The effect of metoprolol and aspirin on cardiovascular risk in bereavement: A randomized controlled trial.

BACKGROUND: Bereavement is associated with an increased risk of cardiovascular disease; however, no reports exist of interventions to reduce risk. In a randomized, double-blind, placebo-controlled trial of 85 recently bereaved participants, we determined whether ß-blocker (metoprolol 25 mg) and aspirin (100 mg) reduce cardiovascular risk markers and anxiety, without adversely affecting bereavement intensity. METHODS: Participants were spouses (n = 73) or parents (n = 12) of deceased from 5 hospitals in Sydney, Australia, 55 females, 30 males, aged 66.1 ±â€¯9.4 years. After assessment within 2 weeks of bereavement, subjects were randomized to 6 weeks of daily treatment or placebo, and the effect evaluated using ANCOVA, adjusted for baseline values (primary analysis). RESULTS: Participants on metoprolol and aspirin had lower levels of home systolic pressure (P = .03), 24-hour average heart rate (P < .001) and anxiety (P = .01) platelet response to arachidonic acid (P < .001) and depression symptoms (P = .046) than placebo with no difference in standard deviation of NN intervals index (SDNNi), von Willebrand Factor antigen, platelet-granulocyte aggregates or bereavement intensity. No significant adverse safety impact was observed. CONCLUSIONS: In early bereavement, low dose metoprolol and aspirin for 6 weeks reduces physiological and psychological surrogate measures of cardiovascular risk. Although further research is needed, results suggest a potential preventive benefit of this approach during heightened cardiovascular risk associated with early bereavement.

The complexities of recruiting bereaved family members into a research study in the critical care environment: a discussion paper.

Research on the effects of stressful events on human health and wellbeing has progressed in recent years. One such stress, bereavement, is considered one of life's greatest stresses, requiring significant readjustment. The Cardiovascular Risk in Bereavement study (CARBER) investigated in detail cardiovascular risk factors during the first weeks following the death of a partner or adult child in the critical care environment. The purpose of this paper is to explore the once held perception that the bereaved population should not be involved in research, using an actual illustrative project. The paper specifically focuses on the challenges regarding acceptability and feasibility of recruitment of recently bereaved individuals from the critical care environment. The question of whether bereaved individuals have capacity to consent to involvement in research immediately after loss is considered. The appropriateness of asking newly bereaved individuals to participate in research immediately after the death of their relative is also discussed. The work of the research team demonstrates that early recruitment of bereaved family members into a research project is feasible and acceptable to participants, especially when a multidisciplinary collaborative approach is employed and a personal mode of recruitment used.

The nature of death, coping response and intensity of bereavement following death in the critical care environment.

INTRODUCTION: Bereavement, defined as the situation of having recently lost a significant other, is recognised as one of life's greatest stressors and may lead to decrements in health status, psychological morbidity and excess risk of mortality. AIM: The aim of this study was firstly to describe the relationships between the nature of death and bereavement intensity following death in the adult critical care environment and secondly to examine the modifying effects of coping responses on intensity of bereavement reaction. METHOD: Prospective evaluation of the impact of the nature of death and coping responses on bereavement intensity. 78 participants completed a nature of death questionnaire within 2 weeks of bereavement and at 3 and 6 months completed the Core Bereavement Items Questionnaire (CBI-17) and Brief COPE Inventory. RESULTS: At 6 months, univariate variables significantly associated with bereavement intensity were: being unprepared for the death (p<0.001), a drawn out death (p<0.001), a violent death (p=0.007) and if the deceased appeared to suffer more than expected (p=0.03). Multivariate analysis revealed being unprepared for the death appears to account for these relationships. Regarding coping, there were significant increases from 3 to 6 months in both acceptance scales (p=0.01) and planning (p=0.02) on The Brief COPE Inventory. Greater use of emotional support (p=0.02), self-blame (0.003) and denial (p<0.001) were multivariate variables associated with higher bereavement intensity at 6 months. CONCLUSION: The results from this evaluation provide insight into the impact of bereavement after death in the critical care environment and inform potential preventative approaches at the time of death to reduce bereavement intensity.

Haemodynamic changes during early bereavement: potential contribution to increased cardiovascular risk.

BACKGROUND: bereavement is associated with increased cardiovascular risk, particularly in surviving spouses and parents, however the mechanism is not well understood due to limited studies. The purpose of this study was to evaluate haemodynamic changes (blood pressure (BP) and heart rate (HR)), that may contribute to increased cardiac risk in early bereavement. METHODS: we enrolled 80 bereaved individuals and 80 non-bereaved as a reference group. Twenty-four hour ambulatory blood pressure monitoring was performed within two weeks (acute assessment) and at six months following bereavement. RESULTS: compared to the non-bereaved, the acutely bereaved had higher 24-hour systolic BP (mean (SE) 130.3 (1.5) vs 127.5 (1.4)mmHg, p=0.03), higher daytime systolic BP (135.6 (1.5) vs 131.6 (1.4)mmHg, p=0.02) and higher daytime systolic load (median % 39.0 vs 29.3, p=0.02). By six months the BP of the bereaved tended to be lower than acute measures. This difference was significant amongst those not taking BP lowering medications for 24-hour systolic BP (126.5 (2.4) vs 129.7 (2.3)mmHg, p=0.04), daytime systolic BP (129.8 (2.1) vs 133.9 (2.0)mmHg, p=0.01) and daytime diastolic pressure (76.7 (1.0) vs 78.9 (0.9)mmHg, p=0.03). Twenty-four hour heart rate was also higher acutely in the bereaved compared with the reference group (74.0 (1.2) vs 71.7 (0.9) b/min, p=0.02); at six months heart rate in the bereaved had fallen to non-bereaved levels (70.4 (0.09), p=0.02). CONCLUSION: early bereavement is associated with increased systolic blood pressure and heart rate. These haemodynamic changes may contribute to a time-limited increase in cardiovascular risk.

Therapy for triggered acute risk prevention in subjects at increased cardiovascular risk.

Heavy physical exertion, emotional stress, heavy meals, and respiratory infection transiently increase the risk of myocardial infarction, sudden cardiac death, and stroke; however, it remains uncertain how to use this information for disease prevention. We determined whether it was feasible for those with either risk factors for cardiovascular disease (CVD) or known CVD to take targeted medication for the hazard duration of the triggering activity to reduce their risk. After a run-in of 1 month, 20 subjects (12 women and 8 men) aged 68.6 years (range 58 to 83) recorded for 2 months all episodes of physical and emotional stress, heavy meal consumption, and respiratory infection. For each episode, the subjects were instructed to take either aspirin 100 mg and propranolol 10 mg (for physical exertion and emotional stress) or aspirin 100 mg alone (for respiratory infection and heavy meal consumption) and to record their adherence. Adherence with taking the appropriate medication was 86% according to the diary entries, with 15 of 20 subjects (75%) achieving ≥80% adherence. Propranolol taken before exertion reduced the peak heart rate compared with similar exercise during the run-in period (118 ± 21 vs 132 ± 16 beats/min, p = 0.016). Most subjects (85%) reported that it was feasible to continue taking the medication in this manner. In conclusion, it is feasible for those with increased CVD risk to identify potential triggers of acute CVD and to take targeted therapy at the time of these triggers.

Inflammatory and thrombotic changes in early bereavement: a prospective evaluation.

AIMS: Although there is an increased cardiovascular risk in the immediate weeks following bereavement, the mechanism is not well understood. The aim of this study was to determine whether inflammatory and thrombotic changes were present in acute bereavement. METHODS AND RESULTS: Eighty bereaved spouses or parents were prospectively studied within 2 weeks of bereavement (acute) and at 6 months, and compared to 80 non-bereaved participants. Haemostatic measures were obtained between 8 a.m. and 11 a.m. and processed within 1 h. Compared to non-bereaved participants, those acutely bereaved had a higher neutrophil count (4.34 ± 0.19 vs 3.79 ± 0.15, p = <0.001), von Willebrand factor antigen (132.33 ± 3.6 vs 119.95 ± 3.29, p = 0.02), Factor VIII (1.43 ± 0.06 vs 1.25 ± 0.04, p = 0.02) and platelet/granulocyte aggregates (median 383.0 vs 343.5, p = 0.02). Levels of neutrophils, monocytes, eosinophils, platelet count, platelet/monocyte granulocytes and von Willebrand factor were lower in bereaved at 6 months compared to acutely (all p < 0.05). CONCLUSION: Acute bereavement is associated with inflammatory and prothrombotic changes that may contribute to the increased cardiovascular risk with bereavement and provide clues for future preventative strategies.

Effect of early bereavement on heart rate and heart rate variability.

Early bereavement is associated with increased cardiovascular events. The mechanism, however, has not been well studied. We assessed whether bereavement is associated with an increased heart rate (HR) and decreased heart rate variability that might contribute to increased cardiovascular risk. A total of 78 bereaved spouses and parents (55 women and 23 men; aged 34 to 87 years, mean 65) were studied with 24-hour Holter monitoring within 2 weeks of bereavement (acute) and at 6 months. Their findings were compared to those from a nonbereaved reference group (52 women and 27 men) aged 33 to 91 years (mean 63.6). All participants were in sinus rhythm. We assessed the mean HR, atrial and ventricular arrhythmias, and both time and frequency domain heart rate variability measures. Acute bereavement was associated with increased 24-hour HR (mean ± SE, 75.1 ± 1.1 vs 70.7 ± 1.0; p = 0.004) and reduced heart rate variability, as indicated by lower standard deviation of the NN intervals index (median 45.4 vs 49.9, p = 0.017), total power (7.78 ± 0.10 vs 8.02 ± 0.09, p = 0.03), very low frequency (7.23 ± 0.09 vs 7.44, p = 0.046) and low frequency (5.76 ± 0.12 vs 6.16 ± 0.09, p = 0.01). At 6 months, the bereaved had a significantly lower HR (p = 0.001) and increased standard deviation of the NN intervals index (p = 0.02), square root of the mean square of differences of successive intervals (p = 0.045), number of interval differences of successive NN intervals >50 ms divided by the number of NN intervals (p = 0.039), low-frequency power (p = 0.02), and high frequency (p = 0.002) compared to the initial acute levels. In conclusion, the present study, the first to report 24-hour HR monitoring in the early weeks of bereavement, has demonstrated increased HR and altered autonomic function that might contribute to the increased cardiovascular events in early bereavement.