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Circulation. 2012 May 1;125(17):2100-7. doi: 10.1161/CIRCULATIONAHA.110.989145. Epub 2012 Mar 28.

Multiple biomarkers and risk of clinical and subclinical vascular brain injury: the Framingham Offspring Study.

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  • 1Boston University Schools of Medicine and Public Health, MA, USA.

Abstract

BACKGROUND:

Several biomarkers have been individually associated with vascular brain injury, but no prior study has explored the simultaneous association of a biologically plausible panel of biomarkers with the incidence of stroke/transient ischemic attack and the prevalence of subclinical brain injury.

METHODS AND RESULTS:

In 3127 stroke-free Framingham offspring (age, 59±10 years; 54% female), we related a panel of 8 biomarkers assessing inflammation (C-reactive protein), hemostasis (D-dimer and plasminogen activator inhibitor-1), neurohormonal activity (aldosterone-to-renin ratio, B-type natriuretic peptide, and N-terminal proatrial natriuretic peptides), and endothelial function (homocysteine and urinary albumin/creatinine ratio) measured at the sixth examination (1995-1998) to risk of incident stroke/transient ischemic attack. In a subset of 1901 participants with available brain magnetic resonance imaging (1999-2005), we further related these biomarkers to total cerebral brain volume, covert brain infarcts, and large white-matter hyperintensity volume. During a median follow-up of 9.2 years, 130 participants experienced incident stroke/transient ischemic attack. In multivariable analyses adjusted for stroke risk factors, the biomarker panel was associated with incident stroke/transient ischemic attack and with total cerebral brain volume (P<0.05 for both) but not with covert brain infarcts or white-matter hyperintensity volume (P>0.05). In backward elimination analyses, higher log-B-type natriuretic peptide (hazard ratio, 1.39 per 1-SD increment; P=0.002) and log-urinary albumin/creatinine ratio (hazard ratio, 1.31 per 1-SD increment; P=0.004) were associated with increased risk of stroke/transient ischemic attack and improved risk prediction compared with the Framingham Stroke Risk Profile alone; when the <5%, 5% to 15%, or >15% 10-year risk category was used, the net reclassification index was 0.109 (P=0.037). Higher C-reactive protein (β=-0.21 per 1-SD increment; P=0.008), D-dimer (β=-0.18 per 1-SD increment; P=0.041), total homocysteine (β=-0.21 per 1-SD increment; P=0.005), and urinary albumin/creatinine ratio (β=-0.15 per 1-SD increment; P=0.042) were associated with lower total cerebral brain volume.

CONCLUSION:

In a middle-aged community sample, we identified multiple biomarkers that were associated with clinical and subclinical vascular brain injury and could improve risk stratification.

PMID:
22456473
[PubMed - indexed for MEDLINE]
PMCID:
PMC3427730
Free PMC Article

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