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

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.

• Authors: Aleksandra Pikula, Alexa S Beiser, Charles DeCarli, Jayandra J Himali, Stephanie Debette, Rhoda Au, Jacob Selhub, Geoffrey H Toffler, Thomas J Wang, James B Meigs, Margaret Kelly-Hayes, Carlos S Kase, Philip A Wolf, Ramachandran S Vasan, Sudha Seshadri
• Journal: Circulation (Circulation) Vol. 125 Issue 17 Pg. 2100-7 (May 01 2012) ISSN: 1524-4539 [Electronic] United States
• PMID: 22456473 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Biomarkers
• Blood Proteins
• Hormones
• Homocysteine
• Creatinine

Topics

• Aged
• Albuminuria (urine)
• Biomarkers (blood, urine)
• Blood Proteins (analysis)
• Brain (pathology)
• Brain Injuries (blood, epidemiology, urine)
• Cohort Studies
• Creatinine (urine)
• Endothelium, Vascular (physiopathology)
• Female
• Hemostasis
• Homocysteine (blood)
• Hormones (blood)
• Humans
• Incidence
• Inflammation (blood)
• Ischemic Attack, Transient (blood, epidemiology, urine)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Organ Size
• Prospective Studies
• Risk
• Stroke (blood, epidemiology, urine)
• United States (epidemiology)