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Elevated body weight in adolescence is associated with early cardiovascular disease, but whether this association is traceable to weight in early adulthood, weight in midlife or to weight gain is not known. The aim of this study is to assess the risk of midlife coronary atherosclerosis being associated with body weight at age 20, body weight in midlife and body weight change. We used data from 25,181 participants with no previous myocardial infarction or cardiac procedure in the Swedish CArdioPulmonary bioImage Study (SCAPIS, mean age 57 years, 51% women). Data on coronary atherosclerosis, self-reported body weight at age 20 and measured midlife weight were recorded together with potential confounders and mediators. Coronary atherosclerosis was assessed using coronary computed tomography angiography (CCTA) and expressed as segment involvement score (SIS). The probability of having coronary atherosclerosis was markedly higher with increasing weight at age 20 and with mid-life weight (p < 0.001 for both sexes). However, weight increase from age 20 until mid-life was only modestly associated with coronary atherosclerosis. The association between weight gain and coronary atherosclerosis was mainly seen in men. However, no significant sex difference could be detected when adjusting for the 10-year delay in disease development in women. Similar in men and women, weight at age 20 and weight in midlife are strongly related to coronary atherosclerosis while weight increase from age 20 until midlife is only modestly related to coronary atherosclerosis. [Display omitted] • Weight at age 20 and in midlife is strongly related to coronary atherosclerosis. • Weight gain from age 20 until midlife is modestly related to coronary atherosclerosis. • There is no sex difference in the relation between weight and coronary atherosclerosis. • Weight control programs in early adulthood may reduce cardiac disease later in life. [ABSTRACT FROM AUTHOR]

Background: Early detection of coronary atherosclerosis using coronary computed tomography angiography (CCTA), in addition to coronary artery calcification (CAC) scoring, may help inform prevention strategies. We used CCTA to determine the prevalence, severity, and characteristics of coronary atherosclerosis and its association with CAC scores in a general population.Methods: We recruited 30 154 randomly invited individuals age 50 to 64 years to SCAPIS (the Swedish Cardiopulmonary Bioimage Study). The study includes individuals without known coronary heart disease (ie, no previous myocardial infarctions or cardiac procedures) and with high-quality results from CCTA and CAC imaging performed using dedicated dual-source CT scanners. Noncontrast images were scored for CAC. CCTA images were visually read and scored for coronary atherosclerosis per segment (defined as no atherosclerosis, 1% to 49% stenosis, or ≥50% stenosis). External validity of prevalence estimates was evaluated using inverse probability for participation weighting and Swedish register data.Results: In total, 25 182 individuals without known coronary heart disease were included (50.6% women). Any CCTA-detected atherosclerosis was found in 42.1%; any significant stenosis (≥50%) in 5.2%; left main, proximal left anterior descending artery, or 3-vessel disease in 1.9%; and any noncalcified plaques in 8.3% of this population. Onset of atherosclerosis was delayed on average by 10 years in women. Atherosclerosis was more prevalent in older individuals and predominantly found in the proximal left anterior descending artery. Prevalence of CCTA-detected atherosclerosis increased with increasing CAC scores. Among those with a CAC score >400, all had atherosclerosis and 45.7% had significant stenosis. In those with 0 CAC, 5.5% had atherosclerosis and 0.4% had significant stenosis. In participants with 0 CAC and intermediate 10-year risk of atherosclerotic cardiovascular disease according to the pooled cohort equation, 9.2% had CCTA-verified atherosclerosis. Prevalence estimates had excellent external validity and changed marginally when adjusted to the age-matched Swedish background population.Conclusions: Using CCTA in a large, random sample of the general population without established disease, we showed that silent coronary atherosclerosis is common in this population. High CAC scores convey a significant probability of substantial stenosis, and 0 CAC does not exclude atherosclerosis, particularly in those at higher baseline risk. [ABSTRACT FROM AUTHOR]

Ischemic heart disease is the leading cause of death worldwide, accounting for approximately 11% of all deaths in 2011. Numerous studies have shown that cardiovascular risk correlates positively and powerfully with total or LDL cholesterol (LDL-C) and correlates inversely with HDL cholesterol (HDL-C). Much effort has spent comparing proatherogenic cholesterol markers LDL-C, non-HDL-C, apoB and LDL particle number, while little effort has been spent comparing the markers of the antiatherogenic marker apoA-I and HDL-C. Therefore, this review focused on comparing apoA-I and HDL-C in the prediction of heart disease and myocardial infarction. We identified 28 studies of which 12 indicated that the HDL-C was likely to be a superior marker of risk for heart disease and myocardial infarction compared with eight studies that identified apoA-I to be a superior marker of risk. [ABSTRACT FROM AUTHOR]

Background: Self-efficacy has been determined to be a strong predictor of who will engage in physical activity. We aimed to evaluate the associations between self-efficacy to perform physical activity, self-reported leisure-time physical activity and cardiovascular events in a population-based cohort of middle-aged Swedish men with no previous cardiovascular disease, or treatment with cardiovascular drugs. Methods: Analyses are based on 377 men randomly selected and stratified for weight and insulin sensitivity from a population sample of 58-year-old men (n = 1728) and who had answered a question about their competence to perform exercise (as an assessment of physical self-efficacy). The Saltin-Grimby Physical Activity Level Scale was used to assess self-reported levels of leisure-time physical activity. Cardiovascular events were recorded during 13-years of follow-up. Results: The group with poor self-efficacy to perform physical activity had a significantly higher incidence of cardiovascular events compared with the group with good physical self-efficacy (32.1 % vs 17.1 %, p < 0.01). Multivariate analyses showed that poor physical self-efficacy was associated with an increased relative risk of 2.0 (95 % CI 1.2 to 3.0), of having a cardiovascular event during follow-up also after adjustments for co-variates such as waist to hip ratio, heart rate, fasting plasma glucose, serum triglycerides, systolic blood pressure, apoB/apoA-I ratio and leisure-time physical activity. Conclusion: Self-efficacy to perform physical activity was strongly and independently associated with cardiovascular events and was superior to self-assessed physical activity in predicting cardiovascular events during 13-years of follow-up in a group of middle-aged men, without known CVD or treatment with cardiovascular drugs. [ABSTRACT FROM AUTHOR]

Introduction Previous studies have established a relationship between socioeconomic status (SES) and survival in coronary heart disease. Acute cardiac care in Sweden is considered to be excellent and independent of SES. We studied the influence of area-level socioeconomic status on mortality after hospitalization for acute myocardial infarction (AMI) between 1995 and 2013 in the Gothenburg metropolitan area, which has little over 800,000 inhabitants and includes three city hospitals. Methods Data were obtained from the SWEDEHEART registry (Swedish Websystem for Enhancement of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) and the Swedish Central Bureau of Statistics for patients hospitalized for ST-elevation myocardial infarction (STEMI) and non-STEMI in the city of Gothenburg in Western Sweden. The groups were compared using Cox proportional hazards regression and logistic regression. Results 10,895 (36% female) patients were hospitalized due to AMI during the study period. Patients residing in areas with lower SES had higher rates of smoking and diabetes (P < 0.001), and were also at increased risk of developing complications, including heart failure and cardiogenic shock (P < 0.05). Living in an area with lower SES associated with increased risk of dying after an AMI also in models adjusted for risk factors (P < 0.05). Conclusion Also in a country with strong egalitarian traditions, lower SES associates with worse prognosis after AMI, an association that persists after adjustments for differences in traditional cardiovascular risk factors. [ABSTRACT FROM AUTHOR]

The general population is exposed to cadmium from food and smoking. Cadmium is a widely spread toxic pollutant that seems to be associated with cardiovascular diseases, although little is known if it contributes to the occurrence of atherosclerotic plaques and the process whereby plaques become vulnerable and are prone to rupture. We tested the hypotheses that cadmium exposure is associated not only with an increased subclinical burden of atherosclerotic plaques in different vascular territories and early signs of plaque vulnerability, but also with cadmium content and plaque-rupture in the clinical phase of the disease. Ultrasound technique was used to measure plaque prevalence and echogenicity in the carotid and femoral arteries in a population sample of women (n = 599) in whom blood cadmium was measured. In addition cadmium was measured in snap-frozen endarterectomies and whole blood obtained from patients who were referred to surgery because of symptomatic carotid plaques (n = 37). Sixteen endarterectomies were divided into three parts corresponding to different flow conditions and plaque vulnerability. In the population sample blood cadmium was associated with the number of vascular territories with plaques (p = 0.003 after adjustment for potential confounders). The cadmium concentrations in symptomatic plaques were 50-fold higher in plaque tissue than in blood. Cadmium levels in blood and plaque correlated, also after adjustment for smoking and other cardiovascular risk factors (p<0.001). Compared with the other parts of the plaque, the cadmium content was double as high in the part where plaque rupture usually occurs. In conclusion, the results show that cadmium exposure is associated with the burden of subclinical atherosclerosis in middle-aged women with different degrees of glucose tolerance, and that the content of cadmium in symptomatic plaques in patients is related to that in blood, but much higher, and preferentially located in the part of plaque where rupture often occurs. [ABSTRACT FROM AUTHOR]

Background It has been proposed that diabetic patients are more sensitive to the nephrotoxicity of cadmium (Cd) compared to non-diabetics, but few studies have examined this in humans, and results are inconsistent. Aim To test the hypothesis that women with type 2 diabetes mellitus (DM) or impaired glucose tolerance (IGT) have higher risk of kidney damage from cadmium compared to women with normal glucose tolerance (NGT). Methods All 64-year-old women in Gothenburg, Sweden, were invited to a screening examination including repeated oral glucose tolerance tests. Random samples of women with DM, IGT, and NGT were recruited for further clinical examinations. Serum creatinine was measured and used to calculate estimated glomerular filtration rate (eGFR). Albumin (Alb) and retinol-binding protein (RBP) were analyzed in a 12 h urine sample. Cadmium in blood (B-Cd) and urine (U-Cd) was determined using inductively coupled plasma mass spectrometry. Associations between markers of kidney function (eGFR, Alb, and RBP) and quartiles of B-Cd and U-Cd were evaluated in models, including also blood pressure and smoking habits. Results The mean B-Cd ( n =590) was 0.53 µg/L (median 0.34 µg/L). In multivariable models, a significant interaction was seen between high B-Cd (upper quartile, >0.56 µg/L) and DM (point estimate +0.40 mg Alb/12 h, P =0.04). In stratified analyzes, the effect of high B-Cd on Alb excretion was significant in women with DM (53% higher Alb/12 h, P =0.03), but not in women with IGT or NGT. Models with urinary albumin adjusted for creatinine showed similar results. In women with DM, the multivariable odds ratio (OR) for microalbuminuria (>15 mg/12 h) was increased in the highest quartile of B-Cd vs. B-Cd quartiles 1–3 in women with DM (OR 4.2, 95% confidence interval 1.1–12). No such effect was found in women with IGT or NGT. There were no associations between B-Cd and eGFR or excretion of RBP, and no differences between women with DM, IGT, or NGT regarding effect of B-Cd on eGFR or RBP. Conclusion The present study provides support for the hypothesis that women with DM have higher risk of renal glomerular damage from cadmium exposure compared to women without DM. [ABSTRACT FROM AUTHOR]

We investigated whether serum concentrations of apolipoprotein (apo) B and apoA-I and the apoB/apoA-I ratio provided predictive information on myocardial infarction (MI) and ischemic stroke during 13 years of follow-up in a group of initially clinically healthy 58-year-old men, free from previous cardiovascular disease, diabetes, other established disease, or treatment with cardiovascular drugs. Multivariate logistic regression analysis showed that the apoB/apoA-I ratio and apoB were significant and independent determinants of MI (exponentiation of the B coefficient [Exp(β)] 3.1, 95% confidence interval [CI] 1.6-6.3, P = .001, Exp(β) 2.8, 95% CI 1.1-7.7, P = .045, respectively). The area under the receiver–operating characteristics curve as a relative measure of test efficiency was highest and significant for both apoB/apoA-I ratio and apoB (area under the curve = 0.75, P < .001). In conclusion, the apoB/apoA-I ratio and apoB are independent risk factors for MI and has the highest efficiencies for predicting MI in initially healthy middle-aged men. [ABSTRACT FROM PUBLISHER]

Abstract: Background: Cadmium is a wide-spread pollutant. Observational studies suggest associations between cadmium and prevalence of type 2 diabetes. Experimental studies indicate that cadmium may cause impaired insulin production. Objectives: To examine whether cadmium exposure is associated with impaired glucose tolerance and type 2 diabetes and impaired pancreatic beta-cell function. Methods: Oral glucose tolerance tests were used in a screening examination of 64-year old women (n=2595) to identify all with diabetes, impaired (IGT) and normal (NGT) glucose tolerance. Random samples of women with type 2 diabetes (n=215), IGT (n=207) and NGT (n=194) were recruited in a cross-sectional examination including measurement of pancreatic insulin production (acute insulin response) and insulin sensitivity (homeostasis model assessment). Cadmium concentrations were measured in blood and urine. A follow-up examination was performed after 5.4 years with assessment of new cases with diabetes or impaired glucose tolerance. Results: At baseline, neither blood nor urinary cadmium concentrations showed any statistically significant differences between women with type 2 diabetes, IGT or NGT. The prospective analysis included 68 cases with incident diabetes, 58 with IGT and 118 women with NGT and no associations with cadmium levels at baseline were observed. Blood and urinary cadmium at baseline were not associated with insulin production, blood glucose, HbA1c, or changes in HbA1c during follow-up. Conclusions: This is the first study of cadmium and diabetes with detailed data on pancreatic beta-cell function, insulin sensitivity and glucose tolerance. Cadmium exposure was not associated with increased risk of type 2 diabetes or IGT. [Copyright &y& Elsevier]

Objectives There is currently widespread exposure to the toxic metal cadmium through the diet as well as through smoking, and it has been suggested that cadmium exposure may increase the risk of cardiovascular disease. Here we examined whether cadmium exposure is associated with prevalence and growth of atherosclerotic plaques in the carotid arteries. Design and subjects The analyses were performed in a screening-based cohort of 64-year-old Caucasian women with stratified, random selection to groups with normal glucose tolerance, impaired glucose tolerance and diabetes ( n = 599). We measured cadmium concentrations in blood and urine at baseline. In addition, we performed ultrasound examination to determine the prevalence and area of atherosclerotic plaques in the carotid arteries and assessed smoking history and other cardiovascular risk factors at baseline and at a follow-up examination after a mean of 5.4 years. Results At baseline, blood cadmium levels were associated with increased risk of plaque and a large plaque area after adjustment for confounders. In women who had never smoked, blood cadmium levels correlated positively with plaque area at baseline. The occurrence of large plaques and the change in plaque area at follow-up were associated with blood and creatinine-corrected urinary cadmium concentrations at baseline after adjustment for confounders. Blood and urine cadmium levels added information to established cardiovascular risk factors in predicting progress of atherosclerosis. Conclusions We have shown that cadmium levels in blood and urine are independent factors associated with the development of atherosclerotic plaques at baseline as well as prospectively. This novel observation emphasizes the need to consider cadmium as a pro-atherogenic pollutant. [ABSTRACT FROM AUTHOR]

Circulating C-reactive protein (CRP), reflective of systemic chronic low-grade inflammation, is a marker associated with cardiovascular disease (CVD). One of the mechanisms through which physical activity might promote cardiovascular health is by preventing changes in inflammation biomarkers, such as CRP. The present study examined the association of self-reported physical activity with an inflammation biomarker, high-sensitivity CRP (hs-CRP), in a population-based cohort of clinically healthy 58-year-old men. Compared with a sedentary lifestyle both moderate (1.81 [0.94-3.69] vs 1.28 [0.55-2.90] mg/L; P < .05) and vigorous physical activity (1.81 [0.94-3.69] vs 0.88 [0.42-1.81] mg/L; P < .001) were associated with decrease in hs-CRP levels. In summary, we identified an association between self-reported leisure time physical activity and hs-CRP in a cross-sectional study of healthy 58-year-old men, with decreased levels of CRP by increased intensities of physical activity. [ABSTRACT FROM AUTHOR]

The metabolic syndrome (MetS) is characterized by a cluster of factors that confer an increased risk of cardiovascular morbidity as well as mortality. It is established that physical activity (PA) has a protective role in cardiovascular morbidity and mortality, mainly through favorable effects on traditional risk factors such as body mass and blood pressure. We assessed the prevalence of MetS in a population-based sample of 64-year-old women with impaired glucose tolerance (IGT) with respect to leisure-time PA (LTPA). The results showed an inverse linear association (P < .05) between LTPA and MetS in this group. In conclusion, this study suggests that an increased PA level has an important role in preventing MetS in women with IGT. [ABSTRACT FROM AUTHOR]

The metabolic syndrome (MetS) is characterized by a constellation of factors that confer an increased risk for cardiovascular morbidity and mortality. It is well-known that physical activity (PA) has a protective role on cardiovascular morbidity and mortality, mainly through its favorable effects on traditional risk factors such as body mass and blood pressure (BP). We assessed the prevalence of MetS in a population-based sample of 58-year-old men with respect to leisure-time PA and also to occupational PA. The results showed an inverse linear association (P < .05) between leisure time physical activity (LTPA) and MetS in this group. In conclusion, this study suggests that PA has an important role in controlling MetS. [ABSTRACT FROM PUBLISHER]

Low-density lipoprotein is recognized as a primary vascular risk factor. However, recent data favor apolipoprotein (apo)B and apoA-I as risk factors with higher predictive values than conventional lipids. We investigated how leisure-time physical activity relates to the serum apoB/apoA-I ratio in middle-aged men. The results showed that compared with a sedentary lifestyle, moderate physical activity was associated with a decreased apoB/apoA-I ratio (1.01 ± 0.28 vs 0.87 ± 0.24, P < .05) and increased apoA-I levels (1.30 ± 0.20 g/L vs 1.43 ± 0.22 g/L, P < .05), whereas vigorous activity was required to observe a reduction in apoB levels (1.27 ± 0.28 g/L vs 1.14 ± 0.24 g/L, P < .05). A covariate analysis showed that leisure time physical activity was also associated with reduced apoB/apoA-I ratios after adjustment for smoking, systolic blood pressure and waist circumference. Importantly, this association was seen at moderate levels of physical activity, supporting the notion that some activity is better than none. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide and challenges the capacity of health care systems globally. Atherosclerosis is the underlying pathophysiological entity in two-thirds of patients with CVD. When considering that atherosclerosis develops over decades, there is potentially great opportunity for prevention of associated events such as myocardial infarction and stroke. Subclinical atherosclerosis has been identified in its early stages in young individuals; however, there is no consensus on how to prevent progression to symptomatic disease. Given the growing burden of CVD, a paradigm shift is required—moving from late management of atherosclerotic CVD to earlier detection during the subclinical phase with the goal of potential cure or prevention of events. Studies must focus on how precision medicine using imaging and circulating biomarkers may identify atherosclerosis earlier and determine whether such a paradigm shift would lead to overall cost savings for global health. [Display omitted] • Early-stage subclinical atherosclerosis can be identified in young individuals, but evidence-based strategies are needed to prevent progression of disease and clinical events. • Precision medicine using imaging and circulating biomarkers could facilitate early identification of atherosclerosis and the development of curative interventions. • A paradigm shift based on these principles could reduce the global burden of CVD with enormous implications for population health. [ABSTRACT FROM AUTHOR]

Examines whether renal medullary interstitial infusion of the vasopressin 1 (V[sub 1]) agonist affects the antihypertensive mechanisms of the kidney. Reduction of medullary perfusion and cortical perfusion; Induction of pressure-diuresis-natriuresis; Increase in urine flow and sodium excretion.

Background: Computed tomography (CT) is an imaging modality commonly used for studies of internal body structures and very useful for detailed studies of body composition. The aim of this study was to develop and evaluate a fully automatic image registration framework for inter-subject CT slice registration. The aim was also to use the results, in a set of proof-of-concept studies, for voxel-wise statistical body composition analysis (Imiomics) of correlations between imaging and non-imaging data. Methods: The current study utilized three single-slice CT images of the liver, abdomen, and thigh from two large cohort studies, SCAPIS and IGT. The image registration method developed and evaluated used both CT images together with image-derived tissue and organ segmentation masks. To evaluate the performance of the registration method, a set of baseline 3-single-slice CT images (from 2780 subjects including 8285 slices) from the SCAPIS and IGT cohorts were registered. Vector magnitude and intensity magnitude error indicating inverse consistency were used for evaluation. Image registration results were further used for voxel-wise analysis of associations between the CT images (as represented by tissue volume from Hounsfield unit and Jacobian determinant) and various explicit measurements of various tissues, fat depots, and organs collected in both cohort studies. Results: Our findings demonstrated that the key organs and anatomical structures were registered appropriately. The evaluation parameters of inverse consistency, such as vector magnitude and intensity magnitude error, were on average less than 3 mm and 50 Hounsfield units. The registration followed by Imiomics analysis enabled the examination of associations between various explicit measurements (liver, spleen, abdominal muscle, visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), thigh SAT, intermuscular adipose tissue (IMAT), and thigh muscle) and the voxel-wise image information. Conclusion: The developed and evaluated framework allows accurate image registrations of the collected three single-slice CT images and enables detailed voxel-wise studies of associations between body composition and associated diseases and risk factors. [ABSTRACT FROM AUTHOR]

Aims: Selective participation may hamper the validity of population-based cohort studies. The resulting bias can be alleviated by linking auxiliary register data to both the participants and the non-participants of the study, estimating propensity scores for participation and correcting for participation based on these. However, registry holders may not be allowed to disclose sensitive data on (invited) non-participants. Our aim is to provide guidance on how adequate bias correction can be achieved by using auxiliary register data but without disclosing information that could be linked to the subset of non-participants. Methods: We show how existing methods can be used to estimate generalisation weights under various data disclosure scenarios where invited non-participants are indistinguishable from uninvited ones. We also demonstrate how the methods can be implemented using Nordic register data. Results: Inverse-probability-of-sampling weights estimated within a random sample of the target population in which the non-respondents are disclosed are equivalent in expectation to analogous weights in a scenario where the non-participants and uninvited individuals from the population are indistinguishable. To minimise the risk of disclosure when the entire population is invited to participate, investigators should instead consider inverse-odds-of-sampling weights, a method that has previously been suggested for transporting study results to external populations. Conclusions: Generalisation weights can be estimated from auxiliary register data without disclosing information on invited non-participants. [ABSTRACT FROM AUTHOR]

The relationship between genetically-driven liver fat and coronary heart disease (CHD) remains unclear. ApoB-containing lipoproteins are known causal factors for CHD and may explain this relationship. We conducted a genome-wide association study (GWAS) in the UK Biobank to identify genetic variants associated with liver fat. We then investigated the effects that these genetic variants had on both apoB-containing lipoproteins and CHD. Using Mendelian Randomization (MR) analyses, we examined if the relationship between genetically-driven liver fat and CHD could be attributed to its effect on apoB-containing lipoproteins. We found 25 independent liver-fat associated single-nucleotide polymorphisms (SNPs) with differing effects on lipoprotein metabolism. The SNPs were classified into three groups/clusters. The first cluster (N = 3 SNPs) displayed lipoprotein-raising effects. The second cluster (N = 12 SNPs) displayed neutral effects on lipoproteins and the third cluster (N = 10 SNPs) displayed lipoprotein-lowering effects. For every 1% higher liver fat, the first cluster showed an increased risk of CHD (OR = 1.157 [95% CI: 1.108–1.208]). The second cluster showed a non-significant effect on CHD (OR = 0.988 [95% CI: 0.965–1.012], whereas the third cluster showed a protective effect of increased liver fat on CHD (OR = 0.942 [95% CI: 0.897–0.989]). When adjusting for apoB, the risk for CHD became null. Here, we identify 25 liver-fat associated SNPs. We find that SNPs that increase, decrease or have neutral effects on apoB-containing lipoproteins show increased, decreased or neutral effects on CHD, respectively. Therefore, the relationship between genetically-driven liver fat and CHD is mediated by the causal effect of apoB. [Display omitted] • Liver fat-related genetic variants may or may not raise coronary heart disease risk. • Previous studies have shown different results using different genetic variants. • The effect on apoB-containing lipoproteins may explain previous results. • Here, we were able to directly account for the possible effect on plasma apoB. • We found that the effect on coronary heart disease risk is fully explained by apoB. [ABSTRACT FROM AUTHOR]

Coronary artery calcification (CAC) is an established imaging biomarker of subclinical atherosclerosis, but its relationship to diurnal preference is not well studied. We investigated the association between chronotype and CAC in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. Participants aged 50–64 years were randomly recruited and underwent extensive examination including imaging and accelerometry-assessed physical activity. 771 participants (47.3 % male, 57.6 ± 4.4 years) were included in this cross-sectional analysis. CAC was assessed by non-contrast computed tomography, and a CAC score > 10 was considered significant calcification. Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. 10-year risk of first-onset cardiovascular disease was estimated by the Systemic Coronary Risk Evaluation 2 (SCORE2). Significant CAC was present in 29 % of the cohort. CAC prevalence increased from extreme morning to extreme evening type (22 %, 28 %, 29 %, 27 %, 41 % respectively, p = 0.018). In a multivariate logistic regression model controlling for confounders, extreme evening chronotype was independently associated with increased CAC prevalence compared to extreme morning type (OR 1.90, [95%CI 1.04–3.46], p = 0.037). When stratified by SCORE2 risk category (low: <5 %; moderate: 5 to <10 %; high: ≥10 %), significant CAC was most prevalent among extreme evening chronotypes in the low and moderate-risk groups, while chronotype seemed less important in the high-risk group (p = 0.011, p = 0.023, p = 0.86, respectively). Our findings suggest circadian factors may play an important role in atherosclerosis and should be considered in early cardiovascular prevention. [Display omitted] • Extreme evening chronotype was found to be associated with increased risk of CAC. • The link was more distinct among subjects with low-to-moderate cardiovascular risk. • Circadian misalignment may play an important role in atherosclerosis. • Sleep timing should be considered in cardiovascular prevention. [ABSTRACT FROM AUTHOR]

Objectives: Quantitative CT imaging is an important emphysema biomarker, especially in smoking cohorts, but does not always correlate to radiologists' visual CT assessments. The objectives were to develop and validate a neural network-based slice-wise whole-lung emphysema score (SWES) for chest CT, to validate SWES on unseen CT data, and to compare SWES with a conventional quantitative CT method. Materials and methods: Separate cohorts were used for algorithm development and validation. For validation, thin-slice CT stacks from 474 participants in the prospective cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS) were included, 395 randomly selected and 79 from an emphysema cohort. Spirometry (FEV1/FVC) and radiologists' visual emphysema scores (sum-visual) obtained at inclusion in SCAPIS were used as reference tests. SWES was compared with a commercially available quantitative emphysema scoring method (LAV950) using Pearson's correlation coefficients and receiver operating characteristics (ROC) analysis. Results: SWES correlated more strongly with the visual scores than LAV950 (r = 0.78 vs. r = 0.41, p < 0.001). The area under the ROC curve for the prediction of airway obstruction was larger for SWES than for LAV950 (0.76 vs. 0.61, p = 0.007). SWES correlated more strongly with FEV1/FVC than either LAV950 or sum-visual in the full cohort (r = − 0.69 vs. r = − 0.49/r = − 0.64, p < 0.001/p = 0.007), in the emphysema cohort (r = − 0.77 vs. r = − 0.69/r = − 0.65, p = 0.03/p = 0.002), and in the random sample (r = − 0.39 vs. r = − 0.26/r = − 0.25, p = 0.001/p = 0.007). Conclusion: The slice-wise whole-lung emphysema score (SWES) correlates better than LAV950 with radiologists' visual emphysema scores and correlates better with airway obstruction than do LAV950 and radiologists' visual scores. Clinical relevance statement: The slice-wise whole-lung emphysema score provides quantitative emphysema information for CT imaging that avoids the disadvantages of threshold-based scores and is correlated more strongly with reference tests than LAV950 and reader visual scores. Key Points: • A slice-wise whole-lung emphysema score (SWES) was developed to quantify emphysema in chest CT images. • SWES identified visual emphysema and spirometric airflow limitation significantly better than threshold-based score (LAV950). • SWES improved emphysema quantification in CT images, which is especially useful in large-scale research. [ABSTRACT FROM AUTHOR]

Background: Observational studies investigating the association between accelerometer-measured physical activity and health all use absolute measures of physical activity intensity. However, intervention studies suggest that the physical activity intensity required to improve health is relative to individual fitness. The aim of this study was to investigate the associations between accelerometer-measured absolute and relative physical activity intensity and cardiometabolic health, and what implications these associations may have on the interpretation of health-associated physical activity. Methods: A sample of the cross-sectional Swedish CArdioPulmonary bioImage Study (SCAPIS) consisting of 4,234 men and women aged 55–64 years was studied. Physical activity intensity was measured by accelerometry and expressed as absolute (e.g., metabolic equivalents of task) or relative (percentage of maximal oxygen consumption). Fitness was estimated by the submaximal Ekblom-Bak test. A composite ('metabolic syndrome') score combined measures of waist circumference, systolic blood pressure, high-density lipoprotein, triglycerides, and glycated hemoglobin. Associations of absolute and relative physical activity intensity with the health indicators (i.e., fitness and metabolic syndrome score) were studied by partial least squares regression. Analyses were stratified by fitness level. Results: Both absolute and relative physical activity intensity associated with the health indicators. However, the strongest associations for absolute intensity varied depending on fitness levels, whereas the associations for relative intensity were more synchronized across fitness groups. The dose–response relationship between moderate-to-vigorous intensity and the health indicators was stronger for relative than for absolute intensity. The absolute and relative moderate-to-vigorous intensity cut-offs intersected at the 5th fitness percentile, indicating that the absolute intensity cut-off is too low for 95% of individuals in this sample. While 99% of individuals fulfilled the general physical activity recommendations based on absolute intensity measures, only 21% fulfilled the recommendations based on relative intensity measures. In relation to a "sufficient" fitness level, 9% fulfilled the recommendations. Conclusions: Accelerometer-measured relative physical activity intensity represents the intensity related to health benefits regardless of fitness level. Traditional absolute moderate intensity accelerometer cut-offs are too low for most individuals and should be adapted to the fitness level in the sample studied. Absolute and relative physical activity intensity cannot be used interchangeably. [ABSTRACT FROM AUTHOR]

Background: A subset of obese individuals do not present metabolic abnormalities that commonly define the metabolic syndrome (MetS). This is referred to as a metabolically healthy obese (MHO) phenotype. The aim of the present study was to evaluate the prevalence of the MHO phenotype and its relationship with beta cell dysfunction by measuring C-peptide and proinsulin, anthropometric-, metabolic- and lipid appearance, as well as lifestyle behaviors and self-rated health in a cohort of 64-year-old Swedish women. Methods: The National Cholesterol Education Program definition was used to assess MetS. We defined normal weight as body mass index (BMI) 18.5-24.9 kg/m2 and obesity as BMI =30 kg/m2 to categorize participants as metabolically healthy normal weight, MHO, and metabolically unhealthy obese. Results: The MHO phenotype represented 36.3% of obese participants and 16.3% of total participants. The MHO group were at greater risk of having proinsulin levels >11 pmol/L, indicating impaired beta cell function. Further, homeostatic model assessment for insulin resistance, fasting plasma levels of insulin, and C-peptide showed significant trends, with the MHO phenotype group having intermediate levels among three groups. Health behaviors such as leisure time physical activity and alcohol intake were also intermediate in individuals with the MHO phenotype. Conclusion: In this study, we demonstrate that over a third of the obese women in our sample were MHO. Further, women with the MHO phenotype showed intermediate profiles considering beta cell function and insulin resistance, as well as metabolic variables, and tended to rate their general health as worse than otherwise similar individuals of normal weight. [ABSTRACT FROM AUTHOR]

Background: Patients with type 2 diabetes have an increased risk of death and cardiovascular events and people with diabetes or prediabetes have been found to have increased atherosclerotic burden in the coronary and carotid arteries. This study will estimate the cross-sectional prevalence of atherosclerosis in the coronary and carotid arteries in individuals with prediabetes and diabetes, compared with normoglycaemic individuals in a large population-based cohort. Methods: The 30,154 study participants, 50–64 years, were categorized according to their fasting glycaemic status or self-reported data as normoglycaemic, prediabetes, and previously undetected or known diabetes. Prevalence of affected coronary artery segments, severity of stenosis and coronary artery calcium score (CACS) were determined by coronary computed tomography angiography. Total atherosclerotic burden was assessed in the 11 clinically most relevant segments using the Segment Involvement Score and as the presence of any coronary atherosclerosis. The presence of atherosclerotic plaque in the carotid arteries was determined by ultrasound examination. Results: Study participants with prediabetes (n = 4804, 16.0%) or diabetes (n = 2282, 7.6%) had greater coronary artery plaque burden, more coronary stenosis and higher CACS than normoglycaemic participants (all, p < 0.01). Among male participants with diabetes 35.3% had CACS ≥ 100 compared to 16.1% among normoglycaemic participants. For women, the corresponding figures were 8.9% vs 6.1%. The prevalence of atherosclerosis in the coronary arteries was higher in participants with previously undetected diabetes than prediabetes, but lower than in patients with known diabetes. The prevalence of any plaque in the carotid arteries was higher in participants with prediabetes or diabetes than in normoglycaemic participants. Conclusions: In this large population-based cohort of currently asymptomatic people, the atherosclerotic burden in the coronary and carotid arteries increased with increasing degree of dysglycaemia. The finding that the atherosclerotic burden in the coronary arteries in the undetected diabetes category was midway between the prediabetes category and patients with known diabetes may have implications for screening strategies and tailored prevention interventions for people with dysglycaemia in the future. [ABSTRACT FROM AUTHOR]

Background: Body composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs. Methods: The study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets. Results: The Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909–0.996), UNET++ 0.981 (0.927–0.996), Ghost-UNET 0.961 (0.904–0.991), and Ghost-UNET++ 0.968 (0.910–0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach. Conclusion: Fully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC. [ABSTRACT FROM AUTHOR]

Non-alcoholic fatty liver disease (NAFLD) is associated with increased secretion of apoB-containing lipoproteins and increased risk of coronary heart disease (CHD). ApoB-containing lipoproteins include low-density lipoproteins (LDLs) and triglyceride-rich lipoproteins (TRLs); and since both LDLs and TRLs are causally related to CHD, they may mediate a portion of the increased risk of atherosclerosis seen in people with NAFLD. In a cohort of 4161 middle aged men and women, we performed mediation analysis in order to quantify the mediating effect of apoB-containing lipoproteins in the relationship between liver fat and atherosclerosis—as measured by coronary artery calcium score (CACS). We found plasma apoB to mediate 17.6% (95% CI 11–24) of the association between liver fat and CACS. Plasma triglycerides and TRL-cholesterol (both proximate measures of TRL particles) mediated 22.3% (95% CI 11–34) and 21.6% (95% CI 10–33) of the association respectively; whereas LDL-cholesterol mediated 5.4% (95% CI 2.0–9.4). In multivariable models, the mediating effect of TRL-cholesterol and plasma triglycerides showed, again, a higher degree of mediation than LDL-cholesterol, corroborating the results seen in the univariable models. In summary, we find around 20% of the association between liver fat and CACS to be mediated by apoB-containing lipoproteins. In addition, we find that TRLs mediate the majority of this effect whereas LDLs mediate a smaller effect. These results explain part of the observed CAD-risk burden for people with NAFLD and further suggest that TRL-lowering may be particularly beneficial to mitigate NAFLD-associated coronary artery disease risk. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate associations between psychosocial work exposure and the presence of biological and imaging biomarkers of cardiovascular disease. Methods: This cross-sectional study was conducted in a sub-cohort of the Swedish CArdioPulmonary bioImage Study (SCAPIS). Psychosocial exposure was evaluated with the job demand–control model, and analysed according to the standard categorization: high strain, active, passive and low strain (reference). Biomarkers (blood pressure, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol, coronary artery calcification (CAC) and metabolic syndrome) were measured, or derived through measurements, from clinical examinations. Gender-specific prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated with regression models and adjusted for age, education, smoking, physical activity, general life stress and body mass index (BMI). Results: The analyses included 3882 participants (52.5% women). High strain (high demands–low control) was linked to increased PR for low HDL cholesterol in women, adjusted for all covariates (PR 1.76; 95% CI 1.25–2.48). High strain was also related to moderately increased PR for metabolic syndrome in men, after adjustments for all covariates except BMI (PR 1.25; 95% CI 1.02–1.52). In addition, passive work (low demands–low control) was associated with diastolic hypertension in women (fully adjusted: PR 1.29; 95% CI 1.05–1.59). All relationships between psychosocial factors and LDL cholesterol or CAC (both genders), or hypertension (men), were non-significant. Conclusions: Poor psychosocial job conditions was associated with the presence of low HDL cholesterol and diastolic hypertension in women, and metabolic syndrome in men. These findings contribute to the knowledge of potential pathways between stressful work and coronary heart disease. [ABSTRACT FROM AUTHOR]

OSA is a common sleep-breathing disorder linked to increased risk of cardiovascular disease. Intermittent upper airway obstruction and hypoxia, hallmarks of OSA, have been shown in animal models to induce substantial changes to the gut microbiota composition, and subsequent transplantation of fecal matter to other animals induced changes in BP and glucose metabolism. Does OSA in adults associate with the composition and functional potential of the human gut microbiota? We used respiratory polygraphy data from up to 3,570 individuals 50 to 64 years of age from the population-based Swedish Cardiopulmonary bioimage Study combined with deep shotgun metagenomics of fecal samples to identify cross-sectional associations between three OSA parameters covering apneas and hypopneas, cumulative sleep time in hypoxia, and number of oxygen desaturation events with gut microbiota composition. Data collection about potential confounders was based on questionnaires, onsite anthropometric measurements, plasma metabolomics, and linkage with the Swedish Prescribed Drug Register. We found that all three OSA parameters were associated with lower diversity of species in the gut. Furthermore, in multivariable-adjusted analysis, the OSA-related hypoxia parameters were associated with the relative abundance of 128 gut bacterial species, including higher abundance of Blautia obeum and Collinsella aerofaciens. The latter species was also independently associated with increased systolic BP. Furthermore, the cumulative time in hypoxia during sleep was associated with the abundance of genes involved in nine gut microbiota metabolic pathways, including propionate production from lactate. Finally, we observed two heterogeneous sets of plasma metabolites with opposite association with species positively and negatively associated with hypoxia parameters, respectively. OSA-related hypoxia, but not the number of apneas/hypopneas, is associated with specific gut microbiota species and functions. Our findings lay the foundation for future research on the gut microbiota-mediated health effects of OSA. [ABSTRACT FROM AUTHOR]

Abstract: Atherosclerotic stenotic and nonstenotic plaques of the carotid artery with low echogenicity have been shown to be associated with cardiovascular disease. The aim was to develop a new method for semiautomated ultrasound image analysis to classify nonstenotic carotid plaques, evaluate cases with multiple plaques and examine the association between a new image analysis feature of echogenicity and predictors of cardiovascular disease. The new image analysis feature, percentage white (PW), represents the fraction of bright structures inside a plaque and is integrated in an objective semiautomated method to evaluate echogenicity (SAMEE) in carotid plaques. PW was constructed to take into account overall echogenicity of the image as well as noise surrounding the plaque. Consecutive ultrasound examinations of carotid plaques from a population-based screening of 64-year-old women with varying risk for cardiovascular disease were selected for the present project; 92 far-wall and 47 near-wall plaques were used as a training dataset to develop the SAMEE algorithm with visual classification according to Gray-Weale as reference; 273 plaques were used to validate the method. All plaques were included in an analysis relating predictors of cardiovascular to average PW in all plaques, PW in the biggest plaque and to the plaque with lowest PW in each subject, respectively. In the training dataset the intermethodological variability between SAMEE and visual classification showed a κ of 0.78 and a sensitivity and specificity of 96% and 81%, respectively. In the validation set, SAMEE and visual classification showed a κ of 0.77, a sensitivity of 96% and a specificity of 80%. The reproducibility of PW was high, evidenced by r = 0.96 and CV = 9.85% at repeated examinations. Average PW values were associated with several predictors of cardiovascular risk: lipoprotein (a), HbA1c, blood glucose, apolipoproteinB/apolipoproteinA-I; and associated negatively with the levels of adiponectin and apolipoprotein A-I. In conclusion, PW integrated within a SAMEE is a new feature for assessment of echogenicity in carotid plaques and shows excellent reproducibility and agreement with visual assessment. (E-mail: ulrica.prahl@wlab.gu.se). [Copyright &y& Elsevier]

Objective: In vivo mouse coronary artery circulation is still largely unknown. We demonstrate here in vivo coronary flow velocity profiles in anesthesized mice using a novel high-resolution ultrasound technique. Methods: Seven 10-week-old C57/Bl6 mice were used for ultrasonographic examination under anesthesia. An Acuson Sequoia 512 echocardiograph with a Microson 15L8 transducer was used. Left coronary artery (LCA) anatomy was mapped in situ. Results: The proximal, mid LCA and its anterior (A-LCA) and lateral (L-LCA) branches could be visualized and coronary flow velocity was reproducibly recorded in all animals. Peak flow velocity was 31.3 +/- 1.5 and 20.7 +/- 2.3 cm/s in the mid LCA and L-LCA branches, respectively. Mean flow velocity was 18.4 +/- 0.7 and 13.8 +/- 1.5 cm/s in the respective vessels. Both the peak and mean flow velocities were higher in the mid LCA than in the distal part of the L-LCA (p = 0.006 and 0.01, respectively). Measurements of the velocity time integral show percentage systolic flow was 15.7 +/- 1.6% and 10.2 +/- 1.4% in the mid LCA and L-LCA, respectively. Conclusion: Despite the extremely high heart rate in mice, there are striking similarities between murine and human coronary flow velocity profiles. The presented technique and findings confirm the relevance of the mouse as an animal model in cardiovascular research. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to develop and characterize a multiplex immunoassay for detection of autoantibodies against peptides derived from proteins known to play a role in development of arthritis and that are also expressed in joints. Methods: We selected peptides from the human counterpart of proteins expressed in the joints, based on mouse models that showed these to be targeted by pathogenic or regulatory antibodies in vivo. Using bead‐based flow immunoassays measuring IgG antibodies, we selected triple helical or cyclic peptides, containing the epitopes, to avoid collinear reactivity. We characterized the analytical performance of the immunoassay and then validated it in 3 independent rheumatoid arthritis (RA) cohorts (n = 2,110), Swedish age‐ and sex‐matched healthy controls, and patients with osteoarthritis (OA), patients with psoriatic arthritis (PsA), and patients with systemic lupus erythematosus (SLE). Results: Screening assays showed 5 peptide antigens that discriminated RA patients from healthy controls with 99% specificity (95% confidence interval [CI] 98–100%). In our validation studies, we reproduced the discriminatory capacity of the autoantibodies in 2 other RA cohorts, showing that the autoantibodies had high discriminatory capacity for RA versus OA, PsA, and SLE. The novel biomarkers identified 22.5% (95% CI 19–26%) of early RA patients seronegative for anti–cyclic citrullinated peptide and rheumatoid factor. The usefulness of the biomarkers in identifying seronegative RA patients was confirmed in validation studies using 2 independent cohorts of RA patients and cohorts of patients with OA, PsA, and SLE. Conclusion: A multiplex immunoassay with peptides from disease‐related proteins in joints was found to be useful for detection of specific autoantibodies in RA serum. Of note, this immunoassay had high discriminatory capacity for early seronegative RA. [ABSTRACT FROM AUTHOR]

Results: The prevalence of significant carotid stenosis was 18.9%, and 14.2% were subjected to carotid endarterectomy. A trend of longer delay for surgery was noted for patients first consulting a general practitioner (P=0.069) as compared to hospital-based specialties. For 46.3% of the patients, an ophthalmologist was their first medical contact. No significant difference in time interval to endarterectomy was seen between ophthalmologists and neurologists/internists. Only 31.8% of the patients with significant carotid stenosis had carotid endarterectomy within 2 weeks from the debut of symptoms, and this proportion was smaller for patients residing outside the Gothenburg city area (P=0.038). Conclusion: Initially consulting an ophthalmologist does not delay the time to ultrasound or carotid endarterectomy. The overall time from symptoms to surgery is longer than recommended for a majority of the patients, especially for patients from rural areas and for patients initially consulting a general practitioner. [ABSTRACT FROM AUTHOR]

The volume of epicardial adipose tissue (EATV) is increased in type-2 diabetes (T2D), while its attenuation (EATA) appears to be decreased. Similar patterns have been suggested in pre-diabetes, but data is scarce. In both pre-diabetes and T2D, any independent role of EATV and EATA in disease development remains to be proven, a task complicated by their substantial co-variation with other anthropometrics, e.g. BMI, waist circumference, and abdominal visceral adipose tissue (VAT). EATV and EATA was quantified in computed tomography (CT) images in a population study (n = 1948) using an automatic technique. Data was available on BMI, waist circumference, abdominal visceral adipose tissue (VAT) area, insulin resistance (IR) and glucose tolerance, the latter ranging from normal (NGT), over pre-diabetes (impaired fasting glucose [IFG, n = 414] impaired glucose tolerance [IGT, n = 321] and their combination [CGI, n = 128]), to T2D. EATV was increased in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI, however not when adjusting for waist or VAT. EATA was reduced in pre-diabetes, T2D and IR in univariable analyses and when adjusting for BMI and waist, however not when adjusting for VAT. Adjustment for other co-variates had little influence on the results. In conclusion, EATV is increased and EATA reduced in pre-diabetes, T2D and IR, however, significant co-variation with other anthropometrics, especially VAT, obscures their function in disease development. The current results do not exclude a pathophysiological role of epicardial fat, but future studies need to adjust for anthropometrics, or focus on the microenvironment within the pericardial sac. [ABSTRACT FROM AUTHOR]

Prediabetes is a condition between diabetes and normoglycemia, and is a state of major health concern, as a large proportion of people with prediabetes are likely to develop diabetes which is associated with high mortality and morbidity. The purpose of this study was to investigate whether adverse psychosocial work conditions, based on the Job Demand-Control-social support model, increases risk for early dysregulated glucose metabolism in 50–64-year-old men and women. Job conditions were measured with the Swedish Demand-Control-Support questionnaire. Impaired glucose metabolism was assessed by an oral glucose tolerance test. Differences between groups were analyzed with Chi-square test and one-way ANOVA with Bonferroni post-hoc test. Odds ratios (OR) and 95% confidence intervals (95% CI) between Job Demand-control-support and prediabetes outcome were calculated with multiple logistic regression. Results from an adjusted logistic regression model showed that in men and woman separately, an active work situation (high demands-high control) was associated with significantly lower prediabetes risk (OR 0.657, 95% CI 0.513–0.842). This finding is consistent through all logistic regression models with different levels of adjustments. Further, the current study does not lend support for the hypothesis that work conditions characterized by high demands-low control were associated with dysregulated glucose metabolism in men nor women despite accumulation of many life-style related risk factors in the high strain group. In conclusion, we could show that men and women assessing their work conditions as active, had lower risk for prediabetes. [ABSTRACT FROM AUTHOR]

There are numerous sex-related differences in cardiac electrophysiology and arrhythmia propensity but very little knowledge about the reasons. Difference in body size has been proposed as one reason and was tested in this study of >20 cardiac electrophysiology parameters in 319 (158 women) apparently healthy 50- to 64-yr-old subjects from a randomly enrolled population sample, the pilot SCAPIS (Swedish Cardiopulmonary Bioimaging Study), using Frank vectorcardiography. We studied conventional conduction intervals, parameters reflecting electrical heterogeneity (dispersion) in the ventricles, QRS- and T-vector directions, spatial QRS-T angles, and T-vector loop morphology. Body surface area (BSA; 2 methods) and lean body mass (LBM), both estimated from body weight and height, were used as body size parameters. According to multivariable linear regression analysis adjusted for sex, there was no association between electrophysiological parameters and body size apart from QRS duration and QRSarea. In conclusion, most electrophysiological parameters assessed completely noninvasively and showing statistically significant differences between women and men on the group level show no association with BSA or LBM. Scaling (indexing) the electrophysiological parameters for body size parameters is therefore not an option. Consequently, the explanation for the sex-related electrophysiological differences should be sought along other lines. NEW & NOTEWORTHY We sought explanations for sex-related differences in >20 cardiac electrophysiology parameters including conventional conduction intervals in 319 (158 women) apparently healthy 50- to 64-yr-old subjects using Frank vectorcardiography, a novelty. Our hypothesis that body size was partly explanatory for such differences had to be refuted apart from QRS duration and QRSarea. Scaling (indexing) electrophysiological parameters for body size is therefore not an option and explanations for electrophysiological sex-related differences are to be sought elsewhere. [ABSTRACT FROM AUTHOR]

Background: The role of diabetes in the development of valvular heart disease, and, in particular, the relation with risk factor control, has not been extensively studied.Methods: We included 715 143 patients with diabetes registered in the Swedish National Diabetes Register and compared them with 2 732 333 matched controls randomly selected from the general population. First, trends were analyzed with incidence rates and Cox regression, which was also used to assess diabetes as a risk factor compared with controls, and, second, separately in patients with diabetes according to the presence of 5 risk factors.Results: The incidence of valvular outcomes is increasing among patients with diabetes and the general population. In type 2 diabetes, systolic blood pressure, body mass index, and renal function were associated with valvular lesions. Hazard ratios for patients with type 2 diabetes who had nearly all risk factors within target ranges, compared with controls, were as follows: aortic stenosis 1.34 (95% CI, 1.31-1.38), aortic regurgitation 0.67 (95% CI, 0.64-0.70), mitral stenosis 1.95 (95% CI, 1.76-2.20), and mitral regurgitation 0.82 (95% CI, 0.79-0.85). Hazard ratios for patients with type 1 diabetes and nearly optimal risk factor control were as follows: aortic stenosis 2.01 (95% CI, 1.58-2.56), aortic regurgitation 0.63 (95% CI, 0.43-0.94), and mitral stenosis 3.47 (95% CI, 1.37-8.84). Excess risk in patients with type 2 diabetes for stenotic lesions showed hazard ratios for aortic stenosis 1.62 (95% CI, 1.59-1.65), mitral stenosis 2.28 (95% CI, 2.08-2.50), and excess risk in patients with type 1 diabetes showed hazard ratios of 2.59 (95% CI, 2.21-3.05) and 11.43 (95% CI, 6.18-21.15), respectively. Risk for aortic and mitral regurgitation was lower in type 2 diabetes: 0.81 (95% CI, 0.78-0.84) and 0.95 (95% CI, 0.92-0.98), respectively.Conclusions: Individuals with type 1 and 2 diabetes have greater risk for stenotic lesions, whereas risk for valvular regurgitation was lower in patients with type 2 diabetes. Patients with well-controlled cardiovascular risk factors continued to display higher risk for valvular stenosis, without a clear stepwise decrease in risk between various degrees of risk factor control. [ABSTRACT FROM AUTHOR]

Background and aims Recent evidence suggests that the microbiota may be considered as an environmental factor that contributes to the development of atherosclerosis. Periodontal disease has been associated with cardio- and cerebrovascular events, and inflammation in the periodontium is suggested to increase the systemic inflammatory level of the host, which may in turn influence plaque composition and rupture. We previously showed that bacteria from the oral cavity and the gut could be found in atherosclerotic plaques. Methods To elucidate whether the oral microbiota composition differed between patients with asymptomatic and symptomatic atherosclerosis we performed pyrosequencing of the oral microbiota of 92 individuals including patients with asymptomatic and symptomatic atherosclerosis and control individuals without carotid plaques or previous stroke or myocardial infarction. Results The overall microbial structure was similar in controls and atherosclerosis patients, but patients with symptomatic atherosclerosis had higher relative abundance of Anaeroglobus (mean 0.040% (SD 0.049)) than the control group (0.010% (SD 0.028)) ( P = 0.03). Using linear regression analysis, we found that Parvimonas associated positively with uCRP and Capnocytophaga , Catonella and Lactobacillus associated with blood lipid markers. In conclusion, abundance of Anaeroglobus in the oral cavity could be associated with symptomatic atherosclerosis. [ABSTRACT FROM AUTHOR]

Chronotype reflects individual preferences for timing activities throughout the day, determined by the circadian system, environment and behavior. The relationship between chronotype, physical activity, and cardiovascular health has not been established. We studied the association between chronotype, physical activity patterns, and an estimated 10-year risk of first-onset cardiovascular disease (CVD) in the Swedish CArdioPulmonary bioImage Study (SCAPIS) pilot cohort. A cross-sectional analysis was performed in a middle-aged population (n = 812, 48% male). Self-assessed chronotype was classified as extreme morning, moderate morning, intermediate, moderate evening, or extreme evening. Time spent sedentary (SED) and in moderate to vigorous physical activity (MVPA) were derived from hip accelerometer. The newly introduced Systematic COronary Risk Evaluation 2 (SCORE2) model was used to estimate CVD risk based on gender, age, smoking status, systolic blood pressure, and non-HDL cholesterol. Extreme evening chronotypes exhibited the most sedentary lifestyle and least MVPA (55.3 ± 10.2 and 5.3 ± 2.9% of wear-time, respectively), with a dose-dependent relationship between chronotype and SED/MVPA (p < 0.001 and p = 0.001, respectively). In a multivariate generalized linear regression model, extreme evening chronotype was associated with increased SCORE2 risk compared to extreme morning type independent of confounders (β = 0.45, SE = 0.21, p = 0.031). Mediation analysis indicated SED was a significant mediator of the relationship between chronotype and SCORE2. Evening chronotype is associated with unhealthier physical activity patterns and poorer cardiovascular health compared to morning chronotype. Chronotype should be considered in lifestyle counseling and primary prevention programs as a potential modifiable risk factor. [ABSTRACT FROM AUTHOR]

The present study aims to describe accelerometer‐assessed physical activity (PA) patterns and fulfillment of PA recommendations in a large sample of middle‐aged men and women, and to study differences between subgroups of socio‐demographic, socio‐economic, and lifestyle‐related variables. A total of 27 890 (92.5% of total participants, 52% women, aged 50–64 years) middle‐aged men and women with at least four days of valid hip‐worn accelerometer data (Actigraph GT3X+, wGT3X+ and wGT3X‐BT) from the Swedish CArdioPulmonary bioImage Study, SCAPIS, were included. In total, 54.5% of daily wear time was spent sedentary, 39.1% in low, 5.4% in moderate, and only 0.1% in vigorous PA. Male sex, higher education, low financial strain, born in Sweden, and sedentary/light working situation were related to higher sedentary time, but also higher levels of vigorous PA. High BMI and having multiple chronic diseases associated strongly with higher sedentary time and less time in all three PA intensities. All‐year physically active commuters had an overall more active PA pattern. The proportion fulfilling current PA recommendations varied substantially (1.4% to 92.2%) depending on data handling procedures and definition used. Twenty‐eight percent was defined as having an "at‐risk" behavior, which included both high sedentary time and low vigorous PA. In this large population‐based sample, a majority of time was spent sedentary and only a fraction in vigorous PA, with clinically important variations between subgroups. This study provides important reference material and emphasizes the importance of a comprehensive assessment of all aspects of the individual PA pattern in future research and clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: To study the value of combining individual- and neighborhood-level sociodemographic data to predict study participation and assess the effects of baseline selection on the distribution of metabolic risk factors and lifestyle factors in the Swedish CardioPulmonary bioImage Study (SCAPIS). Methods: We linked sociodemographic register data to SCAPIS participants (n = 30,154, ages: 50–64 years) and a random sample of the study's target population (n = 59,909). We assessed the classification ability of participation models based on individual-level data, neighborhood-level data, and combinations of both. Standardized mean differences (SMD) were used to examine how reweighting the sample to match the population affected the averages of 32 cardiopulmonary risk factors at baseline. Absolute SMDs >0.10 were considered meaningful. Results: Combining both individual-level and neighborhood-level data gave rise to a model with better classification ability (AUC: 71.3%) than models with only individual-level (AUC: 66.9%) or neighborhood-level data (AUC: 65.5%). We observed a greater change in the distribution of risk factors when we reweighted the participants using both individual and area data. The only meaningful change was related to the (self-reported) frequency of alcohol consumption, which appears to be higher in the SCAPIS sample than in the population. The remaining risk factors did not change meaningfully. Conclusions: Both individual- and neighborhood-level characteristics are informative in assessing study selection effects. Future analyses of cardiopulmonary outcomes in the SCAPIS cohort can benefit from our study, though the average impact of selection on risk factor distributions at baseline appears small. [ABSTRACT FROM AUTHOR]

Lead exposure is associated with cardiovascular disease. Atherosclerosis has been hypothesized to be one of the underlying mechanisms behind this association. To investigate whether lead exposure is associated with an increased risk of atherosclerosis in the carotid arteries in a large Swedish population-based cohort. We performed a cross-sectional study using data from the population-based Swedish CardioPulmonary bioImage Study (SCAPIS), including 5622 middle-aged men and women, enrolled 2013–2018. Blood lead (B–Pb), measured by inductively coupled plasma mass spectrometry, was used as exposure biomarker. The presence of atherosclerotic plaque in the carotid arteries (yes/no), total plaque area (mm2) and the presence of large plaques (>25 mm2) were determined by ultrasonography. Associations between B–Pb and the different outcomes were analysed using Poisson and linear regression models, adjusted for potential confounders. Atherosclerotic plaque was present in 57% of the individuals, for whom the median total plaque area was 16 mm2 (range: 0.2–222). The median B–Pb concentration was 14 μg/L (range: 0.75–203). After adjusting for potential confounders, individuals in the fourth quartile of B–Pb (Q4) had a prevalence ratio (PR) for plaque of 1.08 (95% CI: 1.01, 1.16) when compared with the first quartile (Q1). A 10 μg/L increase in B–Pb concentrations was associated with an increase of 0.92 mm2 (95% CI: 0.14, 1.71) in total plaque area. The PR for large plaque was 1.09 (95% CI: 0.84, 1.42 for Q4 vs Q1). This study shows an association between B–Pb and atherosclerosis in the carotid arteries providing some support for the hypothesis that atherosclerosis is one of the mechanisms underlying the association between lead exposure and cardiovascular disease. • Few studies have assessed the association between lead exposure and risk for plaque. • We studied a large cohort of Swedish middle-aged men and women (n = 5622). • Individuals in Q4 of blood lead had an 8% increased risk for plaque compared to Q1. • Increasing blood lead was associated with a larger total plaque area. • Atherosclerosis may be one underlying mechanism in the link between lead and CVD. [ABSTRACT FROM AUTHOR]

To develop a fully automatic model capable of reliably quantifying epicardial adipose tissue (EAT) volumes and attenuation in large scale population studies to investigate their relation to markers of cardiometabolic risk. Non-contrast cardiac CT images from the SCAPIS study were used to train and test a convolutional neural network based model to quantify EAT by: segmenting the pericardium, suppressing noise-induced artifacts in the heart chambers, and, if image sets were incomplete, imputing missing EAT volumes. The model achieved a mean Dice coefficient of 0.90 when tested against expert manual segmentations on 25 image sets. Tested on 1400 image sets, the model successfully segmented 99.4% of the cases. Automatic imputation of missing EAT volumes had an error of less than 3.1% with up to 20% of the slices in image sets missing. The most important predictors of EAT volumes were weight and waist, while EAT attenuation was predicted mainly by EAT volume. A model with excellent performance, capable of fully automatic handling of the most common challenges in large scale EAT quantification has been developed. In studies of the importance of EAT in disease development, the strong co-variation with anthropometric measures needs to be carefully considered. [ABSTRACT FROM AUTHOR]

We examined whether high-sensitivity C-reactive protein (hsCRP) ≥2.0 mg/L was associated with increased intima-media thickness (IMT), plaque burden, and plaque echolucency in carotid arteries. Women (n = 635) from a population sample of 64-year-old females with varying degrees of glucose tolerance underwent risk factor assessment, measurement of hsCRP, and ultrasound examinations of the carotid arteries. Participants with hsCRP levels ≥2.0 mg/L had elevated carotid bulb IMT independently of other cardiovascular risk factors compared with those with hsCRP <2.0 mg/L. The participants with plaques in the highhsCRP group had larger total plaque area compared to those with plaque in the lower hsCRP group. Plaque echolucency did not differ between groups. High-sensitivity CRP levels ≥2.0 mg/L were accompanied by elevated IMT in the carotid bulbs independently of other cardiovascular risk factors. Total plaque area was larger among women with plaques in the high hsCRP group versus the lower hsCRP group. [ABSTRACT FROM PUBLISHER]

Objectives: This study aimed to establish non-invasive methods of assessing coronary artery morphology in normal and atherosclerotic mice in vivo. Background: Coronary flow velocity reserve (CFVR) has been shown to correlate with coronary minimal lumen diameter (MLD) in patients with coronary artery stenosis. In mice, there are no existing non-invasive imaging techniques allowing quantitative measurement of the coronary artery morphology and function. Methods: Systemic hemodynamic effects of adenosine were studied in seven C57BL/6 mice. In 17 C57BL/6 mice, CFVR was measured in the mid left coronary artery (LCA) using either hypoxia- or adenosine-induced coronary hyperemia. Further, in another 10 atherosclerotic low-density lipoprotein receptor (LDLR)−/− mice, the hypoxia-induced CFVR was performed and proximal LCA MLD was measured using ultrasound biomicroscopy (UBM). Histologic sections of the LCA were collected. Results: The adenosine dose of 160 μg/kg/min induced maximal coronary hyperemia without any systemic hemodynamic effects. Adenosine and hypoxia-induced CFVR values averaged at 2.0 ± 0.1 and 1.9 ± 0.3, respectively, in C57BL/6 mice (p = NS). In LDLR−/− mice, CFVR and MLD ranged between 1.4 to 2.9 μm and 190 to 370 μm, respectively. Histology revealed proximal lumen-narrowing plaques in the LCA. Significant correlation was found between hypoxia-induced CFVR and the MLD (p &#60; 0.005, R2 = 0.8707). Conclusions: The CDE and UBM technique can be used to measure atherosclerosis-related lumen narrowing of the LCA in living mice. These non-invasive techniques may provide us with novel tools for following up disease status in mouse coronary arteries in a quantitative manner. [Copyright &y& Elsevier]

Chronic airflow limitation (CAL) can be defined as fixed ratio of forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) < 0.70 after bronchodilation. It is unclear which is the most optimal ratio in relation to respiratory morbidity. The aim was to investigate to what extent different ratios of FEV1/FVC were associated with any respiratory symptom. In a cross‐sectional general population study, 15,128 adults (50–64 years of age), 7,120 never‐smokers and 8,008 ever‐smokers completed a respiratory questionnaire and performed FEV1 and FVC after bronchodilation. We calculated different ratios of FEV1/FVC from 0.40 to 1.0 using 0.70 as reference category. We analysed odds ratios (OR) between different ratios and any respiratory symptom using adjusted multivariable logistic regression. Among all subjects, regardless of smoking habits, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.82, OR 0.48 (95% CI 0.41–0.56). Among never‐smokers, the lowest odds for any respiratory symptom was at FEV1/FVC = 0.81, OR 0.53 (95% CI 0.41–0.70). Among ever‐smokers, the odds for any respiratory symptom was lowest at FEV1/FVC = 0.81, OR 0.43 (95% CI 0.16–1.19), although the rate of inclining in odds was small in the upper part, that is FEV1/FVC = 0.85 showed similar odds, OR 0.45 (95% CI 0.38–0.55). We concluded that the odds for any respiratory symptoms continuously decreased with higher FEV1/FVC ratios and reached a minimum around 0.80–0.85, with similar results among never‐smokers. These results indicate that the optimal threshold associated with respiratory symptoms may be higher than 0.70 and this should be further investigated in prospective longitudinal studies. [ABSTRACT FROM AUTHOR]