Low-Dose Aspirin for Prevention of Cardiovascular Risk in Bereavement: Results from a Feasibility Study

this visit. In this task, participants were asked to recall a situation where they felt alone and abandoned. The overall sample had a mean age of 58.59 (SD = 13.94), was 54.55% female, and 90.91% were White (vs. non-White). Bereaved versus nonbereaved and aspirin versus placebo groups did not differ at p < 0.05 on any of these characteristics. Change scores were used to reduce the number of variables in the analyses. Cohen’s d is reported as a measure of effect size. Bereaved participants reported more depressive symptoms than nonbereaved participants at baseline: CES-D score 23.80 (SD = 10.29) versus 8.42 (SD = 9.18) (F = 10.09, p < 0.001, d = 1.46). All 5 bereaved participants receiving aspirin reported fewer depressive symptoms at the second visit, compared to only 1 (of 5) bereaved participants receiving placebo. A dichotomous variable (decrease vs. no decrease in depressive symptoms) showed a significant difference (χ2 = 6.67, p < 0.01, d = 3.54). When including all participants, the separation recall task elicited an increase in systolic blood pressure: 129.21 mm Hg (SD = 13.64) to 137.60 mm Hg (SD = 13.16) (t = 3.59, p < 0.01, d = 0.63) and diastolic blood pressure: 78.36 mm Hg (SD = 11.46) to 83.07 mm Hg (SD = 10.88) (t = 4.58, p < 0.001, d = 0.42). There was also an increase in anxiety measured with the State-Trait Anxiety Inventory: 33.05 (SD = 7.75) to 39.85 (SD = 9.78) (t = 4.47, p < 0.001, d = 0.78). Heart rate increased from 74.12 beats per minute (bpm) (SD = 10.12) to 75.79 bpm (SD = 8.14) (t = 2.17, p < 0.05, d = 0.18) and decreased after the separation recall task: from 74.12 bpm (SD = 10.12) to 69.62 bpm (SD = 7.97) (t = 6.64, p < 0.001, d = 0.50). Participants receiving aspirin recovered faster from the separation recall than participants receiving placebo (Fig. 1). Heart rate decreased significantly more in the aspirin group: 5.97 bpm (SD = 2.95) versus 2.32 bpm (SD = 1.50) (F = 10.38, p < 0.005, d = 1.64). Using post hoc analysis, we had 71% power to detect this effect. HRV increased significantly in the aspirin group: log RSA 4.15 (SD = 1.96) to 4.57 (SD = 1.80) (t = 2.31, p < 0.05, d = 0.22). The change score of HRV was significantly higher in the aspirin group: log RSA placebo group –0.17 (SD = 0.38) versus aspirin group +0.42 (SD = 0.62) (F = 5.69, p < 0.03, d = 1.18). To summarize, our results show an attenuated physiological reactivity to a grief-related stress task and a beneficial effect on depressive symptoms in the aspirin group. Higher cardiovascular reactivity to emotional stressors in bereavement could amplify increased cardiovascular risk. Aspirin may have a potential preventive benefit targeting increased cardiovascular risk in bereavement. The effect of aspirin on depressive symptoms is consistent with previous studies linking depressive symptoms with inflammation [8]. Further research is needed to investigate this potential link. The use of aspirin in secondary prevention of cardiovascular disease is well established. In primary prevention, aspirin is deIn the 24 h following the death of a significant person, the incidence of acute myocardial infarction increases 21.1-fold [1]. Bereavement acutely increases mortality and cardiovascular risk in the surviving spouse for a limited time [2]. Aside from expectable psychological distress, acute bereavement is associated with an elevation of heart rate and blood pressure, a decrease in heart rate variability (HRV), and inflammatory and prothrombotic changes [2, 3]. Acute bereavement as a cardiovascular risk factor is amenable to preventive approaches, because it is predictable and temporary. Despite clear evidence for this risk, no studies to date have attempted primary prevention. Low-dose aspirin could be a suitable prevention strategy in acute bereavement. It targets the main cardiovascular risk factors during bereavement, is inexpensive, is widely available, does not require a prescription, and is feasible in other short-term interventions. Low-dose aspirin is widely used for its antiplatelet effect, has anti-inflammatory properties, and positively influences depressed mood [4], HRV [5], and blood pressure [6]. To investigate aspirin as a feasible preventive intervention, acutely bereaved participants (n = 10) were recruited on average within 30 days (SD = 14.67) of the death of their spouse; nonbereaved controls (n = 12) were also recruited. We assessed hemodynamic markers (blood pressure, heart rate, HRV) and depressive symptoms (Center for Epidemiologic Studies Depression Scale; CES-D) during 2 laboratory visits. The first laboratory visit was used to assess baseline values. Using simple randomization, all participants were then randomized to receive tablets containing either 81 mg of aspirin (n = 12, 41.67% bereaved), the standard dosage used for prevention in the USA, or placebo (n = 10, 50% bereaved) on the 5 days prior to the second laboratory visit. This visit was scheduled on average 10.55 days (SD = 7.51) after the first visit. We also included a separation recall task [7] to assess reactivity during Received: May 17, 2017 Accepted after revision: September 24, 2017 Published online: February 21, 2018