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12-03-2013 | Neurology | Article

Blood holds clues to white matter hyperintensity, stroke risk after menopause


Free abstract

medwireNews: Thrombogenic risk factors appear to contribute to the volume and progression of white matter hyperintensities (WMH) in the aging brain, which are thought to increase the risk for cognitive impairment and stroke, report researchers.

"Modifying activation state of platelets may serve as a therapeutic target to prevent progression of WMH in the brain," suggest Kejal Kantarci (Mayo Clinic, Rochester, Minnesota, USA) and team.

The study indicated that activated platelets are associated with WMH load and progression in recently menopausal women, aged 42-59 years, and within 6 months to 3 years past their last period.

"Because most studies of WMH were conducted in elderly and predominantly male cohorts… we evaluated WMH load in healthy, recently menopausal women without a history of cardiovascular or cerebrovascular disease," explains the team.

The researchers studied 95 women enrolled in the Kronos Early Estrogen Prevention Study who were randomly allocated to different hormone treatments after undergoing a baseline magnetic resonance imaging (MRI) scan and blood sampling. Follow-up MRI scans were performed at 18, 36, and 48 months.

As reported in Neurology, analysis of the baseline MRI scans showed that WMHs were present in all of the women.

Using a semi automated segmentation algorithm based on fluid-attenuated inversion recovery (FLAIR) MRI to quantify WMH volume, the researchers found that the mean WMH volume among the women was 1909 mm3.

At 36 months, the volume of WMH increased by 122.1 mm3 from baseline, and at 48 months it increased by 155.4 mm3 from baseline, whereas it did not significantly differ from baseline at 18 months.

The baseline WMH volume and changes in WMH volume at 36 and 48 months were not significantly associated with baseline markers for conventional cardiovascular risk factors, including body mass index, systolic and diastolic blood pressure, triglycerides, high-density lipoprotein, low-density lipoprotein, fasting glucose, and smoking status.

However, platelet activation, as measured by glycoprotein IIb/IIIa expression, was significantly associated with WMH volume at baseline, after adjustment for confounding factors.

In addition, the change in WMH volume at 36 and 48 months was significantly associated with baseline total numbers of thrombogenic microvesicles, as measured by binding to annexin V. And change in WMH at 48 months was associated with the number of platelet-derived microvesicles (those positive for CD42a antibody).

"The association between platelet derived and thrombogenic microvesicles at baseline and WMH progression after 3 to 4 years might suggest that prothrombotic characteristics of the blood contribute to structural changes in the WM of healthy postmenopausal women," write the researchers.

"As the clinical significance of WMH in younger populations remains controversial, additional research is needed to determine the underlying mechanisms of WMH development and progression in recently menopausal women," they conclude.

By Sally Robertson, medwireNews Reporter

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