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Background: Aortic valve calcification (AVC) is an underlying pathophysiological mechanism in aortic stenosis, which shares many risk factors with diabetes. However, the association between dysglycemia and early stages of AVC remains unclear. The aim was to examine the associations between stages of dysglycemia and signs of AVC among middle-aged individuals from the general population.

Methods: This was a cross-sectional study from the Swedish CArdioPulmonary bioImage Study (SCAPIS) randomly enrolling 30,154 middle-aged men and women from six study sites in Sweden between 2013 and 2018. Glycemic status was based on the World Health Organization criteria (fasting blood glucose and/or HbA1c) and questionnaire-based answers on previous diseases and categorized as normoglycemia, prediabetes, newly detected diabetes and known diabetes. AVC was assessed on cardiac computed tomography (CT) and defined as evident or not.

Results: Of 29,331 individuals with data on glycemic status and AVC available, mean age was 57.5 years and normoglycemia was present in 76%, prediabetes in 16%, newly detected diabetes in 3% and known diabetes in 5%. The prevalence of AVC increased progressively across glycemic categories, particularly in males (8%, 11%, 14% and 17%; P < 0.01) compared to females (5%, 6%, 8% and 9%; P < 0.01). There was an association with AVC already in the early stages of dysglycemia; prediabetes (OR 1.16, 95% CI 1.02–1.31), newly detected diabetes (1.34 [1.05–1.71]) and known diabetes (1.61 [1.34–1.93]) after adjusting for age, sex, smoking, study site, low density lipoprotein-cholesterol and hypertension.

Conclusions: In this large, contemporary, and randomly selected population of middle-aged individuals, prediabetes, newly detected diabetes and known diabetes were all associated with CT-detected AVC. Further studies are warranted to investigate if managing dysglycemia, even in its early stages, may help slow down AVC progression.

Objectives: Although continuous positive airway pressure (CPAP) effectively prevents sleep apnea and reduces blood pressure, many patients do not use CPAP every night. This trial investigates cardiovascular effects after sleeping five nights without CPAP.

Methods: We randomized 100 patients (67 men and 33 women with a mean age 64±9 years) using CPAP treatment for moderate-to-severe sleep apnea to either withdraw treatment for five nights (n=50) or to continue with CPAP (n=50). The primary outcomes were arterial stiffness and 24h blood pressure.

Results: The 24h SBP increased by a mean of 2.8mmHg [95% confidence interval (CI) 0.2-5.4mmHg] (P=0.035) and DBP increased by a mean of 1.7mmHg (95% CI 0.1-3.3mmHg) (P=0.032) in the group without CPAP compared to the CPAP group. There was a significant effect on blood pressure in women but not in men. In women, SBP increased by 5.1mmHg (95% CI 1.0-9.5mmHg) (P=0.017) and DBP by 2.9mmHg (95% CI 0.4-5.6mmHg) (P=0.029). Arterial stiffness remained unaffected. Secondary outcomes that worsened in patients without CPAP included apnea-hypopnea index, oxygen desaturation index, hemoglobin levels, and daytime sleepiness.

Conclusion: Blood pressure is affected after five nights of CPAP interruption, along with a rapid return of sleep apneas, nocturnal hypoxic events, daytime sleepiness and increased hemoglobin levels, but arterial stiffness was not affected. Blood pressure was affected in women only, suggesting a sex-related CPAP effect on blood pressure.

Purpose: Myocardial infarctions (MIs) can occur in underlying obstructive coronary artery disease (MI-CAD) or in non-obstructive coronary arteries (MINOCA). The primary objectives of the study were to investigate the prevalence of MI-CAD and MINOCA in people with CAL, and to explore if CAL is an independent risk factor for MI-CAD and MINOCA. Secondary objectives were to explore these research questions stratified by sex and by smoking history.

Patients and Methods: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of people aged 50–64 years. CAL was defined as a post-bronchodilator ratio of forced expiratory volume in one second and forced vital capacity below 0.70. MI-CAD was defined as a self-reported MI with coronary computed tomography angiography findings of previous revascularization or at least one significant coronary stenosis (>50%), and MINOCA as self-reported MI with no previous revascularization and no significant coronary stenosis.

Results: In total, 1735 (8.3%) of 20,882 included participants had CAL. MI-CAD was more common than MINOCA both in people with (2.8 vs 0.6%) and without CAL (1.2 vs 0.3%). Compared with those without CAL, people with CAL had an almost doubled independent risk of both MI-CAD ([adjusted OR] 1.72; [95% CI] 1.22–2.42) and MINOCA (1.99; 1.02–3.86). In men, CAL was associated with increased risk of MINOCA (2.63; 1.23–5.64), and in women with increased risk for MI-CAD (3.43; 1.68–1.26).

Conclusion: Middle-aged people with CAL have an almost doubled risk of both MI-CAD and MINOCA, compared with people without CAL. In contrast to people without CAL, the risk of MINOCA is increased in men and the risk of MI-CAD is increased in women. In a clinical context, both MI types should be considered in CAL.

Background: Systemic sclerosis (SSc) is an autoimmune disease characterized by fibrosis of the skin and internal organs, mostly affecting young and middle-aged women. Significant questions remain as to its pathogenesis, especially the triggers for the associated interstitial lung disease (SSc-ILD). We examined the extent to which SSc and SSc-ILD were related to oxidative stress and altered metal homeostasis at the air-lung interface.

Methods: In this case-control study, we recruited 20 SSc patients, of which 11 had SSc-ILD. Eighteen healthy individuals were recruited as age-matched healthy controls, for a total of 38 study participants. Low molecular weight antioxidants (ascorbate, urate and glutathione), metal transport and chelation proteins (transferrin and ferritin) and metals (Fe and Cu) concentrations, including a measure of the catalytically active metal pool, were determined in respiratory tract lining fluid (RTLF) collected by bronchoalveolar lavage from the SSc group and compared with healthy controls.

Results: In the SSc group, 14 individuals were of female sex (70%) and the median age was 57 years (range 35–75). We observed evidence of oxidative stress in the RTLFs of SSc patients, characterised by increased concentrations of glutathione disulphide (GSSG, P<0.01), dehydroascorbate (DHA, P<0.05) and urate (P<0.01). This was associated with elevated RTLF Fe (P=0.07) and Cu (P<0.001), and evidence of a catalytic metal pool, demonstrated by an enhanced rate of ascorbate oxidation in the recovered lavage fluid (p<0.01). Cu concentrations were significantly associated with the ascorbate depletion rate (r=0.76, P<0.001), and GSSG (r=0.38, P<0.05) and protein carbonyl (r=0.44, P<0.01) concentrations. Whilst these markers were all increased in SSc patients, we found no evidence for an association with SSc-ILD.

Conclusions: These data confirm the presence of oxidative stress in the airways of SSc patients and, for the first time, suggest that an underlying defect in metal homeostasis at the air-lung interface may play a role in disease progression.

Objectives: The adipocyte-derived hormone leptin has been associated with the pathogenesis of cardiovascular disease. The mechanisms underlying this association are unclear but may relate to effects on the vascular endothelium. Our aim was to explore the effects of leptin on endothelial vasomotor and fibrinolytic function in healthy volunteers and patients with coronary artery disease.

Design: The vascular effects of leptin were assessed infusing recombinant human leptin in healthy volunteers during measuring vasomotor response by venous occlusion plethysmography. Additionally, circulating levels of leptin were analysed in relation to endothelial dysfunction in patients with established coronary artery disease.

Results: In healthy male volunteers, intra-arterial infusion of recombinant human leptin (80, 800 and 8,000 ng/min; n = 10) did not affect basal forearm blood flow, plasma tissue plasminogen activator (tPA) or plasminogen activator inhibitor type 1 concentrations (all p > 0.05). However, during concomitant co-infusion with leptin (800 ng/min; n = 10), drug-induced vasodilatation was reduced (p = 0.001), and tPA activity increased (p = 0.002). In patients with coronary artery disease, those with the high plasma leptin levels had reduced drug-induced vasodilatation (p < 0.001), and increased net release of tPA antigen and activity (p < 0.001 and p = 0.03, respectively) compared to those with low levels. The study has been registered retrospectively at Clinical Trials with number NCT04374500.

Conclusion: Intrabrachial leptin infusion did not affect the basal vascular tone, whereas acute and chronic hyperleptinemia was associated with blunted vasoreactivity in healthy volunteers, and in patients with coronary artery disease.

Background: Exposure to standard petrodiesel exhaust is linked to adverse health effects. Moreover, there is a mounting request to replace fossil-based fuels with renewable and sustainable alternatives and, therefore, rapeseed methyl ester (RME) and other biofuels have been introduced. However, recent toxicological research has indicated that biodiesel exhaust may also induce adverse health-related events.

Aim: To determine whether exposure to 100% RME biodiesel (BD100) exhaust would cause an acute airway neutrophilic recruitment in humans.

Methods: Fourteen healthy subjects underwent exposure to diluted BD100 exhaust and filtered air for 1-h, in a blinded, random fashion. Bronchoscopy with endobronchial mucosal biopsies, bronchial wash (BW) and bronchoalveolar lavage (BAL) was performed six hours after exposure. Differential cell counts and inflammatory markers were determined in the supernatant and biopsies were stained immunohistochemically.

Results: Compared with filtered air, BD100 exhaust exposure increased bronchial mucosal endothelial P-selectin adhesion molecule expression, as well as neutrophil, mast cell and CD68 + macrophage numbers. An increased influx of neutrophils and machrophages was also seen in BW.

Conclusion: Exposure to biodiesel exhaust was associated with an acute airway inflammation that appeared similar to preceding petrodiesel exposure studies. The present findings, together with the recently reported adverse cardiovascular effects after similar biodiesel exposure, indicate that biodiesel is not free of toxicity and may affect human health.

Background: The ankle–brachial index (ABI) is the ratio of the ankle and brachial systolic blood pressures. In the clinical setting, low ABI (< 0.9) is an indicator of peripheral atherosclerosis, while high ABI (> 1.4) is a sign of arterial stiffness and calcification. The purpose of the current study was to investigate the association between ABI and physical activity levels, measured by accelerometer.

Methods: The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a Swedish nationwide population-based cross-sectional cohort for the study of cardiovascular and pulmonary diseases, in which individuals aged 50–64 years were randomly invited from the general population. The study population with data on ABI, physical activity, and sedentary time based on accelerometry was 27,737. Differences between ABI categories and associations to sedentary behavior, moderate to vigorous physical activity (MVPA), and other metabolic characteristics were compared. ABI was categorized as low, ABI ≤ 0.9, borderline, ABI 0.91–0.99, normal, ABI 1.0-1.39, and high, ABI ≥ 1.4.

Results: Prevalence of low ABI was higher in the most sedentary quartiles compared to the least sedentary (0.6% vs. 0.1%, p < 0.001). The most sedentary individuals also exhibited higher BMI, higher prevalence of diabetes and hypertension. The proportion of wake time spent in MVPA was lowest in those with low ABI (0.033 ± 0.004; p < 0.001) and highest in those with ABI > 1.4 (0.069 ± 0.001; p < 0.001) compared to those with normal ABI. Compared to normal ABI, the proportion of sedentary time was highest in those with low ABI (0.597 ± 0.012; p < 0.001) and lowest in those with ABI > 1.4 (0.534 ± 0.002; p = 0.004).

Conclusion: This population-based study shows that middle-aged individuals with ABI > 1.4 have the highest level of physical activity, while individuals with a lower ABI, especially those with ABI < 0.9, are less active and spend more time sedentary. Future studies are needed to understand the relationships between ABI, physical activity, and the risk of peripheral arterial and cardiovascular disease in the general population.

Background: Breathlessness is common in the population and can be related to a range of medical conditions. We aimed to evaluate the burden of breathlessness related to different medical conditions in a middle-aged population.

Methods: Cross-sectional analysis of the population-based Swedish CArdioPulmonary bioImage Study of adults aged 50–64 years. Breathlessness (modified Medical Research Council [mMRC] ≥ 2) was evaluated in relation to self-reported symptoms, stress, depression; physician-diagnosed conditions; measured body mass index (BMI), spirometry, venous haemoglobin concentration, coronary artery calcification and stenosis [computer tomography (CT) angiography], and pulmonary emphysema (high-resolution CT). For each condition, the prevalence and breathlessness population attributable fraction (PAF) were calculated, overall and by sex, smoking history, and presence/absence of self-reported cardiorespiratory disease.

Results: We included 25,948 people aged 57.5 ± [SD] 4.4; 51% women; 37% former and 12% current smokers; 43% overweight (BMI 25.0–29.9), 21% obese (BMI ≥ 30); 25% with respiratory disease, 14% depression, 9% cardiac disease, and 3% anemia. Breathlessness was present in 3.7%. Medical conditions most strongly related to the breathlessness prevalence were (PAF 95%CI): overweight and obesity (59.6–66.0%), stress (31.6–76.8%), respiratory disease (20.1–37.1%), depression (17.1–26.6%), cardiac disease (6.3–12.7%), anemia (0.8–3.3%), and peripheral arterial disease (0.3–0.8%). Stress was the main factor in women and current smokers.

Conclusion: Breathlessness mainly relates to overweight/obesity and stress and to a lesser extent to comorbidities like respiratory, depressive, and cardiac disorders among middle-aged people in a high-income setting—supporting the importance of lifestyle interventions to reduce the burden of breathlessness in the population.

Background: Breathlessness is a troublesome and prevalent symptom in the population, but knowledge of related factors is scarce. The aim of this study was to identify the factors most strongly associated with breathlessness in the general population and to describe the shapes of the associations between the main factors and breathlessness.

Methods: A cross-sectional analysis was carried out of the multicentre population-based Swedish CArdioPulmonary bioImage Study (SCAPIS) of adults aged 50 to 64 years. Breathlessness was defined as a modified Medical Research Council breathlessness rating ⩾2. The machine learning algorithm extreme gradient boosting (XGBoost) was used to classify participants as either breathless or nonbreathless using 449 factors, including physiological measurements, blood samples, computed tomography cardiac and lung measurements, lifestyle, health conditions and socioeconomics. The strength of the associations between the factors and breathlessness were measured by SHapley Additive exPlanations (SHAP), with higher scores reflecting stronger associations.

Results :A total of 28 730 participants (52% women) were included in the study. The strongest associated factors for breathlessness were (in order of magnitude): body mass index (SHAP score 0.39), forced expiratory volume in 1 s (0.32), physical activity measured by accelerometery (0.27), sleep apnoea (0.22), diffusing lung capacity for carbon monoxide (0.21), self-reported physical activity (0.17), chest pain when hurrying (0.17), high-sensitivity C-reactive protein (0.17), recent weight change (0.14) and cough (0.13).

Conclusion: This large population-based study of men and women aged 50–64 years identified the main factors related to breathlessness that may be prevented or amenable to public health interventions.

In urban areas, inhalation of fine particles from combustion sources such as diesel engines causes adverse health effects. For toxicity testing, a substantial amount of particulate matter (PM) is needed. Conventional sampling involves collection of PM onto substrates by filtration or inertial impaction. A major drawback to those methodologies is that the extraction process can modify the collected particles and alter their chemical composition. Moreover, prior to toxicity testing, PM samples need to be resuspended, which can alter the PM sample even further. Lastly, the choice of the resuspension medium may also impact the detected toxicological responses. In this study, we compared the toxicity profile of PM obtained from two alternative sampling systems, using in vitro toxicity assays. One system makes use of condensational growth before collection in water in an impinger – BioSampler (CG-BioSampler), and the other, a Dekati® Gravimetric Impactor (DGI), is based on inertial impaction. In addition, various methods for resuspension of DGI collected PM were compared. Tested endpoints included cytotoxicity, formation of cellular reactive oxygen species, and genotoxicity. The alternative collection and suspension methods affected different toxicological endpoints. The water/dimethyl sulfoxide mixture and cell culture medium resuspended particles, along with the CG-BioSampler sample, produced the strongest responses. The water resuspended sample from the DGI appeared least toxic. CG-BioSampler collected PM caused a clear increased response in apoptotic cell death. We conclude that the CG-BioSampler PM sampler is a promising alternative to inertial impaction sampling.