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May 3rd, 2012 posted by Paul Rega, MD, FACEP May 3, 2012 @ 8:13 pm

Biomarkers and Risk of Clinical and Subclinical Vascular Brain Injury

Multiple Biomarkers and Risk of Clinical and Subclinical Vascular Brain Injury / Clinical Perspective : The Framingham Offspring Study



Circulation. 2012;125:2100-2107, published online before print March 28 2012, doi:10.1161/CIRCULATIONAHA.110.989145

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.


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