Grief and CVD: Simple Regimen May Lower Risk

A low-dose beta-blocker and aspirin regimen may buffer some of the physiologic stress of losing a loved one that puts newly grieving individuals at risk for cardiovascular events, Australian researchers suggest.

Among people mourning the loss of a spouse or child, taking the combination therapy for 6 weeks resulted in lower morning systolic BP compared with placebo. The intervention group also had lower 24-hour heart rate and less anxiety and depression. No major adverse effects of the regimen were seen.

“There is a paucity of proven interventions preventing adverse physical health during bereavement, which is a unique life stress with a complex combination of psychological symptoms,” write Geoffrey H. Tofler, MD (Royal North Shore Hospital, St Leonards, Australia), and colleagues in the paper published online November 13, 2019, in the American Heart Journal. They say the finding that the therapy appears to attenuate risk may be relevant to other causes of grief including job loss, the end of a relationship, or the death of a beloved pet.

Commenting for TCTMD, Donald Edmondson, PhD (Columbia University Medical Center, New York, NY), noted that intense trauma and emotion as catalysts for CV events has been documented in a variety of situations, from people who lived through Hurricane Katrina in New Orleans to fans devastated by the outcome of high-drama sporting events in Europe.

Edmondson said confirmation of the protective effect of low-dose metoprolol and aspirin in larger randomized trials could represent a major public health benefit.

“Depending on how you classify trauma, north of three-quarters of people will experience a potentially traumatic event in their life,” he said. “Here we have a therapy that's very simple, with very few side effects, that can disrupt the sort of vicious cycle that seems to occur after these very emotional events.”

Long-lasting Effect Seen

The study authors say they chose the regimen based on published data showing the ability of beta-blockers to protect against emotional triggers of ACS, and to work best in the morning when adrenergic activity increases and CVD rates tends to peak. Other actions of beta-blockers that may be helpful in high-stress situations include their ability to attenuate stress-related surges in heart rate, BP, and ischemia, as well as to decrease arrhythmia, improve autonomic function, and possibly reduce coagulability. Similarly, they say, studies have shown that anger-associated MI can be reduced with aspirin, and that aspirin therapy may “modify the link between inflammation and depression.”

For the study, they recruited 85 people who were spouses, partners, or parents of patients who died at one of five participating hospitals in Sydney. Participants were not seriously ill themselves or taking beta-blockers, other heart rate-lowering drugs, aspirin, or other antiplatelet or antithrombotic medications. They had heart rate below 60 beats per minute and systolic BP below 120 mm Hg at screening or first assessment.

Study participants were randomized to 25 mg metoprolol and 100 mg aspirin (n = 42) or placebo (n = 43) for 6 weeks, with assessments continuing at 6 weeks and 6 months after medications had ceased. The average time to enrollment was 12 days after the death of the loved one.

Morning systolic BP averaged 132.1 ± 2.6 mm Hg after 6 weeks on the combination regimen versus 139.5 ± 2.4 mm Hg in the placebo group and remained lower at the assessment done 6 weeks after treatment ceased. Even after 12 weeks off treatment, the intervention group maintained the morning systolic advantage relative to placebo (132.2 ± 2.1 mm Hg vs 141.6 ± 2.0 mm Hg).

The intervention group also maintained lower levels of anxiety and depression out to 6 months.

“What's important about that is that it's further shows the bidirectional link between our psychological and physiological experience,” Edmondson noted. “Our brains are sensitive to our physiological state and tend to interpret those things for us as anxiety and depression.”

He added that the study, while small and having had some issues with crossover and unblinding, sets the stage for larger trials that could offer the intervention earlier in the grief process by identifying populations who might need it, such as loved ones of dying patients.

Edmondson added that it is important that individuals who are grieving not think that the therapy is meant to somehow medicate human emotions. 

“You’re not taking away the experience of grief. Nothing about this therapy is going to in any way reduce, or medicalize, or treat the experience of grieving,” he said. What it may offer, however, is a way to “buffer the human body from the downstream consequences of those normative psychological experiences,” he concluded.