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Combination of Caregiving Stress and Hormone Replacement Therapy is Associated With Prolonged Platelet Activation to Acute Stress Among Postmenopausal Women

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

Address correspondence and reprint requests to Igor Grant, Department of Psychiatry, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California, 92093-0680. E-mail: igrant{at}ucsd.edu

Objective: To investigate the combined effects of caregiving and hormone replacement therapy (HRT) on platelet hyperactivity to acute psychological stress. Both HRT and the chronic stress of caregiving have been associated with increased cardiovascular risk, potentially through a mechanism of platelet hyperactivity.

Methods: A total of 78 elderly postmenopausal women (51 caregivers (CG) and 27 noncaregivers (NC)) were assessed for platelet activation in response to a laboratory speech test. Half the sample was taking HRT. Blood was sampled at baseline, post speech, and after 14 minutes of recovery. Platelet activation was assessed through whole blood flow cytometry assays of % aggregates (Agg), and expression of % fibrinogen receptors (FbR) and % P-selectin (P-sel) on platelet surface.

Results: Multivariate repeated-measures analysis of variance revealed that CG taking HRT exhibited significantly prolonged platelet activation in response to acute stress. There was an interaction between HRT and CG on recovery from stress for Agg (F (1,71) = 5.260, p = .025), P-Sel (F(1,71 = 6.426, p = .013), and FbR (F(1,71 = 6.653, p = .012), controlling for age, cardiovascular disease, and aspirin. Among HRT users, regression analysis revealed that CG had delayed recovery of Agg (ß = 0.354, t(34) = 2.154, p = .038) and P-sel (ß = 0.498, t(34)=3.126, p = .004) from stress relative to NC. No caregiving effects on recovery were present among non-HRT users. In addition, these effects were maintained after controlling for health behaviors, medications, and medical conditions.

Conclusion: Chronic dementia caregiving stress in combination with HRT may impair recovery of platelet activation after acute mental stress (i.e., activation levels do not quickly return to resting levels), thereby potentially increasing cardiovascular risk among CG who take HRT.

Key Words: P-selectin • fibrinogen receptor • GP IIb/IIIa • platelet aggregates • dementia • Alzheimer's disease

Abbreviations: HRT = hormone replacement therapy; CG = caregivers; NC = noncaregivers; Agg = % platelet aggregates; P-sel = % platelet P-selectin expression; FbR = % platelet fibrinogen receptor expression; CAM = cellular adhesion molecule; CVD = cardiovascular disease; CAD = coronary artery disease; UCSD = University of California, San Diego; GSI = Global Symptom Inventory; MANOVA = multivariate repeated-measures analysis of variance.