Growth differentiation factor 15 in a community-based sample: age-dependent reference limits and prognostic impact

Abstract

BackgroundDespite the growing body of evidence on growth differentiation factor 15 (GDF-15) reference values for patients with existing cardiovascular disease, limited investigation has been dedicated to characterizing the distribution and prognostic impact of GDF-15 in predominantly healthy populations. Furthermore, current cutoff values for GDF-15 fail to account for the well-documented age-dependence of circulating GDF-15.MethodsFrom 810 community-dwelling older adults, we selected a group of apparently healthy participants (n = 268). From this sample, circulating GDF-15 was modeled using the generalized additive models for location scale and shape (GAMLSS) to develop age-dependent centile values. Unadjusted and adjusted Cox proportional hazards models were used to assess the association between the derived GDF-15 reference values (expressed as centiles) and all-cause mortality.ResultsSmoothed centile curves showed increasing GDF-15 with age in the apparently healthy participants. An approximately three-fold difference was observed between the 95th and 5th GDF-15 centiles across ages. In a median 8.0 years of follow-up, 97 all-cause deaths were observed in 806 participants with eligible values. In unadjusted Cox regression analyses, the hazard ratio (95% CI) for all-cause mortality per 25-unit increase in GDF-15 centile was 1.80 (1.48–2.20) and dichotomized at the 95th centile, ≥95th versus <95th, was 3.04 (1.99–4.65). Age-dependent GDF-15 centiles remained a significant predictor of all-cause mortality in all subsequent adjusted models.ConclusionsAge-dependent GDF-15 centile values developed from a population of apparently healthy older adults are independently predictive of all-cause mortality. Therefore, GDF-15 reference values could be a useful tool for risk-stratification in a clinical setting.ClinicalTrials.gov IdentifierNCT01452178.

Pro- and Anti-Inflammatory Responses in Severe COVID-19-Induced Acute Respiratory Distress Syndrome—An Observational Pilot Study

“…Thus, we cannot offer valid data on the extent of lung water. Furthermore, moderately elevated levels of GDF-15 (usually below 2 ng/ml) can be found in obesity ( 47 ), aging ( 48 ), autoimmune comorbidities ( 49 ) or cardiovascular disease ( 50 ). Levels similar to our COVID-19 patients are limited to conditions like pregnancy ( 51 ), diabetic nephropathy ( 52 ) and advanced cancers ( 53 ).…”

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

“…Although not directly comparable with the current analysis, data from the general population [ 23 ] or from several patient cohorts [ 26 ] demonstrated any meaningful association with all-cause mortality at much higher concentrations. Interestingly, the 50th percentile of GDF-15 concentration within the general population was found to be 945 ng/L at an age of 65 years [ 39 ]. Transferring these reference values to our results, one might conclude that subjects with OA have a 56% increased risk of dying, even being within the age-related reference limit of GDF-15.…”

Is low‐level HIV‐1 viraemia associated with elevated levels of markers of immune activation, coagulation and cardiovascular disease?

“…Elevated GDF‐15 plasma levels have been associated with heart failure and acute coronary syndrome, but also neoplasms such as colorectal and pancreatic cancer . GDF‐15 levels increase with age, and age‐stratified reference values have been proposed . In PLHIV, higher GDF‐15 levels compared with noninfected controls have been reported, with independent associations with mortality and pulmonary hypertension .…”

“…Similarly, controlling for age and CD4 count nadir did not affect this result. However, we did not have access to data on body mass index (BMI) and smoking, factors that might influence GDF‐15 expression .…”