Physiology of oxygen uptake kinetics: Insights from incremental cardiopulmonary exercise testing in the Study of Health in Pomerania.

BACKGROUND: Cardiopulmonary exercise testing allows for assessment of cardiac and respiratory limitation, but is often affected by patient effort. Indices of oxygen kinetics, including the oxygen uptake efficiency slope (OUES), oxygen uptake-work-rate slope (VO2-WR slope) and the heart rate-oxygen uptake slope (HR-VO2 slope) are relatively effort independent but may be affected by patient characteristics. The objective of this study is to identify the impact of factors, such as age, gender, body size, respiratory function, smoking and beta-blockade on these parameters, as well as generate predictive equations. METHODS: 1708 volunteers from the population-based Study of Health in Pomerania underwent an incremental bicycle exercise protocol. Markers of oxygen kinetics were calculated. Participants with structural heart disease, echocardiographic or lung function pathology were excluded, leaving 577 males and 625 females. Age, height, weight, smoking, forced expiratory volume in 1 s (FEV1) and beta-blockers were analysed for their influencing power by gender. Quantile regression analysis determined the reference equations for each parameter. RESULTS: Age, gender, height, weight and FEV1 (but not percent predicted FEV1) are strongly related to OUES. Participants using beta-blockers and male smokers had significantly lower OUES values. VO2-WR slope was minimally affected by age, gender, weight and FEV1. Gender, height, weight and beta-blocker use, but not FEV1 and smoking status, were related to the HR-VO2 slope whilst age was only related in females. CONCLUSIONS: Markers of oxygen kinetics are differentially affected by patient characteristics. This study provides normal reference values for these variables thereby facilitating interpretation of oxygen uptake kinetics in health and disease.

Large-scale genome-wide association studies and meta-analyses of longitudinal change in adult lung function.

BACKGROUND: Genome-wide association studies (GWAS) have identified numerous loci influencing cross-sectional lung function, but less is known about genes influencing longitudinal change in lung function. METHODS: We performed GWAS of the rate of change in forced expiratory volume in the first second (FEV1) in 14 longitudinal, population-based cohort studies comprising 27,249 adults of European ancestry using linear mixed effects model and combined cohort-specific results using fixed effect meta-analysis to identify novel genetic loci associated with longitudinal change in lung function. Gene expression analyses were subsequently performed for identified genetic loci. As a secondary aim, we estimated the mean rate of decline in FEV1 by smoking pattern, irrespective of genotypes, across these 14 studies using meta-analysis. RESULTS: The overall meta-analysis produced suggestive evidence for association at the novel IL16/STARD5/TMC3 locus on chromosome 15 (P  =  5.71 × 10(-7)). In addition, meta-analysis using the five cohorts with ≥3 FEV1 measurements per participant identified the novel ME3 locus on chromosome 11 (P  =  2.18 × 10(-8)) at genome-wide significance. Neither locus was associated with FEV1 decline in two additional cohort studies. We confirmed gene expression of IL16, STARD5, and ME3 in multiple lung tissues. Publicly available microarray data confirmed differential expression of all three genes in lung samples from COPD patients compared with controls. Irrespective of genotypes, the combined estimate for FEV1 decline was 26.9, 29.2 and 35.7 mL/year in never, former, and persistent smokers, respectively. CONCLUSIONS: In this large-scale GWAS, we identified two novel genetic loci in association with the rate of change in FEV1 that harbor candidate genes with biologically plausible functional links to lung function.

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.

Genome-wide association analysis identifies six new loci associated with forced vital capacity.

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10(-8)) with FVC in or near EFEMP1, BMP6, MIR129-2-HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease.

SFTA3, a novel protein of the lung: three-dimensional structure, characterisation and immune activation.

The lung constantly interacts with numerous pathogens. Thus, complex local immune defence mechanisms are essential to recognise and dispose of these intruders. This work describes the detection, characterisation and three-dimensional structure of a novel protein of the lung (surfactant-associated protein 3 (SFTA3/SP-H)) with putative immunological features. Bioinformatics, biochemical and immunological methods were combined to elucidate the structure and function of SFTA3. The tissue-specific detection and characterisation was performed by using electron microscopy as well as fluorescence imaging. Three-dimensional structure generation and analysis led to the development of specific antibodies and, as a consequence, to the localisation of a novel protein in human lung under consideration of cystic fibrosis, asthma and sepsis. In vitro experiments revealed that lipopolysaccharide induces expression of SFTA3 in the human lung alveolar type II cell line A549. By contrast, the inflammatory cytokines interleukin (IL)-1ß and IL-23 inhibit expression of SFTA3 in A549. Sequence- and structure-based prediction analysis indicated that the novel protein is likely to belong to the family of lung surfactant proteins. The results suggest that SFTA3 is an immunoregulatory protein of the lung with relevant protective functions during inflammation at the mucosal sites.

Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.

Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood. We present here an agnostic investigation of genetic determinants of circulating AAT levels in a general population sample by performing a genome-wide association study (GWAS) in 1392 individuals of the SAPALDIA cohort. Five common SNPs, defined by showing minor allele frequencies (MAFs) >5%, reached genome-wide significance, all located in the SERPINA gene cluster at 14q32.13. The top-ranking genotyped SNP rs4905179 was associated with an estimated effect of ß = -0.068 g/L per minor allele (P = 1.20*10(-12)). But denser SERPINA1 locus genotyping in 5569 participants with subsequent stepwise conditional analysis, as well as exon-sequencing in a subsample (N = 410), suggested that AAT serum level is causally determined at this locus by rare (MAF<1%) and low-frequent (MAF 1-5%) variants only, in particular by the well-documented protein inhibitor S and Z (PI S, PI Z) variants. Replication of the association of rs4905179 with AAT serum levels in the Copenhagen City Heart Study (N = 8273) was successful (P<0.0001), as was the replication of its synthetic nature (the effect disappeared after adjusting for PI S and Z, P = 0.57). Extending the analysis to lung function revealed a more complex situation. Only in individuals with severely compromised pulmonary health (N = 397), associations of common SNPs at this locus with lung function were driven by rarer PI S or Z variants. Overall, our meta-analysis of lung function in ever-smokers does not support a functional role of common SNPs in the SERPINA gene cluster in the general population.

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.

Exercise blood pressure and heart rate reference values.

BACKGROUND: Besides their prognostic impact blood pressure and peak heart rate are widely used endpoint parameters for incremental exercise tests. Reference equations and ranges on both are sparse. OBJECTIVE: This study aims to describe prediction equations and reference ranges for systolic and diastolic blood pressure as well as for peak heart rate assessed during a symptom limited incremental exercise test based on a population based study--the Study of Health in Pomerania. DESIGN: For this purpose, 1708 individuals aged 25-85 years underwent cardiopulmonary exercise testing. RESULTS: After exclusion of subjects with cardiopulmonary diseases and antihypertensive medications regression analyses revealed age, sex and body mass index as statistically significant interfering factors. In accordance, prediction equations and reference ranges for blood pressure and peak heart rate with respect to sex, age and BMI have been established. CONCLUSION: This study provides a reliable set of prediction equations for blood pressure and heart rate values at peak exercise, assessed in a general population over a wide age range.

Influence of smoking and obesity on alveolar-arterial gas pressure differences and dead space ventilation at rest and peak exercise in healthy men and women.

BACKGROUND AND AIMS: Besides exercise intolerance, the assessment of ventilatory and perfusion adequacy allows additional insights in the disease pathophysiology in many cardiovascular or pulmonary diseases. Valid measurements of dead space/tidal volume ratios (VD/VT), arterial (a') - end-tidal (et) carbon dioxide (CO2) and oxygen (O2) pressure differences (p(a'-et)CO2) and (p(et-a')O2), and alveolar (A)-a' O2 pressure differences (p(A-a')O2) require using blood samples in addition to gas exchange analyses on a breath-by-breath-basis. Smoking and nutritional status are also important factors in defining disorders. Using a large healthy population we considered the impact of these factors to develop useful prediction equations. METHODS AND RESULTS: Incremental cycle exercise protocols were applied to apparently healthy volunteer adults who did not have structural heart disease or echocardiographic or lung function pathologies. Age, height, weight, and smoking were analysed for their influence on the target parameters in each gender. Reference values were determined by regression analyses. The final study sample consisted of 476 volunteers (190 female), aged 25-85 years. Smoking significantly influences p(A-a')O2 and p(a'-et)CO2 at rest and peak exercise, and VD/VT during exercise. Obesity influences upper limits of VD/VT, p(a'-et)CO2 and p(et-a')O2 at rest as well as p(A-a')O2 and p(et-a')O2 at exercise. Reference equations for never-smokers as well as for apparently healthy smokers considering influencing factors are given. CONCLUSION: Gender, age, height, weight, and smoking significantly influence gas exchange. Considering all of these factors this study provides a comprehensive set of reference equations derived from a large number of participants of a population-based study.

Static lung volumes and airway resistance reference values in healthy adults.

BACKGROUND AND OBJECTIVE: The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones. METHODS: Body plethysmography was applied in 1809 participants (885 males) of a cross-sectional, population-based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack-year smoking history >10 years and participants with a body mass index >30 kg/m(2) were excluded. In total, 686 healthy individuals (275 males) aged 25-85 years were assessed. RESULTS: Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight. CONCLUSIONS: The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up-to-date reference equations.

Genome-wide joint meta-analysis of SNP and SNP-by-smoking interaction identifies novel loci for pulmonary function.

Genome-wide association studies have identified numerous genetic loci for spirometic measures of pulmonary function, forced expiratory volume in one second (FEV(1)), and its ratio to forced vital capacity (FEV(1)/FVC). Given that cigarette smoking adversely affects pulmonary function, we conducted genome-wide joint meta-analyses (JMA) of single nucleotide polymorphism (SNP) and SNP-by-smoking (ever-smoking or pack-years) associations on FEV(1) and FEV(1)/FVC across 19 studies (total N = 50,047). We identified three novel loci not previously associated with pulmonary function. SNPs in or near DNER (smallest P(JMA = )5.00×10(-11)), HLA-DQB1 and HLA-DQA2 (smallest P(JMA = )4.35×10(-9)), and KCNJ2 and SOX9 (smallest P(JMA = )1.28×10(-8)) were associated with FEV(1)/FVC or FEV(1) in meta-analysis models including SNP main effects, smoking main effects, and SNP-by-smoking (ever-smoking or pack-years) interaction. The HLA region has been widely implicated for autoimmune and lung phenotypes, unlike the other novel loci, which have not been widely implicated. We evaluated DNER, KCNJ2, and SOX9 and found them to be expressed in human lung tissue. DNER and SOX9 further showed evidence of differential expression in human airway epithelium in smokers compared to non-smokers. Our findings demonstrated that joint testing of SNP and SNP-by-environment interaction identified novel loci associated with complex traits that are missed when considering only the genetic main effects.

Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function.

Pulmonary function measures reflect respiratory health and are used in the diagnosis of chronic obstructive pulmonary disease. We tested genome-wide association with forced expiratory volume in 1 second and the ratio of forced expiratory volume in 1 second to forced vital capacity in 48,201 individuals of European ancestry with follow up of the top associations in up to an additional 46,411 individuals. We identified new regions showing association (combined P < 5 × 10(-8)) with pulmonary function in or near MFAP2, TGFB2, HDAC4, RARB, MECOM (also known as EVI1), SPATA9, ARMC2, NCR3, ZKSCAN3, CDC123, C10orf11, LRP1, CCDC38, MMP15, CFDP1 and KCNE2. Identification of these 16 new loci may provide insight into the molecular mechanisms regulating pulmonary function and into molecular targets for future therapy to alleviate reduced lung function.

Mental health problems, obstructive lung disease and lung function: findings from the general population.

OBJECTIVE: There is cumulative evidence for a strong association of obstructive lung disease, i.e. asthma and COPD, with poor mental health, particularly with anxiety disorders and major depression. However, studies relating mental health problems to objective measures of lung function as assessed by spirometry are lacking. METHODS: The 12-month prevalence of specific psychopathological syndromes among 1772 adults from the general population was estimated by a structured interview. Additionally, participants underwent spirometry and were asked about obstructive lung disease in the year prior to the study. Logistic and linear regression models were used to relate obstructive lung disease and spirometrically defined airway obstruction to mental health problems. RESULTS: Mental health problems were found in 35.7% of the participants. After adjusted for sociodemographic, clinical and life-style factors, asthma and chronic bronchitis were associated with almost all domains of mental health problems. In contrast, independent of its definition, spirometric airflow limitation was only related to generalized anxiety (odds ratios ranging from 2.3 to 2.7). A reduced ratio of forced expiratory volume in one second to forced vital capacity was associated with mental health problems in general and panic and general anxiety in particular. CONCLUSION: Our findings suggest an association of objective measure of airflow limitation to generalized anxiety and panic. While the causal relationship between obstructive lung disease, airflow limitation and anxiety remains to be determined, clinicians should pay diagnostic attention to the significant overlap of these conditions.

Serum thyrotropin levels and blood pressure response to exercise in a population-based study.

BACKGROUND: Studies on the relation between thyroid function and exercise blood pressure (EBP) are rare and not population-based, and have yielded inconsistent results. The aim of this study was to investigate whether serum thyrotropin (TSH) levels are related to increased EBP. METHODS: Cross-sectional data from 1438 subjects (711 women) aged 25-83 years without histories of cardiovascular diseases from the 5-year follow-up of the population-based Study of Health in Pomerania (SHIP-1) were analyzed. Blood pressure was measured at the 100 W stage of a symptom-limited bicycle ergometry test. Increased EBP was defined as a value above the sex- and age-specific 80th percentile of participants with serum TSH levels within the reference range (0.25-2.12 mIU/L). RESULTS: There was no association between serum TSH levels and EBP after adjusting for sex, age, waist circumference, diabetes mellitus, smoking status, and antihypertensive medication. The odds for increased systolic EBP (odds ratio 1.24, 95% confidence interval 0.88; 1.76) and diastolic EBP (odds ratios 0.98, 95% confidence interval 0.70; 1.39) as well as for exercise-induced increase of systolic and diastolic blood pressure were not significantly different between subjects with high and low serum TSH levels within the reference range. Similar findings were found for both subjects with TSH levels below and above the reference range, respectively. CONCLUSIONS: We conclude that serum TSH levels are not associated with exercise-related blood pressure response.

Peripheral endothelial dysfunction is associated with gas exchange inefficiency in smokers.

AIMS: To assess the cross-sectional association between exercise capacity, gas exchange efficiency and endothelial function, as measured by flow-mediated dilation (FMD) and nitroglycerin-mediated dilation (NMD) of the brachial artery, in a large-scale population-based survey. METHODS: The study population was comprised of 1416 volunteers 25 to 85 years old. Oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2) and ventilatory efficiency (VE vs. VCO2 slope and VE/VCO2@AT) were assessed on a breath-by-breath basis during incremental symptom-limited cardiopulmonary exercise. FMD and NMD measurements at rest were performed using standardised ultrasound techniques. RESULTS: Multivariable logistic regression analyses revealed a significant association between FMD and ventilatory efficiency in current smokers but not in ex-smokers or non-smokers. There was no association between FMD and VO2@AT or peak VO2. In current smokers, for each one millimetre decrement in FMD, VE/VCO2@AT improved by -3.6 (95% CI -6.8, -0.4) in the overall population [VE vs. VCO2 slope -3.9 (-7.1, -0.6)]. These results remained robust after adjusting for all major influencing factors. Neither exercise capacity nor ventilatory efficiency was significantly associated with NMD. CONCLUSION: In current smokers, FMD is significantly associated with ventilatory efficiency. This result may be interpreted as a potential clinical link between smoking and early pulmonary vasculopathy due to smoking.

Association between serum testosterone and sex hormone-binding globulin and exercise capacity in men: results of the Study of Health in Pomerania (SHIP).

Testosterone exerts a widespread pattern of effects on metabolism and body composition, and interest is gaining in its correlation with physical fitness. The main focus of our study was to investigate the association of total serum testosterone and sex hormone-binding globulin (SHBG) levels on exercise capacity and maximal power output in men using a cross-sectional, population-based adult cohort. From the Study of Health in Pomerania (SHIP), 624 men age 25 to 85 years who underwent a standardized progressive incremental exercise protocol on a cycle ergometer were included in the analyses. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (V'O(2) at L) and peak exercise (V'O(2 peak)) as well as maximal power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity, and smoking were performed. Further, linear regression analyses with cubic splines and sensitivity analyses were undertaken. At peak exercise performance, testosterone and SHBG levels showed no associations with V'O(2 peak), V'O(2) at L as well as maximal power output, even after controlling for confounding factors including age, body mass index, physical activity, and smoking. An adverse association between the free testosterone index and V'O(2) at L was found. Linear regression analyses with cubic splines did not change the main results. In conclusion, this is the first study focusing on the association of total serum testosterone and SHBG on exercise capacity and physical performance in healthy volunteers based on a large-scale population-based study. After adjustment for relevant influencing factors, neither total serum testosterone nor SHBG levels had any interference with peak exercise capacity, aerobic exercise capacity, or maximal power output in men.

Omalizumab treatment and exercise capacity in severe asthmatics - results from a pilot study.

BACKGROUND: In patients with moderate to severe allergic asthma, clinical effectiveness of omalizumab, an approved anti-IgE-reacting substance, is usually assessed by pulmonary function testing (PFT), symptom scores and physicians judgement. AIMS: We postulate that cardiopulmonary exercise testing (CPET) may provide an additional option to verify symptomatic changes in patients with allergic asthma. METHODS: Ten consecutive patients with allergic asthma were treated with omalizumab. Prior to and after 16 weeks of treatment all patients underwent PFT and symptom-limited CPET. Results were compared to 10 asthmatic controls without omalizumab medication. Symptoms were assessed according to investigators judgement (IGETE). RESULTS: All 20 patients showed a significantly impaired exercise capacity at baseline [peak oxygen uptake (VO(2)) 71 ± 16% predicted]. In patients with omalizumab, peakVO(2) increased from 13.8 (8.4-21.4) to 16.8 (11.2-23.9) ml/kg/min (p < 0.05), VO(2) at anaerobic threshold increased by 22% [9.8 (3.3-15.2) to 12.3 (6.7-14.4) ml/kg/min (p < 0.05)]. There was no improvement in the controls. The increase in VO(2) was significantly correlated to the improvement in symptoms. All patients revealed dynamic hyperinflation under exercise with a decreasing extent with omalizumab treatment. CONCLUSION: This study suggests that CPET may provide additional and useful tools to assess and verify the individual clinical response to omalizumab treatment. An improvement in exercise capacity can reliably mirror changes in quality of life and IGETE. Patients with omalizumab experience significant improvements in their initially impaired exercise capacity. CPET can be safely accomplished in patients with severe asthma.

Lung function reference values in different German populations.

BACKGROUND: Spirometry is a frequently performed lung function test and an important tool in medical surveillance examinations of pulmonary diseases. The interpretation of lung function relies on the comparison to reference values derived from a healthy population. The study aim was to compare the lung function data of three representative population-based German studies (Study of Health in Pomerania [SHIP-1], Cooperative Health Research in the Region of Augsburg [KORA-S3] and European Community Respiratory Health Survey Erfurt [ECRHS-I Erfurt]) with existing European spirometry reference values and to establish a new set of comprehensive German prediction equations. METHODS: Spirometry was performed in 4133 participants of three population-based surveys using almost identical standardised methods. Current and former smokers, subjects with cardiopulmonary disorders or on medication with potential influence on lung function were excluded. Sex specific prediction equations were established by quantile regression analyses. Comparison was performed to existing European reference values. RESULTS: The healthy reference sample consisted of 1302 (516 male) individuals, aged 20-80 years. Sex specific comprehensive prediction equations adjusted for age and height are provided. Significant differences were found in comparison to previous studies with pronounced lower values of the current population if applying historic prediction equations. CONCLUSION: The results contribute to the interpretation of lung function examination in providing a comprehensive set of spirometry reference values obtained in a large number of healthy volunteers. Whereas the differences in between the investigated studies are negligible, striking divergence was detected in comparison to historic and recent European spirometry prediction values.

Association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in healthy volunteers: results of the Study of Health in Pomerania.

BACKGROUND: Insulin-like growth factor I (IGF-I) and its binding protein 3 (IGFBP-3) are central mediators of endocrine effects of growth hormone and there is increasing evidence for an association with muscle strength and exercise capacity. The aim of the present study was to clarify the possible association of circulating IGF-I and IGFBP-3 concentrations and exercise capacity in a general adult population. MATERIALS AND METHODS: From the Study of Health in Pomerania (SHIP) 1332 subjects aged 25 to 85 years participated in a standardised symptom limited cardiopulmonary exercise test on a bicycle. Exercise capacity was characterized by oxygen uptake at anaerobic threshold (VO2@AT), peak exercise (peakVO2), oxygen pulse and maximum power output at peak exertion. Multivariable linear regression analyses adjusted for age, sex, body mass index, physical activity and smoking were performed. RESULTS: At peak exercise performance, in women IGF-I showed significant associations to peakVO2 and maximum power output, IGF-I/IGFBP-3 ratio was associated with maximum power output. In men, this association was not consistently reproducible. Neither IGF-I nor IGFBP-3 did reveal any association to VO2@AT in both genders. CONCLUSION: Serum IGF-I concentrations are associated with peak exercise capacity in healthy women, but not in men over a wide range in ages, body sizes and activity scores.