Incidence of Lyme Carditis and Lyme Carditis as a Cause of Pacemaker Implantation: A Nationwide Registry-Based Case-Control Study.

Background: Lyme borreliosis (LB) of the heart is called Lyme carditis (LC), which often manifests with high-grade atrioventricular block (AVB) requiring pacemaker implantation. LC is treated with antibiotics, and most patients recover fully after treatment. The overall incidence of LC, and of LC as a cause of pacemaker implantation, has not previously been systematically studied. Methods: This was a case-control study based on data from Swedish national registers. The study was divided into two parts; part 1 including all patients diagnosed with AVB between 2001 and 2018, and part 2 including all patients who had received a pacemaker due to AVB between 2010 and 2018. Patients diagnosed with LB 90 days before and 180 days after the AVB diagnosis were identified among the patients and compared to matched control groups generated from the general population. Results: Of 81 063 patients with AVB, 102 were diagnosed with LB. In the control group, 27 were diagnosed with LB. The yearly incidence of LC was 0.056 per 100 000 adults and year. Of 25 241 patients who had received a pacemaker for AVB, 31 were diagnosed with LB. In the control group, 8 were diagnosed with LB. The yearly incidence of LC as a cause of pacemaker implantation was 0.033 per 100 000 adults and year. The estimated risk for patients with LC to receive a permanent pacemaker was 59%. Conclusions: LC is a rare cause of AVB. Nevertheless, more than half of patients with LC receive a permanent pacemaker for a condition that is easily cured with antibiotics.

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.

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.

COVID-19 is associated with bystander polyclonal autoreactive B cell activation as reflected by a broad autoantibody production, but none is linked to disease severity.

Coronavirus disease 2019 (COVID-19) is associated with autoimmune features and autoantibody production in a small subset of the population. Pre-existing neutralizing antitype I interferons (IFNs) autoantibodies are related to the severity of COVID-19. Plasma levels of IgG and IgM against 12 viral antigens and 103 self-antigens were evaluated using an antibody protein array in patients with severe/critical or mild/moderate COVID-19 disease and uninfected controls. Patients exhibited increased IgGs against Severe acute respiratory syndrome coronavirus-2 proteins compared to controls, but no difference was observed in the two patient groups. 78% autoreactive IgGs and 93% autoreactive IgMs were increased in patients versus controls. There was no difference in the plasma levels of anti-type I IFN autoantibodies or neutralizing anti-type I IFN activity of plasma samples from the two patient groups. Increased anti-type I IFN IgGs were correlated with higher lymphocyte accounts, suggesting a role of nonpathogenic autoantibodies. Notably, among the 115 antibodies tested, only plasma levels of IgGs against human coronavirus (HCOV)-229E and HCOV-NL63 spike proteins were associated with mild disease outcome. COVID-19 was associated with a bystander polyclonal autoreactive B cell activation, but none of the autoantibody levels were linked to disease severity. Long-term humoral immunity against HCOV-22E and HCOV-NL63 spike protein was associated with mild disease outcome. Understanding the mechanism of life-threatening COVID-19 is critical to reducing mortality and morbidity.

Sex difference in circulating soluble form of ACE2 protein in moderate and severe COVID-19 and healthy controls.

Introduction: Membrane-bound angiotensin-converting enzyme-2 (ACE2) in epithelial cells is the main receptor for SARS-CoV-2. The extracellular portion of ACE2 may be shedded to plasma in which process ADAM17 (a disintegrin and metalloproteinase 17) is important. Results on the relationship between circulating levels of the soluble form of ACE2 (sACE2) and disease severity are inconclusive. This study investigates if sACE2 concentration correlates with COVID-19 severity, and whether this is affected by sex. Materials and methods: Soluble form of ACE2 was analyzed in three groups: 104 patients (23 women and 81 men) with severe COVID-19 admitted to an intensive care unit (ICU), patients with moderate COVID-19 who required hospital care (n = 19, 4 women and 15 men), and age and sex matched healthy controls (n = 20, 4 women and 16 men). Blood samples were collected at hospital admission between 18 March 2020, and 3 May 2021, and at follow-up between 27 October 2020, and 19 October 2021. Circulating sACE2 (µg/L) was measured in EDTA plasma with a sensitive enzyme-linked immunosorbent assay. Additionally, CRP, ferritin, and lymphocyte count were analyzed during hospital stay. Results: In total, 23 patients (22%) died in the ICU. When comparing healthy controls [mean age 58.1 (SD 11.4) years] and patients with moderate COVID-19 [mean age 61.0 (SD 13.2) years] with patients in the ICU [mean age 63.6 (SD 11.6) years], we found that sACE2 concentration decreased (70% reduction) with disease severity in men (p = 0.002) but increased 3.7-fold with severity in women (p = 0.043), suggesting a sex-related difference in how COVID-19 severity is related to sACE2 concentration. Moreover, we identified a relationship between inflammatory biomarkers and sACE2 concentration during the intensive care treatment, such that higher CRP and higher ferritin concentration correlated with lower sACE2 concentration in men. Conclusion: The decrease in sACE2 concentration, selectively in men, in severe COVID-19 is of pathophysiological interest since men are affected more severely by the disease compared to women. Additionally, the inflammatory biomarkers, CRP and ferritin, correlated inversely with sACE2 concentration, suggesting a role in severe disease. Our findings imply that sACE2 is a possible biomarker of disease severity in a sex-specific manner.

COVID-19 in people aged 18-64 in Sweden in the first year of the pandemic: Key factors for severe disease and death.

Background: Studies on risk factors for severe COVID-19 in people of working age have generally not included non-working persons or established population attributable fractions (PAFs) for occupational and other factors. Objectives: We describe the effect of job-related, sociodemographic, and other exposures on the incidence, relative risks and PAFs of severe COVID-19 in individuals aged 18-64. Methods: We conducted a registry-based study in Swedish citizens aged 18-64 from 1 January 2020 to 1 February 2021 with respect to COVID-19-related hospitalizations and death. Results: Of 6,205,459 persons, 272,043 (7.5%) were registered as infected, 3399 (0.05%) needed intensive care, and 620 (0.01%) died, with an estimated case fatality rate of 0.06% over the last 4-month period when testing was adequate. Non-Nordic origin was associated with a RR for need of intensive care of 3·13, 95%CI 2·91-3·36, and a PAF of 32·2% after adjustment for age, sex, work, region and comorbidities. In a second model with occupation as main exposure, and adjusted for age, sex, region, comorbidities and origin, essential workers had an RR of 1·51, 95%CI, 1·35-1·6, blue-collar workers 1·18, 95%CI 1·06-1·31, school staff 1·21, 95%CI 1·01-1·46, and health and social care workers 1·89, 95%CI 1·67-2·135) compared with people able to work from home, with altogether about 13% of the PAF associated with these occupations. Essential workers and blue-collar workers, but no other job categories had higher risk of death, adjusted RRs of 1·79, 95%CI 1·34-2·38 and 1·37, 95%CI 1·04-1·81, with adjusted PAFs of altogether 9%. Conclusion: Among people of working age in Sweden, overall mortality and case fatality were low. Occupations that require physical presence at work were associated with elevated risk of needing intensive care for COVID-19, with 14% cases attributable to this factor, and 9% of deaths.

Psychosocial job stressors and risk of suicidal behavior - an observational study among Swedish men.

OBJECTIVE: This study aimed to explore the relationship between psychosocial job stressors and suicidal behavior (fatal and non-fatal) among Swedish men while controlling for potential confounders. METHODS: Population-based Swedish longitudinal cohort study of male conscripts without previous self-harm (N=1 483 310) enlisting 1968-2002. Conscription examinations included measures of IQ, stress resilience and psychiatric diagnoses. Job demand-control (JDC) exposure was assessed using the Swedish Job Exposure Matrix linked to specific occupations. Suicidal behavior among men aged 30-64 was identified in the National Hospital Register (non-fatal self-harm) and Swedish Cause of Death Register (suicide) during follow-up 2002-2014. Cox regression models were used to estimate associations between JDC category and suicidal behavior. RESULTS: In fully adjusted models, passive jobs (low demand-low control) showed the highest risk of suicidal behavior [hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.25-1.43] compared to those with low strain (low demand-high control), followed by high strain (high demand-low control) (HR 1.12, 95% Cl 1.03-1.22). A lower risk of suicidal behavior was found in the active category, where levels of both demand and control are high (HR 0.64, 95% Cl 0.60-0.70). Separate analyses for suicide as outcome revealed a lower risk of suicide in persons with active jobs (high demands-high control). The passive category showed a higher risk for suicide, but the association did not remain after adjustment for stress resilience and IQ. CONCLUSIONS: These results show that psychosocial job stressors among men are associated with risk for suicidal behavior. Improving job control has the potential to decrease suicidal behavior for this group.

No effect of remdesivir or betamethasone on upper respiratory tract SARS-CoV-2 RNA kinetics in hospitalised COVID-19 patients: a retrospective observational study.

BACKGROUND: The viral kinetics of SARS-CoV-2 has been considered clinically important. While remdesivir and corticosteroids are recommended for COVID-19 patients requiring oxygen support, there is a limited number of published reports on viral kinetics in hospitalised patients with COVID-19 treated with remdesivir or corticosteroids. METHODS: We conducted a retrospective study by collecting longitudinal samples from the nasopharynx/throat of 123 hospitalised patients (median age 55 years, 74% male) with COVID-19, to evaluate the effects of remdesivir and corticosteroid treatment on viral RNA levels. The subjects were divided into four groups: those receiving remdesivir (n = 25), betamethasone (n = 41), both (n = 15), or neither (n = 42). Time to viral RNA clearance was analysed using Kaplan-Meier plots, categorical data were analysed using Fisher's exact test, and Kruskal-Wallis for continuous data. Viral RNA decline rate was analysed using a mixed effect model. RESULTS: We found no significant difference in SARS-CoV-2 RNA decline rate or time to SARS-CoV-2 RNA clearance between the groups. Moreover, clinical status at baseline was not correlated with time to viral clearance. CONCLUSIONS: Since SARS-CoV-2 RNA kinetics was not affected by treatment, repeated sampling from the upper respiratory tract cannot be used to evaluate treatment response.

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.

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.

Fitness, strength and severity of COVID-19: a prospective register study of 1 559 187 Swedish conscripts.

OBJECTIVE: To investigate the possible connection between cardiorespiratory fitness (CRF) and muscle strength in early adulthood and severity of COVID-19 later in life. DESIGN: Prospective registry-based cohort study. PARTICIPANTS: 1 559 187 Swedish men, undergoing military conscription between 1968 and 2005 at a mean age of 18.3 (SD 0.73) years. MAIN OUTCOME MEASURES: Hospitalisation, intensive care or death due to COVID-19 from March to September 2020, in relation to CRF and muscle strength. RESULTS: High CRF in late adolescence and early adulthood had a protective association with severe COVID-19 later in life with OR (95% CI) 0.76 (0.67 to 0.85) for hospitalisation (n=2 006), 0.61 (0.48 to 0.78) for intensive care (n=445) and 0.56 (0.37 to 0.85) for mortality (n=149), compared with the lowest category of CRF. The association remains unchanged when controlled for body mass index (BMI), blood pressure, chronic diseases and parental education level at baseline, and incident cardiovascular disease before 2020. Moreover, lower muscle strength in late adolescence showed a linear association with a higher risk of all three outcomes when controlled for BMI and height. CONCLUSIONS: Physical fitness at a young age is associated with severity of COVID-19 many years later. This underscores the necessity to increase the general physical fitness of the population to offer protection against future viral pandemics.

Increased immune activation and signs of neuronal injury in HIV-negative people on preexposure prophylaxis.

OBJECTIVE: Persistent immune activation in the central nervous system and systemically are common in people living with HIV (PLHIV) despite antiretroviral therapy. It is not known whether this is generated by HIV replication or by other components such as coinfections and lifestyle-related factors. DESIGN: The aim of this study was to determine the importance of different factors; it is crucial to find well matched HIV-negative controls. In this context, HIV-negative persons on preexposure prophylaxis (PrEP) may constitute a suitable control group to PLHIV with similar lifestyle-related factors. METHODS: Cerebrospinal fluid (CSF) and blood were collected from 40 HIV-negative persons on PrEP and 20 controls without PrEP. Biomarkers of immune activation, blood--brain barrier (BBB) integrity and neuronal injury were analysed. RESULTS: CSF and serum ß2-microglobulin, serum neopterin and CSF neurofilament light protein were higher in persons on PrEP compared with controls. Furthermore, persons on PrEP had higher CSF/plasma albumin ratio, and matrix metalloproteinase-3 concentrations, indicating BBB dysfunction. Of persons on PrEP, 90% were cytomegalovirus (CMV)-positive compared to 65% of the controls. CMV-positive individuals as a group had higher levels of serum ß2-microglobulin than CMV-negative individuals (P < 0.05). Drug users had higher serum ß2-microglobulin compared to nonusers (P < 0.01). CONCLUSION: HIV-negative persons on PrEP had higher levels of biomarkers for immune activation, BBB impairment and neuronal injury, compared with volunteers without PrEP. Moreover, serum ß2-microglobulin was higher in CMV-positive than in CMV-negative individuals and in drug users compared with nonusers. These findings are important to consider when analysing immune activation and CNS injury in PLHIV, and emphasize the importance of appropriate controls.

Cumulative Incidence of Infective Endocarditis in Patients with Congenital Heart Disease: A Nationwide, Case-Control Study Over Nine Decades.

BACKGROUND: Congenital heart disease (CHD) is a lifelong predisposing condition for infective endocarditis (IE). As a consequence of advances in pediatric care, the number of adults with CHD is now exceeding the number of children. The goal of the present study was to determine the cumulative incidence of IE in patients with CHD and detect temporal changes compared with controls. METHODS: Nationwide registry-based case-control study of patients with CHD born 1930-2017 matched with 10 random controls. Infective endocarditis episodes were linked using the Swedish 10-digit personal identification number. RESULTS: In total, 89 541 patients with CHD and 890 470 matched controls were included. In patients with CHD, 1477 IE episodes were registered and 447 episodes in controls. Patients with CHD had 8.5% cumulative incidence of IE at age 87 years, compared with 0.7% in matched controls. Incidence rate of IE per 100 000 person-years was 65.5 (95% confidence interval [CI] 62.2-68.9) and 1.8 (95% CI: 1.7-2.0) in CHD patients and controls, respectively. By age 18 years, patients with CHD had an IE incidence similar to that of 81-year-old controls. Incidence of IE differed by age but not by birth year. Bacterial etiology was registered from 1997 in half of the IE episodes; among CHD IE cases, 43.3% were caused by streptococci and 29.8% by Staphylococcus aureus. CONCLUSIONS: Infective endocarditis remains an important complication in patients with CHD. Incidence correlate with age and the number of IE episodes are expected to increase as the CHD population grow older.

Serum neopterin levels in relation to mild and severe COVID-19.

BACKGROUND: The COVID-19 pandemic, caused by the coronavirus SARS-CoV-2, is rapidly spreading worldwide. There is limited information about prognostic markers that could help clinicians to identify COVID-19 patients with a poor prognosis. Serum levels of the immune activation marker neopterin has shown to be of prognostic value in patients with SARS. The aim of this study was to investigate whether serum neopterin is associated with the severity of COVID-19. METHODS: We included 34 patients with confirmed COVID-19 between March 3 and March 30, 2020. Fifteen patients had mild disease and did not require hospitalization, whereas 19 patients developed severe COVID-19 requiring intensive care. Concentrations of serum neopterin, tryptophan, and kynurenine were measured at and repeatedly after inclusion. RESULTS: We found a more than two-fold higher mean concentration of neopterin in severely ill patients (mean value 42.0 nmol/L (SD 18.2)) compared to patients with mild symptoms (16.9 nmol/L (SD 11.0)). All of the severe cases had elevated neopterin concentrations (> 9.1 nmol/L) at the initial sampling with values ranging from 17.2 to 86.7 nmol/L. In comparison, 10 of 15 patients with mild disease had neopterin levels above 9.1 nmol/L, with concentrations in the range from 4.9 to 31.6 nmol/L. Neopterin levels gradually decreased during the course of COVID-19, but severe cases maintained elevated levels for a longer period. Moreover, lower levels of tryptophan and higher levels of kynurenine, indicating an increased tryptophan catabolism, were seen in the group with severe cases. CONCLUSIONS: In conclusion, we found that serum neopterin levels are associated with the severity of COVID-19. Our findings suggest that neopterin could be used as a prognostic marker, but further studies are needed to elucidate how it can be used in the clinic.

[The virtual ward - the students' clinical education during the current pandemic]. / Verksamhetsförlagd utbildning på distans under pandemin.

On March 17, 2020, the Swedish Government recommended all higher education institutions to move to online and distance learning during the COVID-19 pandemic. The integrated course in Infection, Microbiology, and Immunity at the Programme in Medicine at University of Gothenburg had to be completely transformed. Creative solutions have now replaced the clinical training that normally takes place during the students' clinical education at the hospital. We developed a digital concept entitled "the virtual ward", in which we interact with the students in real time. Here, the students are able to follow their patients on a daily basis during teacher-guided sessions.

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.

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.

Resting heart rate in late adolescence and long term risk of cardiovascular disease in Swedish men.

AIM: To investigate the association of resting heart rate (RHR) measured in late adolescence with the long term risk of myocardial infarction (MI), ischemic stroke (IS), heart failure (HF), atrial fibrillation (AF), cardiovascular- and all-cause death. METHODS AND RESULTS: We followed a cohort of Swedish men enrolled for conscription in 1968-2005 (n = 1,008,485; mean age = 18.3 years) until December 2014. Outcomes were collected from the national inpatient - (IPR), outpatient - (OPR) and cause of death registries. Cox proportional hazard models were used to analyze the longitudinal association between RHR and outcomes while adjusting for potential confounders. While we found no independent association between RHR and risk of IS or MI when comparing the highest with the lowest quintile of the RHR distribution, but a positive association persisted between RHR and incident HF (Hazard ratio (HR) = 1.39 [95% confidence interval (CI) = 1.29-1.49]) after adjustment for body mass index (BMI) and blood pressure (BP). In similarly adjusted models, an inverse association was found for AF while there were weaker associations with death from cardiovascular disease (CVD) and all causes (adjusted HR = 1.12 [CI = 1.04-1.21] and 1.20 [CI = 1.17-1.24]). After further adjustment for cardiorespiratory fitness (CRF), the associations persisted for HF (HR = 1.26 [1.17-1.35] for any diagnostic position and HR = 1.43 [1.28-1.60] for HF as a main diagnosis) and for all-cause death (HR 1.09 [1.05-1.12]) but not for CVD death. CONCLUSION: Adolescent RHR is associated with future risk of HF and death, independently of BP, BMI and CRF, but not with CVD death, MI or IS, suggesting a causal pathway between elevated heart rate and myocardial dysfunction.

Cognitive performance in late adolescence and long-term risk of early heart failure in Swedish men.

AIMS: Heart failure (HF) incidence appears to increase among younger individuals, raising questions of how risk factors affect the younger population. We investigated the association of cognitive performance in late adolescence with long-term risk of early HF. METHODS AND RESULTS: We followed a cohort of Swedish men enrolled in mandatory military conscription in 1968-2005 (n = 1 225 300; mean age 18.3 years) until 2014 for HF hospitalization, using data from the Swedish National Inpatient Registry. Cognitive performance (IQ) was measured through a combination of tests, separately evaluating logical, verbal, visuospatial, and technical abilities. The results were standardized, weighted, and presented as stanines of IQ. The association between IQ and risk of HF was estimated using Cox proportional hazards models. In follow-up, there were 7633 cases of a first HF hospitalization (mean age at diagnosis 50.1 years). We found an inverse relationship between global IQ and risk of HF hospitalization. Using the highest IQ stanine as reference, the adjusted hazard ratio for the lowest IQ with risk of HF was 3.11 (95% confidence interval 2.60-3.71), corresponding to a hazard ratio of 1.32 (95% CI 1.28-1.35) per standard deviation decrease of IQ. This association proved persistent across predefined categories of HF with respect to pre-existing or concomitant co-morbidities; it was less apparent among obese conscripts (P for interaction =0.0004). CONCLUSION: In this study of young men, IQ was strongly associated with increased risk of early HF. The medical profession needs to be aware of this finding so as to not defer diagnosis.