Incidence, outcome, risk factors, and long-term prognosis of cryptogenic transient ischaemic attack and ischaemic stroke: a population-based study

Abstract

SummaryBackgroundA third of transient ischaemic attacks (TIAs) and ischaemic strokes are of undetermined cause (ie, cryptogenic), potentially undermining secondary prevention. If these events are due to occult atheroma, the risk-factor profile and coronary prognosis should resemble that of overt large artery events. If they have a cardioembolic cause, the risk of future cardioembolic events should be increased. We aimed to assess the burden, outcome, risk factors, and long-term prognosis of cryptogenic TIA and stroke.MethodsIn a population-based study in Oxfordshire, UK, among patients with a first TIA or ischaemic stroke from April 1, 2002, to March 31, 2014, we compared cryptogenic events versus other causative subtypes according to the TOAST classification. We compared markers of atherosclerosis (ie, risk factors, coronary and peripheral arterial disease, asymptomatic carotid stenosis, and 10-year risk of acute coronary events) and of cardioembolism (ie, risk of cardioembolic stroke, systemic emboli, and new atrial fibrillation [AF] during follow-up, and minor-risk echocardiographic abnormalities and subclinical paroxysmal AF at baseline in patients with index events between 2010 and 2014).FindingsAmong 2555 patients, 812 (32%) had cryptogenic events (incidence of cryptogenic stroke 0·36 per 1000 population per year, 95% CI 0·23–0·49). Death or dependency at 6 months was similar after cryptogenic stroke compared with non-cardioembolic stroke (23% vs 27% for large artery and small vessel subtypes combined; p=0·26) as was the 10-year risk of recurrence (32% vs 27%; p=0·91). However, the cryptogenic group had fewer atherosclerotic risk factors than the large artery disease (p<0·0001), small vessel disease (p=0·001), and cardioembolic (p=0·008) groups. Compared with patients with large artery events, those with cryptogenic events had less hypertension (adjusted odds ratio [OR] 0·41, 95% CI 0·30–0·56; p<0·0001), diabetes (0·62, 0·43–0·90; p=0·01), peripheral vascular disease (0·27, 0·17–0·45; p<0·0001), hypercholesterolaemia (0·53, 0·40–0·70; p<0·0001), and history of smoking (0·68, 0·51–0·92; p=0·01), and compared with small vessel and cardioembolic subtypes, they had no excess risk of asymptomatic carotid disease (adjusted OR 0·64, 95% CI 0·37–1·11; p=0·11) or acute coronary events (adjusted hazard ratio [HR] 0·76, 95% CI 0·49–1·18; p=0·22) during follow-up. Compared with large artery and small vessel subtypes combined, patients with cryptogenic events also had no excess of minor-risk echocardiographic abnormalities (cryptogenic 37% vs 45%; p=0·18) or paroxysmal AF (6% vs 10%; p=0·17) at baseline or of new AF (adjusted HR 1·23, 0·78–1·95; p=0·37) or presumed cardioembolic events (1·16, 0·62–2·17; p=0·64) during follow-up.InterpretationThe clinical burden of cryptogenic TIA and stroke is substantial. Although stroke recurrence rates are comparable with other subtypes, cryptogenic events have the fewest atherosclerotic markers and no excess of cardioembolic markers.FundingWellcome Trust, Wolfson Foundation, UK Stro...

Incidence and functional outcome of atrial fibrillation and non-atrial fibrillation- related cardioembolic stroke in Joinville, Brazil: a population-based study

“…These outcomes are significantly higher than those reported for other ischemic stroke subtypes 2 . Therefore, knowing the incidence of CE stroke is crucial for primary and secondary prevention policies 1,2,3 . …”

“…The first one is demographic: as age is a risk factor for both atrial fibrillation (AF) and stroke, the aging of the population will progressively increase the burden of CE stroke in many countries. 1,2 The second reason involves outcomes: in a population-based study in Oxfordshire, UK, 2,555 ischemic stroke subtypes were followed up from 2002 to 2014. After six months, two thirds were dependent.…”

Detection and management of atrial fibrillation after cryptogenic stroke or embolic stroke of undetermined source

“…1 The cause of ischemic stroke remains undetermined after hospitalization in 10% to 40% of cases; this is often referred to as "cryptogenic" stroke (CS). 2 Differences in the definition and diagnostic workup contribute to this variable incidence in published series. To mitigate this limitation, the term "embolic stroke of undetermined source" (ESUS) has recently been proposed to identify those cases where the etiology of nonlacunar ischemic stroke remains elusive after a standardized diagnostic pathway.…”

Patent Foramen Ovale Closure for Stroke Prevention and Other Disorders

“…Approximately one‐third of all ischemic strokes are considered cryptogenic 4. The causal relationship between patent foramen ovale (PFO) and cryptogenic stroke has historically been controversial.…”