For Younger MI Survivors, Stress Boosts Adverse Outcomes

Young and middle-age adults who survive an MI face a nearly twofold increase in MACE over the subsequent 5 years if they suffer from psychological distress after their initial event, observational data show.

The association between psychological stress and subsequent events was attenuated after adjusting for markers of inflammation, such as monocyte chemoattract protein-1 (MCP-1) and interleukin-6 (IL-6). That finding, said lead investigator Mariana Garcia, MD (Emory University, Atlanta, GA), suggests “mechanisms involving inflammation may be implicated.”

The study results are set to be presented next week at the American College of Cardiology 2021 Scientific Session.

Much progress has been made over the past few decades in terms of reducing MI risk, but heart disease remains the leading cause of death in the United States. Moreover, the gains haven’t been as great in younger adults, who also tend to be more vulnerable to post-MI stress because they have a “higher prevalence of mental health disorders compared to older adults,” Garcia told the media in an ACC press conference.

Mental health is known to affect CVD risk in both positive and negative ways, as an American Heart Association scientific statement detailed earlier this year, with stress being an established trigger for acute events after an initial MI. Also, as reported by TCTMD, earlier research has drawn a connection between childhood trauma and early-onset MI.

Cardiologists should consider the value of regular psychological assessments, especially in younger patients. Mariana Garcia

Overall “there’s been a continued need to identify new complementary targets for prevention, one of these being stress,” Garcia said, adding that it appears that chronic exposure to stress plays a larger role in determining prognosis in high-risk people with existing CAD than it does in contributing to disease development.

“However, not much is known about psychological distress and residual risk, particularly in the young and middle-aged population with recent myocardial infarction,” Garcia pointed out.

Ron Blankstein, MD (Brigham and Women's Hospital, Boston, MA), principal investigator for the YOUNG-MI registry, said that despite its small size and use of a composite endpoint, the new study is interesting. “We’ve seen this in many areas of cardiovascular medicine—that psychological stress does contribute to the development of cardiovascular disease, and there are multiple mechanisms, including higher levels of stress hormones, more inflammation, and higher blood pressure. This is another study showing that there are negative consequences,” he noted.

Key questions, though, are whether psychological stress is modifiable and whether curbing such stress would help, said Blankstein.

MIMS2 Data

Using data from the Myocardial Infarction and Mental Stress 2 (MIMS2) cohort, Garcia et al studied 283 MI survivors ≤ 61 years old (mean age 51 years), of whom 64% were Black and half were women. Within 8 months of being hospitalized for MI, the participants completed questionnaires that assessed depression, anxiety, anger, perceived stress, and posttraumatic stress disorder.

These results were then compiled into a composite score of “psychological distress,” rated as mild, moderate, or high. Patients with higher distress were more likely to be Black, to be unmarried, and to have less education, lower income, and higher likelihood of being unemployed. They also were more apt to smoke, be hypertensive, or have diabetes.

At 5-year follow-up, 80 post-MI patients (28%) experienced subsequent MI or stroke, heart failure-related hospitalization, or cardiovascular death. For patients categorized as experiencing high distress, the adverse event rate was 37%, whereas only 17% of those with mild distress had such an event (HR 2.7; 95% CI 1.5-4.9). The link between high distress and cardiovascular outcome was slightly attenuated when adjusting for demographic factors (HR 2.5; 95% CI 1.4-4.6) and clinical risk factors (HR 1.9; 95% CI 1.0-3.8). Adjusted for inflammatory markers, specifically MCP-1 and IL-6, the relationship lost statistical significance (HR 1.5; 95% CI 0.7-3.3).

This is a very important association, but what exactly drives it and how can we mitigate it? Ron Blankstein

Press conference moderator Eugene Yang, MD (UW Medicine, Bellevue, WA), said the results are in line with other studies that have hinted at social determinants of health having an impact on cardiovascular outcomes. “I think the question about the inflammatory markers is interesting,” he added, asking why these MCP-1 and IL-6 were used rather than more-conventional C-reactive protein (CRP).

Garcia said they did in fact look at several circulating markers of acute inflammation, including CRP, but MCP-1 and IL-6 were the only two to have a direct positive association with stress and outcomes.

“What we’re thinking is that these markers have shown a significant association in patients with established coronary disease and adverse outcomes, and they are specifically increased during acute mental stress. . . . This mechanistic effect—it might involve plaque vulnerability, rupture, and thrombogenesis—may be quite specifically more impactful in the young and middle-aged patient population,” she explained.

Yang agreed with this possibility, pointing to recent data from the YOUNG-MI study showing heightened long-term mortality in younger patients with inflammatory disorders. He asked: “Where do you see additional ways of trying to assess this link between psychological distress and its impact on inflammatory pathways?”

Garcia said that it’s a great question, pointing out that the lengthy evaluation they employed in their study would be difficult to apply in practice. More important, she said, are the clinical insights the research offers.

“Cardiologists should consider the value of regular psychological assessments, especially in younger patients,” Garcia advised. Equally important is to “explore treatment modalities for ameliorating this psychological distress, whether that be relaxation techniques, holistic approaches, meditation, in addition obviously to traditional medical therapy and cardiac rehab.” Lastly, outreach is needed to raise awareness that mental health matters for these patients.

Blankstein made the point that the apparent impact of psychological stress may be confounded by other factors. “People that have higher stress don’t eat as well, and don’t exercise, and have a harder time taking their medications,” he said, adding that socioeconomic factors also may come into play. “That’s the challenge here. This is a very important association, but what exactly drives it and how can we mitigate it?”

Ultimately, he suspects inflammation is just one piece of the puzzle. “This is a significant difference in event rates in a relatively small population,” he commented, “so I would think that there is more at hand here than just a small increase in inflammation.”

Chronic stress—such as taking care of an ill family member or going through a divorce—is more influential than comparatively brief stressful events, he said. “It kind of all adds up. . . . Things can accumulate in 5 years.”

Activities like yoga, smartphone apps, and other relaxing pursuits can help, but Blankstein says he’s uncertain if they will make a difference in outcomes. “I don’t think that’s going to be the answer.” He stressed, though, that this doesn’t detract from the key message: “Chronic exposure to high levels of stress is not a good thing for the cardiovascular system.”