Anxiety is a better predictor of platelet reactivity in coronary artery disease patients than depression

Abstract

Aims: Depression and anxiety are linked to coronary events but the mechanism(s) remains unclear. We investigated the associations of depression and anxiety with serotonin-mediated platelet hyperactivity in coronary artery disease (CAD) patients in a cross-sectional study.

Methods and results: Three months after an acute coronary event, stable CAD patients (n = 83) on aspirin and clopidogrel were evaluated for depression (beck depression inventory) and anxiety (hospital anxiety and depression scale), and their platelet reactivity was measured (optical aggregometry and flow cytometric fibrinogen binding in response to adenosine diphosphate (ADP = 5 microM) and two serotonin + epinephrine doses [5HT:E (L) = 4 microM + 4 microM and 5HT:E (H) = 10 microM + 4 microM]. Platelet reactivity was significantly higher in depressed and anxious than in depressed only or non-depressed-and-non-anxious patients. Aggregation (mean +/- SE) was 41.9 +/- 2.6% vs. 32.2 +/- 2.6% vs. 30.4 +/- 3.7% with 5HT:E (L) and 46.9 +/- 2.7% vs. 35.6 +/- 2.7% vs. 31.7 +/- 3.8% with 5HT:E (H) (P < 0.05 for both). Differences in ADP aggregations were not significant, perhaps because of clopidogrel therapy. Flow cytometry findings were similar. In a multivariate linear regression model adjusted for age, body mass index, and each other, anxiety symptoms independently predicted all 5HT:E-mediated platelet reactivity measures, whereas depression predicted none.

Conclusion: Anxiety is associated with elevated serotonin-mediated platelet reactivity in stable CAD patients and symptoms of anxiety show strong, independent correlations with platelet function.

Figure 1

Flow chart of the study design. MSMC, Mount Sinai Medical Center; ACS, acute coronary syndrome.

Figure 2

Top panel shows platelet aggregation result (estimated means ± standard error) in stable CAD patients grouped into non-depressed and non-anxious (Dep− Anx−), depressed only (Dep+ Anx−), and depressed and anxious (Dep+ Anx+). Bottom panel presents linear relations of depressive and anxious symptoms (BDI and HADS-A scores expressed in standard deviations from their means) to aggregation after controlling for age, BMI, and each other. *P < 0.05.

Figure 3

Top panel presents flow cytometric measurement of platelet surface receptor activation (estimated means ± standard error) in stable CAD patients grouped into non-depressed and non-anxious (Dep− Anx−), depressed only (Dep+ Anx−), and depressed and anxious (Dep+ Anx+). Bottom panel presents linear relations of depressive and anxious symptoms (BDI and HADS-A scores expressed in standard deviations from their means) to platelet surface receptor activation after controlling for age, BMI, and each other. *P < 0.05.