Association between excessive premature atrial complexes and cryptogenic stroke: results of a case–control study

OBJECTIVE: Recent anticoagulation trials in all-comer cryptogenic stroke patients have yielded equivocal results, reinvigorating the focus on identifying reproducible markers of an atrial myopathy. We investigated the role of excessive premature atrial complexes (PACs) in ischaemic stroke, including cryptogenic stroke and its association with vascular risk factors. METHODS AND RESULTS: A case–control study was conducted utilising a multicentre institutional stroke database to compare 461 patients with an ischaemic stroke or transient ischaemic attack (TIA) with a control group consisting of age matched patients without prior history of ischaemic stroke/TIA. All patients underwent 24-hour Holter monitoring during the study period and atrial fibrillation was excluded. An excessive PAC burden, defined as ≥200 PACs/24 hours, was present in 25.6% and 14.7% (p<0.01), of stroke/TIA and control patients, respectively. On multivariate regression, excessive PACs (OR 1.97; 95% CI 1.29 to 3.02; p<0.01), smoking (OR 1.58; 95% CI 1.06 to 2.36; p<0.05) and hypertension (OR 1.53; 95% CI 1.07 to 2.17; p<0.05) were independently associated with ischaemic stroke/TIA. Excessive PACs remained the strongest independent risk factor for the cryptogenic stroke subtype (OR 1.95; 95% CI 1.16 to 3.28; p<0.05). Vascular risk factors that promote atrial remodelling, increasing age (≥75 years, OR 3.64; 95% CI 2.08 to 6.36; p<0.01) and hypertension (OR 1.54; 95% CI 1.01 to 2.34; p<0.05) were independently associated with excessive PACs. CONCLUSIONS: Excessive PACs are independently associated with cryptogenic stroke and may be a reproducible marker of atrial myopathy. Prospective studies assessing their utility in guiding stroke prevention strategies may be warranted.