Atherosclerotic Burden Findings in Young Cryptogenic Stroke Patients With and Without a Patent Foramen Ovale

Abstract

Background and Purpose-To further determine the mechanisms of cryptogenic stroke or transient ischemic attack in young patients, we evaluated indices of atherosclerosis in patients Յ55 years old diagnosed with cryptogenic cerebrovascular event comparing those with patent foramen ovale (PFO) with those without PFO. Methods-This was a prospective study including 100 consecutive patients Յ55 years old (mean age, 45Ϯ8 years; 56 males) diagnosed with cryptogenic stroke/transient ischemic attack. PFO was identified in 59 of these patients with the use of transesophageal echocardiography with contrast study. The following surrogate markers of atherosclerosis were evaluated in all patients: carotid intima media thickness as measured by carotid ultrasonography and endothelial function as determined by brachial flow-mediated vasodilation. The same measurements were obtained in a control group of 50 age-and sex-matched control subjects. Results-Patients without PFO were more likely to be current smokers and obese and more frequently had a history of hypertension and dyslipidemia. Carotid intima media thickness measurements were higher (PϽ0.0001) in patients without PFO (1.03Ϯ0.31 mm) compared with those with PFO (0.75Ϯ0.20 mm) and control subjects (0.79Ϯ0.17 mm). The absence of PFO was also associated with lower brachial flow-mediated vasodilation (without PFO: 5.04Ϯ3.39%; with PFO: 7.16Ϯ4.09%; control subjects: 7.33Ϯ4.07%; Pϭ0.02). There were no differences in carotid intima media thickness and flow-mediated vasodilation between patients with stroke/transient ischemic attack with PFO and control subjects. The presence of PFO was independently associated with reduced carotid intima media thickness (PϽ0.0001) and increased flow-mediated vasodilation (Pϭ0.019). Conclusions-In patients Յ55 years old diagnosed with cryptogenic stroke/transient ischemic attack, the presence of PFO was associated with a lower atherosclerotic burden as measured by carotid intima media thickness and endothelial function with no differences compared with a control group without cerebrovascular event. These results suggest that an atherosclerotic-mediated mechanism may be involved in cryptogenic stroke/transient ischemic attack in patients without PFO, whereas a nonatherosclerotic mechanism may mediate the cerebrovascular event in the presence of PFO.

Low cerebrovascular event rate in subjects with patent foramen ovale and different clinical presentations

“…Another point of interest is represented from the presence, in more than half of our pts with cerebrovascular events (7 out of 12, 58%) during follow-up, of other clinical and echocardiographic features potentially responsible for cardioembolism, such as atrial fibrillation, mitral valve disease, thoracic aortic atherosclerosis, in alternative to PFO, confirming previous studies [42][43][44][45]. Prompt detection of these abnormalities is relevant both for understanding the "failure" of PFO treatment in preventing new cerebrovascular events and for selecting the appropriate therapeutic option.…”

An index to identify stroke-related vs incidental patent foramen ovale in cryptogenic stroke

“…Because of inconsistent data collection across the component databases, we were unable to include in our predictive model several variables that may be predictive of PFO among CS patients. 6,8,19 These include obesity, index stroke severity, a history of deep venous thrombosis or pulmonary embolism, hypercoagulable states, prolonged travel/forced immobility, migraine, Valsalva at stroke onset, and "wake up" stroke/TIA. 20 Thus, further improvement in stratification and discrimination may be possible.…”

“…For example, the prevalence is known to be higher in younger patients and patients without conventional stroke risk factors. [6][7][8] Thus, application of Bayes theorem would yield a more patient-specific estimate of attributable fraction by substituting a patient-specific prevalence of PFO in CS patients, conditional on the specific patient's characteristics. To apply Bayes theorem in this way, we make the following assumptions: 1) if not for those strokes that are PFOattributable, the prevalence of PFO in a CS patient would be the same as in the general population (controls); 2) the rate of PFO-attributable strokes in PFO-negative CS patients is nearzero (i.e., false-negative rate with transesophageal echocardiography is low and any missed PFOs did not cause strokes); and 3) PFO prevalence in patients without CS is unrelated to those characteristics that determine its prevalence in CS patients (i.e., there is a constant control rate across strata).…”

Inclusion of Stroke in Cardiovascular Risk Prediction Instruments

“…The risk of recurrence for most young patients with patent foramen ovale and unexplained stroke is usually low, [125][126][127][128] and atherosclerotic burden is much lower in these patients. 128,129 In a systematic review and meta-analysis of observational studies, the risk of recurrent stroke among those with cryptogenic stroke or TIA was similar in those with versus those without a patent foramen ovale. 130 In the individual stroke patient, it can be challenging to determine whether a patent foramen ovale is indeed the underlying cause of the stroke.…”