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To describe functional and structural impairments of the pulmonary system in middle-aged people with cervical and upper thoracic spinal cord injuries (SCI), and compare findings to the general population. To determine if the neurological level of injury (NLI) is related to functional and structural impairments, and if age is related to structural impairments.Cross-sectional study with matched controls. Data from the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA). Matched control data were obtained from the Swedish CArdioPulmonary bioImage Study (SCAPIS).Outpatient SCI unit in southern Sweden.25 people (20% women, mean age 58 years, mean time since injury 28 years, NLIs C2-T6, American Spinal Injury Association Impairment Scale A-C).Not applicable.Lung function was assessed with spirometry, diffusing capacity and impulse oscillometry. Structural assessments were performed with computed tomography.Pulmonary function was generally worse compared to the controls. Structural impairments were common (75% of the participants and 65% of the controls; P = 0.36, NS). NLI was significantly related to some of the functional and structural impairments.Middle-aged people with long-term cervical and upper thoracic SCI can have substantial pulmonary functional impairments, whereas structural impairments do not differ considerably from the general population. Further larger and longitudinal studies should focus on the clinical impact of these impairments over time.

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.

Background and aims: 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. Methods: 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). Results: 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. Conclusions: 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.

Red cell distribution width (RDW) is a measure of the variability of erythrocyte volumes. RDW has been associated with incidence of cardiovascular diseases. However, the underlying mechanisms for the increased cardiovascular risk are still unclear. This study aimed to examine associations of RDW and coronary atherosclerosis in the general population. Computed tomography was performed and RDW was measured in fresh blood from 5772 subjects (aged 50–64 years) from the Swedish CArdioPulmonary bioImage Study (SCAPIS). Multinomial logistic regression was conducted to examine the associations between RDW and coronary artery calcium score (CACS). A total of 3902 (67.6%) individuals had low CACS (≤10), 18.6% had moderate CACS (>10 and ≤100) and 13.8% had high CACS (>100). The proportion with high CACS was 11.7%, 12.7%, 13.7% and 18.3%, respectively, in quartile 1–4 of RDW. After controlling for traditional risk factors, there were significant associations between RDW and high CACS: odds ratio = 1.51, 95% confidence interval: 1.18–1.94, and P = .001, for 4th vs 1st quartile of RDW. Elevated RDW is associated with coronary artery calcification in the middle-aged general population. RDW could be a reproducible and easily assessable biomarker of coronary calcification and cardiovascular risk.

The carotid-to-femoral pulse wave velocity, determined by pulse transit time (PTT) and distance, is a well-established measure of arterial stiffness and predicts adverse outcomes. However, its predictive value decreases with aging. To explore new risk indicator in the elderly, we investigated if the variation of carotid-to-femoral pulse wave velocity, registered as beat-to-beat variability of carotid-to-femoral PTT (cf-PTT), could predict outcome. Totally 3015 (median age, 72.4 years; 39.6% men) and 1181 (75.6 years; 42.2% men) subjects from communities of Malmö, Sweden, and Shanghai, China, were analyzed, respectively. Continuous pulse waves for 10 seconds were recorded sequentially at carotid and femoral arterial sites with applanation tonometry (SphygmoCor, Atcor, Australia). During a median of 6.6 and 10.2 years, 389 and 427 deaths occurred in the Malmö and Shanghai cohorts, respectively. Each one-SD increase in the log-transformed coefficient of variation of cf-PTT was associated with 24% (95% CI, 13%–37%) and 21% (10%–33%) increased risk for all-cause mortality in the Malmö and Shanghai subjects, and 60% (33%–91%) for cardiovascular mortality in the Malmö subjects. Adding the coefficient of variation of cf-PTT to the models including conventional risk factors and carotid-to-femoral pulse wave velocity significantly ( P

As cardio metabolic disease manifestations tend to cluster in families there is a need to better understand the underlying mechanisms in order to further develop preventive strategies. In fact, genetic markers used in genetic risk scores, important as they are, will not be able alone to explain these family clusters. Therefore, the search goes on for the so called missing heritability to better explain these associations. Shared lifestyle and social conditions in families, but also early life influences may be of importance. Gene-environmental interactions should be explored. In recent years interest has grown for the role of diet-microbiota associations, as microbiota patterns may be shared by family members. In the Malmö Offspring Study that started in 2013, we have so far been able to examine about 4700 subjects (18–71 years) representing children and grandchildren of index subjects from the first generation, examined in the Malmö Diet Cancer Study during 1991 to 1996. This will provide rich data and opportunities to analyse family traits of chronic disease across three generations. We will provide extensive genotyping and phenotyping including cardiovascular and respiratory function, as well as markers of glucose metabolism. In addition, also cognitive function will be assessed. A 4-day online dietary recall will be conducted and gut as well as oral microbiota analysed. The ambition is to provide one of the first large-scale European family studies with individual data across three generations, which could deepen our knowledge about the role of family traits for chronic disease and its underlying mechanisms. Electronic supplementary material The online version of this article (10.1007/s10654-020-00695-4) contains supplementary material, which is available to authorized users.

Although the causality of the obesity--hypertension association is established, the potential for prevention is not. We hypothesized that weight gain between early adulthood and mid-life is associated with higher mid-life blood pressure.We investigated the hypothesis using a large contemporaneous population-based mid-life cohort of men and women aged 50-64 years. Recalled body weight at age 20 years was self-reported, and mid-life body weight and office blood pressures were measured in accordance with a detailed protocol.On average, men had gained 14.9 (95% CI 14.6-15.2) kg of weight, and women 14.6 (95% CI 14.4-14.9) kg, between age 20 years and the mid-life examination, corresponding to 0.40 (95% CI 0.39-0.41) kg/year for men and women. Both weight at age 20 years and weight at the mid-life examination were associated with mid-life blood pressures. On average, a 10 kg weight increase between age 20 years and mid-life was associated with 2.2 (95% CI 0.9-3.5) mmHg higher systolic and 1.7 (95% CI 0.9-2.5) mmHg higher diastolic mid-life blood pressure in men, and 3.2 (2.5-4.0) mmHg higher systolic and 2.4 (1.9-2.9) mmHg higher diastolic mid-life blood pressure in women. Mid-life weight was more closely associated than weight at age 20 years with mid-life blood pressure. For a given mid-life weight, blood pressure was higher in persons with higher weight gain from age 20 years.In sum, weight gain between early adulthood and mid-life was associated with higher mid-life blood pressure. The magnitude of the association indicates a potentially great public health impact of strategies to prevent weight gain throughout adulthood.

AIM: The metabolite 3-Carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF) is a fatty fish-intake biomarker. We investigated the association between plasma levels of CMPF in relation to gingival inflammation and periodontitis case definition, as well as extent and severity variables. METHODS: The Malmö Offspring Study (MOS) is a population-based study, and the Malmö Offspring Dental Study (MODS) is its dental arm, including periodontal charting. Plasma CMPF was measured using liquid chromatography-mass spectrometry and studied in relation to periodontal diagnosis and parameters using multivariable linear or logistic regression modelling adjusting for age, sex, education, BMI, fasting glucose and smoking. RESULTS: Metabolite data were available for 922 MODS participants. Higher CMPF levels were associated with less gingival inflammation (beta -2.12, p=0.002), and lower odds of severe periodontitis (OR 0.74, 95% CI=0.56-0.98). Higher CMPF levels were also associated with more teeth (beta 0.19, p=0.001), lower number of periodontal pockets (>4 mm) (beta -1.07, p=0.007) and lower odds of having two or more >6 mm periodontal pockets (OR 0.80, 95% CI=0.65-0.98) in fully adjusted models. CONCLUSION: CMPF, a validated biomarker of fatty fish consumption, is associated with less periodontal inflammation and periodontitis. Residual confounding cannot be ruled out and future studies are warranted. This article is protected by copyright. All rights reserved.

Objectives: Coronary artery calcium score (CACS) is a marker of subclinical atherosclerosis. However, there is little data related to the association between arterial stiffness and CACS in the general population. The aim of this study was to explore the association between carotid femoral-pulse wave velocity (c-f PWV), a widely accepted marker of arterial stiffness, and CACS. Methods: Participants with complete measurements on c-f PWV, CACS and confounding variables from the Swedish CArdioPulmonary biolmage Study (SCAPIS) cohort were included in the final study population (n=8725). CACS was divided into three categories (10 and 100) and multinomial logistic regression was performed to explore the association between these categories of CACS and quartiles of c-f PWV, and for per one standard deviation (SD) increment of c-f PWV. Results: CACS 10 and 100 were present in 69.3, 17.8 and 12.9% of the study population, respectively. The odds ratio (OR) for CACS >100 for the fourth quartile (Q4) of c-f PWV vs. Q1 (reference category) was 1.62 (95% confidence interval [CI] 1.25-2.12) after adjustments. One standard deviation increase in c-f PWV was independently associated with a higher odds of having a CACS category >100 (OR: 1.25, 95% CI 1.14-1.36) in the final multivariable model. Conclusion: c-f PWV is positively associated with increased risk of higher CACS, and can be valuable in identifying individuals at risk for sub-clinical atherosclerosis. Funding Agencies|Swedish Heart and Lung Foundation [2016-0315]; Knut and Alice Wallenberg Foundation [2014-0047]; Swedish Research Council [822-2013-2000]; VINNOVA (Swedens Innovation agency) [2012-04476]; University of Gothenburg; Swedish Heart Lung foundation; Sahlgrenska University Hospital; Karolinska Institutet; Stockholm county council; Linkoping University; University Hospital; Lund University; Skane University Hospital; Umea University; University Hospital, Uppsala University

The factors that influence the atherosclerotic disease process in high-risk individuals remain poorly understood. Here, we used a combination of vascular imaging, risk factor assessment, and biomarkers to identify factors associated with 3-year change in carotid disease severity in a cohort of high-risk subjects treated with preventive therapy (n = 865). The results show that changes in intima-media thickness (IMT) are most pronounced in the carotid bulb. Progression of bulb IMT demonstrates independent associations with baseline bulb IMT, the plaque gray scale median (GSM), and the plasma level of platelet-derived growth factor (PDGF) (standardized β-coefficients and 95% confidence interval [CI] −0.14 [−0.06 to −0.02] p = 0.001, 0.15 [0.02–0.07] p = 0.001, and 0.20 [0.03–0.07] p < 0.001, respectively). Plasma PDGF correlates with the plaque GSM (0.23 [0.15–0.29] p < 0.001). These observations provide insight into the atherosclerotic process in high-risk subjects by showing that progression primarily occurs in fibrotic plaques and is associated with increased levels of PDGF.

BACKGROUND AND AIM: Lead exposure is associated with an increased risk of cardiovascular mortality. Atherosclerosis has been hypothesized to be one mechanism underlying this association. Recently, ...

BACKGROUND AND AIM: The general population is ubiquitously exposed to cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infar...

BackgroundLow resting heart rate and premature atrial contractions (PACs) predict incident atrial fibrillation (AF) and could be interdependent, since PACs occur in the gaps between normal beats.ObjectiveTo study the association between low heart rate at 24hECG, PACs and incident AF in a prospective population-based cohort.MethodsIn the Malmö Diet and Cancer study, 24hECGs were performed in 377 AF-free subjects. The endpoint was clinical AF retrieved from national hospital (mean follow-up 17 years). The interaction between increased supraventricular activity (SVA) top quartile of either PACs/hour or supraventricular tachycardias/hour) and mean heart rate (mHR) as regards AF risk was assessed in multivariable Cox regression analyses adjusted for age, sex, height, BMI, systolic blood pressure, antihypertensive medication, smoking and homeostasis model assessment of insulin resistance.ResultsThere were 80 (21%) incident cases of AF. Below median mHR (80 bpm/75 bpm for women/men) was associated with increased AF incidence (HR: 1.89, 95% CI 1.18 to 3.02, p=0.008). There was no correlation between mHR and SVA (p=0.6) or evidence of a multiplicative interaction between these factors for AF risk (p for interaction=0.6) In the group with both increased SVA and below median mHR (17% of the population) the relative risk of AF was very high (HR 4.5, 95% CI 2.2 to 9.1, p=0.001).ConclusionLow mHR at 24hECG independently predicts AF, but there is no association between mHR and SVA, and these factors are independent as regards AF risk. Subjects with both low mHR and increased SVA have high AF risk.

OBJECTIVES: Elevated plasma levels of the vasodilating hormone adrenomedullin (ADM) predict cardiovascular disease and have been associated with hypertension and obesity. We aimed to examine the independent relationship between ADM and the progression of major cardiometabolic risk factors during long-term follow-up. METHODS: We studied midregional pro-ADM (MR-proADM) in fasting plasma in 3298 participants from the population-based Malmo Diet and Cancer Study - Cardiovascular Cohort, re-examined after 17 years of follow-up and related baseline MR-proADM to cardiometabolic risk factors cross-sectionally and longitudinally. RESULTS: At baseline, after full adjustment, each SD increment of MR-proADM was independently related to (beta ± standard error, P value) higher SBP (0.956 ± 0.319 mmHg, P = 0.003), BMI (0.912 ± 0.061 kg/m, P = 1.42 × 10), waist (2.28 ± 0.158 cm, P = 8.46 × 10) and fasting blood glucose (0.046 ± 0.018 mmol/l, P = 0.01). After full adjustment, including the baseline level of the risk factor whose degree of progression was studied, each SD increment of MR-proADM predicted significantly reduced progression of SBP (-1.170 ± 0.337 mmHg, P = 0.001) and fasting blood glucose (-0.055 ± 0.023 mmol/l, P = 0.015), but greater increase of BMI (0.101 ± 0.051 kg/m, P = 0.047) and waist (0.600 ± 0.144 cm, P = 3.1 × 10). CONCLUSION: Despite cross-sectional associations with higher levels of blood pressure and glucose, high levels of MR-proADM predict a slower progression of blood pressure and glycemia during long-term follow-up. Conversely, the cross-sectional associations with higher levels of MR-proADM and obesity were paralleled by a faster progression of obesity markers over time. These results may be important for assessment of long-term effects of therapies modulating levels of ADM. (Less)

Background Circulating C3 has been associated with diabetes and hypertension, which are the leading causes of chronic kidney disease (CKD). C3 activation is considered to contribute to several renal diseases. Here we examined whether elevated C3 concentration is associated with hospitalization due to CKD in the general population, and whether this relationship is mediated by factors such as diabetes and hypertension. Methods Baseline plasma C3 was quantified in 4552 participants, without previous hospital admission due to CKD, from the Malmö Diet and Cancer cohort study. Incidence of first hospitalization due to CKD (main diagnosis) was investigated in relation to C3 levels using Cox proportional hazards regression models after a mean follow-up of 19.2 ± 4.16 years. Traditional risk factors of CKD including diabetes, blood pressure, C-reactive protein and baseline renal function were considered in adjustments and sensitivity analyses. Results During the follow-up period, 94 subjects were admitted to hospital due to CKD. After multivariate adjustment, the hazard ratios (95% confidence interval) for hospitalization from CKD across quartiles of C3 were 1.00 (reference), 1.68 (0.69, 4.13), 2.71 (1.15, 6.39), and 3.16 (1.36, 7.34) (p for trend = 0.003). Results were generally consistent across different sensitivity analyses. Conclusions These findings indicate that C3 is associated with incidence of first hospitalization due to CKD in the general population. The observed relationship cannot be entirely attributed to hyperglycemia and hypertension.

Background: The general population is ubiquitously exposed to the toxic metal cadmium through the diet and smoking. Cadmium exposure is associated with increased morbidity and mortality in myocardial infarction and stroke. Atherosclerosis is the main underlying mechanism of myocardial infarction. However, associations between cadmium and coronary artery atherosclerosis have not been examined. Objectives: Our study sought to examine the hypothesis that blood cadmium (B-Cd) is positively associated with coronary artery calcification, as a measure of coronary artery atherosclerosis in the population-based Swedish SCAPIS study. Methods: Our analysis included 5,627 individuals (51% women), age 50–64 y, enrolled from 2013 to 2018. The coronary artery calcium score (CACS) was obtained from computed tomography. Blood cadmium was determined by inductively coupled plasma mass spectrometry (ICP-MS). Associations between B-Cd and coronary artery calcium score (CACS Agatston score) were evaluated using prevalence ratios (PRs) in models adjusted for sex, age, smoking, hypertension, diabetes, low-density cholesterol/high-density cholesterol ratio, and family history. Results: The median B-Cd concentration was 0.24μg/L. The prevalence of positive coronary artery calcium (CACS>0) was 41% and the prevalence of CACS≥100 was 13%. Relative to the lowest quartile (Q) of B-Cd (0 (PR 1.1; 95% CI: 1.0, 1.3), and a greater relative increase in CACS≥100 (PR 1.6; 95% CI: 1.3, 2.0). When restricted to 2,446 never-smokers, corresponding PRs were 1.1 (95% CI 0.9, 1.3) for CACS>0 (63 cases in Q4) and 1.7 (95% CI 1.1, 2.7) for CACS≥100 (17 cases in Q4). Discussion: Blood cadmium in the highest quartile was associated with CACS in a general population sample with low to moderate cadmium exposure. This supports the hypothesis that atherosclerosis is an important mechanism underlying the associations between cadmium and incident cardiovascular disease. The findings suggest that public health measures to reduce cadmium exposure are warranted. https://doi.org/10.1289/EHP8523

Low-grade inflammation and arterial stiffness are key factors in the development of vascular aging. However, the interplay between arterial stiffness and inflammation for cardiovascular (CV) disease is unclear. Aortic pulse wave velocity (aPWV) and the inflammatory markers, high-sensitivity C-reactive protein (CRP) and orosomucoid, were measured in 2710 participants (median age: 72 years). These participants were followed up for a mean of 7.6 years for a composite CV disease end point. Per 1 interquartile range increment of CRP and orosomucoid, respectively, aPWV increased by 0.19 m/s (95% CI: 0.07-0.32) and 0.19 m/s (0.11-0.27), after multifactorial adjustment. Mediation analysis showed that aPWV, after multifactorial adjustment, mediated 8% (−4, 20) of the CV disease risk associated with CRP and 8% (−4, 18) of orosomucoid risk. The associated risk increased with combinations of high aPWV and high CRP or orosomucoid. We found no evidence that arterial PWV acted as an important mediator of the relationship between systemic inflammation and CV disease risk in this elderly population. The results instead indicate an additive effect. Our study supports the view that arterial stiffness and chronic inflammation affects CV risk mainly through separate causal pathways.

Background: Arterial ageing is characterised by degradation of elastic fibres and increased stiffness of elastic arteries. Although low lung function and arterial stiffness are strongly related to age, the association between lung function and arterial ageing has not been widely explored. We used a large population-based study of 50-64 year olds to assess the association between lung function (measured by spirometry and CO diffusing capacity (D-LCO)) and arterial stiffness (measured by carotid-femoral pulse-wave velocity (c-f PWV)). Methods: Participants from the Swedish CArdioPulmonary bioImage Study (SCAPIS) cohort with information on spirometry (n = 8941) and D-LCO (n = 8616) were included. General linear models (lung function quartiles) and linear regression was used to determine the association between lung function and c-f PWV. Results: FEV1 (L), FVC (L), D-LCO (mmol/(min kPa)) and D-LCO/V-A (mmol/(min kPa L)) were significantly and inversely associated with c-f PWV after adjustments; mean PWV (m/s) in Q1 (highest lung function) vs Q4: FEV1; 8.45 vs 8.60, p-value 0.001; FVC; 8.45 vs 8.57, p-value 0.018; D-LCO; 8.46 vs 8.60, p-value 0.002; and D-LCO/V-A; 8.47 vs 8.58, p-value 0.001. In sex-stratified analyses, significant findings were reflected for FEV1 and D-LCO in men only. The results remained significant for D-LCO in all never smokers and in all participants without COPD or airflow limitation on spirometry. Conclusions: A reduction in spirometry and D-LCO is associated with elevated arterial stiffness in middle-aged men. A reduction in D-LCO is associated with higher c-f PWV even in never smokers and in those without COPD or airflow limitation on spirometry. Funding Agencies|Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2014-0047]; Swedish Research CouncilSwedish Research CouncilEuropean Commission [822-2013-2000, 2019-01236]; VINNOVA (Swedens Innovation agency)Vinnova [2012-04476]; Linoping University and University Hospital; Lund University; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation [2020-0173]; Skane University Hospital; Swedish Heart and Lung FoundationSwedish Heart-Lung Foundation

Postural orthostatic tachycardia syndrome (POTS) is a cardiovascular autonomic disorder with poorly understood etiology and underlying pathophysiology. Since cardiovascular morbidity has been linked to growth hormone (GH), we studied GH levels in patients with POTS. We conducted an age-sex-matched case–control study in patients with POTS (age 31 ± 9 years; n = 42) and healthy controls (32 ± 9 years; n = 46). Plasma GH levels were measured using high-sensitivity chemiluminescence sandwich immunoassay. The burden of orthostatic intolerance symptoms was assessed by the Orthostatic Hypotension Questionnaire (OHQ), consisting of a symptom assessment scale (OHSA) and a daily activity scale (OHDAS). POTS patients had significantly higher composite OHQ score than controls, more symptoms and less activity. Supine heart rate and diastolic blood pressure (BP), but not systolic BP, were significantly higher in POTS. Median plasma GH levels were significantly lower in POTS (0.53 ng/mL) than controls (2.33 ng/mL, p = 0.04). GH levels were inversely related to OHDAS in POTS and supine systolic BP in POTS and controls, but not heart rate neither group. POTS is associated with lower GH levels. Impairment of daily life activities is inversely related with GH in POTS. A higher supine diastolic BP is inversely associated with GH levels in POTS and healthy individuals.

Background Although coronary events (CE) and ischemic stroke share many risk factors, there are also some important differences. The aim of this paper was to assess the association of risk factors in relation to incident CE and ischemic stroke and to evaluate the heterogeneity in patterns of risk factors between the two outcomes. Method Traditional risk factors and inflammatory markers associated with coronary events and ischemic stroke were measured in the Malmö Diet and Cancer Cohort (MDCS, n = 26 519), where a total of 2270 incident ischemic stroke and 3087 incident CE occurred during a mean follow up time 19 ± 6 years, and in relation to inflammatory markers in the cardiovascular sub-cohort (MDC-CV, n = 4795). Cox regression analysis was used to obtain hazard ratios. A modified Lunn-McNeil competing risk analysis was conducted to assess the significance of any differences in risk profiles of these outcomes. Results Most cardiovascular risk factors were associated both with incident CE and ischemic stroke. However, current smoking, ApoB, low ApoA1, male sex and education level of ≤ 9 years of schooling were preferentially associated with CE compared to ischemic stroke. Conversely, age showed a stronger association with ischemic stroke than with CE. Conclusion CE and ischemic stroke have broadly similar risk factors profiles. However, there are some important differential associations, as well as substantial differences in the magnitude of the association. These could reflect the distinct biology of atherogenesis in different vascular beds. The difference in the determinants highlights the importance of looking at CE and ischemic stroke, two manifestations of cardiovascular disease, separately.

Supplemental Digital Content is available in the text., 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.

Background It is not clear if the European Systematic Coronary Risk Evaluation algorithm is useful for identifying prevalent subclinical atherosclerosis in a population of apparently healthy individuals. Our aim was to explore the association between the risk estimates from Systematic Coronary Risk Evaluation and prevalent subclinical atherosclerosis. Design The design of this study was as a cross-sectional analysis from a population-based study cohort. Methods From the general population, the Swedish Cardiopulmonary Bioimage Study randomly invited individuals aged 50-64 years and enrolled 13,411 participants mean age 57 (standard deviation 4.3) years; 46% males between November 2013-December 2016. Associations between Systematic Coronary Risk Evaluation risk estimates and coronary artery calcification and plaques in the carotid arteries by using imaging data from a computed tomography of the heart and ultrasonography of the carotid arteries were examined. Results Coronary calcification was present in 39.5% and carotid plaque in 56.0%. In men, coronary artery calcium score amp;gt;0 ranged from 40.7-65.9% and presence of carotid plaques from 54.5% to 72.8% in the age group 50-54 and 60-65 years, respectively. In women, the corresponding difference was from 17.1-38.9% and from 41.0-58.4%. A doubling of Systematic Coronary Risk Evaluation was associated with an increased probability to have coronary artery calcium score amp;gt;0 (odds ratio: 2.18 (95% confidence interval 2.07-2.30)) and to have amp;gt;1 carotid plaques (1.67 (1.61-1.74)). Conclusion Systematic Coronary Risk Evaluation estimated risk is associated with prevalent subclinical atherosclerosis in two major vascular beds in a general population sample without established cardiovascular disease or diabetes mellitus. Thus, the Systematic Coronary Risk Evaluation risk chart may be of use for estimating the risk of subclinical atherosclerosis. Funding Agencies|Swedish Heart-Lung FoundationSwedish Heart-Lung Foundation [2019-0012]; Knut and Alice Wallenberg FoundationKnut & Alice Wallenberg Foundation [2014-0047]; Swedish Research CouncilSwedish Research Council [822-2013-2000]; VINNOVA (Swedens Innovation agency)Vinnova [2012-04476]; University of Gothenburg; Sahlgrenska University Hospital; Karolinska InstitutetKarolinska Institutet; Karolinska University HospitalKarolinska Institutet; Linkoping University; University Hospital; Lund University; Skane University Hospital; Swedish Heart Lung FoundationSwedish Heart-Lung Foundation; Swedish government [ALFGBG-718851, ALF-VLL-548791, ALF-LIO-700841]; county councils, the ALF-agreement [ALFGBG-718851, ALF-VLL-548791, ALF-LIO-700841]; AFA Insurance [160334]

Objective: While existing evidence supports beneficial cardiovascular effects of glucagon-like peptide-1 (GLP-1), emerging studies suggest that glucose-dependent insulinotropic peptide (GIP) and/or signaling via the GIP receptor may have untoward cardiovascular effects. Indeed, recent studies show that fasting physiological GIP levels are associated with total mortality and cardiovascular mortality, and it was suggested that GIP plays a role in pathogenesis of coronary artery disease.. We investigated the associations between fasting and post-challenge GIP and GLP-1 concentrations and subclinical atherosclerosis as measured by intima-media thickness in the common carotid artery (IMTmeanCCA), and intima-media thickness in the carotid bifurcation (IMTmaxBulb). Research design and methods: Participants at re-examination within the Malmö Diet and Cancer cardiovascular cohort study (n=3734, mean age 72.5 years; 59.3% women; 10.8% subjects with diabetes; fasting GIP available for 3342 subjects; fasting GLP-1 available for 3299 subjects) underwent oral glucose tolerance testing and carotid ultrasound. Results: In linear regression analyses, each 1 SD increment of fasting GIP was associated with increased (per mm) IMTmeanCCA (β=0.010, p=0.010) and IMTmaxBulb (β=0.014; p=0.040) in models adjusted for known risk factors and glucose metabolism. In contrast, each 1 SD increment of fasting GLP-1 was associated with decreased IMTmaxBulb (per mm; β=-0.016, p=0.014). These associations remained significant when subjects with diabetes were excluded from analyses. Conclusion In a Swedish elderly population, physiologically elevated levels of fasting GIP are associated with increased IMTmeanCCA, while GLP-1 is associated with decreased IMTmaxBulb, further emphasizing diverging cardiovascular effects of these two incretin hormones.

Even though abdominal aortic aneurysm (AAA) and coronary heart disease (CHD) are both related to atherosclerosis, there could be important differences in risk factors. Based on Malmö Diet and Cancer Cohort, the incidence of AAA and CHD was followed prospectively. Cox regression was used to calculate the association of each factor with AAA and CHD and hazards ratio were compared using a modified Lunn-McNeil method; 447 participants developed AAA and 3129 developed CHD. After multivariate adjustments, smoking, antihypertensive medications, lipid-lowing medications, systolic and diastolic blood pressures, apolipoprotein (Apo) A1 (inversely), ApoB, ApoB/ApoA1 ratio, total leukocyte count, neutrophil count, and neutrophil to lymphocyte ratio were associated with the risks of both AAA and CHD. When comparing risk factor profiles for the 2 diseases, smoking, diastolic blood pressure, ApoA1, and ApoB/ApoA1 ratio had stronger associations with risk of AAA than with risk of CHD, while diabetes and unmarried status showed increased risk of CHD, but not of AAA (all P values for equal association

Background Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive heart rate increase on standing and orthostatic intolerance. Previous data indicate autoimmune involvement. We studied serum activity against G protein–coupled receptors in relation to symptoms in patients with POTS and controls using a commercial cell‐based assay. Methods and Results Forty‐eight patients with POTS (aged 28.6±10.5 years; 44 women) and 25 healthy individuals (aged 30.7±8.6 years; 21 women) were included. The 10‐item Orthostatic Hypotension Questionnaire (OHQ) was completed by 33 patients with POTS and all controls. Human embryonic kidney 293 cells overexpressing one G protein–coupled receptor: adrenergic α 1 receptor, adrenergic β 2 receptor, cholinergic muscarinic type 2 receptor, and opioid receptor‐like 1 were treated with sera from all patients. Receptor response was analyzed using a β‐arrestin–linked transcription factor driving transgenic β‐lactamase transcription by fluorescence resonance energy transfer method. Receiver operating characteristic curves were constructed. G protein–coupled receptor activation was related to OHQ indices in linear regression models. Sera from patients with POTS activated all 4 receptors to a higher degree compared with controls ( P P 1 receptor activation associated with OHQ composite score (β=0.77 OHQ points per SD of activity, P =0.009) and with reduced tolerability for prolonged standing ( P =0.037) and walking for short ( P =0.042) or long ( P =0.001) periods. All 4 receptors were associated with vision problems ( P Conclusions Our results indicate the presence of circulating proteins activating adrenergic, muscarinic, and nociceptin receptors in patients with POTS. Serum‐mediated activation of these receptors has high predictive value for POTS. Activation of adrenergic α 1 receptor is associated with orthostatic symptoms severity in patients with POTS.

The aim of the study was to present the methodology, cohort demographics, and initial results of the Swedish SPinal Cord Injury Study on Cardiopulmonary and Autonomic Impairment (SPICA).The SPICA is based on the Swedish CArdioPulmonary BioImage Study, a study on cardiopulmonary diseases in a cohort of 30,000 people. The assessments in the SPICA cover the structure and function of the cardiopulmonary and autonomic systems using bioimaging and functional analyses, together with a study-specific questionnaire and generic and spinal cord injury-specific assessment tools. The inclusion criteria were as follows: age 50-65 yrs, traumatic spinal cord injury of 5 yrs or more, and injury levels C1-T6, American Spinal Injury Association Impairment Scale A-C.Of 38 potential participants, 25 comprised the final sample (20% women, mean age 58 yrs, mean time since injury 28 yrs). Eight percent had sustained a cardiovascular event, and 72% were classified as a high risk for cardiovascular disease. Asthma was previously diagnosed in only 8%, and none had chronic obstructive pulmonary disease.The risk for cardiovascular disease in people with severe high-level spinal cord injury is a major clinical concern. Forthcoming studies in the SPICA will provide new knowledge of cardiopulmonary health in this cohort, which can guide future research and be used to develop long-term management.

Aims/hypothesis Evidence that glucose-dependent insulinotropic peptide (GIP) and/or the GIP receptor (GIPR) are involved in cardiovascular biology is emerging. We hypothesised that GIP has untoward effects on cardiovascular biology, in contrast to glucagon-like peptide 1 (GLP-1), and therefore investigated the effects of GIP and GLP-1 concentrations on cardiovascular disease (CVD) and mortality risk. Methods GIP concentrations were successfully measured during OGTTs in two independent populations (Malmö Diet Cancer–Cardiovascular Cohort [MDC-CC] and Prevalence, Prediction and Prevention of Diabetes in Botnia [PPP-Botnia]) in a total of 8044 subjects. GLP-1 (n = 3625) was measured in MDC-CC. The incidence of CVD and mortality was assessed via national/regional registers or questionnaires. Further, a two-sample Mendelian randomisation (2SMR) analysis between the GIP pathway and outcomes (coronary artery disease [CAD] and myocardial infarction) was carried out using a GIP-associated genetic variant, rs1800437, as instrumental variable. An additional reverse 2SMR was performed with CAD as exposure variable and GIP as outcome variable, with the instrumental variables constructed from 114 known genetic risk variants for CAD. Results In meta-analyses, higher fasting levels of GIP were associated with risk of higher total mortality (HR[95% CI] = 1.22 [1.11, 1.35]; p = 4.5 × 10−5) and death from CVD (HR[95% CI] 1.30 [1.11, 1.52]; p = 0.001). In accordance, 2SMR analysis revealed that increasing GIP concentrations were associated with CAD and myocardial infarction, and an additional reverse 2SMR revealed no significant effect of CAD on GIP levels, thus confirming a possible effect solely of GIP on CAD. Conclusions/interpretation In two prospective, community-based studies, elevated levels of GIP were associated with greater risk of all-cause and cardiovascular mortality within 5–9 years of follow-up, whereas GLP-1 levels were not associated with excess risk. Further studies are warranted to determine the cardiovascular effects of GIP per se.