Patients with ST-segment elevation myocardial infarction (STEMI), but without standard modifiable cardiovascular risk factors (SMuRFs), had a higher risk of Thrombolysis in Myocardial Infarction (TIMI) flow grade of 0 or 1 pre-percutaneous coronary intervention (PCI), a new patient-level pooled analysis of 10 clinical trials reports.
The study, published online Monday and in the June 13 issue of JACC: Cardiovascular Interventions, examined differences in infarct characteristics and clinical outcomes in patients with versus without SMuRFs such as dyslipidemia, hypertension, diabetes mellitus and smoking.
Led by Gemma A. Figtree, MBBS, PhD, from the University of Sydney, the authors noted that their research group previously reported an increase in the proportion of ST-segment elevation myocardial infarction (STEMI) patients who have no SMuRFs over a 10-year period: from 11% to 27%.
“In addition to the absolute and increasing proportion of SMuRF-less patients with STEMI, these patients have been reported to have increased in-hospital and 30-day all-cause and cardiovascular mortality,” they said, citing later follow-up analyses.
“As such, detailed characterization of the severity and characteristics of the infarcted myocardium in SMuRF-less patients with STEMI might provide significant insights into the underlying pathophysiologic mechanisms that may affect short- and long-term clinical outcomes,” they said.
Findings from the new patient-level pooled analysis report that SMuRF-less STEMI patients were more likely to have TIMI flow grade 0/1 pre-PCI. However, after adjustment, there were no significant associations between SMuRF-less status and infarct size, left ventricular (LV) ejection fraction or mortality, said the team.
Figtree and colleagues pooled individual patient-level data from 10 randomized trials that had enrolled patients with STEMI and confirmed coronary artery disease (CAD) undergoing primary PCI into a common database at the Cardiovascular Research Foundation.
Infarct size was measured within 1 month by either cardiac magnetic resonance or technetium-99m sestamibi single-photon emission computed tomography imaging in all trials, with first-presentation STEMI classified into two groups according to the presence or absence of at least one SMuRF.
A total of 2,862 patients with first STEMI were included in the analysis, of whom 2,534 had magnetic resonance imaging or nuclear LV and infarct imaging outcomes available. Of those, 524 (18.3%) were SMuRF-less, and 2,338 (81.7%) had at least one SMuRF.
The authors noted a differential distribution of SMuRF-less STEMI patients across the 10 studies, with an approximate twofold higher proportion of SMuRF-less STEMI patients in the three studies restricting enrollment to patients with anterior STEMI (271/ 994, 27.3%) versus those who were recruiting also non-anterior MI (253/1,868, 13.5%; P < 0.0001).
At baseline, patients with no SMuRFs were similar in age to those with at least 1 SMuRF (61.0 ±12 years vs 60.7 ± 12 years, P = 0.62) and more likely to be male (82% vs 75%, P < 0.001). Of those participants with at least one SMuRF, 53% were current smokers, 60% had hypertension, 21% had diabetes, and 35% had a diagnosis of hyperlipidemia
After adjusting for study effect, Figtree and colleagues revealed that SMuRF-less patients had more frequent poor pre-PCI TIMI flow 0/1 compared with patients with at least one SMuRF (72.0% vs 64.1%; odds ratio [OR]: 1.35; 95% confidence interval [CI]: 1.08-1.70).
However, the team noted that there were no independent associations between the presence or absence of SMuRFs at baseline and infarct size (estimate = -0.35; 95% CI: -1.93 to 1.23), LV ejection fraction (estimate = -0.06; 95% CI: -1.33 to 1.20), or mortality at 30 days (HR: 0.46; 95% CI: 0.19-1.07) and 1 year (HR: 0.74; 95% CI: 0.43-1.29).
“Although this is a known prognostic factor for poor outcome, after adjustment, SMuRF-less patients were observed to have similar infarct size, cardiac function, and comparable clinical outcomes to their counterparts with at least 1 risk factor,” said the research team.
They added that further studies may help to confirm whether factors involved in heightened susceptibility to coronary atherosclerosis and myocardial infarction (MI) in the absence of risk factors may also be associated with TIMI flow grade 0/1, contributing to the demonstrated higher mortality of SMuRF-less STEMI patients.
Emerging pathophysiological pathways
Writing in an accompanying editorial, Massimo Volpe, MD, and Giovanna Gallo, MD, PhD, from the Sant’Andrea Hospital and Sapienza University of Rome, said the prominent role of traditional SMuRFs in the development of MI “represents a pillar of contemporary cardiovascular medicine and of recommended strategies to prevent acute coronary syndromes.”
However, the editorialists noted that a growing interest has been generated by the observation that a large proportion of patients suffer a STEMI in the absence of dyslipidemia, hypertension, diabetes, and smoking (SMuRF-less patients).
“Another important and emerging aspect that will need further investigation and that might be of particular relevance in SMuRF-less patients is the potential role of emerging pathophysiological pathways and [risk factors] leading to MI,” said the expert commentators.
“Causes of STEMI other than plaque rupture, ulceration, fissuring, or erosion have gained increasing clinical attention, leading to a shift from the concept of ‘vulnerable plaque’ to that of ‘vulnerable patients,’ which includes not only the atherosclerotic lesions of coronary arteries, but also circulating biomarkers and the response of the injured myocardium.”
They concluded that the development of novel technologies in the next few years, with the purpose to achieve the spreading of integrated panels of genes, biomarkers and proteins, “may contribute to further refine [cardiovascular] risk assessment.”
Figtree GA, Redfors B, Kozor R, et al. Clinical Outcomes in Patients With ST-Segment Elevation MI and No Standard Modifiable Cardiovascular Risk Factors. JACC Cardiovasc Interv 2022;15:1167-1175.
Volpe M, Gallo G. Myocardial Infarction in Patients Without Cardiovascular Risk Factors: Advanced Prediction Models to Unlock the Clinical Dilemma? JACC Cardiovasc Interv 2022;15:1176-1178.
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