Growth differentiation factor 15 and geriatric conditions in acute coronary syndrome

Sanchís, Juan; Ruíz, Vicente; Bonanad, Clara; Sastre, Clara; Ruescas, Arantxa; Diaz-Gimenez, Macarena; Rodríguez, Enrique; Valero, Ernesto; García‐Blas, Sergio; Carratalá, Arturo; Núñez, Eduardo; Núñez, Julio

doi:10.1016/j.ijcard.2019.05.034

Cited by 21 publications

(10 citation statements)

References 19 publications

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“…Notably, among 1301 circulating proteins measured in a cohort of older people from the In Chianti study, GDF15 proved to be among the strongest predictors of mobility limitations when assessed at 9 years follow‐up 12 . Thus, circulating GDF15 is considered a potential core biomarker of frailty in older people 13,14 . Interestingly, a close relationship between GDF15 and another hallmark of ageing, that is, chronic low‐grade inflammation has been demonstrated, but the interplay between these biomarkers and how they contribute to muscle dysfunction are not fully elucidated 3,9,15,16 .…”

Section: Introductionmentioning

confidence: 99%

Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study

Alcázar

Frandsen

Prokhorova

et al. 2021

J cachexia sarcopenia muscle

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Background Although growth differentiation factor 15 (GDF15) is known to increase with disease and is associated with low physical performance, the role of GDF15 in normal ageing is still not fully understood. Specifically, the influence of circulating GDF15 on impairments in maximal muscle power (a major contributor to functional limitations) and the underlying components has not been investigated. Methods Data from 1305 healthy women and men aged 20 to 93 years from The Copenhagen Sarcopenia Study were analysed. Circulating levels of GDF15 and markers of inflammation (tumor necrosis factor‐alpha, interleukin‐6, and high‐sensitivity C‐reactive protein) were measured by ELISA (R&D Systems) and multiplex bead‐based immunoassays (Bio‐Rad). Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to leg muscle mass) muscle power were assessed by the Nottingham power rig [leg extension power (LEP)] and the 30 s sit‐to‐stand (STS) muscle power test. Total body fat, visceral fat, and leg lean mass were assessed by dual energy X‐ray absorptiometry. Leg skeletal muscle index was measured as leg lean mass normalized to body height squared. Results Systemic levels of GDF15 increased progressively as a function of age in women (1.1 ± 0.4 pg·mL−1·year−1) and men (3.3 ± 0.6 pg·mL−1·year−1) (both P < 0.05). Notably, GDF15 increased at a faster rate from the age of 65 years in women (11.5 ± 1.2 pg·mL−1·year−1, P < 0.05) and 70 years in men (19.3 ± 2.3 pg·mL−1·year−1, P < 0.05), resulting in higher GDF15 levels in men compared with women above the age of 65 years (P < 0.05). Independently of age and circulatory markers of inflammation, GDF15 was negatively correlated to relative STS power (P < 0.05) but not LEP, in both women and men. These findings were mainly explained by negative associations of GDF15 with specific STS power in women and men (both P < 0.05). Conclusions A J‐shaped relationship between age and systemic GDF15 was observed, with men at older age showing steeper increases and elevated GDF15 levels compared with women. Importantly, circulating GDF15 was independently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people.

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Section: Introductionmentioning

confidence: 99%

Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study

Alcázar

Frandsen

Prokhorova

et al. 2021

J cachexia sarcopenia muscle

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“…Here, we report, for the first time, an independent association between GDF15 and frailty as assessed with the Katz score, after weighting the association for structural, functional or other bio-humoral parameters. Previous reports have shown that GDF15 levels reflect progressive patients' functional impairment (including muscle wasting) and renal dysfunction, being associated with both aging and, independently, with frailty indices (not including the Katz Score) [14][15][16]. Our report therefore proposes the possible usefulness of this new biomarker in the realm of AVR.…”

Section: Gdf15 and Frailty Before Aortic Valve Replacementmentioning

confidence: 58%

“…GDF15 has been recently shown to be superior to natriuretic peptides for predicting risk in patients undergoing TAVI, and has incremental value over the logistic Euroscore [9]. Limited previous reports showed that GDF15 levels may reflect functional impairment associated with age and some frailty indices [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Fabiani

Santoni

Angelillis

et al. 2020

JCM

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Background: Frailty is an important outcome predictor in patients with aortic stenosis who are candidates for transcatheter or surgical aortic valve replacement (AVR). Growth/differentiation factor 15 (GDF15) is a cytokine playing a role in the pathophysiology of ventricular remodeling. We assessed its potential role as an independent soluble biomarker of frailty in these patients. Methods: We studied 62 patients (age, mean 79 years, 95% confidence interval (CI) 77–81; 54.8% female) with severe aortic valve stenosis and candidates for AVR. We systematically assessed pre-intervention GDF15 levels for their relationship with frailty (Katz score) and echocardiographic parameters of left ventricular dysfunction/remodeling. Fifteen hypertensive patients with left ventricular (LV) hypertrophy served as controls. Results: Patients with aortic valve stenosis featured higher GDF15 levels than controls (1773, 95% CI 1574–1971 pg/mL vs. 775, 95% CI 600–950 pg/mL, respectively, p < 0.0001). Subjects in the upper GDF15 tertile were older (p = 0.004), with a more advanced NYHA functional class (p = 0.04) and a higher prevalence of impaired renal function (p = 0.004). Such patients also showed a higher frailty score (p = 0.04) and higher indices of LV dysfunction, including reduced global longitudinal strain (p = 0.01) and a higher left ventricular mass (p = 0.001). GDF15 was significantly related to the Katz score, and predicted (OR 1.05; 95% CI 0.9–1.1; p = 0.03) a low (<5) Katz score, independent of the relationship with LV mass, age, renal function or indices of LV dysfunction. Conclusions: GDF15 is increased in patients with severe aortic stenosis and appears to be a soluble correlate of patients’ frailty, independent of indices of left ventricular dysfunction.

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“…Growth differentiation factor-15 (GDF-15) reflects cardiovascular function and disease status, which is an inflammation-related biomarker and belongs to the transforming growth factor-β (TGF-β) cytokine superfamily. While weakly expressed in physiological conditions, GDF-15 is strongly induced under pathological stress response related to inflammation or tissue injury (7). The elevated GDF-15 levels had been detected in human macrophages of the atherosclerotic plaque (8).…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of growth differentiation factor-15 in patients with coronary artery disease: A meta-analysis and systematic review

Zhang

Hao

et al. 2023

Front. Cardiovasc. Med.

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Background and aimsThe predictive value of growth differentiation factor-15 (GDF-15) for individual cardiovascular outcomes remained controversial in patients with coronary artery disease (CAD). We aimed to investigate the effects of GDF-15 on all-cause death, cardiovascular death, MI and stroke in CAD patients.MethodsWe searched PubMed, EMBASE, Cochrane library and Web of Science till 30 December, 2020. Hazard ratios (HRs) were combined with fixed or random effect meta-analyses. Subgroup analyses were performed in different disease types. Sensitivity analyses were used to evaluate the stability of the results. Publication bias was tested using funnel plots.ResultsA total of 10 studies with 49,443 patients were included in this meta-analysis. Patients with the highest GDF-15 concentrations had significantly increased risk of all-cause death (HR 2.24; 95% CI: 1.95–2.57), cardiovascular death (HR 2.00; 95% CI: 1.66–2.42), MI (HR 1.42; 95% CI: 1.21–1.66) after adjusting clinical characteristics and prognostic biomarkers (hs-TnT, cystatin C, hs-CRP, and NT-proBNP) but except for stroke (HR 1.43; 95% CI: 1.01–2.03, p = 0.05). For the outcome of all-cause death and cardiovascular death, subgroup analyses revealed consistent results. Sensitivity analyses showed that the results were stable. Funnel plots showed that there was no publication bias.ConclusionIn CAD patients with elevated GDF-15 levels on admission, there were independently significant risks for all-cause death and cardiovascular death. The highest concentrations of GDF-15 had a lower predictive effect on MI than all-cause death and cardiovascular death. The association of GDF-15 with the outcome of stroke needs to be further studied.

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Growth differentiation factor 15 and geriatric conditions in acute coronary syndrome

Cited by 21 publications

References 19 publications

Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study

Changes in systemic GDF15 across the adult lifespan and their impact on maximal muscle power: the Copenhagen Sarcopenia Study

Growth Differentiation Factor 15 in Severe Aortic Valve Stenosis: Relationship with Left Ventricular Remodeling and Frailty

Prognostic value of growth differentiation factor-15 in patients with coronary artery disease: A meta-analysis and systematic review

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