Anne Obst

Cohort Profile: The Study of Health in Pomerania

Henry Volzke, y Dietrich Alte,1y Carsten Oliver Schmidt, Dorte Radke, Roberto Lorbeer, Nele Friedrich, Nicole Aumann, Katharina Lau, Michael Piontek, Gabriele Born, Christoph Havemann, Till Ittermann, Sabine Schipf, Robin Haring, Sebastian E Baumeister, Henri Wallaschofski, Matthias Nauck, Stephanie Frick, Andreas Arnold, Michael Junger, Julia Mayerle, Matthias Kraft, Markus M Lerch, Marcus Dorr, Thorsten Reffelmann, Klaus Empen, Stephan B Felix, Anne Obst, Beate Koch, Sven Glaser, Ralf Ewert, Ingo Fietze, Thomas Penzel, Martina Doren, Wolfgang Rathmann, Johannes Haerting, Mario Hannemann, Jurgen Ropcke, Ulf Schminke, Clemens Jurgens, Frank Tost, Rainer Rettig, Jan A Kors, Saskia Ungerer, Katrin Hegenscheid, Jens-Peter Kuhn, Julia Kuhn, Norbert Hosten, Ralf Puls, Jorg Henke, Oliver Gloger, Alexander Teumer, Georg Homuth, Uwe Volker, Christian Schwahn, Birte Holtfreter, Ines Polzer, Thomas Kohlmann, Hans J Grabe, Dieter Rosskopf, Heyo K Kroemer, Thomas Kocher, Reiner Biffar,17,y Ulrich John20y and Wolfgang Hoffmann1y

Agreement of different methods for assessing sleep characteristics: a comparison of two actigraphs, wrist and hip placement, and self-report with polysomnography

OBJECTIVE To assess the agreement of sleep parameters measured by two actigraphs (SOMNOwatch plus, ActiGraph GT3X+) at two different placements (wrist, hip) and of self-reported sleep with polysomnography (PSG). METHODS We estimated agreement with PSG for total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), number of awakenings after sleep onset (NASO), and sleep efficiency (SE%) for 100 participants of the general population, aged 18-75 years by judging mean differences to PSG and intervals of agreement using Bland-Altman plots. RESULTS Mean difference to PSG for TST was 8.3 min (95% confidence intervals [CI] -7.4; 24.1) for SOMNOwatch plus (wrist), 39.8 min (95% CI 24.3; 55.3) for self-report, -79.0 min (95% CI -89.0; -68.9) for SOMNOwatch plus (hip), and -81.1 min (95% CI -91.9; -70.4) for GT3X+ (hip), respectively. The width of intervals of agreement differed with the placement of the devices. Mean differences to PSG were higher for hip-based measurements compared with wrist placement for most parameters. CONCLUSIONS Agreement of sleep parameters assessed by actigraphy with PSG differs with the placement of the device and is limited for hip-based measurements. Agreement of self-report with PSG is comparable to that of actigraphy for some parameters.

Incremental prognostic value of cardiopulmonary exercise testing and resting haemodynamics in pulmonary arterial hypertension

BACKGROUND Pulmonary arterial hypertension (PAH) is a fatal disease despite recent treatment advances. Individual risk stratification is important. Exercise capacity and invasive haemodynamic data are both relevant, but data on the combined prognostic power are lacking. METHODS 226 consecutive patients with idiopathic or familial PAH were included at seven specialised tertiary centres. All patients underwent right heart catheterization and cardiopulmonary exercise testing (CPET). RESULTS During follow-up (1508 ± 1070 days) 72 patients died and 30 underwent transplantation. On multivariate analysis percentage of predicted peak oxygen uptake (%predicted peak VO2 [risk ratio 0.95]), pulmonary vascular resistance (PVR [1.105,]) and increase in heart rate during exercise (ΔHR [0.974]) were independent prognostic predictors (all p<0.0001). Peak VO2 allowed for risk stratification with a survival of 100, 92.9, 87.4 and 69.6% at 1 year and 97.7, 63.2, 41 and 23% at 5 years for the 4th, 3rd, 2nd and 1st quartiles, respectively. Dichotomizing by median peak VO2 and intra-group median PVR showed a worse 1-year survival for patients with low peak VO2/higher PVR compared to patients with low peak VO2/low PVR, high peak VO2/high PVR and high peak VO2/low PVR (65 vs. 93, 93, 100%, p<0.001). At 10 years survival was different for all 4 subgroups (19 vs. 25 vs. 48 vs. 75%, adjusted p<0.05). CONCLUSIONS Peak VO2, PVR and ΔHR independently predict prognosis in patients with PAH. Low peak VO2, high PVR and low ΔHR refer to poor prognosis. Combined use of peak VO2 and PVR provides accurate risk stratification underlining the complementary prognostic information from cardiopulmonary exercise testing and resting invasive haemodynamic data.

Are serum thyrotropin levels within the reference range associated with endothelial function

AIMS High serum thyrotropin (TSH) levels within the reference range might be associated with an increased cardiovascular risk. In the present study, we investigated the association between serum TSH levels and flow-mediated dilation (FMD) as a measure of endothelial dysfunction. METHODS AND RESULTS The study population comprised 1364 subjects (670 women) aged 25-85 years with serum TSH levels between 0.25 and 2.12 mIU/L recruited from 5-year follow-up of the Study of Health in Pomerania. No interventions were performed. Measurements of FMD and nitrate-mediated dilation (NMD) were performed in the supine position using standardized ultrasound techniques. FMD and NMD values below the median of each distribution were considered decreased. Analyses adjusted for age, sex, smoking, and systolic and diastolic blood pressure revealed a non-significant inverse trend between serum TSH levels and FMD (P = 0.130). Subjects with serum TSH levels above the highest quartile had lower median FMD values relative to subjects with serum TSH levels below the lowest quartile (4.86 vs. 5.43%, P < 0.05). A linear inverse trend between serum TSH levels and decreased FMD barely missed statistical significance (P = 0.138). Subjects with high serum TSH levels had higher odds of decreased FMD relative to subjects with low serum TSH levels (odds ratio 1.42; 95% confidence interval 1.02; 1.96; P < 0.05). These associations were more pronounced in men than in women. There were no such associations for NMD. CONCLUSION Serum TSH levels within the upper reference range are associated with impaired endothelial function. Our findings contribute to the discussion on whether the upper TSH reference limit should be redefined.

Association of airflow limitation with trauma exposure and post-traumatic stress disorder

Trauma exposure and post-traumatic stress disorder (PTSD) are associated with self-reported asthma and chronic obstructive pulmonary disease. However, these conditions have not yet been related to objective measures of lung function. 1,772 adults from the general population were assessed regarding their medical histories and spirometric lung function. Additionally, they were administered a PTSD interview, and assigned to three groups: no trauma; trauma, but no PTSD; and trauma with PTSD. Adjusting for sociodemographic, clinical and lifestyle factors, subjects with PTSD had significantly higher odds ratios for most asthma-related symptoms than PTSD-negative participants (OR 3.2–8.8). The mean ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) was lowest in the PTSD group and highest in those without trauma exposure. Traumatic stress was independently associated with FEV1 and FEV1/FVC. Participants with PTSD, compared with those without, had a significantly increased risk for airflow limitation independent of its definition (OR 4.2–7.8). This is the first study relating traumatic stress and PTSD, respectively, to objective parameters of lung function. Our findings suggest an association of trauma exposure and PTSD with airflow limitation, which may be mediated by inflammatory processes.

Subclinical hyperthyroidism is not associated with progression of cardiac mass and development of left ventricular hypertrophy in middle-aged and older subjects: results from a 5-year follow-up

Background  Decreased serum TSH levels are associated with increased cardiovascular mortality in elderly, and subclinical hyperthyroidism (SCH) was associated with left ventricular hypertrophy (LVH) as a predictor of cardiovascular mortality in some cross‐sectional and case‐control studies. The aim was to assess whether SCH independently impacts development of LVH over time.

Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences–Comorbidities Network Study

Rationale: Knowledge about the prevalence of objectively assessed peripheral artery disease (PAD) and its clinical relevance in patients with chronic obstructive pulmonary disease (COPD) is scarce. Objectives: We aimed to: (1) assess the prevalence of PAD in COPD compared with distinct control groups; and (2) study the association between PAD and functional capacity as well as health status. Methods: The ankle‐brachial index was used to diagnose PAD (ankle‐brachial index ≤ 0.9). The 6‐minute‐walk distance, health status (St. Georges Respiratory Questionnaire), COPD Assessment Test, and EuroQol‐5‐Dimensions were assessed in patients enrolled in the German COPD and Systemic Consequences‐Comorbidities Network cohort study. Control groups were derived from the Study of Health in Pomerania. Measurements and Main Results: A total of 2,088 patients with COPD (61.1% male; mean [SD] age, 65.3 [8.2] years, GOLD (Global Initiative for Chronic Obstructive Lung Disease) stages I‐IV: 9.4, 42.5, 37.5, and 10.5%, respectively) were included, of which 184 patients (8.8%; GOLD stage I‐IV: 5.1, 7.4, 11.1, and 9.5%, respectively, vs. 5.9% in patients with GOLD stage 0 in the COPD and Systemic Consequences‐Comorbidities Network) had PAD. In the Study of Health in Pomerania, PAD ranged from 1.8 to 4.2%. Patients with COPD with PAD had a significantly shorter 6‐minute‐walk distance (356 [108] vs. 422 [103] m, P < 0.001) and worse health status (St. Georges Respiratory Questionnaire: 49.7 [20.1] vs. 42.7 [20.0] points, P < 0.001; COPD Assessment Test: 19.6 [7.4] vs. 17.9 [7.4] points, P = 0.004; EuroQol‐5‐Dimensions visual analog scale: 51.2 [19.0] vs. 57.2 [19.6], P < 0.001). Differences remained significant after correction for several confounders. Conclusions: In a large cohort of patients with COPD, 8.8% were diagnosed with PAD, which is higher than the prevalence in control subjects without COPD. PAD was associated with a clinically relevant reduction in functional capacity and health status.

Pulmonary Hypertension in Patients with Idiopathic Pulmonary Fibrosis – The Predictive Value of Exercise Capacity and Gas Exchange Efficiency

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.

Impact of Different Definitions of Airflow Limitation on the Prevalence of Chronic Obstructive Pulmonary Disease in the General Population

Background: Recent surveys report a surprisingly high prevalence of chronic obstructive pulmonary disease (COPD) worldwide. However, there is evidence that the application of a fixed ratio of forced expiratory volume in 1 s (FEV1) to forced vital capacity (FVC) may result in a relevant misclassification of airflow limitation. Objectives: The definition of airflow limitation does have a significant impact on its prevalence. Methods: Individual values of lung volumes were assessed in comparison to a reference population by applying either a fixed ratio below 0.7 or the fifth percentile of FEV1 in relation to FVC. Based on a large-scale population-based survey, reference equations for lung volumes were derived by quantile regression analysis based on 1,809 subjects aged 25–85 years. Both functional definitions were applied to calculate the prevalence of airflow limitation. Results: The prevalence of airflow limitation was significantly higher when applying the fifth percentile compared to the fixed ratio of 0.7 for all age groups and both sexes (all 6.7 vs. 1.9%; women 6.7 vs. 1.3%; men 6.6 vs. 2.6%). Almost 26% of the subjects with airflow limitation complained of dyspnea, whereas COPD had not been previously diagnosed by a physician in 87%. Conclusion: The definition of airflow limitation has a major impact on the observed prevalence rates.

Oxygen Uptake Efficiency Slope and Breathing Reserve, Not Anaerobic Threshold, Discriminate Between Patients With Cardiovascular Disease Over Chronic Obstructive Pulmonary Disease.

Objectives The study sought to compare the relative discrimination of various cardiopulmonary exercise testing (CPX) variables between cardiac and respiratory disease. Background CPX testing is used in many cardiorespiratory diseases. However, discrimination of cardiac and respiratory dysfunction can be problematic. Anaerobic threshold (AT) and oxygen-uptake to work-rate relationship (VO2/WR slope) have been proposed as diagnostic of cardiac dysfunction, but multiple variables have not been compared. Methods A total of 73 patients with chronic obstructive pulmonary disease (COPD) (n = 25), heart failure with reduced ejection fraction (HFrEF) (n = 40), or combined COPD and HFrEF (n = 8) were recruited and underwent CPX testing on a bicycle ergometer. Following a familiarization test, each patient underwent a personalized second test aiming for maximal exercise after ∼10 min. Measurements from this test were used to calculate area under the receiver-operator characteristic curve (AUC). Results Peak VO2 was similar between the 2 principal groups (COPD 17.1 ± 4.6 ml/min/kg; HFrEF 16.4 ± 3.6 ml/min/kg). Breathing reserve (AUC: 0.91) and percent predicted oxygen uptake efficiency slope (OUES) (AUC: 0.87) had the greatest ability to discriminate between COPD and HFrEF. VO2/WR slope performed significantly worse (AUC: 0.68). VO2 at the AT did not discriminate (AUC for AT as percent predicted peak VO2: 0.56). OUES and breathing reserve remained strong discriminators when compared with an external cohort of healthy matched controls, and were comparable to B-type natriuretic peptide. Conclusions Breathing reserve and OUES discriminate heart failure from COPD. Despite it being considered an important determinant of cardiac dysfunction, the AT could not discriminate these typical clinical populations while the VO2/WR slope showed poor to moderate discriminant ability. (Identifying an Ideal Cardiopulmonary Exercise Test Parameter [PVA]; NCT01162083)