Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke.

Abstract

BACKGROUND AND PURPOSE:

Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the Framingham Offspring cohort.

METHODS:

We followed 3374 stroke- and dementia-free individuals (mean age, 59.0±9.7 years; 53% women) attending the Framingham Offspring sixth examination cycle 11.8±3.0 years for incident stroke. A subsample of 2463 individuals underwent brain magnetic resonance imaging and neuropsychological testing ≈4.0±1.7 years after the sixth examination.

RESULTS:

After adjustment for traditional cardiovascular risk factors, B-type natriuretic peptide, high-sensitivity C-reactive protein, and urine albumin levels, higher stress biomarker levels were associated cross-sectionally with lower brain volumes (β coefficients for intracranial volume comparing fourth [Q4] versus first biomarker [Q1] quartiles: -0.71% for GDF-15; P=0.002 and 0.47% for sST2; P=0.02) and worse performance on the visual reproduction test (β coefficients for Q4 versus Q1: -0.62 for GDF-15; P=0.009 and -0.40 for sST2; P=0.04). Higher GDF-15 concentrations were also associated with greater log-transformed white-matter hyperintensity volumes (β for Q4 versus Q1=0.19; P=0.01). Prospectively, a total of 203 (6%) individuals developed incident stroke/transient ischemic attack during follow-up. After multivariable adjustment, sST2 remained significantly associated with stroke/transient ischemic attack, hazard ratio for Q4 versus Q1 of 1.76, 95% confidence interval of 1.06 to 2.92, and P=0.03.

CONCLUSIONS:

Circulating GDF-15 and sST2 are associated with subclinical brain injury and cognitive impairment. Higher sST2 concentrations are also associated with incident stroke, suggesting potential links between cardiac stress biomarkers and brain injury.

• Authors: Charlotte Andersson, Sarah R Preis, Alexa Beiser, Charles DeCarli, Kai C Wollert, Thomas J Wang, James L Januzzi Jr, Ramachandran S Vasan, Sudha Seshadri
• Journal: Stroke (Stroke) Vol. 46 Issue 9 Pg. 2568-75 (Sep 2015) ISSN: 1524-4628 [Electronic] United States
• PMID: 26219649 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 American Heart Association, Inc.

Chemical References

• Biomarkers
• Growth Differentiation Factor 15
• IL1RL1 protein, human
• Interleukin-1 Receptor-Like 1 Protein
• Receptors, Cell Surface

Topics

• Aged
• Biomarkers (blood)
• Brain (pathology, physiopathology)
• Cerebrovascular Trauma (blood)
• Cognition Disorders (blood)
• Cross-Sectional Studies
• Female
• Growth Differentiation Factor 15 (blood)
• Humans
• Interleukin-1 Receptor-Like 1 Protein
• Ischemic Attack, Transient (blood)
• Longitudinal Studies
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Receptors, Cell Surface (blood)
• Stroke (blood)