The foramen ovale is a physiological channel during the fetal period, which allows the blood in the right atrium to flow into the left atrium and maintain the blood circulation of the fetus [15]. After the fetus is born, with the establishment of its own pulmonary circulation, most will gradually close 5–7 months after birth. But some people will not be completely closed, leaving a gap-like defect, called PFO. Studies have shown that the incidence of PFO in the normal population is approximately 25% -30% [16]. But for a long time, the foramen oval is not considered to cause serious clinical consequences. In recent years, more and more studies have shown that the foramen ovale can lead to the occurrence of ischemic stroke [17]. The research on the foramen ovale and ischemic stroke has become a hot spot. Studies have shown that the incidence of PFO in patients with ischemic stroke is increased, the incidence of PFO in normal adults is 17–35%, and the incidence of stroke patients is as high as 40–45% [18]. A related meta-analysis found that the prevalence of PFO was 6 times higher in patients with cryptogenic stroke < 55 years of age than those with a clear etiology of the same age [19]. A summary of the meta-analysis of 29 cohort studies from 1988 to 2008 showed that 27 of them confirmed the correlation between PFO and cryptogenic stroke [20]. The results of Cabanes et al. [21] also showed that the relative risk of thromboembolic events in PFO was four times that of the normal control group, indicating that PFO was positively correlated with the risk of ischemic stroke. Kent et al. [22] used the Risk of Paradoxical Embolism (RoPE) scale to analyze the correlation between stroke and PFO. The scale includes risk factors such as cortical stroke, diabetes, hypertension, smoking, previous stroke or transient ischemic attack, and age. Calculate the score to determine whether PFO is the cause of stroke. If the RoPE score is high, it is more likely to consider PFO-related stroke. It also indicates that the fewer patients have traditional cerebrovascular risk factors, the more likely PFO is the cause of stroke. However, researches on elderly patients is still lacking.
This study focuses on elderly patients with ischemic stroke. In this study, there were 62 stroke patients in the Test Group and 62 patients in the Control Group. There was no statistical difference in age and gender between the two groups. Among them, there were 17 stroke patients with PFO in the Test Group, and the incidence of PFO was 27.42%, the number of people with PFO in the Control Group was 4 and the incidence of PFO was 6.45%. The incidence of PFO in the Test Group was significantly higher than that in the Control Group, suggested that the PFO was closely related to stroke. Further regression analysis of the risk factors of ischemic stroke in the two groups showed that PFO was a risk factor for ischemic stroke.
The mechanism of the PFO leading to ischemic stroke is currently unclear. However, there are the following mechanisms for the ischemic stroke caused by the PFO, and the most likely mechanism is considered to be abnormal embolism. That is, when the right heart pressure increases, such as pulmonary hypertension, cough, Valsalva action, the venous system or right heart embolism enters the systemic circulation, resulting in the abnormal right-to-left shunt channel formed by PFO, resulting in the occurrence of ischemic stroke. Some studies proposed that the diagnostic criteria for abnormal embolism include deep vein thrombosis and pulmonary embolism, there is an abnormal channel between the left and right hearts, and there is a pressure gradient from right to left shunt in the heart, with imaging or pathology [23, 24]. However, it has been found in clinical work that only a few patients with PFO-related ischemic stroke can find venous thrombosis. At the same time, many patients do not have pulmonary hypertension or do not perform Valsalva maneuvers at the time of onset. Therefore, there is no source of emboli or incentives to increase the pressure of the right heart, which does not support the theory of abnormal embolism [25]. However, some scholars have pointed out that the emboli that cause PFO-related ischemic stroke are mostly from the deep veins and are asymptomatic. Studies have found that the incidence of pelvic deep vein thrombosis in stroke patients with unclear etiology is significantly higher than that of stroke with clear etiology patients (20% vs 4%) [26]. However, the sensitivity of current auxiliary examination methods is too low, and ultrasound examination cannot detect pelvic deep vein thrombosis, and even the detection rate of deep vein thrombosis of the lower extremities is also low. High conditions also limit the clinical traceability of the source of emboli. Eaggers et al. [27] believe that the mechanism of abnormal embolism of PFO without venous thrombosis may be related to the hypercoagulable state caused by transient platelet activation induced by the load state, causing transient thrombosis, and thus the occurrence of embolism. In situ thrombosis caused by PFO is also considered to be one of the mechanisms. PFO is a structure similar to a pipe, in which blood may accumulate, theoretically causing the generation of local eddy currents and forming thrombus. However, no case report of PFO thrombosis in situ has been found. Other mechanisms include arrhythmias such as paroxysmal atrial fibrillation, abnormal coagulation functions such as S protein dysfunction, abnormal protein C activation, and prothrombin gene mutations such as G20210AF2, leading to thrombosis [27, 28].
Several studies have found that embolism caused by PFO is related to the size and shunt volume of PFO [29, 30]. The larger the diameter of PFO, the greater the shunt volume, and the higher the probability of cerebral embolism [31]. In this study, there were 4 patients with large and moderate PFO in the Test Group, accounting for 23.53%. A large number of shunt patients were not found in the Control Group. The Test Group was significantly higher than the Control Group, suggesting that medium and large shunts may be a high-risk factor for ischemic stroke, and also suggested that abnormal embolism may be the mechanism of stroke.
Common risk factors for ischemic stroke include hypertension, diabetes, coronary heart disease, hyperlipidemia, and carotid atherosclerosis [32, 33]. However, the risk factors for ischemic stroke with PFO have their own characteristics. Josep et al. [34] compared the risk factors of stroke patients with PFO and stroke patients without PFO and found that stroke patients with PFO were younger and had fewer traditional vascular risk factors such as hypertension, dyslipidemia and smoke, etc [35]. In this study, we compared the common risk factors of stroke patients in PFO (+) group and PFO (-) group to explore the characteristics of risk factors of patients with ischemic stroke combined with PFO. We found that the proportion of patients with migraine in the PFO (+) group was significantly higher than those in the PFO (-) group, suggesting that stroke patients with PFO were more likely to have migraine. And related research shows that PFO is closely related to migraine, especially with migraine with aura [36].