By Michael H. Crawford, MD

Professor of Medicine, Lucy Stern Chair in Cardiology, University of California, San Francisco

SYNOPSIS: ST-elevation myocardial infarction patients without standard risk factors recorded a higher all-cause mortality rate that was particularly evident in women. Using proper therapy in these patients may attenuate this risk.

SOURCE: Figtree GA, Vernon ST, Hadziosmanovic N, et al. Mortality in STEMI patients without standard modifiable risk factors: A sex-disaggregated analysis of SWEDEHEART registry data. Lancet 2021;397:1085-1094.

Acute ST-elevation myocardial infarction (STEMI) in patients without a history of standard modifiable cardiovascular risk factors for atherosclerosis occurs in about 10-25% of patients. Generally, clinicians believe such patients fare better short and long term compared to their counterparts with standard risk factors, but this notion has not been examined adequately. To test this hypothesis in general and by sex, Figtree et al analyzed the SWEDEHEART database. The authors identified patients with the first presentation of a STEMI and no history of coronary artery disease (CAD). Among 62,048 such patients, 33% were women, and 15% presented without a standard risk factor (17% men and 11% women; P < 0.001). The standard modifiable cardiovascular risk factors included hypertension (70%), elevated LDL cholesterol (higher than 135 mg/dL or total cholesterol higher than 212 mg/dL; 48%), smoking one or more cigarettes per day (33%), and diabetes (21%) — all diagnosed before their STEMI. The primary endpoint was all-cause mortality at 30 days. Secondary endpoints were major cardiac or cerebral events (MACCE) in hospital at 30 days, five years, and at the end of follow-up or death.

The primary endpoint was 11.3% in the group without risk factors vs. 7.9% in the group with risk factors (P < 0.0001). The HR was 1.47 (95% CI, 1.37-1.57; P < 0.001), which still was significant when the authors considered a multivariate adjustment for other factors known to be associated with 30-day mortality (HR, 1.24; 95% CI, 1.10-1.39; P < 0.0003). Mortality at 30 days in women without standard risk factors was 17.6% vs. 11.2% in women with standard risk factors. The mortality rate in men without standard risk factors was 9.3% vs. 6.1% in men with standard risk factors. In-hospital death and five-year cardiovascular death were higher in men without standard risk factors than in men with standard risk factors. In women, this difference was similar and persisted for 12 years. There were several significant differences in the characteristics of the two groups, but few were clinically significant. Importantly, using angiotensin-receptor blockers, beta-blockers, and statins were less frequent in the group without standard risk factors (P < 0.0001). The authors concluded the STEMI patients without standard risk factors record a higher all-cause mortality rate that is particularly evident in women. Further, using proper therapy in these patients may attenuate this risk.

COMMENTARY

Figtree et al explored other characteristics of patients without standard risk factors that would explain their higher death rate after MI. However, body mass index and triglycerides were lower, and HDL cholesterol was higher in the group without standard risk factors. C-reactive protein levels were not different, and there was no difference in door-to-balloon or thrombolysis time. Spontaneous coronary artery dissection was considered and was more common in the group without standard risk factors (1.7% vs. 0.8%), but is unlikely to explain all the differences observed. Of course, there could be multiple risk factors at just below the diagnostic or therapeutic threshold that, in aggregate, could explain the differences in outcomes. Perhaps this is why those treated with standard risk reduction therapy fared better. Also, the excess mortality was early and diminished over time, which suggests it may have been caused by arrhythmias. Renin-angiotensin-aldosterone system inhibitors and beta-blockers reduce arrhythmias and early post-MI mortality. Accordingly, Figtree et al suggested STEMI patients without risk factors be treated just as aggressively pharmacologically as those with risk factors.

There were several strengths to this study. It was large, and the follow-up period was long. Also, there were comprehensive data collected on these patients, which allowed the authors to examine many potentially meaningful clinical factors. There also were several limitations. This was an observational study, so there could have been unmeasured confounders and biases. The authors used cutpoints for who did or did not have a risk factor when it is likely that risk factors are a continuous gradient. Importantly, there were no data on family history, socioeconomic factors, or psychosocial factors. Thus, the findings must be considered hypothesis-generating. However, the findings do counter the prevalent concept that an MI usually is self-induced because of inadequate management of treatable risk factors.