Linus Schiöler

Effectiveness and safety of metformin in 51 675 patients with type 2 diabetes and different levels of renal function: a cohort study from the Swedish National Diabetes Register

Objective To evaluate the effectiveness and safety of metformin use in clinical practice in a large sample of pharmacologically treated patients with type 2 diabetes and different levels of renal function. Design Observational study between July 2004 and December 2010, mean follow-up 3.9 years. Setting Hospital outpatient clinics and primary care in Sweden. Participants 51 675 men and women with type 2 diabetes, registered in the Swedish National Diabetes Register, and on continuous glucose-lowering treatment with oral hypoglycaemic agents (OHAs) or insulin. Main outcome measures Risks of cardiovascular disease (CVD), all-cause mortality and acidosis/serious infection, associated with each treatment regimens, were analysed in all patients and in subgroups with different estimated glomerular filtration rate (eGFR) intervals. Covariance adjustment and propensity scores were used to adjust for several baseline risk factors and characteristics at Cox regression. Results Compared with metformin in monotherapy, HRs for fatal/non-fatal CVD and all-cause mortality with all other OHAs combined (approximately 80% sulphonylureas) in monotherapy were 1.02 (95% CI 0.93 to 1.12) and 1.13 (1.01 to 1.27), while 1.18 (1.07 to 1.29) and 1.34 (1.19 to 1.50) with insulin in monotherapy, adjusting using propensity scores. Metformin, compared with any other treatment, showed reduced risks of acidosis/serious infection (adjusted HR 0.85, 95% CI 0.74 to 0.97) and all-cause mortality (HR 0.87, 95% CI 0.77 to 0.99), in patients with eGFR 45–60 ml/min/1.73 m2, and no increased risks of all-cause mortality, acidosis/serious infection or CVD were found in patients with eGFR 30–45 ml/min/1.73 m2. Conclusions Metformin showed lower risk than insulin for CVD and all-cause mortality and slightly lower risk for all-cause mortality compared with other OHA, in these 51 675 patients followed for 4 years. Patients with renal impairment showed no increased risk of CVD, all-cause mortality or acidosis/serious infection. In clinical practice, the benefits of metformin use clearly outbalance the risk of severe side effects.

Cardiovascular and cognitive fitness at age 18 and risk of early-onset dementia

Patients with early-onset dementia are a significantly under-recognized subgroup of patients with an increasing prevalence. Epidemiological studies are limited and studies of modifiable risk factors, such as physical fitness, are lacking. We aimed to investigate the associations between cardiovascular fitness individually and in combination with cognitive performance at age 18 and risk of early-onset dementia and mild cognitive impairment later in life. We performed a population-based cohort study of over 1.1 million Swedish, 18-year-old, male conscripts, who underwent conscription exams between 1968 and 2005. These males were then followed for up to 42 years. Objective data on cardiovascular fitness and cognitive performance were collected during conscription exams and were subsequently linked with hospital registries to calculate later risk of early-onset dementia and mild cognitive impairment using Cox proportional hazards models controlling for several confounders. The scores from the exams were divided into tertiles (low, medium, high) for the analyses. The mean follow-up time for the analyses was 25.7 years (standard deviation: 9.3) and the median was 27 years. In total, 30 195 315 person-years of follow-up were included in the study. In fully adjusted models, both low cardiovascular fitness and cognitive performance (compared to high) at age 18 were associated with increased risk for future early-onset dementia (cardiovascular fitness, n = 662 events: hazard ratio 2.49, 95%, confidence interval 1.87-3.32; cognitive performance, n = 657 events: hazard ratio 4.11, 95%, confidence interval 3.19-5.29) and mild cognitive impairment (cardiovascular fitness, n = 213 events: hazard ratio 3.57, 95%, confidence interval 2.23-5.74; cognitive performance, n = 212 events: hazard ratio 3.23, 95%, confidence interval 2.12-4.95). Poor performance on both cardiovascular fitness and cognitive tests was associated with a >7-fold (hazard ratio 7.34, 95%, confidence interval 5.08-10.58) and a >8-fold (hazard ratio 8.44, 95%, confidence interval 4.64-15.37) increased risk of early-onset dementia and early-onset mild cognitive impairment, respectively. In conclusion, lower cardiovascular fitness and cognitive performance in early adulthood were associated with an increased risk of early-onset dementia and mild cognitive impairment later in life, and the greatest risks were observed for individuals with a combination of low cardiovascular fitness and low cognitive performance.

A longitudinal general population-based study of job strain and risk for coronary heart disease and stroke in Swedish men

Objectives The aim was to investigate whether psychosocial stress based on the job-demand-control (JDC) model increased the risk for coronary heart disease (CHD) and stroke. Setting Swedish men. Participants The Primary Prevention Study (PPS) comprises 6070 men born between 1915 and 1925 free from previous history of CHD and stroke at baseline (1974–1977). Psychosocial workplace exposure was assessed using a job-exposure matrix (JEM) for the JDC model based on occupation at baseline. The participants were followed from baseline examination, until death, until hospital discharge or until 75 years of age, whichever occurred first, using the Swedish national register on cause of death and the Swedish hospital discharge register for non-fatal and fatal stroke and CHD events. Cox regression models were used with stroke or CHD as the outcome, using JDC model and age as explanatory variables, as well as stratified models with regard to smoking, self-reported stress, socioeconomic status, obesity, hypertension and diabetes. Primary and secondary outcome measures Risk for stroke and CHD. Results There was an increased risk (HR) for CHD in relation to high strain (HR 1.31, 95% CI 1.01 to 1.70). The risk was further increased among ever-smokers and among blue-collar workers. There was a relation between low control and increased risk for CHD (HR 1.19, 95% CI 1.06 to 1.35). There was no increased risk for stroke in any of the JDC categories. Conclusions Exposure to occupational psychosocial stress defined as job strain or low control increased the risk for CHD, especially among smokers and blue-collar workers. There was no increased risk for stroke in any of the JDC categories.

Gender differences in antihypertensive drug treatment: results from the Swedish Primary Care Cardiovascular Database (SPCCD)

There are gender differences in antihypertensive treatment. This study aimed to investigate if gender differences in treatment could be explained by comorbidities. In addition, we aimed to study whether blood pressure control is different in women and men, and whether women interrupt treatment more often with angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) compared with men.This cohort study within the Swedish Primary Care Cardiovascular Database included 40,825 patients with hypertension attending primary health care from 2007 to 2008. Cardiovascular comorbidities, with the exception of heart failure, were more common in men. Women were more often treated with diuretics, and men with ACEI, as were hypertensive patients with diabetes. Comorbidities could not entirely explain gender differences in antihypertensive treatment in a regression model. Women had higher systolic and lower diastolic blood pressure; this was also true in subgroups with cardiovascular comorbidity. Men more often than women were prescribed ACEIs/ARBs and interrupted treatment. Women and men are treated with different antihypertensive drugs, and this is not fully explained by differences in comorbidities. Women have higher systolic blood pressures, irrespective of comorbidity. Men have interrupted treatment more often with ACEIs/ARBs. These gender differences could affect outcome and warrant further investigation.

Body weight in adolescence and long-term risk of early heart failure in adulthood among men in Sweden

Abstract Aims To study the relation between body mass index (BMI) in young men and risk of early hospitalization with heart failure. Methods and results In a prospective cohort study, men from the Swedish Conscript Registry investigated 1968–2005 (n = 1 610 437; mean age, 18.6 years were followed 5–42 years (median, 23.0 years; interquartile range, 15.0–32.0), 5492 first hospitalizations for heart failure occurred (mean age at diagnosis, 46.6 (SD 8.0) years). Compared with men with a body mass index (BMI) of 18.5–20.0 kg/m2, men with a BMI 20.0–22.5 kg/m2 had an hazard ratio (HR) of 1.22 (95% CI, 1.10–1.35), after adjustment for age, year of conscription, comorbidities at baseline, parental education, blood pressure, IQ, muscle strength, and fitness. The risk rose incrementally with increasing BMI such that men with a BMI of 30–35 kg/m2 had an adjusted HR of 6.47 (95% CI, 5.39–7.77) and those with a BMI of ≥35 kg/m2 had an HR of 9.21 (95% CI, 6.57–12.92). The multiple-adjusted risk of heart failure per 1 unit increase in BMI ranged from 1.06 (95% CI, 1.02–1.11) in heart failure associated with valvular disease to 1.20 (95% CI, 1.18–1.22) for cases associated with coronary heart disease, diabetes, or hypertension. Conclusion We found a steeply rising risk of early heart failure detectable already at a normal body weight, increasing nearly 10-fold in the highest weight category. Given the current obesity epidemic, heart failure in the young may increase substantially in the future and physicians need to be aware of this.

Predictions by early indicators of the time and height of the peaks of yearly influenza outbreaks in Sweden.

Aims: Methods for prediction of the peak of the influenza from early observations are suggested. These predictions can be used for planning purposes. Methods: In this study, new robust methods are described and applied to weekly Swedish data on influenza-like illness (ILI) and weekly laboratory diagnoses of influenza (LDI). Both simple and advanced rules for how to predict the time and height of the peak of LDI are suggested. The predictions are made using covariates calculated from data in early LDI reports. The simple rules are based on the observed LDI values, while the advanced ones are based on smoothing by unimodal regression. The suggested predictors were evaluated by cross-validation and by application to the observed seasons. Results: The relationship between ILI and LDI was investigated, and it was found that the ILI variable is not a good proxy for the LDI variable. The advanced prediction rule regarding the time of the peak of LDI had a median error of 0.9 weeks, and the advanced prediction rule for the height of the peak had a median deviation of 28%. Conclusions: The statistical methods for predictions have practical usefulness.

The association between job strain and atrial fibrillation in Swedish men

Objectives The purpose of this study was to investigate whether psychosocial stress defined as high strain based on the job demand–control model increases risk for atrial fibrillation. Methods The present study comprised 6035 men born between 1915 and 1925 and free from previous coronary heart disease, atrial fibrillation and stroke at baseline (1974–1977). Work-related psychosocial stress was measured using a job-exposure matrix for the job demand–control model based on occupation at baseline. The participants were followed from baseline examination until death, hospital discharge or 75 years of age, using the Swedish national register on cause of death and the Swedish hospital discharge register for any registration for atrial fibrillation, resulting in the identification of 436 cases. Data were analysed with Cox regression models with atrial fibrillation as the outcome using high strain as the explanatory variable adjusted for age, smoking, body mass index, hypertension, diabetes and socioeconomic status. Results There was an increased risk for atrial fibrillation in relation to high strain (HR 1.32, 95% CI 1.003 to 1.75). When the four categories of the job-strain model were included and low strain was used as reference, the risk for high strain decreased (HR 1.23, 95% CI 0.84 to 1.82). Conclusions Exposure to occupational psychosocial stress defined as high strain may be associated with increased risk for atrial fibrillation. The observed increase in risk is small and residual confounding may also be present.

Sufficient Reduction in Multivariate Surveillance

The relation between change points in multivariate surveillance is important but seldom considered. The sufficiency principle is here used to clarify the structure of some problems, to find efficient methods, and to determine appropriate evaluation metrics. We study processes where the changes occur simultaneously or with known time lags. The surveillance of spatial data is one example where known time lags can be of interest. A general version of a theorem for the sufficient reduction of processes that change with known time lags is given. A simulation study illustrates the benefits or the methods based on the sufficient statistics.

Cardiorespiratory fitness and muscle strength in late adolescence and long-term risk of early heart failure in Swedish men

Aims To investigate the association between cardiorespiratory fitness (CRF) and muscle strength in late adolescence and the long-term risk of heart failure (HF). Methods A cohort was created of Swedish men enrolled in compulsory military service between 1968 and 2005 with measurements for CRF and muscle strength (n = 1,226,623; mean age 18.3 years). They were followed until 31 December 2014 for HF hospitalization as recorded in the Swedish national inpatient registry. Results During the follow-up period (median (interquartile range) 28.4 (22.0–37.0) years), 7656 cases of first HF hospitalization were observed (mean ± SD age at diagnosis 50.1 ± 7.9 years). CRF and muscle strength were estimated by maximum capacity cycle ergometer testing and strength exercises (knee extension, elbow flexion and hand grip). Inverse dose–response relationships were found between CRF and muscle strength with HF as a primary or contributory diagnosis with an adjusted hazards ratio (95% confidence interval) of 1.60 (1.44–1.77) for low CRF and 1.45 (1.32–1.58) for low muscle strength categories. The associations of incident HF with CRF and muscle strength persisted, regardless of adjustments for the other potential confounders. The highest risk was observed for HF associated with coronary heart disease, diabetes or hypertension. Conclusions In this longitudinal study of young men, we found inverse and mutually independent associations between CRF and muscle strength with risk of hospitalization for HF. If causal, these results may emphasize the importance of the promotion of CRF and muscle strength in younger populations.

Nocturnal GERD – a risk factor for rhinitis/rhinosinusitis: the RHINE study

It has been suggested that gastroesophageal reflux disease (GERD) is a risk factor for developing rhinitis/rhinosinusitis, but data are lacking. This is a prospective 10‐year follow‐up study of a large multicenter cohort from Northern Europe, evaluating the relationship between nocturnal GERD and noninfectious rhinitis (NIR).