Explore the vast range of titles available.

Despite abundant knowledge about the relationship between inflammation and coronary atherosclerosis, it is still unknown whether systemic inflammation measured as high-sensitivity C-reactive protein (hsCRP) is associated with coronary atherosclerosis in a general population. This study aimed to examine the association between hsCRP and coronary computed tomography angiography (CCTA)-detected coronary atherosclerosis in a population-based cohort. Out of 30,154 randomly invited men and women aged 50 to 64 years in the Swedish Cardiopulmonary Bioimage Study (SCAPIS), 25,408 had a technically acceptable CCTA and analysed hsCRP. Coronary atherosclerosis was defined as presence of plaque of any degree in any of 18 coronary segments. HsCRP values were categorised in four groups. Compared with hsCRP below the detection limit, elevated hsCRP (≥ 2.3 mg/L) was weakly associated with any coronary atherosclerosis (OR 1.15, 95% CI 1.07–1.24), coronary diameter stenosis ≥ 50% (OR 1.27, 95% CI 1.09–1.47), ≥ 4 segments involved (OR 1.13, 95% CI 1.01–1.26 ) and severe atherosclerosis (OR 1.33, 95% CI 1.05–1.69) after adjustment for age, sex and traditional risk factors. The associations were attenuated after further adjustment for body mass index (BMI), although elevated hsCRP still associated with noncalcified plaques (OR 1.16, 95% CI 1.02–1.32), proposed to be more vulnerable. In conclusion, the additional value of hsCRP to traditional risk factors in detection of coronary atherosclerosis is low. The association to high-risk noncalcified plaques, although unlikely through a causal pathway, could explain the relationship between hsCRP and clinical coronary events in numerous studies.

It has been hypothesized but seldom tested that the winter excess in cardiovascular disease (CVD) is related to hypovitaminosis D. The present study examined the association between CVD and (i) seasonality of 25-hydroxyvitamin D (25[OH]D) and (ii) individual 25(OH)D concentrations. Harmonized 25(OH)D data were obtained from the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project, including 79,570 participants examined between 1984 and 2010. One 25(OH)D measurement was available per participant. Primary endpoints were CVD incidence (coronary heart disease or stroke; n = 6006) and CVD mortality (n = 2985). To study (i), Poisson regression-derived rate ratios were compared according to two-month categories, ordered by baseline 25(OH)D concentrations. To study (ii), Cox regression-derived hazard ratios were compared according to quarters of baseline 25(OH)D concentrations. With respect to (i), despite a median 25(OH)D concentration ratio of 1:1.79, the trough months of 25(OH)D in March and April had a similar CVD incidence as the peak months of 25(OH)D in August and September (rate ratio: 1.07, 95% CI: 0.98-1.17). CVD mortality was slightly higher in the trough months compared to the peak months (rate ratio: 1.27, 95% CI: 1.12-1.44) but not compared to the other months (despite median 25[OH]D concentration ratios up to 1:1.62; p ≥ 0.077). The CVD mortality peak in January preceded the 25(OH)D trough, not adhering to the temporality criterion of Bradford Hill. With respect to (ii), compared to the lowest quarter, the highest quarter of 25(OH)D was associated with lower CVD incidence (hazard ratio: 0.82, 95% CI: 0.76-0.89) and CVD mortality (hazard ratio: 0.64, 95% CI: 0.57-0.72). The present study does not support the hypothesis that seasonal increases in CVD are driven by short-term reductions in 25(OH)D. As in most observational studies, higher 25(OH)D concentrations were inversely associated with CVD.

ObjectiveTo assess the contemporary prevalence of, and factors associated with angina pectoris symptoms, and to examine the relationship to coronary atherosclerosis in a middle-aged, general population.MethodsData were based on the Swedish CArdioPulmonary bioImage Study (SCAPIS), in which 30 154 individuals were randomly recruited from the general population between 2013 and 2018. Participants that completed the Rose Angina Questionnaire were included and categorised as angina or no angina. Subjects with a valid coronary CT angiography (CCTA) were categorised by degree of coronary atherosclerosis; ≥50% obstruction (obstructive coronary atherosclerosis), <50% obstruction or any atheromatosis (non-obstructive coronary atherosclerosis) or none (no coronary atherosclerosis).ResultsThe study population consisted of 28 974 questionnaire responders (median age 57.4 years, female 51.6%, hypertension 19.9%, hyperlipidaemia 7.9%, diabetes mellitus 3.7%), of which 1025 (3.5%) fulfilled the criteria of angina. Coronary atherosclerosis was more common in individuals having angina compared with those with no angina (n=24 602, obstructive coronary atherosclerosis 11.8% vs 5.4%, non-obstructive coronary atherosclerosis 38.9% vs 37.0%, no coronary atherosclerosis 49.4% vs 57.7%, all p<0.001). Factors independently associated with angina were birthplace outside of Sweden (OR 2.58 (95% CI 2.10 to 2.92)), low educational level (OR 1.41 (1.10 to 1.79)), unemployment (OR 1.51 (1.27 to 1.81)), poor economic status (OR 1.85 (1.38 to 2.47)), symptoms of depression (OR 1.63 (1.38 to 1.92)) and high degree of stress (OR 2.92 (1.80 to 4.73)).ConclusionAngina pectoris symptoms are common (3.5%) among middle-aged individuals of the general population of Sweden, though with low association to obstructive coronary atherosclerosis. Sociodemographic and psychological factors are highly associated with angina symptoms, irrespective of degree of coronary atherosclerosis.

This is the first of two papers that document the creation of the New European Wind Atlas (NEWA). It describes the sensitivity analysis and evaluation procedures that formed the basis for choosing the final setup of the mesoscale model simulations of the wind atlas. The suitable combination of model setup and parameterizations, bound by practical constraints, was found for simulating the climatology of the wind field at turbine-relevant heights with the Weather Research and Forecasting (WRF) model. Initial WRF model sensitivity experiments compared the wind climate generated by using two commonly used planetary boundary layer schemes and were carried out over several regions in Europe. They confirmed that the most significant differences in annual mean wind speed at 100 m a.g.l. (above ground level) mostly coincide with areas of high surface roughness length and not with the location of the domains or maximum wind speed. Then an ensemble of more than 50 simulations with different setups for a single year was carried out for one domain covering northern Europe for which tall mast observations were available. We varied many different parameters across the simulations, e.g. model version, forcing data, various physical parameterizations, and the size of the model domain. These simulations showed that although virtually every parameter change affects the results in some way, significant changes in the wind climate in the boundary layer are mostly due to using different physical parameterizations, especially the planetary boundary layer scheme, the representation of the land surface, and the prescribed surface roughness length. Also, the setup of the simulations, such as the integration length and the domain size, can considerably influence the results. We assessed the degree of similarity between winds simulated by the WRF ensemble members and the observations using a suite of metrics, including the Earth Mover's Distance (EMD), a statistic that measures the distance between two probability distributions. The EMD was used to diagnose the performance of each ensemble member using the full wind speed and direction distribution, which is essential for wind resource assessment. We identified the most realistic ensemble members to determine the most suitable configuration to be used in the final production run, which is fully described and evaluated in the second part of this study .

Background Aortic valve calcification (AVC) is an underlying pathophysiological mechanism in aortic stenosis, which shares many risk factors with diabetes. However, the association between dysglycemia and early stages of AVC remains unclear. The aim was to examine the associations between stages of dysglycemia and signs of AVC among middle-aged individuals from the general population. Methods This was a cross-sectional study from the Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly enrolling 30,154 middle-aged men and women from six study sites in Sweden between 2013 and 2018. Glycemic status was based on the World Health Organization criteria (fasting blood glucose and/or HbA1c) and questionnaire-based answers on previous diseases and categorized as normoglycemia, prediabetes, newly detected diabetes and known diabetes. AVC was assessed on cardiac computed tomography (CT) and defined as evident or not. Results Of 29,331 individuals with data on glycemic status and AVC available, mean age was 57.5 years and normoglycemia was present in 76%, prediabetes in 16%, newly detected diabetes in 3% and known diabetes in 5%. The prevalence of AVC increased progressively across glycemic categories, particularly in males (8%, 11%, 14% and 17%; P  < 0.01) compared to females (5%, 6%, 8% and 9%; P  < 0.01). There was an association with AVC already in the early stages of dysglycemia; prediabetes (OR 1.16, 95% CI 1.02–1.31), newly detected diabetes (1.34 [1.05–1.71]) and known diabetes (1.61 [1.34–1.93]) after adjusting for age, sex, smoking, study site, low density lipoprotein-cholesterol and hypertension. Conclusions In this large, contemporary, and randomly selected population of middle-aged individuals, prediabetes, newly detected diabetes and known diabetes were all associated with CT-detected AVC. Further studies are warranted to investigate if managing dysglycemia, even in its early stages, may help slow down AVC progression. Graphical abstract

Purpose Vitamin D, produced through cutaneous photosynthesis or ingested via foods or supplements, has generated considerable research interest due to its potential health effects. However, epidemiological data on the time trends of vitamin D status are sparse, especially from northern Europe. We examined the time trend of vitamin D concentrations in northern Sweden between 1986 and 2014. Methods We used data on 11,129 men and women (aged 25–74 years) from seven population-based surveys (the Northern Sweden MONICA study), recruited between 1986 and 2014. Serum vitamin D (25-hydroxyvitamin D) status was measured using a one-step immunoassay (Abbott Architect). Multivariable linear regression models, adjusted for age, sex, and a number of other variables, were used to estimate the time trend of vitamin D concentrations. Results The mean value of vitamin D in the entire study population was 19.9 ng/mL [standard deviation (SD) 7.9], with lower values in men (19.4 ng/mL; SD 7.5) than in women (20.5 ng/mL; SD 8.2). Using the survey in 1986 as reference category, the multivariable-adjusted mean difference [95% confidence interval (CI)] in ng/mL was 2.7 (2.2, 3.3) in 1990, 3.2 (2.7, 3.7) in 1994, 1.6 (1.0, 2.1) in 1999, − 2.0 (− 2.5, − 1.4) in 2004, 1.0 (0.4, 1.5) in 2009, and 3.1 (2.5, 3.6) in 2014. Conclusion In this large cross-sectional study, we observed no clear upward or downward trend of vitamin D concentrations in northern Sweden between 1986 and 2014.

Even though sunlight is viewed as the most important determinant of 25-hydroxyvitamin D (25(OH)D) status, several European studies have observed higher 25(OH)D concentrations among north-Europeans than south-Europeans. We studied the association between geographical latitude (derived from ecological data) and 25(OH)D status in six European countries using harmonised immunoassay data from 81 084 participants in the Biomarkers for Cardiovascular Risk Assessment in Europe (BiomarCaRE) project (male sex 48·9 %; median age 50·8 years; examination period 1984–2014). Quantile regression models, adjusted for age, sex, decade and calendar week of sampling and time from sampling to analysis, were used for between-country comparisons. Up until the median percentile, the ordering of countries by 25(OH)D status (from highest to lowest) was as follows: Sweden (at 65·6–63·8°N), Germany (at 48·4°N), Finland (at 65·0–60·2°N), Italy (at 45·6–41·5°N), Scotland (at 58·2–55·1°N) and Spain (at 41·5°N). From the 75th percentile and upwards, Finland had higher values than Germany. As an example, using the Swedish cohort as a comparator, the median 25(OH)D concentration was 3·03, 3·28, 5·41, 6·54 and 9·28 ng/ml lower in the German, Finnish, Italian, Scottish and Spanish cohort, respectively (P-value < 0·001 for all comparisons). The ordering of countries was highly consistent in subgroup analyses by sex, age, and decade and season of sampling. In conclusion, we confirmed the previous observation of a north-to-south gradient of 25(OH)D status in Europe, with higher percentile values among north-Europeans than south-Europeans.

Objectives Fear of falling (FoF) is a common problem among older adults. It can lead to reduced quality of life and less physical activity, which increases fall risk. Earlier work has shown that FoF can be a manifestation of executive dysfunction in adults over 50 years, but studies on people over age 75 years are lacking. Executive functions (EFs) are cognitive functions associated with the frontal lobes and the prefrontal cortex. The aim of this study was to assess associations of EFs and FoF among people aged 80 years or older. Methods This cross-sectional study was based on data from the Northern Sweden Silver-MONICA study and included 434 participants aged 80 years or older. EFs were assessed with the Frontal Assessment Battery (FAB) and FoF with the Falls Self-Efficacy Scale–International (FES-I). Multivariable linear regression analysis was used to examine associations among EF, FoF, and a comprehensive set of adjustment factors. Pearson correlation analysis was used to evaluate associations of FES-I and the subitems of the FAB. Results EFs as measured by FAB were inversely associated with FoF (β = -0.23; 95% confidence interval, -0.42 to -0.03; p  = 0.021), even after comprehensive adjustments. The FAB subitems measuring lexical fluency, inhibitory control, sustained attention, self-organization, motor programming, and planning also were inversely associated with FoF. Conclusions Lower EF is associated with higher FoF among people aged 80 years or older. This information is important for treating and preventing FoF in this population.

Defective LDL-C clearance and hence its elevation in the circulation is an established risk factor for cardiovascular diseases (CVDs) such as myocardial infarction (MI). A soluble LDL-receptor (sLDL-R) has been detected in human plasma which correlates strongly with circulating LDL-C and classical conditions that promote chronic inflammation. However, the mechanistic interplay between sLDL-R, inflammation, and CVDs remains to be investigated. Here, we report that stimulation of HepG2 cells with TNF-α induces the release of sLDL-R into culture supernatants. In addition, TNF-α induces gene expression of peptidases ADAM-17 and MMP-14 in HepG2 cells, and inhibiting these peptidases using TMI 1 significantly reduces the TNF-α induced sLDL-R release. We found that a soluble form of recombinant LDL-R (100 nM) can strongly bind to LDL-C and form a stable complex (KD = E-12). Moreover, incubation of HepG2 cells with this recombinant LDL-R resulted in reduced LDL-C uptake in a dose-dependent manner. In a nested case-control study, we found that baseline sLDL-R in plasma is positively correlated with plasma total cholesterol level. Furthermore, a twofold increase in plasma sLDL-R was associated with a 55% increase in the risk of future MI [AOR = 1.55 (95% CI = 1.10–2.18)]. Nevertheless, mediation analyses revealed that a significant proportion of the association is mediated by elevation in plasma cholesterol level (indirect effect β = 0.21 (95% CI = 0.07–0.38). Collectively, our study shows that sLDL-R is induced by a pro-inflammatory cytokine TNF-α via membrane shedding. Furthermore, an increase in sLDL-R could inhibit hepatic clearance of LDL-C increasing its half-life in the circulation and contributing to the pathogenesis of MI.Key messagesTNF-α causes shedding of hepatocytic LDL-R through induction of ADAM-17 and MMP-14.sLDL-R binds strongly to LDL-C and inhibits its uptake by hepatocytic cells.Plasma sLDL-R is positively correlated with TNF-α and cholesterol.Plasma sLDL-R is an independent predictor of myocardial infarction (MI).Plasma cholesterol mediates the association between sLDL-R and MI.

Background The risk of heart failure among diabetic individuals is high, even under tight glycemic control. The correlates and mediators of heart failure risk in individuals with diabetes need more elucidation in large population-based cohorts with long follow-up times and a wide panel of biologically relevant biomarkers. Methods In a population-based sample of 3834 diabetic and 90,177 non-diabetic individuals, proportional hazards models and mediation analysis were used to assess the relation of conventional heart failure risk factors and biomarkers with incident heart failure. Results Over a median follow-up of 13.8 years, a total of 652 (17.0%) and 5524 (6.1%) cases of incident heart failure were observed in participants with and without diabetes, respectively. 51.4% were women and the mean age at baseline was 48.7 (standard deviation [SD] 12.5) years. The multivariable-adjusted hazard ratio (HR) for heart failure among diabetic individuals was 2.70 (95% confidence interval, 2.49–2.93) compared to non-diabetic participants. In the multivariable-adjusted Cox models, conventional cardiovascular disease risk factors, such as smoking (diabetes: HR 2.07 [1.59–2.69]; non-diabetes: HR 1.85 [1.68–2.02]), BMI (diabetes: HR 1.30 [1.18–1.42]; non-diabetes: HR 1.40 [1.35–1.47]), baseline myocardial infarction (diabetes: HR 2.06 [1.55–2.75]; non-diabetes: HR 2.86 [2.50–3.28]), and baseline atrial fibrillation (diabetes: HR 1.51 [0.82–2.80]; non-diabetes: HR 2.97 [2.21–4.00]) had the strongest associations with incident heart failure. In addition, biomarkers for cardiac strain (represented by nT-proBNP, diabetes: HR 1.26 [1.19–1.34]; non-diabetes: HR 1.43 [1.39–1.47]), myocardial injury (hs-TnI, diabetes: HR 1.10 [1.04–1.16]; non-diabetes: HR 1.13 [1.10–1.16]), and inflammation (hs-CRP, diabetes: HR 1.13 [1.03–1.24]; non-diabetes: HR 1.29 [1.25–1.34]) were also associated with incident heart failure. In general, all these associations were equally strong in non-diabetic and diabetic individuals. However, the strongest mediators of heart failure in diabetes were the direct effect of diabetes status itself (relative effect share 43.1% [33.9–52.3] and indirect effects (effect share 56.9% [47.7-66.1]) mediated by obesity (BMI, 13.2% [10.3–16.2]), cardiac strain/volume overload (nT-proBNP, 8.4% [-0.7–17.4]), and hyperglycemia (glucose, 12.0% [4.2–19.9]). Conclusions The findings suggest that the main mediators of heart failure in diabetes are obesity, hyperglycemia, and cardiac strain/volume overload. Conventional cardiovascular risk factors are strongly related to incident heart failure, but these associations are not stronger in diabetic than in non-diabetic individuals. Active measurement of relevant biomarkers could potentially be used to improve prevention and prediction of heart failure in high-risk diabetic patients.