Exertional breathlessness related to medical conditions in middle-aged people: the population-based SCAPIS study of more than 25,000 men and women.

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.

Pulmonary function and atherosclerosis in the general population: causal associations and clinical implications.

Reduced lung function is associated with cardiovascular mortality, but the relationships with atherosclerosis are unclear. The population-based Swedish CArdioPulmonary BioImage study measured lung function, emphysema, coronary CT angiography, coronary calcium, carotid plaques and ankle-brachial index in 29,593 men and women aged 50-64 years. The results were confirmed using 2-sample Mendelian randomization. Lower lung function and emphysema were associated with more atherosclerosis, but these relationships were attenuated after adjustment for cardiovascular risk factors. Lung function was not associated with coronary atherosclerosis in 14,524 never-smokers. No potentially causal effect of lung function on atherosclerosis, or vice versa, was found in the 2-sample Mendelian randomization analysis. Here we show that reduced lung function and atherosclerosis are correlated in the population, but probably not causally related. Assessing lung function in addition to conventional cardiovascular risk factors to gauge risk of subclinical atherosclerosis is probably not meaningful, but low lung function found by chance should alert for atherosclerosis.

Consequences of Using Post- or Prebronchodilator Reference Values in Interpreting Spirometry.

Rationale: Postbronchodilator spirometry is used for the diagnosis of chronic obstructive pulmonary disease. However, prebronchodilator reference values are used for spirometry interpretation. Objectives: To compare the resulting prevalence rates of abnormal spirometry and study the consequences of using pre- or postbronchodilator reference values generated within SCAPIS (Swedish CArdioPulmonary bioImage Study) when interpreting postbronchodilator spirometry in a general population. Methods: SCAPIS reference values for postbronchodilator and prebronchodilator spirometry were based on 10,156 and 1,498 never-smoking, healthy participants, respectively. We studied the associations of abnormal spirometry, defined by using pre- or postbronchodilator reference values, with respiratory burden in the SCAPIS general population (28,851 individuals). Measurements and Main Results: Bronchodilation resulted in higher predicted medians and lower limits of normal (LLNs) for FEV1/FVC ratios. The prevalence of postbronchodilator FEV1/FVC ratio lower than the prebronchodilator LLN was 4.8%, and that of postbronchodilator FEV1/FVC lower than the postbronchodilator LLN was 9.9%, for the general population. An additional 5.1% were identified as having an abnormal postbronchodilator FEV1/FVC ratio, and this group had more respiratory symptoms, emphysema (13.5% vs. 4.1%; P < 0.001), and self-reported physician-diagnosed chronic obstructive pulmonary disease (2.8% vs. 0.5%, P < 0.001) than subjects with a postbronchodilator FEV1/FVC ratio greater than the LLN for both pre- and postbronchodilation. Conclusions: Pre- and postbronchodilator spirometry reference values differ with regard to FEV1/FVC ratio. Use of postbronchodilator reference values doubled the population prevalence of airflow obstruction; this was related to a higher respiratory burden. Using postbronchodilator reference values when interpreting postbronchodilator spirometry might enable the identification of individuals with mild disease and be clinically relevant.

Polygenic scores for low lung function and the future risk of adverse health outcomes.

AIMS: Reduced lung function and adverse health outcomes are often observed. This study characterizes genetic susceptibility for reduced lung function and risk of developing a range of adverse health outcomes. METHODS: We studied 27,438 middle-aged adults from the Malmö Diet and Cancer study (MDCS), followed up to 28.8 years. Trait-specific Polygenic scores (PGS) for forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were constructed for each participant using MDCS genetic data and summary statistics from the latest GWAS of lung function. Linear regression models and cox proportional hazards regression models were used to assess associations between adverse health outcomes and lung function-PGS. RESULTS: FEV1-PGS and FVC-PGS were significantly associated with mean sBP at baseline after adjustments (FEV1-PGS Q1 (highest PGS = highest lung function): 140.7mmHg vs. Q4: 141.5mmHg, p-value 0.008). A low FVC-PGS was significantly associated with the risk of future diabetic events after adjustments (Q4 vs. Q1 HR: 1.22 (CI 1.12-1.32), p-trend < 0.001) and had added value to risk prediction models for diabetes. Low FEV1-PGS was significantly associated with future coronary events (Q4 vs. Q1 HR: 1.13 (CI: 1.04-1.22), p-trend 0.008). No significant association was found between PGS and sudden cardiac death, chronic kidney disease or all-cause mortality. Results remained largely unchanged in a subgroup of subjects when further adjusted for apolipoproteins. CONCLUSION: Genetic susceptibility for reduced lung function is associated with higher sBP, increased risk of diabetes and to a lesser extent, future coronary events, suggesting etiological roles of lung function on these outcomes. Using PGS, high-risk groups could be early detected to implement early lifestyle changes to mitigate the risk.

Comparison of risk factors for ischemic stroke and coronary events in a population-based cohort.

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.

Low lung function and the risk of incident chronic kidney disease in the Malmö Preventive Project cohort.

BACKGROUND: Although the prevalence of kidney disease is higher in those with reduced lung function, the longitudinal relationship between low lung function and future risk of chronic kidney disease (CKD) has not been widely explored. METHODS: Baseline lung function was assessed in 20,700 men and 7325 women from 1974 to 1992. Mean age was 43.4 (±6.6) and 47.5 (±7.9) for men and women respectively. Sex-specific quartiles of FEV1 and FVC (L) were created (Q4: highest, reference) and the cohort was also divided by the FEV1/FVC ratio (≥ or < 0.70). Cox proportional hazards regression was used to determine the risk of incident CKD events (inpatient or outpatient hospital diagnosis of CKD) in relation to baseline lung function after adjustment for various confounding factors. RESULTS: Over 41 years of follow-up there were 710 and 165 incident CKD events (main diagnosis) in men and women respectively. Low FEV1 was strongly associated with future risk of CKD in men (Q1 vs Q4 adjusted HR: 1.46 (CI:1.14-1.89), p-trend 0.002). Similar findings were observed for FVC in men (1.51 (CI:1.16-1.95), p-trend 0.001). The adjusted risks were not found to be significant in women, for either FEV1 or FVC. FEV1/FVC < 0.70 was not associated with increased incidence of CKD in men or women. CONCLUSION: Low FEV1 and FVC levels at baseline are a risk factor for the development of future incident CKD in men. Monitoring kidney function in those with reduced vital capacity in early life could help with identifying those at increased risk of future CKD.

Socioeconomic circumstances and incidence of chronic obstructive pulmonary disease (COPD) in an urban population in Sweden.

The association between socioeconomic circumstances and incidence of chronic obstructive pulmonary disease (COPD) was investigated in an urban population in Sweden. The study included all 40-89 year-old inhabitants in Malmö, Sweden (N = 117,479) without previous hospitalization due to COPD, who were followed over 14 years for COPD related hospital admissions. The Malmö Preventive Project (MPP) cohort (n = 27,358) with information on biological and lifestyle factors was also used to study the association between socioeconomic circumstances and COPD. The Swedish hospital discharge register was used to record incidence of COPD hospitalizations. A total of 2,877 individuals (47.5% men) were discharged from hospital with COPD as the primary diagnosis during follow-up in Malmö. Low annual income (hazard ratio (HR): 2.23; 95%CI: 1.97-2.53, P < 0.001) and rented (vs. self-owned) housing (HR: 1.41; 1.30-1.52, P < 0.001) were associated with a higher risk for COPD. In addition, compared to married subjects, divorced (HR: 1.61; 1.46-1.78, P < 0.001) and widowed (HR: 1.30; 1.16-1.46, P < 0.001) individuals had an increased risk for hospitalization due to COPD. Low income, low occupation and being divorced or widowed were similarly associated with COPD in the MPP cohort, after adjustments for smoking, FEV1, BMI, age and sex. However, socioeconomic circumstances were not associated with COPD in analyses restricted to never smokers. Low socioeconomic circumstances were associated with an increased risk of COPD after adjustments for biological and lifestyle risk factors including smoking status. However, this relationship was not significant in those who never smoked.

The Association of Lung Clearance Index with COPD and FEV1 Reduction in 'Men Born in 1914'.

Lung Clearance Index (LCI) provides an overall measurement of ventilation inhomogeneity. This population-based study examines whether LCI predicts pulmonary obstruction and incidence of chronic obstructive pulmonary disease (COPD) events over a long-term follow-up. Multiple breath nitrogen washout and spirometry were performed in 674 men from the cohort "Men born in 1914" at age 55 years. Subjects were classified into quartiles (Q) of LCI and according to LCI above and below upper limit of normal (ULN). Incidence of COPD events (COPD hospitalisations or COPD-related deaths) were monitored over the remaining life span of the men, by linkage with national hospital registers. In addition, development of pulmonary obstruction (i.e., FEV1/vital capacity below lower limit of normal (LLN)) was studied in 387 men who were re-examined with spirometry at 68 years of age. Over 44 years of follow-up, there were 85 incident COPD events. Hazards ratios (HRs) for COPD across quartiles of LCI were: Q1 1.00 (reference), Q2 1.30 (95% confidence interval: 0.61-2.74), Q3 1.97 (0.97-3.98) and Q4 3.99 (2.06-7.71) (p value for trend <0.001). This relationship remained significant after adjustments for confounding factors, including smoking and FEV1 (HR, Q4 vs Q1: 2.34 (1.17-4.69); p value for trend: 0.006). Reduction of FEV1 between 55 and 68 years of age and incidence of pulmonary obstruction was highest in those with high LCI. High LCI is associated with future development of pulmonary obstruction and incidence of COPD hospitalisations in men from the general population.

Lung function, forced expiratory volume in 1†s decline and COPD hospitalisations over 44†years of follow-up.

The use of baseline lung function in the prediction of chronic obstructive pulmonary disease (COPD) hospitalisations, all-cause mortality and lung function decline was assessed in the population-based "Men Born in 1914" cohort.Spirometry was assessed at age 55 years in 689 subjects, of whom 392 had spirometry reassessed at age 68  years. The cohort was divided into three groups using fixed ratio (FR) and lower limit of normal (LLN) criterion: forced expiratory volume in 1 s (FEV1)/vital capacity (VC) ≥70%, FEV1/VC <70% but ≥LLN (FR(+)LLN(-)), and FEV1/VC <70% and

The temporal relationship between poor lung function and the risk of diabetes.

BACKGROUND: The association between impaired lung function and diabetes risk has been established in the past, however the temporal and causal relationships between the two remain unclear. We assessed the relationship between baseline FEV1 and FVC and risk of incident diabetes at different time intervals for participants in the Malmö Preventive Project cohort. METHODS: Baseline lung function was assessed in 20,295 men and 7416 women during 1974-1992; mean age 43.4 ± 6.6 and 47.6 ± 7.8, respectively. Sex-specific quartiles of FEV1%predicted and FVC%predicted were created (Q4 = highest; reference). Follow-up time was divided into 10-year time intervals from baseline examination. Cox proportional hazards regression was used to assess the incidence of diabetes according to quartiles of FEV1 and FVC%predicted, after adjustments for baseline glucose and potential confounding factors. RESULTS: Over 37-years' follow-up there were 3753 and 993 incident diabetes events in men and women, respectively. When comparing FEV1%predicted in men (Q1 vs. Q4), the HR for diabetes was 1.64 (1.21-2.22) for events <10 years after baseline, 1.52 (1.27-1.81) for events 10-20 years after baseline, 1.39 (1.22-1.59) for events 20-30 years after baseline, and 1.46 (1.08-1.97) for events occurring >30 years after baseline. A broadly similar pattern was seen for FVC%predicted and for women. CONCLUSIONS: Low FEV1 precedes and significantly predicts future diabetes. This risk is still significant many years after the baseline FEV1 measurement in middle-aged men. These results suggest that there is a relationship between impaired lung function and diabetes risk beyond the effects of hyperglycemia on lung function.

Inhomogeneity of ventilation in smokers and mild COPD assessed by the ratio of alveolar volume to total lung capacity.

BACKGROUND: Previous studies have shown that the ratio between alveolar volume (VA) and total lung capacity (TLC) reflects ventilation heterogeneity in subjects with chronic obstructive pulmonary disease (COPD). However, the ratio and its correlation to respiratory symptoms had to our knowledge not previously been investigated in subjects with mild chronic airflow obstruction or without airflow obstruction (normal ratio FEV1/VC). The purpose of this study was to investigate potential connection between VA/TLC and respiratory symptoms, smoking habits and lung function parameters in subjects with normal spirometry and with mild chronic airflow obstruction. METHODS: We examined 450 subjects (82 non-smokers with normal spirometry, 298 subjects who smoked or had smoked earlier but had a normal spirometry and 70 subjects with chronical airflow obstruction) with routine lung function tests and a questionnaire regarding respiratory symptoms. RESULTS: This study showed 31 out of 54 subjects with a low VA/TLC had a normal ratio FEV1/VC. Of these subjects, 58.1 % had respiratory symptoms, compared to the group with normal ratio for both VA/TLC and FEV1/VC where 35.8 % had respiratory symptoms (p-value 0.02). CONCLUSION: This study has shown that within the group of subjects with a normal ratio FEV1/VC, those with a decreased ratio VA/TLC had a higher prevalence of respiratory symptoms compared to subjects with a normal VA/TLC ratio. These findings indicate that including the ratio VA/TLC in the evaluation of a pulmonary function test assessment might increase the possibility to identify subjects with early or at risk of lung disease.

Impulse oscillometry indices in relation to respiratory symptoms and spirometry in the Swedish Cardiopulmonary Bioimage Study.

Background: Impulse oscillometry (IOS) is sensitive in detecting lung function impairment. In small studies, impaired IOS relates better to respiratory symptoms than spirometry. We studied how IOS related to spirometry and respiratory symptoms in a large population of individuals (n=10 360) in a cross-sectional analysis. Methods: Normal values for IOS and spirometry were defined in healthy, never-smoking individuals, aged 50-64 years, from the Swedish CArdioPulmonary bioImage Study (n=3664 for IOS and 3608 for spirometry). For IOS, abnormal values for resistance at 5 Hz (R5) and at 20 Hz and area of reactance were defined using the 95th percentile. Abnormal reactance at 5 Hz for IOS and abnormal conventional spirometry indices (forced expiratory volume in 1 s (FEV1), forced and slow vital capacity and their ratios) were defined using the 5th percentile. Results: Abnormal IOS parameters were found in 16% of individuals and were associated with increased odds ratios for nearly all respiratory symptoms when adjusted for age, gender and smoking. In individuals with normal spirometry, abnormal IOS resistance was related to cough and dyspnoea, while abnormal reactance was related to wheeze. In these individuals, the combination of abnormal R5 with abnormal reactance resulted in approximately two-fold higher likelihood for having cough, chronic bronchitis and dyspnoea, even when further adjusting for FEV1, expressed as % predicted. Conclusions: Abnormal IOS is related to increased respiratory burden in middle-aged individuals with normal spirometry, especially when resistance and reactance parameters are combined. The different relationships between respiratory symptoms and reactance and resistance warrant further research.

Cardiovascular disease-linked plasma proteins are mainly associated with lung volume.

Background: Epidemiological studies have shown that impaired lung function is common and associated with increased risk of cardiovascular disease. Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. Methods: We used a discovery and replication approach in two community-based cohorts, EpiHealth and the Malmö Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease- and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. A false discovery rate of 5% was used as the significance threshold in the discovery cohort. Results: Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. Fatty acid-binding protein 4, fibroblast growth factor 21, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FVC and agouti-related protein, insulin-like growth factor-binding protein 2, paraoxonase 3 and receptor for advanced glycation end products were positively associated therewith. No proteins were associated with FEV1/FVC ratio. A sensitivity analysis in EpiHealth revealed only minor changes after excluding individuals with known cardiovascular disease, diabetes or obesity. Conclusions: Five proteins were associated with both FEV1 and FVC. Four proteins associated with only FVC and none with FEV1/FVC ratio, suggesting associations mainly through lung volume, not airway obstruction. However, additional studies are needed to investigate underlying mechanisms for these findings.

High prevalence of interstitial lung abnormalities in middle-aged never-smokers.

Background: Interstitial lung abnormalities (ILA) are incidental findings on chest computed tomography (CT). These patterns can present at an early stage of fibrotic lung disease. Our aim was to estimate the prevalence of ILA in the Swedish population, in particular in never-smokers, and find out its association with demographics, comorbidities and symptoms. Methods: Participants were recruited to the Swedish CArdioPulmonary BioImage Study (SCAPIS), a population-based survey including men and women aged 50-64 years performed at six university hospitals in Sweden. CT scan, spirometry and questionnaires were performed. ILA were defined as cysts, ground-glass opacities, reticular abnormality, bronchiectasis and honeycombing. Findings: Out of 29 521 participants, 14 487 were never-smokers and 14 380 were men. In the whole population, 2870 (9.7%) had ILA of which 134 (0.5%) were fibrotic. In never-smokers, the prevalence was 7.9% of which 0.3% were fibrotic. In the whole population, age, smoking history, chronic bronchitis, cancer, coronary artery calcium score and high-sensitive C-reactive protein were associated with ILA. Both ILA and fibrotic ILA were associated with restrictive spirometric pattern and impaired diffusing capacity of the lung for carbon monoxide. However, individuals with ILA did not report more symptoms compared with individuals without ILA. Interpretation: ILA are common in a middle-aged Swedish population including never-smokers. ILA may be at risk of being underdiagnosed among never-smokers since they are not a target for screening.

Triglyceride-Glucose Index is a Risk Marker of Incident COPD Events in Women.

Purpose: The triglyceride-glucose index (TyG index) is a marker of insulin resistance and metabolic dysfunction and has the advantage of being universally available. Although recent evidence suggests the TyG index has relevance to respiratory health, there have been no prospective studies assessing its value as a biomarker for chronic lung diseases. We aim to assess the TyG index as a potential risk marker for future incident COPD events in the general population. Patients and Methods: Baseline TyG index was assessed in 28,282 middle-aged men and women without previous history of chronic obstructive pulmonary disease (COPD) from the Malmö Preventive Project (men between 1974 and 1982 and women between 1982 and 1992). All subjects were followed up prospectively, and Cox proportional hazards regression was used to assess incident COPD events according to quartiles of TyG index. Results: After an average of 31 years of follow-up, TyG index was a strong predictor of future COPD events even after adjusting for potential confounders (Q4 (highest TyG index) HR (95% CI): 1.21 (1.09-1.35) vs Q1 (reference), p-trend <0.001). After stratifying by sex, the results remained statistically significant in women only (Q4 vs Q1 HR 1.72 (1.41-2.09)). Additionally, the risk remained significant in a cohort of life-long never smokers (Q4 vs Q1 HR 1.47 (1.08-2.01)). Conclusion: A raised TyG index is a novel risk marker of future incident COPD events in women. Insulin resistance as reflected by the TyG index can precede the development of obstructive lung disease and as such may be an easily measurable and useful predictor of COPD in women.

Triglyceride-glucose (TyG) index is a predictor of arterial stiffness, incidence of diabetes, cardiovascular disease, and all-cause and cardiovascular mortality: A longitudinal two-cohort analysis.

Background: Triglyceride-glucose (TyG) index is a useful low-cost marker of insulin resistance. We aimed to evaluate the association between TyG index and arterial stiffness, incidence of diabetes, adverse cardiovascular outcomes, and all-cause and cardiovascular mortality in two large prospective Swedish cohorts, the Malmö Diet and Cancer Study-Cardiovascular Cohort (MDCS-CV) and the Malmö Preventive Project (MPP). Methods: Association between baseline TyG index and arterial stiffness, measured by carotid femoral pulse wave velocity (c-f PWV), was assessed using linear regression and general linear models, adjusting for covariates. Cox proportional hazard regression was used to assess the association between TyG index and incidence of diabetes, coronary events (CE), stroke, atrial fibrillation (AF), heart failure, and all-cause and cardiovascular mortality. Results: After multivariable adjustment, baseline TyG index was significantly associated with increased arterial stiffness (ß for c-f PWV = 0.61, p = 0.018). Participants in the highest quartile of TyG index vs. lowest quartile had an increased incidence of diabetes (HR: 3.30, 95% CI: 2.47-4.41), CE (HR: 1.53, 95% CI: 1.41-1.68), stroke (HR: 1.30, 95% CI: 1.18-1.44), all-cause mortality (HR: 1.22, 95% CI: 1.16-1.28), and cardiovascular mortality (HR: 1.37, 95% CI: 1.26-1.49) after adjustment for covariates. Per unit increase in TyG index was associated with increased heart failure risk. No significant association was observed for incident AF. Conclusion: Elevated TyG index is positively associated with increased arterial stiffness and increased incidence of diabetes, CE, stroke, and all-cause and cardiovascular mortality. The results suggest that TyG index can potentially be useful in the identification of those at increased long-term risk of adverse health outcomes.

Elevated premature ventricular complex counts on 24-hour electrocardiogram predict incident atrial fibrillation and heart failure-A prospective population-based cohort study.

Background: Premature ventricular complexes (PVCs) are known to predict heart failure (HF) and premature atrial contractions (PACs) are known to predict atrial fibrillation (AF) and stroke. PVCs and PACs share pathophysiological mechanisms; however, the combined effects of PVCs and PACs on HF, AF, and stroke risk have not been studied. Objectives: To study elevated PVC counts on 24-hour electrocardiogram monitoring (24hECG) in relation to incidence of AF, HF, and stroke, and whether this effect is altered by PAC frequency. Methods: The prospective population-based Malmö Diet and Cancer study includes 24hECG registrations in 375 AF- and HF-free subjects (mean age 65 years, 55% women). During 17 years of follow-up there were 28 HF, 89 AF, and 28 stroke events. The hazard ratios (HR) of elevated PVC counts (defined as the top quartile, ≥77/24 hours) vs lower quartiles were assessed using multivariable adjusted Cox regression models. Results: Elevated PVC counts predicted incident AF (HR 1.9, 95% confidence interval [CI] 1.2-3.0) and HF (HR 3.1, 95% CI 1.4-7.0). Results were similar after adjustment for NT-proBNP and PACs. Multiform PVCs were associated with even higher risks (HR 2.8, 95% CI: 1.7-4.6 for AF; HR 5.0, 95% CI 2.2-11.7 for HF), as was the presence of both elevated PACs and PVCs (9% of the population, HR 4.1, 95% CI 2.4-6.8 for AF and HR 4.3, 95% CI 1.7-11.4 for HF). No significant association was found between elevated PVC counts and incident stroke. Conclusion: Elevated PVC counts predict incident AF and HF, particularly if PVCs are multiform or occur in combination with elevated PAC counts.

Circulating Hepatocyte Growth Factor Reflects Activation of Vascular Repair in Response to Stress.

Hepatocyte growth factor (HGF) is released by stressed human vascular cells and promotes vascular cell repair responses in both autocrine and paracrine ways. Subjects with a low capacity to express HGF in response to systemic stress have an increased cardiovascular risk. Human atherosclerotic plaques with a low content of HGF have a more unstable phenotype. The present study shows that subjects with a low ability to express HGF in response to metabolic stress have an increased risk to suffer myocardial infarction and stroke.

Lung function is associated with tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) levels in school-aged children.

BACKGROUND: Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) is a cytokine with inflammatory and apoptotic properties. A complex relationship exists between TRAIL and the lung where both elevated TRAIL and TRAIL deficiency are associated with lung impairment. In neonatal mice, TRAIL is thought to translate respiratory infections into chronic lung disease but the association between TRAIL and lung function in childhood has not been assessed. AIM: To assess the cross-sectional relationship between TRAIL levels and lung function in school-aged children. METHODS: The study cohort consisted of 170 school-aged children attending four schools in Malmö, Sweden. Lung volumes, impulse oscillometry (IOS) and serum TRAIL were measured for all children. Linear regression was used to assess changes in lung function per 1-SD increase in TRAIL. General linear models were used to assess mean lung function by tertiles (T) of TRAIL. RESULTS: Mean age was 9.9 years (±0.6). A 1-SD increase in TRAIL was associated with lower values of FEV1 and FEV1/VC (change in FEV1 (L) and FEV1/VC ratio: -0.047, p-value 0.002, and -0.011, p-value 0.020, respectively) and higher values of lung resistance (change in R5 and R20 (kPa/(L/s)): 0.035, p-value <0.001 and 0.027, p-value 0.004, respectively). These associations remained significant after excluding children with pre-existing lung disease. Higher TRAIL levels were associated with more negative values for X5 in general linear models (Mean X5 (kPa/(L/s)) in T1 (low TRAIL): -0.193 vs T3 (high TRAIL): -0.216, p-value 0.026). CONCLUSIONS: High TRAIL levels are significantly associated with markers of pulmonary airflow obstruction in school-aged children.

Low lung function, sudden cardiac death and non-fatal coronary events in the general population.

BACKGROUND: Many of those who suffer from a first acute coronary event (CE) die suddenly during the day of the event, most of them die outside hospital. Poor lung function is a strong predictor of future cardiac events; however, it is unknown whether the pattern of lung function impairment differs for the prediction of sudden cardiac death (SCD) versus non-fatal CEs. We examined measures of lung function in relation to future SCD and non-fatal CE in a population-based study. METHODS: Baseline spirometry was assessed in 28 584 middle-aged subjects, without previous history of CE, from the Malmö Preventive Project. The cohort was followed prospectively for incidence of SCD (death on the day of a first CE, inside or outside hospital) or non-fatal CE (survived the first day). A modified version of the Lunn McNeil's competing risk method for Cox regression was used to run models for both SCD and non-fatal CE simultaneously. RESULTS: A 1-SD reduction in forced expiratory volume in 1 s (FEV1) was more strongly associated with SCD than non-fatal CE even after full adjustment (FEV1: HR for SCD: 1.23 (1.15 to 1.31), HR for non-fatal CE 1.08 (1.04 to 1.13), p value for equal associations=0.002). Similar associations were found for forced vital capacity (FVC) but not FEV1/FVC. The results remained significant even in life-long never smokers (FEV1: HR for SCD: 1.34 (1.15 to 1.55), HR for non-fatal CE: 1.11 (1.02 to 1.21), p value for equal associations=0.038). Similar associations were seen when % predicted values of lung function measures were used. CONCLUSIONS: Low FEV1 is associated with both SCD and non-fatal CE, but consistently more strongly associated with future SCD. Measurement with spirometry in early life could aid in the risk stratification of future SCD. The results support the use of spirometry for a global assessment of cardiovascular risk.