Dataset Information

Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.

ABSTRACT:

Background

Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.

Methods

We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation experiments, we used liquid chromatography-tandem mass spectrometry to measure total serum GDF-11 and GDF-8, along with follistatin and FSTL-3 by immunoassay, in 2 longitudinal cohorts of older adults.

Results

In 2 599 participants (age 75.2 ± 4.3) followed for 10.8 ± 5.6 years, 721 HF events occurred. After adjustment, neither GDF-11 (HR per doubling: 0.93 [0.67, 1.30]) nor GDF-8 (HR: 1.02 per doubling [0.83, 1.27]) was associated with incident HF or its subtypes. Positive associations with HF were detected for follistatin (HR: 1.15 [1.00, 1.32]) and FLST-3 (HR: 1.38 [1.03, 1.85]), and with HF with preserved ejection fraction for FSTL-3 (HR: 1.77 [1.03, 3.02]). (All HRs per doubling of biomarker.) FSTL-3 associations with HF appeared stronger at higher follistatin levels and vice versa, and also for men, Blacks, and lower kidney function.

Conclusions

Among older adults, serum follistatin and FSTL-3, but not GDF-11 or GDF-8, were associated with incident HF. These findings do not support the concept that low serum levels of total GDF-11 or GDF-8 contribute to HF late in life, but do implicate transforming growth factor-β superfamily pathways as potential therapeutic targets.

SUBMITTER: Kizer JR

PROVIDER: S-EPMC10733168 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.

Kizer Jorge R JR Patel Sheena S Ganz Peter P Newman Anne B AB Bhasin Shalender S Lee Se-Jin SJ Cawthon Peggy M PM LeBrasseur Nathan K NK Shah Sanjiv J SJ Psaty Bruce M BM Tracy Russell P RP Cummings Steven R SR

The journals of gerontology. Series A, Biological sciences and medical sciences 20240101 1

<h4>Background</h4>Heterochronic parabiosis has identified growth differentiation factor (GDF)-11 as a potential means of cardiac rejuvenation, but findings have been inconsistent. A major barrier has been lack of assay specificity for GDF-11 and its homolog GDF-8.<h4>Methods</h4>We tested the hypothesis that GDF-11 and GDF-8, and their major antagonists follistatin and follistatin-like (FSTL)-3, are associated with incident heart failure (HF) and its subtypes in elders. Based on validation expe ...[more]

PMID: 37624693

Similar Datasets

Project description:AimsThere is an increasing proportion of hospitalized heart failure (HF) patients classified as HF with preserved ejection fraction (HFpEF) around the world. Growth differentiation factor 15 (GDF-15) is a promising biomarker in HFpEF prognostication; however, the majority of the existing data has been derived from the research on undifferentiated HF, whereas the studies focusing on HFpEF are still limited. This study aimed to determine the prognostic power of GDF-15 in the hospitalized patients with HFpEF in a Chinese cohort.Methods and resultsWe analysed the levels of serum GDF-15 in 380 patients hospitalized for acute onset of HFpEF measured by heart ultrasound at admission in a prospective cohort. The associations of GDF-15 with 1 year risk of all-cause death and 1 year HF readmission were assessed by the Cox proportional hazards model. Area under the receiver operating characteristic curves was used to compare predictive accuracy. GDF-15 was strongly correlated with 1 year HF readmission and 1 year all-cause death, with event rates of 24.8%, 40.0%, and 50.0% for 1 year HF readmission (P < 0.001), respectively, and with 11.2%, 13.6%, and 24.6% for 1 year all-cause death (P = 0.004) in the corresponding tertile, respectively. In the multivariate linear regression model, GDF-15 had a significantly negative correlation with haemoglobin (P = 0.01) and a positive correlation with creatinine (P = 0.01), alanine transaminase (P = 0.001), and therapy of aldosterone antagonist (P = 0.018). The univariate Cox regression model of GDF-15 showed that c-statistic was 0.632 for 1 year HF readmission and 0.644 for 1 year all-cause death, which were superior to the N-terminal pro-brain natriuretic peptide (NT-proBNP) model with c-statistics of 0.595 and 0.610, respectively. In the multivariable Cox regression model, GDF-15 tertiles independently predicted 1 year HF readmission (hazard ratio 2.25, 95% confidence interval: 1.43-3.54, P < 0.001) after adjusting for baseline Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-HF) risk score, history of HF, NT-proBNP, and high-sensitivity cardiac troponin T. Compared with the model including all the adjusted variables, the model with the addition of GDF-15 improved predictive power, with c-statistic increasing from 0.643 to 0.657 for 1 year HF readmission and from 0.638 to 0.660 for 1 year all-cause death.ConclusionsIn hospitalized patients with HFpEF, GDF-15 measured within 48 h of admission is a strong independent biomarker for 1 year HF readmission and even better than NT-proBNP. GDF-15 combined with the traditional indicators provided incremental prognostic value in this population.

Dataset Information

Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.

Background

Methods

Results

Conclusions

Publications

Circulating Growth Differentiation Factors 11 and 8, Their Antagonists Follistatin and Follistatin-Like-3, and Risk of Heart Failure in Elders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets