Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

Limor Raz, M. Jayachandran, Nirubol Tosakulwong, Timothy G. Lesnick, Samantha M. Wille, Matthew Murphy, Matthew L. Senjem, Jeffrey L. Gunter, Prashanthi D Vemuri, Clifford R Jr. Jack, Virginia M Miller, Kejal M Kantarci

Research output: Contribution to journalArticle

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Abstract

Objective: To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women. Methods: Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE e4 status in linear regression analysis. Results: At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm3 (95% confidence interval: 2164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm 3 (95% confidence interval: 292.13, 599.4) at 48 months (p < 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03). Conclusion: Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

Original languageEnglish (US)
Pages (from-to)911-918
Number of pages8
JournalNeurology
Volume80
Issue number10
DOIs
StatePublished - Mar 5 2013

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Platelet Activation
White Matter
Confidence Intervals
Activation
Random Allocation
Menopause
Platelet Count
Linear Models
Estrogens
Blood Platelets
Regression Analysis
Conventional
Confidence Interval
Risk Factors
Hormones
Lipids
Inversion
Blood
Segmentation
Randomization

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

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Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women. / Raz, Limor; Jayachandran, M.; Tosakulwong, Nirubol; Lesnick, Timothy G.; Wille, Samantha M.; Murphy, Matthew; Senjem, Matthew L.; Gunter, Jeffrey L.; Vemuri, Prashanthi D; Jack, Clifford R Jr.; Miller, Virginia M; Kantarci, Kejal M.

In: Neurology, Vol. 80, No. 10, 05.03.2013, p. 911-918.

Research output: Contribution to journalArticle

Raz, Limor ; Jayachandran, M. ; Tosakulwong, Nirubol ; Lesnick, Timothy G. ; Wille, Samantha M. ; Murphy, Matthew ; Senjem, Matthew L. ; Gunter, Jeffrey L. ; Vemuri, Prashanthi D ; Jack, Clifford R Jr. ; Miller, Virginia M ; Kantarci, Kejal M. / Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women. In: Neurology. 2013 ; Vol. 80, No. 10. pp. 911-918.
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T1 - Thrombogenic microvesicles and white matter hyperintensities in postmenopausal women

AU - Raz, Limor

AU - Jayachandran, M.

AU - Tosakulwong, Nirubol

AU - Lesnick, Timothy G.

AU - Wille, Samantha M.

AU - Murphy, Matthew

AU - Senjem, Matthew L.

AU - Gunter, Jeffrey L.

AU - Vemuri, Prashanthi D

AU - Jack, Clifford R Jr.

AU - Miller, Virginia M

AU - Kantarci, Kejal M

PY - 2013/3/5

Y1 - 2013/3/5

N2 - Objective: To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women. Methods: Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE e4 status in linear regression analysis. Results: At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm3 (95% confidence interval: 2164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm 3 (95% confidence interval: 292.13, 599.4) at 48 months (p < 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03). Conclusion: Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

AB - Objective: To determine the association of conventional cardiovascular risk factors, markers of platelet activation, and thrombogenic blood-borne microvesicles with white matter hyperintensity (WMH) load and progression in recently menopausal women. Methods: Women (n = 95) enrolled in the Mayo Clinic Kronos Early Estrogen Prevention Study underwent MRI at baseline and at 18, 36, and 48 months after randomization to hormone treatments. Conventional cardiovascular risk factors, carotid intima-medial thickness, coronary arterial calcification, plasma lipids, markers of platelet activation, and thrombogenic microvesicles were measured at baseline. WMH volumes were calculated using a semiautomated segmentation algorithm based on fluid-attenuated inversion recovery MRI. Correlations of those parameters with baseline WMH and longitudinal change in WMH were adjusted for age, months past menopause, and APOE e4 status in linear regression analysis. Results: At baseline, WMH were present in all women. The WMH to white matter volume fraction at baseline was 0.88% (0.69%, 1.16%). WMH volume increased by 122.1 mm3 (95% confidence interval: 2164.3, 539.5) at 36 months (p = 0.003) and 155.4 mm 3 (95% confidence interval: 292.13, 599.4) at 48 months (p < 0.001). These increases correlated with numbers of platelet-derived and total thrombogenic microvesicles at baseline (p = 0.03). Conclusion: Associations of platelet-derived, thrombogenic microvesicles at baseline and increases in WMH suggest that in vivo platelet activation may contribute to a cascade of events leading to development of WMH in recently menopausal women.

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