Silent myocardial infarction increases risk for future ischemic stroke

A prospective study of community-dwelling older adults demonstrated an independent relationship between silent myocardial infarction and subsequent ischemic stroke.

The study data, published in Neurology, further showed that overt myocardial infarction also correlated with ischemic stroke both in the short and long term.

“Similar to overt [myocardial infarction], silent [myocardial infarction] leads to scar formation and ventricular dysfunction and may be capable of thrombus formation and subsequent cardiac embolism and stroke,” the researchers wrote. “Cross-sectional studies have found associations between silent [myocardial infarction] on cardiac MRI and cerebral infarction on brain MRI, but whether silent [myocardial infarction] is a risk factor for subsequent ischemic stroke remains uncertain.”

Alexander E. Merkler, MD, MS, assistant attending neurologist at New York-Presbyterian Hospital and assistant professor of neurology and neuroscience at Weill Cornell Medical College and Cornell University, and colleagues aimed to determine whether silent myocardial infarction represented a risk factor for ischemic stroke among individuals in the Cardiovascular Health Study, which prospectively enrolled community-dwelling individuals aged 65 years and older. Merkler and colleagues included patients with no history of prevalent stroke or baseline evidence for myocardial infarction. Incident ischemic stroke served as the primary outcome. Secondary outcomes included ischemic stroke subtypes: non-lacunar, lacunar and other/unknown.

The researchers used Cox proportional hazards analysis to model the relationship between time-varying myocardial infarction status, including silent, overt or no myocardial infarction, and stroke following adjustment for baseline demographics and vascular risk factors, according to the study results.

Study results

The study included 4,224 participants (mean age, 72.6 years; men, 40.1%). Among these participants, the researchers reported incident silent myocardial infarction in 362 individuals (8.6%), incident overt myocardial infarction in 421 individuals (10%) and incident ischemic stroke in 377 individuals (8.9%) over a median follow-up period of 9.8 years.

Following adjustment for information related to demographics and comorbidities, Merkler and colleagues found that silent myocardial infarction independently correlated with subsequent ischemic stroke (HR = 1.51; 95% CI, 1.03-2.21). The researchers also observed a relationship between overt myocardial infarction and ischemic stroke in the short term (HR = 80; 95% CI, 53-119) and the long term (HR = 1.6; 95% CI, 1.04-2.44).

Secondary analyses of specific ischemic stroke subtypes showed that only the link between overt MI and non-lacunar ischemic stroke “violated the proportional hazards assumption,” according to the study results. The researchers observed a link between overt MI and non-lacunar ischemic stroke in the short term (HR = 210; 95% CI, 127-348) and the long term (HR = 2.21; 95% CI, 1.16-4.22). Overt MI also correlated with other/unknown stroke in the short term (HR = 29; 95% CI, 12-72) but not in the long term (HR = 1.57; 95% CI, 0.84-2.94). However, Merkler and colleagues noted that there were only two participants who had an overt myocardial infarction prior to ischemic stroke, so they were unable to “reliably evaluate the association been silent MI and lacunar stroke.”

The results indicated that silent myocardial infarction may represent a novel risk factor for stroke “that may explain some proportion of ischemic strokes that currently lack an identifiable source,” according to the researchers. They also noted that the results of the study may have clinical relevance.

“One-fifth of ischemic strokes have no known etiology, but have clinical and radiographic characteristics that suggest they arise from a distant source, and thus are considered to be embolic strokes of undetermined source,” Merkler and colleagues wrote. “Failure to identify the mechanism of these strokes precludes targeted secondary stroke preventive strategies, and there is a high risk of recurrent stroke with standard antiplatelet therapy. Some [embolic strokes of undetermined source] cases may therefore be explained by preceding silent [myocardial infarctions].”

Related editorial

In a related editorial, Seemant Chaturvedi, MD, of the department of neurology and the stroke program at the University of Maryland School of Medicine, and Marc Chimowitz, MBChB, of the department of neurology at the Medical University of South Carolina, noted that the results from Merkler and colleagues have “potentially important implications,” given that their findings provide “the strongest data yet” that silent myocardial infarction represents a risk factor for non-lacunar stroke. Additionally, if silent myocardial infarction serves as a potential cardioembolic source, as Merkler and colleagues suggested, Chaturvedi and Chimowitz wrote that “it is possible” that forthcoming studies may determine anticoagulation is superior to antiplatelet therapy along for preventing recurring stroke in these patients.

Chaturvedi and Chimowitz acknowledged limitations of the results from Merkler and colleagues, including increases in diabetes and obesity in the United States since the enrollment of the patient cohort used in the study. They also noted the older age of the study cohort and the inclusion of a patient population that was 95% white, which “raises questions about generalizability to the broader U.S. stroke population.” However, Chaturvedi and Chimowitz wrote that the study from Merkler and colleagues — despite these limitations — “does convey a potentially important message” for neurologists who treat patients who have had a stroke.

“When silent MIs are encountered on an ECG in patients with stroke, we should not dismiss them, since they could be associated with an increased risk of stroke,” Chaturvedi and Chimowitz wrote. “Although there are no current data suggesting that alternative antithrombotic therapy to antiplatelet therapy is required in this situation, future therapeutic studies in patients with stroke and silent [myocardial infarction] and other newly recognized potential cardioembolic mechanisms may lead to different treatment paradigms.”

Reference:

Chaturvedi S & Chimowitz M. Neurology. 2021;doi:10.1212/WNL.0000000000012248.