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Spousal Caregivers of Patients With Alzheimer's Disease Show Longitudinal Increases in Plasma Level of Tissue-Type Plasminogen Activator Antigen

From the Department of Psychiatry (B.T.M., R.v.K., K.A., S.K.R., J.E.D., P.J.M., T.L.P., S.A.-I., I.G.), University of California, San Diego, La Jolla, California; Department of General Internal Medicine (R.v.K.), University Hospital Berne, Berne, Switzerland; Department of Medicine (M.G.Z.), University of California, San Diego, La Jolla, California; Veterans Affairs San Diego Healthcare System (S.A.-I.), San Diego, California.

Address correspondence and reprint requests to Brent T. Mausbach, Department of Psychiatry (0680), University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0680. E-mail: bmausbach{at}ucsd.edu

Objective: To determine if caregivers of spouses with Alzheimer's disease demonstrate greater increase in tissue plasminogen activator (t-PA) antigen relative to noncaregiving controls. Caring for a spouse with Alzheimer's disease has been associated with increased mortality and reduced time to developing cardiovascular disease (CVD), possibly due to impaired fibrinolysis resulting from chronic stress.

Methods: Annual in-home assessments of plasma t-PA antigen were collected from 165 participants (112 caregivers and 53 noncaregivers) enrolled in the University of California, San Diego Alzheimer caregiver study. Participants were married, living with their spouses, at least 55 years of age, and free of serious medical conditions (e.g., cancer). Caregivers provided in-home care for their spouse with Alzheimer's disease at the time of enrollment. Exclusion criteria included taking anticoagulant medication or evidenced severe hypertension (>200/120 mm Hg). Mixed (random effects) regression was used to assess slopes for t-PA antigen over the study period at the same time controlling for medical and demographic characteristics associated with t-PA antigen.

Results: Caregivers demonstrated significantly greater increases in t-PA antigen over the 5-year study period compared with noncaregiving controls (p = .02), even when controlling for body mass index, mean blood pressure, age, gender, and use of CVD medication.

Conclusions: The accelerated rate of developing a prothrombotic environment including elevated t-PA antigen may provide one mechanism by which caregiving is associated with greater morbidity and mortality and the development of CVD.

Key Words: cardiovascular disease • chronic stress • fibrinolysis • aging

Abbreviations: CVD = cardiovascular disease; IL-6 = interleukin-6; t-PA = tissue plasminogen activator; PAI-1 = plasminogen activator inhibitor; CHD = coronary heart disease; MAP = mean arterial pressure; BMI = body mass index; BP = blood pressure; HAM-D = Hamilton Scale for Depression.