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The Cardiovascular Health Study

W. T. Longstreth, Jr, MD, MPH; Ronit Katz, PhD; Jean Olson, MD, MPH; Charles Bernick, MD; J. Jeffrey Carr, MD, MS; M. René Malinow, MD; David L. Hess, PhD; Mary Cushman, MD, MSc; Stephen M. Schwartz, PhD

Arch Neurol. 2004;61:67-72.

Background  An elevated plasma total homocysteine (tHcy) level is associated with an increased risk of vascular disease. Some studies have shown associations between tHcy level and small-vessel disease of the brain on magnetic resonance imaging (MRI).

Design  In the Cardiovascular Health Study, 622 elderly participants without a history of transient ischemic attack or stroke had results for tHcy level and cranial MRI. We sought associations between tHcy level and MRI findings of ventricular grade, sulcal grade, white matter grade, and infarcts. We controlled for other factors, including levels of creatinine, folate, and vitamins B₆ and B₁₂ and methylenetetrahydrofolate reductase genotype.

Results  After controlling for age and sex, tHcy level was not associated with the individual MRI findings. Further adjustments for other factors and other blood tests had little effect on these findings. The only significant finding was a linear trend across quintiles of tHcy level and a pattern of MRI findings combining infarcts and high white matter grade. The linear trend remained significant after controlling for other risk factors and atherosclerotic markers (top quintile vs bottom quintile odds ratio, 3.3; 95% confidence interval, 0.96-11.20; P = .04 for linear trend) but was slightly diminished after further controlling for creatinine, folate, and vitamins B₆ and B₁₂ (odds ratio, 3.2; 95% confidence interval, 0.81-13.10; P = .07 for linear trend).

Conclusion  We were unable to confirm the results of previous studies with respect to tHcy level and individual MRI findings, although an association was seen for an MRI pattern combining infarcts and high white matter grade.

From the Departments of Neurology (Dr Longstreth), Epidemiology (Drs Longstreth and Schwartz), and Biostatistics (Dr Katz), University of Washington, Seattle; Division of Epidemiology and Clinical Applications, National Heart, Lung, and Blood Institute, Bethesda, Md (Dr Olson); Division of Neurology, University of Nevada, Las Vegas (Dr Bernick); the Department of Radiology, Wake Forest University, Winston-Salem, NC (Dr Carr); Divisions of Pathobiology and Immunology (Dr Malinow) and Reproductive Sciences (Dr Hess), Oregon National Primate Research Center, Oregon Health Sciences University, Portland; and Departments of Medicine and Pathology, University of Vermont, Colchester (Dr Cushman).

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