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Change in Growth Differentiation Factor 15 Concentrations Over Time Independently Predicts Mortality in Community-Dwelling Elderly Individuals
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Uppsala kliniska forskningscentrum (UCR).
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2013 (engelsk)Inngår i: Clinical Chemistry, ISSN 0009-9147, E-ISSN 1530-8561, Vol. 59, nr 7, s. 1091-1098Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

BACKGROUND:

Growth differentiation factor 15 (GDF-15) is emerging as a powerful risk indicator in both cardiovascular disease patients and community-dwelling individuals. We investigated GDF-15 concentrations and their changes over 5 years in elderly individuals from the community, together with the underlying conditions and prognostic implications of these measurements.

METHODS:

We analyzed GDF-15 concentrations using a sandwich immunoassay in participants from the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study. Measurements were performed at both 70 (n = 1004) and 75 (n = 813) years of age. Median follow-up was 8.0 years.

RESULTS:

Over time, GDF-15 concentrations increased by 11.0% (P < 0.001). These changes were related to male sex, hypertension, diabetes, heart failure, renal function, and concentrations of N-terminal pro–B-type natriuretic peptide (NT-proBNP). Significant relationships also emerged between changes in GDF-15 and NT-proBNP, C-reactive protein, and renal function between ages 70 and 75. The R2 value of this model was 0.20. GDF-15 concentrations independently predicted all-cause mortality [hazard ratio 4.0 (95% CI 2.7–6.0)] with results obtained at ages 70 and 75 as updated covariates. Baseline GDF-15 concentrations improved prognostic discrimination and reclassification [c-statistic 0.06 (P = 0.006); integrated discrimination improvement = 0.030 (P = 0.004); category-free net reclassification improvement = 0.281 (P = 0.006)]. Change in GDF-15 concentrations over time independently predicted even all-cause mortality occurring after age 75 [hazard ratio 3.6 (95% CI 2.2–6.0)].

CONCLUSIONS:

GDF-15 concentrations and their changes over time are powerful predictors of mortality in elderly community-dwelling individuals. GDF-15 concentrations increase with aging, and these changes are explained only partially by cardiovascular risk factors, indicators of neurohumoral activation and inflammation, and renal function. Thus GDF-15 reflects both cardiovascular and other biological processes closely related to longevity.

sted, utgiver, år, opplag, sider
2013. Vol. 59, nr 7, s. 1091-1098
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Identifikatorer
URN: urn:nbn:se:uu:diva-198200DOI: 10.1373/clinchem.2012.201210ISI: 000321549400015PubMedID: 23529704OAI: oai:DiVA.org:uu-198200DiVA, id: diva2:615417
Tilgjengelig fra: 2013-04-10 Laget: 2013-04-10 Sist oppdatert: 2022-01-28bibliografisk kontrollert

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Eggers, Kai MWallentin, Lars

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