Viktor Hamrefors

Background: Diffusing capacity for carbon monoxide (D _LCO ) is a measure of gas exchange in the lungs. Reduced D _LCO with normal spirometry is a common finding that is incompletely understood. Aim: To assess determinants of isolated, reduced D _LCO in an unselected population. Methods: The Swedish CArdioPulmonary bioImage Study (SCAPIS) is a multicentre population-based study of adults aged 50–64 years. The 5th percentile of D _LCO in healthy never smokers was used as the lower limit of normal (LLN). Using multivariable analysis, we studied factors associated with D _LCO < LLN in 24 261 subjects with normal spirometry, defined as FEV1, FVC and FEV1/FVC > LLN. Emphysema and interstitial lung abnormalities (ILA) were assessed through computed tomography, physical activity through accelerometry and other factors through questionnaires. Results: Isolated D _LCO < LLN ( n = 1 472) was independently associated with emphysema (odds ratio and 95% confidence interval: 2.6 (2.2, 3.2)), lung disease other than asthma or COPD (1.8 (1.2, 2.8)), exertional chest pain (1.6 (1.3, 2.1)), smoking (per-10-pack-years) (1.6 (1.4, 1.9)), ILA (1.4 (1.2, 1.7)), breathing problems (1.4 (1.1, 1.8)), male sex (1.3 (1.1, 1.6)) and coughing (1.2 (1.1, 1.5)). D _LCO < LLN was less likely if subjects were older, had asthma or had higher BMI, haemoglobin, FVC or physical activity. Conclusion: Isolated, reduced D _LCO in a large middle-aged population cohort is associated with numerous previously known factors, including emphysema, ILA, smoking and self-reported lung disease. However, several symptoms, including exertional chest pain, breathing problems and coughing, are also independently associated with isolated reduced D _LCO .

Background: The prognostic significance of myocardial infarction with non-obstructive coronary arteries (MINOCA) in older adults remains uncertain, particularly in comparison with revascularized acute coronary syndromes (ACS) and other acute myocardial injury phenotypes. Methods: In the prospective population-based cohort of the Malmö Diet and Cancer Study (n = 30,466), 925 participants who experienced an incident coronary event between 2009 and 2018 were classified as revascularized ACS, MINOCA, or other acute myocardial injury phenotypes. All-cause mortality was assessed using Kaplan–Meier estimates and Cox proportional-hazards models. Results: Of 925 patients (mean age, 81 ± 7 years; female sex, 57%), 136 (14.7%) had a non-revascularized event, including 49 (36%) classified as MINOCA and 87 (64%) as other acute myocardial injuries. All non-revascularized cases underwent detailed review of angiographic and clinical records. During a median follow-up of 2.5 years, mortality was substantial across all groups (81%, overall). In unadjusted analyses, survival did not differ significantly among event categories (p = 0.302). In multivariable analysis, MINOCA was associated with increased mortality compared with revascularized ACS (aHR 1.48; 95% CI 1.07–2.05; p = 0.018) and with other acute myocardial injury phenotypes (aHR 1.44; 95% CI 1.01–2.04; p = 0.041). Other acute myocardial injury phenotypes did not differ significantly from revascularized ACS (aHR 1.03; 95% CI 0.78–1.35). Conclusions: MINOCA is associated with higher mortality than both revascularized ACS and other acute myocardial injury phenotypes. Despite the absence of obstructive coronary disease, MINOCA in later life carries an adverse prognosis and commands systematic diagnostic evaluation, careful phenotypic characterization, and appropriate risk-directed management.

Postural orthostatic tachycardia syndrome (POTS) is associated with multiple autonomic symptoms, including gastrointestinal (GI) complaints, and has been linked to insulin resistance. We aimed to explore HbA1c, circulating metabolic hormones (insulin, C-peptide, GIP, GLP-1, glucagon, leptin, and peptide YY) and cortisol, and their associations with hemodynamic parameters and GI symptoms in POTS. Two POTS cohorts were studied and compared with matched controls. In the fasting cohort, blood samples were drawn in 42 patients and 41 controls, followed by active standing tests with measurement of pulse and blood pressure (BP) in supine and standing positions. In the non-fasting cohort, questionnaires assessed GI symptoms and HbA1c was measured in 43 patients and 52 controls. Fasting C-peptide and insulin levels correlated with BP in POTS (q = 0.002) but not in controls. Fasting insulin tended to be higher in POTS but was not statistically significant after adjustment for BMI (β = 6.85; 95% CI: −1.04–14.74; p = 0.085). Morning cortisol was comparable between groups. In the non-fasting cohort, HbA1c and metabolic hormones were comparable between groups, with no associations with GI symptoms. Together, these findings suggest a potential link between insulin-related pathways and BP regulation in POTS. Future studies are warranted to further investigate insulin dynamics in POTS.

Summary Elevated HDL-C levels are generally regarded as prognostically favorable in cardiovascular disease. Our study shows that higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men. Purpose Increased high-density lipoprotein cholesterol (HDL-C) is associated with reduced risk of cardiovascular disease but inversely associated with bone mineral density. Methods We assessed the relationship between HDL-C and incident fractures using a prospective population-based cohort. In total 18,240 subjects had available data on HDL-C levels (mean age 69 years, 37% women, mean follow-up 13 years). Fracture endpoints were identified through national registers. Follow-up was from 2002 until the first episode of incident fracture or end of follow-up December 31, 2020. The primary and secondary outcomes were total incident fractures and incident fractures of the hip and lower limb, respectively. Results Incident fractures occurred in 26% (n = 4,710) of all subjects (mean follow-up of 13 years). Subjects with incident fractures had higher HDL-C levels (mmol/L ± standard deviation) compared with subjects without fractures (1.5 ± 0.4 vs. 1.4 ± 0.4 mmol/L). In multivariate regression analysis, higher HDL-C levels were associated with increased risk of total incident fractures in the general population (HR 1.12, 95%CI 1.03–1.22, p = 0.006), and in men (HR 1.18, 95%CI 1.04–1.35, p = 0.02). No statistically significant relationship was found in women or between incident fractures of hip and lower limb fractures (p > 0.05). Conclusions Higher HDL cholesterol levels are prospectively associated with 18% increased risk of new-onset fractures in men from the general population but not in women. Higher HDL cholesterol may be a novel risk factor for developing fractures in men.

Background: Preserved ratio impaired spirometry (PRISm) is a spirometry pattern of interest regarding incident airflow obstruction and higher mortality risk. We applied a proteomic approach to gain more insight into the biological mechanisms associated with PRISm.Methods: From the population-based Swedish Cardiopulmonary Bioimage Study (SCAPIS), participants in the Main (n=4835) and Pilot (n=1054) studies, were included as discovery and replication cohorts. The lower limit of normal (LLN) of post-bronchodilator forced expiratory volume in 1 s (FEV₁), forced vital capacity (FVC) and FEV₁/FVC was defined as the fifth percentile in healthy, never-smoking SCAPIS participants. Participants were subdivided into five groups: reference: FEV₁/FVC≥LLN and FEV₁≥LLN and FVC≥LLN (n=4084)); mild chronic airflow limitation (CAL): FEV₁/FVC1≥LLN (n=278); moderate–severe CAL: FEV₁/FVC11/FVC ≥LLN and FVC1/FVC≥LLN and FEV₁<LLN (n=238). Proximity extension assays were used to measure 168 proteins. The associations of each standardised protein were assessed with each study group by multiple linear regression models, adjusting for age, sex, body mass index (BMI), smoking, physical activity and study centres, and corrected for multiple testing to control for a false discovery rate of 5%.Results: Eight proteins were associated with PRISm and replicated: tumour necrosis factor receptor superfamily member 10A, interleukin-6, paraoxonase 3 (negative association), renin, urokinase plasminogen activator surface receptor (U-PAR), E-selectin, matrix metalloproteinase 7 and chitinase-3-like protein 1. Interleukin-6 and U-PAR were also associated with moderate–severe CAL and E-selectin with RSP. In addition, five other proteins were associated with moderate–severe CAL and three with RSP.Conclusion: Protein profile in PRISm differs from other spirometric patterns suggesting specific disease mechanisms.

Aims: Orthostatic hypotension (OH) is an important differential diagnosis in unexplained syncope. Neurogenic OH (nOH) has been postulated to differ from non-neurogenic OH (non-nOH), yet pathophysiological differences are largely unexplored. We aimed to investigate aetiology and tilt table test (TTT)-induced haemodynamic responses in symptomatic OH patients. Methods and results: We performed a retrospective study analysing patients referred for unexplained syncope or highly symptomatic orthostatic intolerance with TTT-verified classical OH (cOH). Medical records were analysed for the presumptive aetiology of cOH. Fifty-two patients (mean age 73 ± 9 years, 46% women) with good quality TTT recordings were divided into three groups on clinical grounds: nOH, non-nOH, and mixed OH. The log-ratio (LR) method was applied to compare the decrease in mean arterial pressure (MAPLR) and corresponding contributions of heart rate (HRLR), stroke volume (SVLR), and total peripheral resistance (TPRLR) during the upright phase of TTT. The prevalence of cOH was 12 (23%) nOH, 14 (27%) non-nOH, and 26 (50%) mixed OH. No difference in MAPLR was observed among the three groups during the 4th upright minute of TTT (nOH: −0.10 ± 0.04 vs. non-nOH: −0.07 ± 0.05 and vs. mixed OH: −0.06 ± 0.05, P = 0.10). The contributions of HRLR, SVLR, and TPRLR to the drop in MAPLR did not differ between groups (all P > 0.05). Conclusion: One-half of highly symptomatic OH patients had mixed OH, whereas one-quarter had either pure neurogenic or non-neurogenic OH, respectively. Different forms of OH were indifferentiable based on haemodynamic responses during TTT, questioning the clinical utility of such classification. Larger studies are needed to confirm these findings.

BACKGROUND: Postural orthostatic tachycardia syndrome (POTS) is a frequently diagnosed cardiovascular disorder after COVID-19 infection. POTS is characterized by the presence of excessive sinus tachycardia on standing without a fall in blood pressure (BP). We investigated the BP profile using 24-hour ambulatory BP monitoring in patients with new-onset POTS after COVID-19 compared with prepandemic population-based controls. METHODS: We performed a case-control study in 100 patients (mean age, 40.0±12.9 years; 85% women) with verified post–COVID-19 new-onset POTS diagnosed by a positive head-up tilt testing versus 100 controls from a population-based cohort with a negative active standing test, no history of syncope, POTS, or endocrine disease (mean age, 42.3±14.0 years; 78% women). Twenty-four-hour BP profile was assessed for circadian BP variation including hypotensive systolic BP (SBP) episodes (P P P P <0.001), independent of age and sex. CONCLUSIONS: Patients with post–COVID-19 POTS demonstrate higher mean 24-hour and nighttime SBP and show disruptions of circadian BP rhythm regulation compared with population-based controls, as well as more daytime hypotensive episodes. Future studies are needed to test whether patients with post–COVID-19 POTS may benefit from tailored BP therapy.

Diffusing capacity for carbon monoxide (D_LCO) is a measure of gas exchange across the alveolar-capillary membrane. It is known to be affected in lung disease, for example COPD; but also by non-respiratory conditions, such as heart failure. Our aim was to study determinants of reduced DLCO in a population-based setting. Swedish CArdioPulmonary bioImage Study (SCAPIS) is a multicenter population-based study of adults aged 50-64 years. We have defined normal values for D_LCO in healthy never-smokers and used 5th percentile as lower limit of normal (LLN). We studied, by means of multivariable analysis, factors associated with D_LCOLCOLCOLCO in a large population-based sample. Strongest association was found with emphysema, but also with other lung diseases than asthma and COPD. The association with chest pain walking uphill might signal for need of cardiovascular risk assessment.