To analyze the association between cardiorespiratory fitness (CRF) and global and local brain volumes.
We studied 2103 adults (21-84 years old) from 2 independent population-based cohorts (Study of ...Health in Pomerania, examinations from June 25, 2008, through September 30, 2012). Cardiorespiratory fitness was measured using peak oxygen uptake (VO
peak), oxygen uptake at the anaerobic threshold (VO
@AT), and maximal power output from cardiopulmonary exercise testing on a bicycle ergometer. Magnetic resonance imaging brain data were analyzed by voxel-based morphometry using regression models with adjustment for age, sex, education, smoking, body weight, systolic blood pressure, glycated hemoglobin level, and intracranial volume.
Volumetric analyses revealed associations of CRF with gray matter (GM) volume and total brain volume. After multivariable adjustment, a 1-standard deviation increase in VO
peak was related to a 5.31 cm³ (95% CI, 3.27 to 7.35 cm³) higher GM volume. Whole-brain voxel-based morphometry analyses revealed significant positive relations between CRF and local GM volumes. The VO
peak was strongly associated with GM volume of the left middle temporal gyrus (228 voxels), the right hippocampal gyrus (146 voxels), the left orbitofrontal cortex (348 voxels), and the bilateral cingulate cortex (68 and 43 voxels).
Cardiorespiratory fitness was positively associated with GM volume, total brain volume, and specific GM and white matter clusters in brain areas not primarily involved in movement processing. These results, from a representative population sample, suggest that CRF might contribute to improved brain health and might, therefore, decelerate pathology-specific GM decrease.
The INSIGHTS-IPF registry provides one of the largest data sets of clinical data and self-reported patient related outcomes including health related quality of life (QoL) on patients with idiopathic ...pulmonary fibrosis (IPF). We aimed to describe associations of various QoL instruments between each other and with patient characteristics at baseline.
Six hundred twenty-three IPF patients with available QoL data (St George's Respiratory Questionnaire SGRQ, UCSD Shortness-of-Breath Questionnaire SoB, EuroQol visual analogue scale and index EQ-5D, Well-being Index WHO-5) were analysed. Mean age was 69.6 ± 8.7 years, 77% were males, mean disease duration 2.0 ± 3.3 years, FVC pred was 67.5 ± 17.8%, DL
pred 35.6 ± 17%.
Mean points were SGRQ total 48.3, UCSD SoB 47.8, EQ-5D VAS 66.8, and WHO-5 13.9. These instruments had a high or very high correlation (exception WHO-5 to EQ-5D VAS with moderate correlation). On bivariate analysis, QoL by SGRQ total was statistically significantly associated with clinical symptoms (NYHA; p < 0.001), number of comorbidities (p < 0.05), hospitalisation rate (p < 0.01) and disease severity (as measured by GAP score, CPI, FVC and 6-min walk test; p < 0.05 each). Multivariate analyses showed a significant association between QoL (by SGRQ total) and IPF duration, FVC, age, NYHA class and indication for long-term oxygen treatment.
Overall, IPF patients under real-life conditions have lower QoL compared to those in clinical studies. There is a meaningful relationship between QoL and various patient characteristics.
The INSIGHTS-IPF registry is registered at Clinicaltrials.gov ( NCT01695408 ).
Quality of life (QoL) is profoundly impaired in patients with idiopathic pulmonary fibrosis (IPF). However, data is limited regarding the course of QoL. We therefore analysed longitudinal data from ...the German INSIGHTS-IPF registry.
Clinical status and QoL were assessed at enrollment and subsequently at 6- to 12-months intervals. A range of different QoL questionnaires including the St. George's Respiratory Questionnaire (SGRQ) were used.
Data from 424 patients were included; 76.9% male; mean age 68.7 ± 9.1 years, mean FVC% predicted 75.9 ± 19.4, mean DL
% predicted 36.1 ± 15.9. QoL worsened significantly during follow-up with higher total SGRQ scores (increased by 1.47 per year; 95% CI: 1.17 to 1.76; p < 0.001) and higher UCSD-SOBQ scores and lower EQ-5D VAS and WHO-5 scores. An absolute decline in FVC% predicted of > 10% was associated with a significant deterioration in SGRQ (increasing by 9.08 units; 95% CI: 2.48 to 15.67; p = 0.007), while patients with stable or improved FVC had no significantly change in SGRQ. Patients with a > 10% decrease of DL
predicted also had a significant increase in SGRQ (+ 7.79 units; 95% CI: 0.85 to 14.73; p = 0.028), while SQRQ was almost stable in patients with stable or improved DL
. Patients who died had a significant greater increase in SGRQ total scores (mean 11.8 ± 18.6) at their last follow-up visit prior to death compared to survivors (mean 4.2 ± 18.9; HR = 1.03; 95% CI: 1.01 to 1.04; p < 0.001). All QoL scores across the follow-up period were significantly worse in hospitalised patients compared to non-hospitalised patients, with the worst scores reported in those hospitalised for acute exacerbations.
QoL assessments in the INSIGHTS-IPF registry demonstrate a close relationship between QoL and clinically meaningful changes in lung function, comorbidities, disease duration and clinical course of IPF, including hospitalisation and mortality.
Abstract Background The German COPD cohort study COSYCONET (“ CO PD and SY stemic consequences- CO morbidities NET work”) investigates the interaction of lung disease, comorbidities and systemic ...inflammation. Recruitment took place from 2010-2013 in 31 study centers. In addition to the baseline visit, follow-up visits are scheduled at 6, 18, 36 and 54 months after baseline. The study also comprises a biobank, image bank, and includes health economic data. Here we describe the study design of COSYCONET and present baseline data of our COPD cohort. Methods Inclusion criteria were broad in order to cover a wide range of patterns of the disease. In each visit, patients undergo a large panel of assessments including e.g. clinical history, spirometry, body plethysmography, diffusing capacity, blood samples, 6-minute walk-distance, electrocardiogram and echocardiography. Chest CTs are collected if available and CTs and MRIs are performed in a subcohort. Data are entered into eCRFs and subjected to several stages of quality control. Results Overall, 2741 subjects with a clinical diagnosis of COPD were included (59% male; mean age 65±8.6 years (range 40-90)). Of these, 8/35/32/9% presented with GOLD stages I-IV; 16% were uncategorized, including the former GOLD-0 category. 24% were active smokers, 68% ex-smokers and 8% never-smokers. Data completeness was 96% for the baseline items. Conclusion The German COPD cohort comprises patients with advanced and less advanced COPD. This is particularly useful for studying the time course of COPD in relation to comorbidities. Baseline data indicate that COSYCONET offers the opportunity to investigate our research questions in a large-scale, high-quality dataset.
Abstract
Study Objectives
Periodic limb movements in sleep (PLMS) are frequent motor phenomena; however, population-based data are scarce. We assessed the prevalence of PLMS and factors associated ...with PLMS within two German population-based cohorts, the SHIP-TREND and BiDirect.
Methods
Single-night polysomnography was performed on 1107 subjects recruited from the general population (mean age: 52.9 years, 54.1% men) in the SHIP-TREND and on 247 participants (mean age: 57.6 years, 50.6% men) in the BiDirect. PLMS were evaluated using the standard criteria of the American Academy of Sleep Medicine. Sociodemographic data, behavioral variables, medical history, current medication, and other sleep disorders were assessed.
Results
The prevalence of PLMS index (PLMSI) >15/hour was 32.4% (SHIP-TREND) and 36.4% (BiDirect). In multivariable models, age (odds ratio OR = 1.05 per +1 year), male gender (OR = 2.20), restless legs syndrome (OR = 2.32), physical inactivity (OR = 1.52), current smoking (OR = 1.49), diabetes (OR = 2.13), antidepressant use (OR = 2.27), lower serum magnesium (OR per −0.1 mmol/L = 1.27) showed a positive, and the intake of beta-blockers an inverse association with PLMSI >15/hour in SHIP-TREND. In BiDirect, age (OR = 1.13 per +1 year), body mass index (OR = 1.11 per +1 kg/m2), and restless legs syndrome (OR = 8.77) were significantly associated with PLMSI >15/hour.
Conclusions
A high PLMSI is frequent in the German population. Age, male gender, restless legs syndrome, physical inactivity, current smoking, obesity, diabetes, antidepressant use, and lower magnesium were independently associated with PLMSI >15/hour in at least one of the cohorts.
A large body of evidence underlines an association between periodontal disease and cardiovascular disease. In contrast, data on its relation with endothelial dysfunction as a marker of early ...subclinical atherosclerosis is inconclusive and limited to patient-cohort studies. We therefore investigated the association between periodontal disease and flow-mediated dilation of the brachial artery (FMD) as a measure of endothelial dysfunction in a general population, and also addressed a possible mediation via inflammation. The study population comprised 1,234 subjects (50.5% men) aged 25-85 years from the 5-year follow-up of the Study of Health in Pomerania, a population-based cohort study. Clinical attachment loss (CAL) and pocket probing depth (PPD) as measures of periodontal disease were assessed half-mouth at four sites per tooth. Subjects were classified according to the periodontitis case definition proposed by Tonetti and Claffey (2005). Measurements of FMD and nitroglycerin-mediated dilation (NMD) were performed using standardized ultrasound techniques. High-sensitive C-reactive protein, fibrinogen and leukocyte count were measured. Fully adjusted multivariate linear regression analyses revealed significant associations of the percentage of sites with PPD ≥ 6 mm with FMD (p(trend)=0.048), with subjects within the highest category having a 0.74% higher FMD compared to subjects within the lowest category (p<0.05). Consistently, FMD values increased significantly across categories of the percentage of sites with CAL ≥ 6 mm (p(trend)=0.01) and the periodontitis case definition (p(trend)=0.006). Restrictions to subjects without antihypertensive or statin medication or current non-smokers confirmed previous results. Systemic inflammation did not seem to mediate the relation. Both PPD and CAL were not consistently associated with NMD. In contrast to previous studies, high levels of periodontal disease were significantly associated with high FMD values. This association was not mediated via systemic inflammation. This study revives the discussion on whether and how periodontitis contributes to endothelial dysfunction.
Objectives
Observational research suggests that periodontitis affects pulmonary function; however, observational studies are subject to confounding and reverse causation, making causal inference and ...the direction of these associations difficult. We used Mendelian randomization (MR) to assess the potential causal association between genetic liability to periodontitis and pulmonary function.
Materials and methods
We used six single-nucleotide polymorphisms (SNPs) associated with periodontitis (
P
< 5 × 10
−6
) from a genome-wide association study (GWAS) of 17,353 European descent periodontitis cases and 28,210 controls from the GeneLifestyle Interactions in Dental Endpoints consortium and the UK Biobank, and related these to SNPs from a lung function GWAS including 79,055 study participants of the SpiroMeta Consortium.
Results
MR analysis suggested no effect of periodontitis on the ratio of forced expiratory volume in one second to lower forced vital capacity (standard deviation increment in outcome per doubling of the odds of the exposure (95% confidence interval) = − 0.004 (− 0.028; 0.020)). Replication analysis using genetic instruments from two different GWAS and sensitivity analyses to address potential pleiotropy led to no substantial changes in estimates.
Conclusions
Collectively, these findings do not support a relationship between genetic liability for periodontitis and pulmonary function.
Clinical relevance
Periodontitis does not seem to be a risk factor for worsening of pulmonary function.
Exercise and statins reduce cardiovascular disease (CVD). Exercise capacity may be assessed using cardiopulmonary exercise testing (CPET). Whether statin medication is associated with CPET parameters ...is unclear. We investigated if statins are related with exercise capacity during CPET in the general population.
Cross-sectional data of two independent cohorts of the Study of Health in Pomerania (SHIP) were merged (n = 3,500; 50% males). Oxygen consumption (VO2) at peak exercise (VO2peak) and anaerobic threshold (VO2@AT) was assessed during symptom-limited CPET. Two linear regression models related VO2peak with statin usage were calculated. Model 1 adjusted for age, sex, previous myocardial infarction, and physical inactivity and model 2 additionally for body mass index, smoking, hypertension, diabetes and estimated glomerular filtration rate. Propensity score matching was used for validation.
Statin usage was associated with lower VO2peak (no statin: 2336; 95%-confidence interval CI: 2287-2,385 vs. statin 2090; 95%-CI: 2,031-2149 ml/min; P < .0001) and VO2@AT (no statin: 1,172; 95%-CI: 1,142-1,202 vs. statin: 1,111; 95%-CI: 1,075-1,147 ml/min; P = .0061) in males but not females (VO2peak: no statin: 1,467; 95%-CI: 1,417-1,517 vs. statin: 1,503; 95%-CI: 1,426-1,579 ml/min; P = 1.00 and VO2@AT: no statin: 854; 95%-CI: 824-885 vs. statin 864; 95%-CI: 817-911 ml/min; P = 1.00). Model 2 revealed similar results. Propensity scores analysis confirmed the results.
In the general population present statin medication was related with impaired exercise capacity in males but not females. Sex specific effects of statins on cardiopulmonary exercise capacity deserve further research.
Interstitial lung disease in systemic sclerosis (SSc-ILD) is a frequent organ complication with considerable mortality. Therapeutically, immunosuppressants are primarily used, particularly ...cyclophosphamide (CYC) and mycophenolate mofetil (MMF). Recently acquired data also showed an efficacy of the biologics rituximab and tocilizumab. The therapeutic options have most recently been expanded by the approval of the antifibrotic drug nintedanib. It is particularly beneficial in progressive fibrosing courses of ILD despite immunosuppression. The data from controlled trials on the efficacy and safety of CYC and MMF compiled in this review argue for a preferential use of MMF; however, the approval of MMF for this indication is still lacking. This is urgently needed for improved and simplified care of patients with SSc-ILD.
Exercise capacity and survival of patients with IPF is potentially impaired by pulmonary hypertension. This study aims to investigate diagnostic and prognostic properties of gas exchange during ...exercise and lung function in IPF patients with or without pulmonary hypertension. In a multicentre setting, patients with IPF underwent right heart catheterization, cardiopulmonary exercise and lung function testing during their initial evaluation. Mortality follow up was evaluated. Seventy-three of 135 patients 82 males; median age of 64 (56; 72 years) with IPF had pulmonary hypertension as assessed by right heart catheterization median mean pulmonary arterial pressure 34 (27; 43) mmHg. The presence of pulmonary hypertension was best predicted by gas exchange efficiency for carbon dioxide (cut off ≥152% predicted; area under the curve 0.94) and peak oxygen uptake (≤56% predicted; 0.83), followed by diffusing capacity. Resting lung volumes did not predict pulmonary hypertension. Survival was best predicted by the presence of pulmonary hypertension, followed by peak oxygen uptake HR 0.96 (0.93; 0.98). Pulmonary hypertension in IPF patients is best predicted by gas exchange efficiency during exercise and peak oxygen uptake. In addition to invasively measured pulmonary arterial pressure, oxygen uptake at peak exercise predicts survival in this patient population.
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