Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale

  • Marco Zuin
  • Gianluca RigatelliEmail author
  • Alberto Rigatelli
  • Federico Ronco
  • Luca Conte
  • Loris Roncon
  • Alberto Mazza
Original Article


The pathophysiological relationship between elevated serum homocysteine (Hcy) levels and patent foramen ovale (PFO) has not yet been completely clarified. In the present study, we assess the correlation between serum homocysteine levels and the RoPE score in PFO patients. We retrospectively reviewed clinical and instrumental data of 244 subjects referred to a single tertiary center for PFO evaluation and/or treatment between January 2010 and January 2018,stratified as closure and control group, respectively. Patients in the closure group had an higher serum Hcy levels compared to the control group (28.5 ± 8.5 vs 10.2 ± 6.6 μg/dL, p < 0.0001). A significant direct correlation was observed between serum Hcy levels and the RoPE Score in the entire population. A positive significant correlation continued to exist also in the closure and control groups (r = 0.472, p < 0.0001 and r = 0.378, p < 0.0001, respectively). A receiver operating characteristics curve identified the optimal cutoff value of homocysteinemia as a predictor of RoPE score > 7 in the closure group (AUC 0.90, 95% CI 0.81–0.94, p < 0.0001) when 19.5 μg/dL. Multivariate logistic regression analysis demonstrated that an Hcy serum level ≥ 19.5 μg/dL predict an RoPE score > 7 (OR 3.21, 95% CI 2.82–3.26, p < 0.0001) in closed patients independently from the presence of permanent right-to-left (RLS) (OR 2.28, 95% CI 2.01–2.43, p = 0.001) and atrial septal aneurysm (ASA) (OR 3.04, 95% CI 2.64–3.51, p < 0.0001). Serum homocysteine levels in PFO patients are positively correlated with the RoPE score. Moreover, a homocysteinemia ≥ 19.5 μg/dL predicts an RoPE score > 7 independently from the presence of a permanent RLS and a concomitant ASA.


Homocysteine PFO RoPE score 



Atrial septal aneurysm




Intracardiac echocardiography


Magnetic resonance


Patent foramen ovale


Transcranial doppler


Transesophageal echocardiography


Transient ischemic attack


Transthoracic echocardiography




Compliance with ethical standards

Conflict of interest

The author(s) declare(s) that there is no confict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


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Copyright information

© Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Section of Internal and Cardiopulmonary MedicineUniversity of Ferrara Medical SchoolFerraraItaly
  2. 2.Cardiovascular Diagnosis and Endoluminal Interventions, Rovigo General HospitalRovigoItaly
  3. 3.Department of EmergencyVerona Borgo Trento Hospital University Medical SchoolVeronaItaly
  4. 4.Interventional Cardiology, Ospedali Dell’angelo e SS Giovanni e PaoloVeniceItaly
  5. 5.Department of CardiologyRovigo General HospitalRovigoItaly
  6. 6.Department of Internal Medicine, Hypertension CentreRovigo General HospitalRovigoItaly

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