A study of biological and lifestyle factors, including within-subject variation, affecting concentrations of growth differentiation factor 15 in serum

2019 ◽  
Vol 57 (7) ◽  
pp. 1035-1043 ◽  
Author(s):  
Magdalena Krintus ◽  
Federica Braga ◽  
Marek Kozinski ◽  
Simona Borille ◽  
Jacek Kubica ◽  
...  
Keyword(s):  
Smoking Status ◽  
Adult Population ◽  
Lifestyle Factors ◽  
Biological Variation ◽  
Healthy Population ◽  
Intraindividual Variation ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Reference Change Value ◽  
Age Related

Abstract Background Growth differentiation factor 15 (GDF-15) is an emerging cardiovascular biomarker, and a fully automated immunoassay has recently become available. The objectives of the study were to identify biological and lifestyle factors affecting serum GDF-15 concentrations and derive robust reference intervals, and to estimate GDF-15 within-subject biological variation and derived indices. Methods A presumably healthy population of 533 questionnaire-screened adults was used to identify the biological and lifestyle determinants of serum GDF-15. Following stringent exclusion criteria, a final group of 173 individuals was selected to establish GDF-15 reference interval. Twenty-six healthy volunteers were enrolled in the biological variation substudy. Results Using a multiple regression model, age, B-type natriuretic peptide and C-reactive protein as well as smoking status were significantly related to serum GDF-15 concentrations. The upper reference limit (URL) for serum GDF-15 concentrations (90% confidence interval [CI]) was 866 ng/L (733–999 ng/L), with no sex-related difference. Although GDF-15 tended to increase with age, the weak dependence of marker from age does not justify age-related URL. The within-subject CV was 6.3% (95% CI, 4.5%–8.5%), with no sex difference in intraindividual variances. The reference change value (RCV) for GDF-15 was 23%, and two are the specimens required to ensure that the mean GDF-15 result is within ±10% of the individual’s homeostatic set point. Conclusions By identifying the main factors influencing serum GDF-15 concentrations, we robustly established the URL to be applied in adult population. As intraindividual variation of GDF-15 is relatively low, monitoring longitudinal changes in its concentrations over time using RCV can be a good alternative for interpreting GDF-15 in clinical setting.

scholarly journals Biological variation and reference change value data for serum copper, zinc and selenium in Turkish adult population

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Ceylan Bal ◽  
Serpil Erdogan ◽  
Gamze Gök ◽  
Cemil Nural ◽  
Betül Özbek ◽  
...  
Keyword(s):  
Adult Population ◽  
Reference Intervals ◽  
Serum Copper ◽  
Biological Variation ◽  
Serum Samples ◽  
Reference Change Value ◽  
Index Of Individuality ◽  
Copper Zinc ◽  
Clinically Significant ◽  
Analytical Variation

Abstract Objectives Calculation of biological variation (BV) components is very important in evaluating whether a test result is clinically significant. The aim of this study is to analyze BV components for copper, zinc and selenium in a cohort of healthy Turkish participants. Methods A total of 10 serum samples were collected from each of the 15 healthy individuals (nine female, six male), once a week, during 10 weeks. Copper, zinc and selenium levels were analyzed by atomic absorption spectrometer. BV parameters were calculated with the approach suggested by Fraser. Results Analytical variation (CVA), within-subject BV (CVI), between-subject BV (CVG) values were 8.4, 7.1 and 4.3 for copper; 4.2, 9.1 and 13.7 for zinc; 7.6, 2.5 and 6.9 for selenium, respectively. Reference change values (RCV) were 30.46, 27.56 and 22.16% for copper, zinc and selenium, respectively. The index of individuality (II) values were 1.65, 0.66 and 0.36 for copper, zinc and selenium, respectively. Conclusions According to the results of this study, traditional reference intervals can be used for copper but we do not recommend using it for zinc and selenium. We think that it would be more accurate to use RCV value for zinc and selenium in terms of following significant changes in recurrent results of a patient.

scholarly journals Growth differentiation factor-15 as a biomarker of strength and recovery in survivors of acute respiratory failure

Thorax ◽  
2019 ◽  
Vol 74 (11) ◽  
pp. 1099-1101 ◽  
Author(s):  
Brian J Rosenberg ◽  
Michio Hirano ◽  
Catarina M Quinzii ◽  
Elizabeth Colantuoni ◽  
Dale M Needham ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Respiratory Failure ◽  
Acute Respiratory Failure ◽  
Mitochondrial Myopathy ◽  
Health Evaluation ◽  
Growth Differentiation Factor 15 ◽  
Hand Grip ◽  
Differentiation Factor ◽  
Age Related

Muscle mitochondrial dysfunction is implicated in intensive care unit-acquired weakness, but there is no serum biomarker of muscle mitochondrial function for critical illness survivors. Higher serum growth differentiation factor-15 (GDF-15) is a biomarker of inherited mitochondrial myopathy disease and is associated with mortality in several age-related diseases. Among 142 older (age ≥ 65 years) survivors of acute respiratory failure, we found that higher serum GDF-15 measured during the week prior to hospital discharge was cross-sectionally associated with weaker diaphragm, limb and hand-grip strength, and longitudinally associated with lower rates of functional recovery over 6 months, independent of age, sex, pre-existing disability, comorbidity, frailty, Acute Physiology and Chronic Health Evaluation II scores and concurrent interleukin-6 levels.

scholarly journals Growth differentiation factor-15 is associated with age-related monocyte immunosenescence

2020 ◽  
Author(s):  
Brandt D. Pence ◽  
Johnathan R. Yarbro ◽  
Russell S. Emmons
Keyword(s):  
Mitochondrial Function ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Immune Cell ◽  
Inflammatory Responses ◽  
Cell Subset ◽  
Cytokine Gene Expression ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Age Related

ABSTRACTBackgroundImmunosenescence is an age-associated decrease in function of immune cells precipitated by a variety of mechanisms and affecting nearly every immune cell subset. In myeloid cell subsets, aging reduces numbers of phagocytes and impairs their functional abilities, including antigen presentation, phagocytosis, and bacterial clearance. Recently, we have described an aging effect on several functions indicating immunosenescence in monocytes, including impaired mitochondrial function and reduced inflammatory cytokine gene expression during stimulation with lipopolysaccharide (LPS). We hypothesized that circulating factors altered by the aging process underly these changes. Growth/differentiation factor-15 (GDF-15) is a distant member of the transforming growth factor-beta superfamily that has known anti-inflammatory effects in macrophages and has recently been shown to be highly differentially expressed during aging. We used biobanked serum and plasma samples to assay circulating GDF-15 levels in subjects from our previous studies and examined correlations between GDF-15 levels and monocyte mitochondrial function and inflammatory responses.ResultsMonocyte interleukin-6 production due to lipopolysaccharide stimulation was negatively correlated to plasma GDF-15 levels. Additionally, serum GDF-15 was positively correlated to circulating CD16+ monocyte proportions and negatively correlated to monocyte mitochondrial respiratory capacity.ConclusionsThe results of these analyses suggest that GDF-15 is a potential circulating factor affecting a variety of monocyte functions and promoting monocyte immunosenescence, and thus may be an attractive candidate for therapeutic intervention to ameliorate this.

scholarly journals Increased Blood Retinol Levels Are Associated With a Reduced Risk of TIA or Stroke in an Adult Population: Lifestyle Factors- and CVDs-Stratified Analysis

2021 ◽  
Vol 8 ◽  
Author(s):  
Linjuan Guo ◽  
Ying Huang ◽  
Rong Wan ◽  
Yang Shen ◽  
Kui Hong
Keyword(s):  
Adult Population ◽  
The United States ◽  
Lifestyle Factors ◽  
Inverse Association ◽  
Cross Sectional ◽  
Chronic Respiratory Diseases ◽  
Age Related ◽  
Multivariable Analyses ◽  
Ischemic Attack ◽  
Stratified Analysis

Background: Data on the existing evidence for the association between blood retinol and transient ischemic attack (TIA)/stroke risk are limited, and the results are inconclusive. This study aimed to further assess the associations between the blood retinol levels and the risk of TIA/stroke after controlling the lifestyle factors and age-related confounders.Methods: The cross-sectional data from 1,113 individuals (aged 34–84 years old) were obtained from the Midlife in the United States (MIDUS) study. The multivariable analyses were performed to investigate the association of blood retinol levels with ever and currently TIA/stroke.Results: There was an inverse association between the blood retinol levels and the risk of ever TIA or stroke (for per 1 μmol/L adjusted odds ration [OR]: 0.93; 95% CI: 0.89–0.97; for per 1-SD adjusted OR: 0.89; 95% CI: 0.83–0.96) and currently diagnosed TIA or stroke (for per 1 μmol/L adjusted OR: 0.91; 95% CI: 0.87–0.96; for per 1-SD adjusted OR: 0.84; 95% CI: 0.80–0.91) after controlling the lifestyle factors and age-related confounders. The significance of these associations was maintained after a sensitivity analysis and involving “ever chronic respiratory diseases” as a covariate. Moreover, the stratified analyses suggested that the inverse associations could be affected by overweight [body mass index (BMI) ≥ 28, kg/m2], hypertension, and diabetes.Conclusions: A significant inverse association between blood retinol and the risk of TIA or stroke was found. This inverse association did not change even after adjustment for many potential confounders. Moreover, the potential protective effect of retinol on TIA/stroke could be blunted by overweight [BMI ≥ 28, kg/m2], hypertension, and diabetes.

scholarly journals Growth Differentiation Factor-15 as a Potent Predictor of Long-Term Mortality among Subjects with Osteoarthritis

2020 ◽  
Vol 9 (10) ◽  
pp. 3107
Author(s):  
Natalie Arnold ◽  
Martin Rehm ◽  
Gisela Büchele ◽  
Raphael Simon Peter ◽  
Rolf Erwin Brenner ◽  
...  
Keyword(s):  
Troponin I ◽  
Smoking Status ◽  
Walking Distance ◽  
Growth Differentiation Factor 15 ◽  
Potent Predictor ◽  
Differentiation Factor ◽  
Bottom Quartile ◽  
Increased Risk ◽  
All Cause Mortality

Background: Subjects with osteoarthritis (OA) are at increased risk for cardiovascular (CV) and all-cause mortality. Whether biomarkers improve outcome prediction in these patients remains to be elucidated. We investigated the association between growth differentiation factor 15 (GDF-15), a novel stress-responsive cytokine, and long-term all-cause mortality among OA patients. Methods: Within the Ulm Osteoarthritis Study, GDF-15 has been measured in the serum of 636 subjects, who underwent hip or knee arthroplasty between 1995 and 1996 (median age 65 years). Results: During a median follow-up of 19.7 years, a total of 402 deaths occurred. GDF-15 was inversely associated with walking distance. Compared to the bottom quartile (Q), subjects within the top quartile of GDF-15 demonstrated a 2.69-fold increased risk of dying (hazard ratio (HR) (95% confidence interval (CI)) 2.69 (1.82–3.96) adjusted for age, sex, BMI, smoking status, localization of OA, diabetes, maximum walking distance, total cholesterol, and cystatin C. Further adjustment for NT-proBNP, troponin I, and hs-C-reactive protein did not change the results appreciably (HR (95%CI) 1.56 (1.07–2.28); 1.75 (1.21–2.55); 2.32 (1.55–3.47) for Q2, Q3, and Q4 respectively, p for trend < 0.001). Conclusions: In subjects with OA, GDF-15 represents a potent predictor of decreased survival over >20 years, independently of conventional CV risk factors, renal, cardiac, and inflammatory biomarkers as well as walking disability, previously associated with increased mortality and lower extremity OA.

scholarly journals Impact of Smoking Status on Growth Differentiation Factor 15 and Mortality in Patients With Suspected or Known Coronary Artery Disease: The ANOX Study

2020 ◽  
Vol 9 (22) ◽  
Author(s):  
Hiromichi Wada ◽  
Masahiro Suzuki ◽  
Morihiro Matsuda ◽  
Yoichi Ajiro ◽  
Tsuyoshi Shinozaki ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Smoking Status ◽  
Linear Regression Analysis ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Former Smokers ◽  
Artery Disease ◽  
Never Smokers ◽  
The Impact

Background Whether circulating growth differentiation factor 15 (GDF‐15) levels differ according to smoking status and whether smoking modifies the relationship between GDF‐15 and mortality in patients with coronary artery disease are unclear. Methods and Results Using data from a multicenter, prospective cohort of 2418 patients with suspected or known coronary artery disease, we assessed the association between smoking status and GDF‐15 and the impact of smoking status on the association between GDF‐15 and all‐cause death. GDF‐15 was measured in 955 never smokers, 1035 former smokers, and 428 current smokers enrolled in the ANOX Study (Development of Novel Biomarkers Related to Angiogenesis or Oxidative Stress to Predict Cardiovascular Events). Patients were followed up during 3 years. The age of the patients ranged from 19 to 94 years; 67.2% were men. Never smokers exhibited significantly lower levels of GDF‐15 compared with former smokers and current smokers. Stepwise multiple linear regression analysis revealed that the log‐transformed GDF‐15 level was independently associated with both current smoking and former smoking. In the entire patient cohort, the GDF‐15 level was significantly associated with all‐cause death after adjusting for potential clinical confounders. This association was still significant in never smokers, former smokers, and current smokers. However, GDF‐15 provided incremental prognostic information to the model with potential clinical confounders and the established cardiovascular biomarkers in never smokers, but not in current smokers or in former smokers. Conclusions Not only current, but also former smoking was independently associated with higher levels of GDF‐15. The prognostic value of GDF‐15 on mortality was most pronounced in never smokers among patients with suspected or known coronary artery disease.

Smoking and prostate cancer risk in young men in Appalachian Kentucky.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e12004-e12004
Author(s):  
Indraneel Gowdar ◽  
Priya Mallikarjun ◽  
Indraneel Reddy ◽  
Anjali Shankar ◽  
Mark Dignan
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Smoking Status ◽  
Adult Population ◽  
Prostate Cancer Risk ◽  
Age At Diagnosis ◽  
Large Hospital ◽  
Age Related ◽  
Increased Risk ◽  
Appalachian Kentucky

e12004 Background: Kentucky has the highest smoking rates in the US, with 25.2% of the adult population considered current smokers compared to 18.4% nationwide (CRC, 2011 statistics), as well as high rates of chronic conditions including diabetes, heart disease, and lung cancer. In particular, the Appalachian area of Kentucky appears to have particularly high rates of both smoking and prostate cancer, beyond what is typical for the state as a whole. Recent data on prostate cancer from the Kentucky State Cancer Registry from 2004-2008 showed an incidence rate of 144 vs. 139.8 per 100,000 for "Appalachia" and Kentucky as a state, respectively. The purpose of this study is to investigate the relationship between smoking and risk of prostate cancer in Appalachian Kentucky. Methods: Data were collected on all prostate cancers diagnosed from 1996-2005 in a large hospital serving the Appalachian region. Data were collected without identifiers. Relevant statistics recorded included age at diagnosis, family history, and smoking status (classified as current smoker, non-smoker, or unknown smoking status). Results: A total of 286 patients with diagnosed prostate cancer were collected. The patients ranged from 45 to 94 years of age at diagnosis (Mean = 71, SD = 9.8). Of the 286, 89 (31.1%) had never smoked, and 94 (32.9%) were current or former cigarette smokers (Mean pack years = 25.4). To control for the age-related increase in cancer risk, patients were separated into two age groups: age 65 and younger (n=86, 30.1%), and older than 65 (n=200, 69.9%). The proportion of the younger group who smoked was significantly greater than that of the older group (44.2% vs. 28%, respectively; p= 0.009, Fischer's exact test). Conclusions: These data suggest that smoking in males younger than 65 is positively associated with an increased risk of prostate cancer in Appalachian Kentucky. Further study is needed to elucidate this relationship, as well as to evaluate any association between smoking severity and Gleason score.

scholarly journals Impact of smoking status on the relationships of growth differentiation factor 15 with mortality and cardiovascular events in patients with suspected or known coronary artery disease: the ANOX study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
H Wada ◽  
M Suzuki ◽  
M Matsuda ◽  
Y Ajiro ◽  
T Shinozaki ◽  
...  
Keyword(s):  
Risk Factors ◽  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Smoking Status ◽  
Funding Source ◽  
Growth Differentiation Factor 15 ◽  
Differentiation Factor ◽  
Total Death ◽  
Artery Disease ◽  
Never Smokers

Abstract Background Growth differentiation factor 15 (GDF-15) is a stress-responsive cytokine that plays an important role in the regulation of the inflammatory response, growth and cell differentiation. An elevated GDF-15 was found in various conditions including cigarette smoking and stable coronary artery disease (CAD), and it was reported to predict mortality and cardiovascular (CV) events in general population and in patients with established CAD. However, the impact of smoking status on the relationships of GDF-15 with mortality and CV events in patients with suspected or known CAD is unclear. Methods Serum GDF-15 levels were measured in 2,418 patients with suspected or known CAD undergoing elective coronary angiography, enrolled in the development of novel biomarkers related to angiogenesis or oxidative stress to predict CV events (ANOX) study, and followed up for 3 years. Patients were divided into 3 groups according to the smoking status: current (n=428), past (n=1,035), and never smokers (n=955). The outcomes were total death, CV death, and major adverse CV events (MACE) defined as a composite of CV death, nonfatal myocardial infarction, and nonfatal stroke. Results During the follow-up, 48 current, 120 past, and 86 never smokers died from any cause, 17 current, 47 past, and 24 never smokers died from CV disease, and 35 current, 80 past, and 50 never smokers developed MACE. After adjustment for established risk factors, GDF-15 levels were significantly associated with total death (hazard ratio [HR] for 1-SD increase, 1.30; 95% confidence interval [CI], 1.03–1.65), but not with CV death (HR, 1.09; 95% CI, 0.69–1.62) or MACE (HR, 0.95; 95% CI, 0.64–1.34) in current smokers; GDF-15 levels were significantly associated with total death (HR, 1.73; 95% CI, 1.46–2.05) and CV death (HR, 1.41; 95% CI, 1.09–1.85), but not with MACE (HR, 1.20; 95% CI, 0.96–1.48) in past smokers; GDF-15 levels were significantly associated with total death (HR, 1.62; 95% CI, 1.32–1.95), CV death (HR, 1.76; 95% CI, 1.22–2.46), and MACE (HR, 1.64; 95% CI, 1.27–2.07) in never smokers. Even after incorporation of N-terminal pro-brain natriuretic peptide, contemporary sensitive cardiac troponin I, and high-sensitivity C-reactive protein into a model with established risk factors, the addition of GDF-15 levels further improved the prediction of total death (P&lt;0.001 for continuous net reclassification improvement [NRI], P=0.001 for integrated discrimination improvement [IDI]) and MACE (P&lt;0.001 for NRI, P=0.045 for IDI), but not that of CV death, in never smokers, while it did not significantly improved the prediction of total death, CV death, or MACE either in current or in past smokers. Conclusions The GDF-15 level was independently associated with total death and MACE in never, but not in current or past smokers with suspected or known CAD. The relationships of GDF-15 with mortality and CV events seem to be attenuated by the presence of current and past smoking. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The ANOX study is supported by a Grant-in-Aid for Clinical Research from the National Hospital Organization.

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