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Endothelial dysfunction is an independent risk factor for stroke patients irrespective of the presence of patent foramen ovale

Endotheliale Dysfunktion stellt einen unabhängigen Risikofaktor für Schlaganfallpatienten ungeachtet des Vorliegens eines offenen Foramen ovale dar

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Abstract

Background

Paradoxical embolization through the patent foramen ovale (PFO) is the major cause of most cryptogenic stroke cases. However, the presence of PFO may simply be an incidental finding in these patients, and endothelial dysfunction may be the underlying reason of ischemic stroke. The aim of this study was to compare the endothelial function of cryptogenic stroke patients according to the presence of PFO.

Methods

Sixty consecutive patients with cryptogenic stroke referred for transesophageal echocardiography (TEE) and 39 consecutive nonstroke patients referred for TEE examination because of suspected PFO were included in the study. Endothelial functions were assessed by brachial artery ultrasonography. PFO was diagnosed by the presence of right-to-left passage of contrast bubbles during TEE. Stroke and nonstroke patients were further subdivided into two groups according to the presence of PFO.

Results

Stroke patients had significantly lower flow-mediated dilation (FMD) values than nonstroke patients (8.36 ± 4.38 % vs. 12.57 ± 4.90 %, p < 0.001). The stroke patients with PFO had significantly lower FMD measures than nonstroke patients with PFO (6.60 ± 3.98 % vs. 10.84 ± 4.40 %, p = 0.001). Similarly, cryptogenic stroke patients without PFO had significantly lower FMD measures than nonstroke patients without PFO (9.90 ± 4.18 % vs. 14.22 ± 4.88, p = 0.002). Logistic regression analysis showed FMD as an independent predictor of cryptogenic stroke when adjusted by age, sex, and presence of PFO (odds ratio: 0.809, 95 % confidence interval: 0.719–0.911, p < 0.001). An FMD value of  11.30 % or lower predicted cryptogenic stroke with a sensitivity of 78.3 %, a specificity of 66.7 %, and positive and negative predictive values of 78.3 and 66.7 %, respectively.

Conclusion

Endothelial dysfunction seems to play a more important role than PFO in the underlying mechanism of cryptogenic stroke.

Zusammenfassung

Hintergrund

Eine paradoxe Embolie durch ein offenes Foramen ovale (PFO) stellt in den meisten Fällen mit kryptogenem Schlaganfall die Hauptursache dar. Allerdings kann das Vorliegen eines PFO lediglich ein Zufallsbefund bei solchen Patienten und eine endotheliale Dysfunktion die zugrunde liegende Ursache des ischämischen Schlaganfalls sein. Ziel der vorliegenden Studie war es, die endotheliale Funktion von Patienten mit kryptogenem Schlaganfall im Hinblick auf das Vorliegen eines PFO zu vergleichen.

Methoden

In die Studie aufgenommen wurden 60 konsekutive Patienten mit kryptogenem Schlaganfall und Überweisung zur transösophagealen Echokardiographie (TEE) sowie 39 konsekutive Patienten ohne Schlaganfall, die bei Verdacht auf ein PFO zur TEE überwiesen wurden. Die endotheliale Funktion wurde mittels Sonographie der A. brachialis erfasst. Ein offenes Foramen ovale wurde diagnostiziert, wenn Kontrastbläschen bei der TEE einen Weg von rechts nach links fanden. Außerdem wurden die Patienten mit und ohne Schlaganfall je nach Vorliegen eines PFO in 2 Gruppen unterteilt.

Ergebnisse

Schlaganfallpatienten wiesen signifikant niedrigere Werte für die flussvermittelte Dilatation („flow-mediated dilation“, FMD) als Patienten ohne Schlaganfall auf (8,36 ± 4,38 % vs. 12,57 ± 4,90 %; p < 0,001). Bei den Schlaganfallpatienten mit PFO wurde ein signifikant niedrigerer FMD-Wert gemessen als bei Patienten ohne Schlaganfall, aber mit PFO (6,60 ± 3,98 % vs. 10,84 ± 4,40 %; p = 0,01). In ähnlicher Weise wiesen Patienten mit kryptogenem Schlaganfall ohne PFO signifikant niedrigere FMD-Werte auf als Patienten ohne Schlaganfall und ohne PFO (9,90 ± 4,18 % vs. 14,22 ± 4,88; p = 0,002). Die logistische Regressionsanalyse zeigte, dass die FMD nach Berücksichtigung von Alter, Geschlecht und Vorliegen eines PFO ein unabhängiger Prädiktor des kryptogenen Schlaganfalls ist (Odds Ratio: 0,809; 95 %-Konfidenzintervall: 0,719–0,911; p < 0,001). Ein FMD-Wert ≤ 11,30 % sagte einen kryptogenen Schlaganfall mit einer Sensitivität von 78,3 %, einer Spezifität von 66,7 % sowie einem positiven bzw. negativen prädiktiven Wert von 78,3 bzw. 66,7 % vorher.

Schlussfolgerung

Die endotheliale Dysfunktion scheint eine bedeutendere Rolle als ein PFO für den zugrunde liegenden Mechanismus des kryptogenen Schlaganfalls zu spielen.

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Conflict of interest

On behalf of all authors, the corresponding author states that there are no conflicts of interest.

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Authors and Affiliations

  1. Department of Cardiology, Marmara University Faculty of Medicine, Üstkaynarca, Pendik/İstanbul, Fevzi Çakmak Mahallesi, Mimar Sinan Caddesi No. 41, Pendik/İstanbul, Turkey

    M. Sunbul, B. Ozben, E. Durmus, A. Kepez & B. Mutlu

  2. Department of Neurology, Marmara University Faculty of Medicine, Istanbul, Turkey

    A. Pehlivan & I. Midi

Authors
  1. M. Sunbul
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  2. B. Ozben
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  3. E. Durmus
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  4. A. Kepez
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  5. A. Pehlivan
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  6. I. Midi
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  7. B. Mutlu
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Correspondence to M. Sunbul.

Additional information

The study was presented as a poster at the EuroEcho Congress 2012, Athens, Greece.

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Sunbul, M., Ozben, B., Durmus, E. et al. Endothelial dysfunction is an independent risk factor for stroke patients irrespective of the presence of patent foramen ovale. Herz 38, 671–676 (2013). https://doi.org/10.1007/s00059-013-3759-5

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  • DOI: https://doi.org/10.1007/s00059-013-3759-5

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