PATENT FORAMEN OVALE AND STROKE--A CASE CONTROL STUDY

Paradoxical embolization through a patent foramen ovale (PFO) is considered a possible mechanisms for ischemic stroke. The coexistence of a deep vein thrombosis (DVT) and/or a hypercoagulable state might predispose patients with PFO to paradoxically embolize to the cerebral circulation, and may explain the origin of some strokes currently labeled as "cryptogenic". A case-control study is proposed to address the following aims: 1. To determine if PFO is a risk factor for ischemic stroke, especially cryptogenic stroke, in patients unselected for age; and, 2. To determine if PFO is associated with DVT and/or hypercoagulable states in stroke patients, especially those with cryptogenic stroke. Secondary aims will be to evaluate the 2-year stroke recurrence risk in patients with and without PFO, differences in the degree of shunt through the PFO between cases and controls, and the potential association between hypercoagulable states and stroke. A total of 300 cases of ischemic stroke and 300 stroke-free controls will be enrolled in this 3-year population-based case-control study. Study subjects will be drawn from the ongoing Northern Manhattan Stroke Study (NOMASS), which will assure recruitment while significantly reducing the cost of the proposal. The presence of a PFO will be ascertained by transthoracic echocardiography with aerated saline injection. Evaluation for DVT in cases will be performed by Doppler ultrasound. A hypercoagulable state will be defined as the presence of elevated prothrombin fragment F1.2 levels, antiphospholipid antibodies, Lupus anticoagulant or functional Protein S deficiency. From the second year of the study, a telephone follow-up will be carried out on cases to ascertain mortality and stroke recurrence. Odds ratios will be calculated and logistic regression will be used to judge the independent significance of the potential exposure variables. On the basis of the associations detected (between PFO and stroke, and between PFO and DVT and/or hypercoagulable states), the study will set the ground for clinical trials to assess the efficacy of therapeutic options (anticoagulation, PFO closure) in reducing the stroke recurrence rate.