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.

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.

Excess risk of hospitalisation for heart failure among people with type 2 diabetes.

AIMS/HYPOTHESIS: Type 2 diabetes is an established risk factor for heart failure, but age-specific data are sparse. We aimed to determine excess risk of heart failure, based on age, glycaemic control and kidney function in comparison with age- and sex-matched control individuals from the general population. METHODS: Individuals with type 2 diabetes registered in the Swedish National Diabetes Registry 1998-2012 (n = 266,305) were compared with age-, sex- and county-matched control individuals without diabetes (n = 1,323,504), and followed over a median of 5.6 years until 31 December 2013. RESULTS: We identified 266,305 individuals with type 2 diabetes (mean age 62.0 years, 45.3% women) and 1,323,504 control individuals. Of the individuals with type 2 diabetes and control individuals, 18,715 (7.0%) and 50,157 (3.8%) were hospitalised with a diagnosis of heart failure, respectively. Comparing individuals with diabetes with those in the control group, men and women with type 2 diabetes who were younger than 55 years of age had HRs for hospitalisation for heart failure of 2.07 (95% CI 1.73, 2.48) and 4.59 (95% CI 3.50, 6.02), respectively, using analyses adjusted for socioeconomic variables and associated conditions. Younger age, poorer glycaemic control and deteriorating renal function were all associated with increased excess risk of heart failure in those with type 2 diabetes compared with the control group. However, people with diabetes who were ≥75 years and without albuminuria or with good glycaemic control (HbA1c ≤52 mmol/mol [≤6.9%]) had a similar risk of hospitalisation for heart failure as control individuals in the same age group. CONCLUSIONS/INTERPRETATION: Men and women aged <55 years with type 2 diabetes are at markedly elevated excess risk of heart failure. The excess risk declined with age, but persisted even with good glycaemic control. However, among those who were 75 years and older, diabetic individuals with well controlled glucose levels or without albuminuria had a risk of heart failure that was on a par with individuals without diabetes.

Body mass index and risk of cancer in young women.

It is unclear how increasing body mass index (BMI) influences risk of cancer in young women. We used data from the Medical Birth, Patient and Cause of Death registers collected between 1982 and 2014 to determine the risk of obesity-related cancer types, breast cancer, all cancer and cancer-related death in relation to BMI in 1,386,725 women, aged between 18 and 45 years, in Sweden. During a median follow-up of 16.3 years (IQR 7.7-23.5), 9808 women developed cancer. The hazard ratio (HR) of endometrial and ovarian cancer increased with higher BMI from 1.08 (95% CI 0.93-1.24) and 1.08 (95% CI 0.96-1.21) among women with BMI 22.5-< 25 to 2.33 (95% CI 1.92-2.83) and 1.48 (95% CI 1.24-1.77), respectively, among women with BMI ≥ 30. There were linear and positive associations between BMI and incident cancer in the ovary, colon, endometrium, pancreas, rectum, gallbladder, esophageal cancer and renal cell carcinoma, as well as death from obesity-related cancer forms. In conclusion, we found that elevated BMI in young women linearly associated with several obesity-related cancer forms, including death from these cancers.

Severe COVID-19 Infection in Type 1 and Type 2 Diabetes During the First Three Waves in Sweden.

OBJECTIVE: Type 2 diabetes is an established risk factor for hospitalization and death in COVID-19 infection, while findings with respect to type 1 diabetes have been diverging. RESEARCH DESIGN AND METHODS: Using nationwide health registries, we identified all patients aged ≥18 years with type 1 and type 2 diabetes in Sweden. Odds ratios (ORs) describe the general and age-specific risk of being hospitalized, need for intensive care, or dying, adjusted for age, socioeconomic factors, and coexisting conditions, compared with individuals without diabetes. Machine learning models were used to find predictors of outcomes among individuals with diabetes positive for COVID-19. RESULTS: Until 30 June 2021, we identified 365 (0.71%) and 11,684 (2.31%) hospitalizations in 51,402 and 504,337 patients with type 1 and 2 diabetes, respectively, with 67 (0.13%) and 2,848 (0.56%) requiring intensive care unit (ICU) care and 68 (0.13%) and 4,020 (0.80%) dying (vs 7,824,181 individuals without diabetes [41,810 hospitalizations (0.53%), 8,753 (0.11%) needing ICU care, and 10,160 (0.13%) deaths). Although those with type 1 diabetes had moderately raised odds of being hospitalized (multiple-adjusted OR 1.38 [95% CI 1.24-1.53]), there was no independent effect on ICU care or death (OR of 1.21 [95% CI 0.94-1.52] and 1.13 [95% CI 0.88-1.48], respectively). Age and socioeconomic factors were the dominating features for predicting hospitalization and death in both types of diabetes. CONCLUSIONS: Type 2 diabetes was associated with increased odds for all outcomes, whereas patients with type 1 diabetes had moderately increased odds of hospitalization but not ICU care and death.

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.

Trajectories in HbA1c and other risk factors among adults with type 1 diabetes by age at onset.

INTRODUCTION: In type 1 diabetes, potential loss of life-years is greatest in those who are youngest at the time of onset. Using data from a nationwide cohort of patients with type 1 diabetes, we aimed to study risk factor trajectories by age at diagnosis. RESEARCH DESIGN AND METHODS: We stratified 30 005 patients with type 1 diabetes aged 18-75 years into categories based on age at onset: 0-10, 11-15, 16-20, 21-25, and 26-30 years. HbA1c, albuminuria, estimated glomerular filtration rate (eGFR), body mass index (BMI), low-denisty lipoprotein (LDL)-cholesterol, systolic blood pressure (SBP), and diastolic blood pressure trends were analyzed using mixed models. Variable importance for baseline HbA1c was analyzed using conditional random forest and gradient boosting machine approaches. RESULTS: Individuals aged ≥16 years at onset displayed a relatively low mean HbA1c level (~55-57 mmol/mol) that gradually increased. In contrast, individuals diagnosed at ≤15 years old entered adulthood with a mean HbA1c of approximately 70 mmol/mol. For all groups, HbA1c levels stabilized at a mean of approximately 65 mmol/mol by about 40 years old. In patients who were young at the time of onset, albuminuria appeared at an earlier age, suggesting a more rapid decrease in eGFR, while there were no distinct differences in BMI, SBP, and LDL-cholesterol trajectories between groups. Low education, higher age, and poor risk factor control were associated with higher HbA1c levels. CONCLUSIONS: Young age at the diabetes onset plays a substantial role in subsequent glycemic control and the presence of albuminuria, where patients with early onset may accrue a substantial glycemic load during this period.

Contrasting Associations of Body Mass Index and Hemoglobin A1c on the Excess Risk of Acute Myocardial Infarction and Heart Failure in Type 2 Diabetes Mellitus.

Background Body mass index (BMI) may be a stronger risk factor for heart failure than for coronary heart disease in type 2 diabetes mellitus, but prior studies have not been powered to investigate the relative and absolute risks for acute myocardial infarction and heart failure in type 2 diabetes mellitus by BMI and glycemic level combined as compared with age- and sex-matched general population comparators. Methods and Results We identified 181 045 patients from The Swedish National Diabetes Registry, registered during 1998 to 2012 and 1538 434 general population comparators without diabetes mellitus, matched for age, sex, and county, all without prior major cardiovascular disease. Cases and comparators were followed with respect to the outcomes through linkage to the Swedish Inpatient Registry. Over a median follow-up time of 5.7 years, there were 28 855 acute myocardial infarction and 33 060 heart failure cases among patients and comparators. Excess risk (above that of comparators in whom no data on hemoglobin A1c and BMI was available), incidence rates and hazard ratios for heart failure were substantially higher among the obese patients compared with those with low BMI, where very obese patients (BMI ≥40 kg/m2) who also had poor glycemic control, suffered a 7-fold risk of heart failure versus comparators (reference level). By contrast, for acute myocardial infarction, the highest absolute and relative risks were found among patients with poor glycemic control, with no additional risk conferred by increasing BMI. Conclusions BMI is a strong independent risk factor for heart failure but not for acute myocardial infarction among patients with type 2 diabetes mellitus.

BMI, Mortality, and Cardiovascular Outcomes in Type 1 Diabetes: Findings Against an Obesity Paradox.

OBJECTIVE: Low weight has been associated with increased mortality risks in type 1 diabetes. We aimed to investigate the importance of weight and weight gain/loss in the Swedish population diagnosed with type 1 diabetes. RESEARCH DESIGN AND METHODS: Patients with type 1 diabetes (n = 26,125; mean age 33.3 years; 45% women) registered in the Swedish National Diabetes Registry from 1998 to 2012 were followed from the first day of study entry. Cox regression was used to calculate risk of death from cardiovascular disease (CVD), major CVD events, hospitalizations for heart failure (HF), and total deaths. RESULTS: Population mean BMI in patients with type 1 diabetes increased from 24.7 to 25.7 kg/m2 from 1998 to 2012. Over a median follow-up of 10.9 years, there were 1,031 deaths (33.2% from CVD), 1,460 major CVD events, and 580 hospitalizations for HF. After exclusion of smokers, patients with poor metabolic control, and patients with a short follow-up time, there was no increased risk for mortality in those with BMI <25 kg/m2, while BMI >25 kg/m2 was associated with a minor increase in risk of mortality, major CVD, and HF. In women, associations with BMI were largely absent. Weight gain implied an increased risk of mortality and HF, while weight loss was not associated with higher risk. CONCLUSIONS: Risk of major CVD, HF, CVD death, and mortality increased with increasing BMI, with associations more apparent in men than in women. After exclusion of factors associated with reverse causality, there was no evidence of an obesity paradox.

BMI and Mortality in Patients With New-Onset Type 2 Diabetes: A Comparison With Age- and Sex-Matched Control Subjects From the General Population.

OBJECTIVE: Type 2 diabetes is strongly associated with obesity, but the mortality risk related to elevated body weight in people with type 2 diabetes compared with people without diabetes has not been established. RESEARCH DESIGN AND METHODS: We prospectively assessed short- and long-term mortality in people with type 2 diabetes with a recorded diabetes duration ≤5 years identified from the Swedish National Diabetes Register (NDR) between 1998 and 2012 and five age- and sex-matched control subjects per study participant from the general population. RESULTS: Over a median follow-up of 5.5 years, there were 17,546 deaths among 149,345 patients with type 2 diabetes (mean age 59.6 years [40% women]) and 68,429 deaths among 743,907 matched control subjects. Short-term all-cause mortality risk (≤5 years) displayed a U-shaped relationship with BMI, with hazard ratios (HRs) ranging from 0.81 (95% CI 0.75-0.88) among patients with diabetes and BMI 30 to <35 kg/m2 to 1.37 (95% CI 1.11-1.71) with BMI ≥40 kg/m2 compared with control subjects after multiple adjustments. Long-term, all weight categories showed increased mortality, with a nadir at BMI 25 to <30 kg/m2 and a stepwise increase up to HR 2.00 (95% CI 1.58-2.54) among patients with BMI ≥40 kg/m2, that was more pronounced in patients <65 years old. CONCLUSIONS: Our findings suggest that the apparent paradoxical findings in other studies in this area may have been affected by reverse causality. Long-term, overweight (BMI 25 to <30 kg/m2) patients with type 2 diabetes had low excess mortality risk compared with control subjects, whereas risk in those with BMI ≥40 kg/m2 was substantially increased.