LOS ANGELES – Older age, female sex, black race, relative anemia, and a history of cardiovascular disease are associated with greater risk for atrial cardiopathy among people who experienced an embolic stroke of undetermined source (ESUS), new evidence suggests.
Atrial cardiopathy is a suspected cause of ESUS independent of atrial fibrillation. However, clinical predictors to help physicians identify which ESUS patients are at increased risk remain unknown.
The risk for atrial cardiopathy was 34% higher for women versus men with ESUS in this analysis. In addition, black participants had a 29% increased risk, compared with others, and each 10 years of age increased risk for atrial cardiopathy by 30% in an univariable analysis.
“Modest effects of these associations suggest that all ESUS patients, regardless of underlying demographic and risk factors, may have atrial cardiopathy,” principal investigator, of Columbia University, New York, said when presenting results at the 2020 International Stroke Conference, sponsored by the American Heart Association.
For this reason, he added, all people with ESUS should be considered for recruitment into the ongoingAtRial Cardiopathy and Antithrombotic Drugs In Prevention After Cryptogenic Stroke) trial, of which he is one of the principal investigators.
ESUS is a heterogeneous condition, and some patients may be responsive to anticoagulants and some might not, Elkind said. This observation “led us to consider alternative ways for ischemic disease to lead to stroke. We would hypothesize that the underlying atrium can be a risk for stroke by itself.”
Not yet available is the primary efficacy outcome of the multicenter, randomized ARCADIA trial comparing apixaban with aspirin in reducing risk for recurrent stroke of any type. However, Dr. Elkind and colleagues have recruited 1,505 patients to date, enough to analyze factors that predict risk for recurrent stroke among people with evidence of atrial cardiopathy.
All ARCADIA participants are 45 years of age or older and have no history of atrial fibrillation. Atrial cardiopathy was defined by presence of at least one of three biomarkers: N-terminal pro-brain natriuretic peptide (NT-proBNP), P wave terminal force velocity, or evidence of a left atrial diameter of 3 cm/m2 or larger on echocardiography.
Of the 1,349 ARCADIA participants eligible for the current analysis, approximately one-third met one or more of these criteria for atrial cardiopathy.
Those with atrial cardiopathy were “more likely to be black and be women, and tended to have shorter time from stroke to screening,” Dr. Elkind said. In addition, heart failure, hypertension, and peripheral artery disease were more common in those with atrial cardiopathy. This group also was more likely to have an elevation in creatinine and lower hemoglobin and hematocrit levels.
“Heart disease, ischemic heart disease and non-hypertensive vascular disease were significant risk factors” for recurrent stroke in the study, Dr. Elkind added.
Elkind said that, surprisingly, there was no independent association between the time to measurement of NT-proBNP and risk, suggesting that this biomarker “does not rise simply in response to stroke, but reflects a stable condition.”
The multicenter ARCADIA trial is recruiting additional participants at 142 sites now, Dr. Elkind said, “and we are still looking for more sites.”
Which comes first?
“He is looking at what the predictors are for cardiopathy in these patients, which is fascinating for all of us,” session moderator, assistant professor of neurology at Johns Hopkins University, Baltimore, said in an interview when asked to comment.
There is always the conundrum of what came first — the chicken or the egg, Johansen said. Do these patients have stroke that then somehow led to a state that predisposes them to have atrial cardiopathy? Or, rather, was it an atrial cardiopathy state independent of atrial fibrillation that then led to stroke?
“That is why looking at predictors in this population is of such interest,” she said. The study could help identify a subgroup of patients at higher risk for atrial cardiopathy and guide clinical decision-making when patients present with ESUS.
“One of the things I found interesting was that he found that atrial cardiopathy patients were older [a mean 69 years]. This was amazing, because ESUS patients in general tend to be younger,” Dr. Johansen said.
“And there is about a 4-5% risk of recurrence with these patients. So. it was interesting that prior stroke or [transient ischemic attack] was not associated.”*
The National Institute of Neurological Disorders and Stroke, the BMS-Pfizer Alliance, and Roche provide funding for ARCADIA. Dr. Elkind and Dr. Johansen disclosed no relevant financial relationships.
SOURCE: Elkind M et al. ISC 2020, Abstract 26.
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*Correction, 4/28/20: An earlier version of this article misstated the risk of recurrence.