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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
  • 19 Downloads

Abstract

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.

Keywords

Homocysteine PFO RoPE score 

Abbreviations

ASA

Atrial septal aneurysm

Hcy

Homocysteine

ICE

Intracardiac echocardiography

MRI

Magnetic resonance

PFO

Patent foramen ovale

TCD

Transcranial doppler

TEE

Transesophageal echocardiography

TIA

Transient ischemic attack

TTE

Transthoracic echocardiography

Notes

Funding

None.

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.

References

  1. 1.
    Sacco RL, Anand K, Lee HS, Boden-Albala B, Stabler S, Allen R, Paik MC (2004) Homocysteine and the risk of ischemic stroke in a triethnic cohort: the NOrthern MAnhattan Study. Stroke 35:2263–2269CrossRefGoogle Scholar
  2. 2.
    Parnetti L, Caso V, Santucci A, Corea F, Lanari A, Floridi A, Conte C, Bottiglieri T (2004) Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke. Neurol Sci 25:13–17CrossRefGoogle Scholar
  3. 3.
    Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesäniemi YA, Hillbom M (2002) Risk factors for cryptogenic ischaemic stroke. Eur J Neurol 9:625–632CrossRefGoogle Scholar
  4. 4.
    Rigatelli G, Zuin M, Dell'Avvocata F, Pedon L, Zecchel R, Carrozza A, Zennaro M, Marzolo M, Russo M, Zanchetta M (2018) A modified anatomical-functional-RoPE (AF-RoPE) score improves patient selection for patent foramen ovale closure. Int Cardiovasc Forum J 12:8–11CrossRefGoogle Scholar
  5. 5.
    Rigatelli G, Pedon L, Zecchel R, Dell'Avvocata F, Carrozza A, Zennaro M, Mazza A, Zuin M, Russo M, Zanchetta M (2016) Long-term outcomes and complications of intracardiac echocardiography-assisted patent foramen ovale closure in 1,000 consecutive patients. J Interv Cardiol 29:530–538CrossRefGoogle Scholar
  6. 6.
    Pristipino C, Anzola GP, Ballerini L, Bartorelli A, Cecconi M, Chessa M, Donti A, Gaspardone A, Neri G, Onorato E, Palareti G, Rakar S, Rigatelli G, Santoro G, Toni D, Ussia GP, Violini R, Italian Society of Invasive Cardiology (SICI-GISE); Italian Stroke Association (ISA-AIS), Italian Association of Hospital Neurologists, Neuroradiologists, Neurosurgeons (SNO), Congenital Heart Disease Study Group of Italian Society Of Cardiology, Italian Association Of Hospital Cardiologists (ANMCO), Italian Society Of Pediatric Cardiology (SICP), Italian Society of Cardiovascular Echography (SIEC), Italian Society of Hemostasis, and Thrombosis (SISET) (2013) Management of patients with patent foramen ovale and cryptogenic stroke: a collaborative, multidisciplinary, position paper: executive summary. Catheter Cardiovasc Interv 82:122–129CrossRefGoogle Scholar
  7. 7.
    Homma S, Sacco RL, Di Tullio MR, Sciacca RR, Mohr JP, PFO in Cryptogenic Stroke Study (PICSS) Investigators (2002) Effect of medical treatment in stroke patients with patent foramen ovale: patent foramen ovale in Cryptogenic Stroke Study. Circulation 105:2625–2631CrossRefGoogle Scholar
  8. 8.
    Messé SR, Silverman IE, Kizer JR, Homma S, Zahn C, Gronseth G, Kasner SE, Quality Standards Subcommittee of the American Academy of Neurology (2004) Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: recurrent stroke with patent foramen ovale and atrial septal aneurysm: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology 62:1042–1050CrossRefGoogle Scholar
  9. 9.
    Christen WG, Cook NR, Van Denburgh M, Zaharris E, Albert CM, Manson JE (2018) Effect of combined treatment with folic acid, vitamin B6, and vitamin B12 on plasma biomarkers of inflammation and endothelial dysfunction in women. J Am Heart Assoc 7:e008517CrossRefGoogle Scholar
  10. 10.
    Bertoia ML, Pai JK, Cooke JP, Joosten MM, Mittleman MA, Rimm EB, Mukamal KJ (2014) Plasma homocysteine, dietary B vitamins, betaine, and choline and risk of peripheral artery disease. Atherosclerosis 235:94–101CrossRefGoogle Scholar
  11. 11.
    Mazza A, Cuppini S, Schiavon L, Zuin M, Ravenni R, Balbi G, Montemurro D, Opocher G, Pelizzo MR, Colletti PM, Rubello D (2014) Hyperhomocysteinemia is an independent predictor of sub-clinical carotid vascular damage in subjects with grade-1 hypertension. Endocrine 46:340–346CrossRefGoogle Scholar
  12. 12.
    Rigatelli G, Hijazi ZM (2006) Intracardiac echocardiography in cardiovascular catheter-based interventions: different devices for different purposes. J Invasive Cardiol 18:225–233Google Scholar
  13. 13.
    Rigatelli G, Nghia NT, Zuin M, Conte L, D'Elia K, Nanjundappa A (2019) Very long-term outcomes of transcatheter secundum atrial septal defect closure using intracardiac echocardiography without balloon sizing. Clin Radiol.  https://doi.org/10.1016/j.crad.2019.05.017 CrossRefPubMedGoogle Scholar
  14. 14.
    Ozdemir AO, Tamayo A, Munoz C, Dias B, Spence JD (2008) Cryptogenic stroke and patent foramen ovale: clinical clues to paradoxical embolism. J Neurol Sci 275:121–127CrossRefGoogle Scholar
  15. 15.
    Spence JD (2016) Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res 36:109–116CrossRefGoogle Scholar
  16. 16.
    Vayá A, Ejarque I, Tembl J, Corella D, Laiz B (2011) Hyperhomocysteinemia, obesity and cryptogenic stroke. Clin Hemorheol Microcirc 47:53–58PubMedGoogle Scholar
  17. 17.
    Carroll JD, Saver JL, Thaler DE, Smalling RW, Berry S, MacDonald LA, Marks DS, Tirschwell DL, RESPECT Investigators (2013) Closure of patent foramen ovale versus medical therapy after cryptogenic stroke. N Engl J Med 368:1092–1100CrossRefGoogle Scholar
  18. 18.
    Rodriguez CJ, Homma S (2003) Hypercoagulable states in patients with patent foramen ovale. Curr Hematol Rep 2:435–441PubMedGoogle Scholar
  19. 19.
    Sreckovic B, Sreckovic VD, Soldatovic I, Colak E, Sumarac-Dumanovic M, Janeski H, Janeski N, Gacic J, Mrdovic I (2017) Homocysteine is a marker for metabolic syndrome and atherosclerosis. Diabetes Metab Syndr 11:179–182CrossRefGoogle Scholar
  20. 20.
    Olivares-Reyes A, Chan S, Lazar EJ, Bandlamudi K, Narla V, Ong K (1997) Atrial septal aneurysm: a new classification in two hundred five adults. J Am Soc Echocardiogr 10:644–656CrossRefGoogle Scholar

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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