrated that aerobic but not strength training lowered resting heart rate and increased cardiac vagal regulation, changes that were reversed by sedentary deconditioning. Here, we focus on the sympathetic nervous system and test whether aerobic training lowers levels of cardiovascular sympathetic activity in rest and that deconditioning would reverse this effect. METHODS: We conducted a randomized controlled trial contrasting the effects of aerobic (A) versus strength (S) training on indices of cardiac (preejection period, or PEP) and vascular (low-frequency blood pressure variability, or LF BPV) sympathetic regulation in 149 young, healthy, and sedentary adults. Participants were studied before and after conditioning, as well as after 4 weeks of sedentary deconditioning. RESULTS: As previously reported, aerobic capacity increased in response to conditioning and decreased after deconditioning in the aerobic, but not the strength, training group. Contrary to prediction, there was no differential effect of training on either PEP (A: mean [SD] -0.83 [7.8] milliseconds versus S: 1.47 [6.69] milliseconds) or LF BPV (A: mean [SD] -0.09 [0.93] ln mm Hg(2) versus S: 0.06 [0.79] ln mm Hg(2)) (both p values > .05). CONCLUSIONS: These findings, from a large randomized controlled trial using an intent-to-treat design, show that moderate aerobic exercise training has no effect on resting state cardiovascular indices of PEP and LF BPV. These results indicate that in healthy, young adults, the cardioprotective effects of exercise training are unlikely to be mediated by changes in resting sympathetic activity. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT00358137.

Development of a social skills training programme to target social isolation using virtual reality technology in primary mental health care.

Introduction: People with severe mental illness often have a small or no network of friends and limited contact with their family and live social isolated lives. We developed a social skills training programme to be administered by public mental health professionals in helping those with mental illness to overcome their social isolation. Methods: The programme was developed over 3 years in close collaboration among psychologists, service users, municipal mental health professionals, mental health service researchers and a local firm providing virtual reality (VR) training. We started with the simplest available equipment, that is, a cardboard headset combined with a smartphone, then we used Oculus Quest and now Oculus Quest 2. Results: The resulting programme is comprised of eight steps from: 1) identify service user's primary and secondary goals to 8) three-month follow-up. Conclusion: Several factors made adoption and implementation of VR technology possible in a relatively short timeframe: namely, the municipality and service users were involved from the beginning of the development process, efforts were made to introduce VR to mental health professionals and allow them to reflect on its usability, solutions were low-tech and low cost, and the long-term research collaboration was established without municipal financial obligations.

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.

Socioeconomic factors and long-term mortality risk after surgical aortic valve replacement.

Background: There is scarce knowledge about the association between socioeconomic status and mortality in patients undergoing surgical aortic valve replacement. This study explores the associations between income, education and marital status, and long-term mortality risk. Methods: In this national registry-based observational cohort study we included all 14,537 patients aged >18 years who underwent isolated surgical aortic valve replacement for aortic stenosis in Sweden 1997-2020. Socioeconomic status and comorbidities were collected from three mandatory national registries. Cox regression models adjusted for patient characteristics and comorbidities were used to estimate the mortality risk. Results: Mortality risk was higher for patients in the lowest versus the highest income quintile (adjusted hazard ratio [aHR] 1.36, 95 % confidence interval [CI]: 1.11-1.65), for patients with <10 years education versus >12 years (aHR 1.20, 95 % CI:1.08-1.33), and for patients who were not married/cohabiting versus those who were (aHR 1.24, 95 % CI:1.04-1.48). Patients with the most unfavorable socioeconomic status (lowest income, shortest education, never married/cohabiting) had an adjusted median survival of 2.9 years less than patients with the most favorable socioeconomic status (14.6 years, 95 % CI: 13.2-17.4 years vs. 11.7 years, 95 % CI: 9.8-14.4). Conclusions: Low socioeconomic status in patients undergoing surgical aortic valve replacement is associated with shorter survival and an increased long-term adjusted mortality risk. These results emphasize the importance of identifying surgical aortic valve replacement patients with unfavorable socioeconomic situation and ensure sufficient post-discharge surveillance.

Pulmonary embolism and deep venous thrombosis after COVID-19: long-term risk in a population-based cohort study.

Background: Venous thromboembolism (VTE) (pulmonary embolism (PE) or deep venous thrombosis (DVT)) is common during acute COVID-19. Long-term excess risk has not yet been established. Objective: To study long-term VTE risk after COVID-19. Methods: Swedish citizens aged 18-84 years, hospitalized and/or testing positive for COVID-19 between January 1, 2020, and September 11, 2021 (exposed), stratified by initial hospitalization, were compared to matched (1:5) non-exposed population-derived subjects without COVID-19. Outcomes were incident VTE, PE or DVT recorded within 60, 60-<180, and ≥180 days. Cox regression was used for evaluation and a model adjusted for age, sex, comorbidities and socioeconomic markers developed to control for confounders. Results: Among exposed patients, 48,861 were hospitalized for COVID-19 (mean age 60.6 years) and 894,121 were without hospitalization (mean age 41.4 years). Among patients hospitalized for COVID-19, fully adjusted hazard ratios (HRs) during 60-<180 days were 6.05 (95% confidence interval (CI) 4.80─7.62) for PE and 3.97 (CI 2.96─5.33) for DVT, compared to non-exposed with corresponding estimates among COVID-19 without hospitalization 1.17 (CI 1.01─1.35) and 0.99 (CI 0.86─1.15), based on 475 and 2,311 VTE events, respectively. Long-term (≥180 days) HRs in patients hospitalized for COVID-19 were 2.01 (CI 1.51─2.68) for PE and 1.46 (CI 1.05─2.01) for DVT while non-hospitalized had similar risk to non-exposed, based on 467 and 2,030 VTE events, respectively. Conclusions: Patients hospitalized for COVID-19 retained an elevated excess risk of VTE, mainly PE, after 180 days, while long-term risk of VTE in individuals with COVID-19 without hospitalization was similar to the non-exposed.

Short- and long-term outcome after surgical aortic valve replacement in patients on dialysis.

Background: There is no consensus on the choice of aortic valve prosthesis for patients with end-stage renal failure. We analyzed short- and long-term complications in dialysis patients who underwent aortic valve replacement (AVR) with either a biological (bAVR) or a mechanical (mAVR) prosthesis. Methods: All patients on dialysis who underwent bAVR or mAVR in Sweden from 1995 to 2017 (n=335) were included in a nationwide, population-based, observational, cohort study. Short and long-term complications were compared. Long-term mortality was compared with multivariable Cox regression analysis adjusted for age, sex, comorbidities, and a propensity score-matched model. Median follow-up was 2.8 (range, 0-16) years. Results: Biological and mechanical valves were implanted in 253 (75.5%) and 82 (24.5%) patients, respectively. The bAVR patients were older and had more comorbidities. There was no significant difference in early complication rate. Thirty-day mortality was 9.1% in bAVR and 7.3% in mAVR patients (P=0.62). The multivariable Cox regression model did not show significant difference in mortality risk between bAVR and mAVR patients [adjusted hazard ratio (aHR) 1.33; 95% CI: 0.84-2.13; P=0.22]. The results were confirmed in the propensity-score matched model. The rate of aortic valve reoperations did not differ significantly between the bAVR and mAVR group. Conclusions: The short- and long-term complication rate is high, and the expected life expectancy limited, in dialysis patients undergoing AVR, without significant difference between biological and mechanical prostheses. The results suggest that biological valve prosthesis, avoiding systemic anticoagulation, is appropriate in most dialysis patients.

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.

Associations between medical therapy after surgical aortic valve replacement for aortic stenosis and long-term mortality: a report from the SWEDEHEART registry.

AIMS: The association between the use of statins, renin-angiotensin system (RAS) inhibitors, and/or ß-blockers and long-term mortality in patients with aortic stenosis (AS) who underwent surgical aortic valve replacement (SAVR) is unknown. METHODS AND RESULTS: All patients with AS who underwent isolated first-time SAVR in Sweden from 2006 to 2017 and survived 6 months after discharge were included. Individual patient data from four mandatory nationwide registries were merged. Cox proportional hazards models, with time-updated data on medication status and adjusted for age, sex, comorbidities, type of prosthesis, and year of surgery, were used to investigate associations between dispensed statins, RAS inhibitors, and ß-blockers and all-cause mortality. In total, 9553 patients were included, and the median follow-up time was 4.9 years (range 0-11); 1738 patients (18.2%) died during follow-up. Statins were dispensed to 49.1% and 49.0% of the patients within 6 months of discharge from the hospital and after 10 years, respectively. Corresponding figures were 51.4% and 53.9% for RAS inhibitors and 79.3% and 60.7% for ß-blockers. Ongoing treatment was associated with lower mortality risk for statins {adjusted hazard ratio (aHR) 0.67 [95% confidence interval (95% CI) 0.60-0.74]; P < 0.001} and RAS inhibitors [aHR 0.84 (0.76-0.93); P < 0.001] but not for ß-blockers [aHR 1.17 (1.05-1.30); P = 0.004]. The associations were robust in subgroups based on age, sex, and comorbidities (P for interactions >0.05). CONCLUSIONS: The results of this large population-based real-world study support the use of statins and RAS inhibitors for patients who underwent SAVR due to AS.

Beta blockers and long-term outcome after coronary artery bypass grafting: a nationwide observational study.

AIMS: Beta blockers are associated with improved outcomes for selected patients with cardiovascular disease. We assessed long-term utilization of beta blockers after coronary artery bypass grafting (CABG) and its association with outcome. METHODS AND RESULTS: All 35 184 patients in Sweden who underwent first-time isolated CABG between 1 January 2006 and 31 December 2017 and were followed for at least 6 months were included in a nationwide observational study. Multivariable Cox regression models using time-updated data on dispensed prescriptions were used to assess associations between different types of beta blockers and outcomes. The primary outcome was major adverse cardiovascular events (MACEs), a composite of all-cause mortality, stroke, and myocardial infarction (MI). Subgroup analyses were performed in patients with and without previous MI, heart failure, and reduced left ventricular ejection fraction (LVEF). Median follow-up was 5.2 years (range 0-11). At baseline, 33 159 (94.2%) patients were dispensed beta blockers, 30 563 (92.2%) of which were cardioselective beta blockers. After 10 years, the dispensing of cardioselective beta blockers had declined to 73.7% of all patients. Ongoing treatment with cardioselective beta blockers was associated with a slight reduction in MACEs [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.89-0.98, P = 0.0063]. The reduction was largely driven by a reduced risk of MI (HR 0.83, 95% CI 0.75-0.92, P = 0.0003), while there was no significant reduction in all-cause mortality (HR 0.99, 95% CI 0.93-1.05) and stroke (HR 0.96, 95% CI 0.87-1.05). The reduced risk for MI was consistent in all the investigated subgroups. CONCLUSION: Ongoing treatment with cardioselective beta blockers after CABG is associated with a reduction in MACEs, mainly because of reduced long-term risk for MI. The association between cardioselective beta blockers and MI was consistent in patients with and patients without previous MI, heart failure, atrial fibrillation, or reduced LVEF.

BMI in early adulthood is associated with severe COVID-19 later in life: A prospective cohort study of 1.5 million Swedish men.

OBJECTIVE: Overweight and obesity have been identified as risk factors for severe COVID-19; however, prospective cohort studies investigating the association between overweight early in life and severity of COVID-19 are lacking. METHODS: This study included 1,551,670 Swedish men, born between 1950 and 1987, with BMI registered at age 18 years. They were followed until January 9, 2021. COVID-19 cases and comorbidities were identified through the National Patient, Intensive Care, and Cause of Death registries. Outcomes included the following: 1) hospitalization; 2) intensive care unit admission; and 3) death. RESULTS: The study found 4,315 cases (mean age = 56.4 years [SD 8.8]) of patients hospitalized because of COVID-19, of which 729 were admitted to an intensive care unit, and altogether there were 224 deaths. The risk for hospital admission increased with higher values of BMI at age 18 years, despite adjustment for comorbidities, from an odds ratio (OR) of 1.19 (95% CI: 1.08-1.31) at BMI = 22.5 to 25 to an OR of 1.68 (95% CI: 1.39-2.02) at BMI ≥ 30, compared with BMI = 18.5 to 20. ORs for intensive care unit admission were 1.44 (95% CI: 1.13-1.84) at BMI = 22.5 to 25 and 2.61 (95% CI: 1.73-3.93) at BMI ≥ 30. CONCLUSIONS: Higher BMI in early adulthood was associated with severe COVID-19 many years later, with a risk increase starting already at BMI ≥ 22.5. This underlines the necessity of preventive actions against overweight in youth to offer protection against coming viral pandemics.

BMI, sex and outcomes in hospitalised patients in western Sweden during the COVID-19 pandemic.

High body mass index (BMI) is associated with severe COVID-19 but findings regarding the need of intensive care (IC) and mortality are mixed. Using electronic health records, we identified all patients in western Sweden hospitalised with COVID-19 to evaluate 30-day mortality or assignment to IC. Adjusted logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for outcomes. Of totally 9761 patients, BMI was available in 7325 (75%), included in the study. There was a marked inverse association between BMI and age (underweight and normal weight patients were on average 78 and 75 years, whereas overweight and obese were 68 and 62 years). While older age, male sex and several comorbidities associated with higher mortality after multivariable adjustment, BMI did not. However, BMI ≥ 30 kg/m2 (OR 1.46, 95% CI 1.21-1.75) was associated with need of IC; this association was restricted to women (BMI ≥ 30; OR 1.96 (95% CI 1.41-2.73), and not significant in men; OR 1.22 (95% CI 0.97-1.54). In this comprehensive hospital population with COVID-19, BMI was not associated with 30-day mortality risk. Among the obese, women, but not men, had a higher risk of assignment to IC.

Body Mass Index in Adolescence and Long-Term Risk of Early Incident Atrial Fibrillation and Subsequent Mortality, Heart Failure, and Ischemic Stroke.

Background We sought to determine the role of obesity in adolescent men on development of atrial fibrillation (AF) and subsequent associated clinical outcomes in subjects diagnosed with AF. Methods and Results We conducted a nationwide, register-based, cohort study of 1 704 467 men (mean age, 18.3±0.75 years) enrolled in compulsory military service in Sweden from 1969 through 2005. Height and weight, blood pressure, fitness, muscle strength, intelligence quotient, and medical disorders were recorded at baseline. Records obtained from the National Inpatient Registry and the Cause of Death Register were used to determine incidence and clinical outcomes of AF. During a median follow-up of 32 years (interquartile range, 24-41 years), 36 693 cases (mean age at diagnosis, 52.4±10.6 years) of AF were recorded. The multivariable-adjusted hazard ratio (HR) for AF increased from 1.06 (95% CI, 1.03-1.10) in individuals with body mass index (BMI) of 20.0 to <22.5 kg/m2 to 3.72 (95% CI, 2.44-5.66) among men with BMI of 40.0 to 50.0 kg/m2, compared with those with BMI of 18.5 to <20.0 kg/m2. During a median follow-up of ≈6 years in patients diagnosed with AF, we identified 3767 deaths, 3251 cases of incident heart failure, and 921 cases of ischemic stroke. The multivariable-adjusted HRs for all-cause mortality, incident heart failure, and ischemic stroke in AF-diagnosed men with baseline BMI >30 kg/m2 compared with those with BMI <20 kg/m2 were 2.86 (95% CI, 2.30-3.56), 3.42 (95% CI, 2.50-4.68), and 2.34 (95% CI, 1.52-3.61), respectively. Conclusions Increasing BMI in adolescent men is strongly associated with early AF, and with subsequent worse clinical outcomes in those diagnosed with AF with respect to all-cause mortality, incident heart failure, and ischemic stroke.