Skip to main content
Top
Published in: Heart and Vessels 5/2020

01-05-2020 | Aneurysm | Original Article

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

Authors: Marco Zuin, Gianluca Rigatelli, Alberto Rigatelli, Federico Ronco, Luca Conte, Loris Roncon, Alberto Mazza

Published in: Heart and Vessels | Issue 5/2020

Login to get access

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.
Literature
1.
go back to reference 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 35:2263–2269CrossRef 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 35:2263–2269CrossRef
2.
go back to reference 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 25:13–17CrossRef 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 25:13–17CrossRef
3.
go back to reference Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesäniemi YA, Hillbom M (2002) Risk factors for cryptogenic ischaemic stroke. Eur J Neurol 9:625–632CrossRef Karttunen V, Alfthan G, Hiltunen L, Rasi V, Kervinen K, Kesäniemi YA, Hillbom M (2002) Risk factors for cryptogenic ischaemic stroke. Eur J Neurol 9:625–632CrossRef
4.
go back to reference 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 12:8–11CrossRef 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 12:8–11CrossRef
5.
go back to reference 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 29:530–538CrossRef 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 29:530–538CrossRef
6.
go back to reference 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 82:122–129CrossRef 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 82:122–129CrossRef
7.
go back to reference 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 105:2625–2631CrossRef 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 105:2625–2631CrossRef
8.
go back to reference 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 62:1042–1050CrossRef 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 62:1042–1050CrossRef
9.
go back to reference 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:e008517CrossRef 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:e008517CrossRef
10.
go back to reference 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 235:94–101CrossRef 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 235:94–101CrossRef
11.
go back to reference 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 46:340–346CrossRef 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 46:340–346CrossRef
12.
go back to reference Rigatelli G, Hijazi ZM (2006) Intracardiac echocardiography in cardiovascular catheter-based interventions: different devices for different purposes. J Invasive Cardiol 18:225–233 Rigatelli G, Hijazi ZM (2006) Intracardiac echocardiography in cardiovascular catheter-based interventions: different devices for different purposes. J Invasive Cardiol 18:225–233
14.
go back to reference 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 275:121–127CrossRef 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 275:121–127CrossRef
15.
go back to reference Spence JD (2016) Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res 36:109–116CrossRef Spence JD (2016) Metabolic vitamin B12 deficiency: a missed opportunity to prevent dementia and stroke. Nutr Res 36:109–116CrossRef
16.
go back to reference Vayá A, Ejarque I, Tembl J, Corella D, Laiz B (2011) Hyperhomocysteinemia, obesity and cryptogenic stroke. Clin Hemorheol Microcirc 47:53–58CrossRef Vayá A, Ejarque I, Tembl J, Corella D, Laiz B (2011) Hyperhomocysteinemia, obesity and cryptogenic stroke. Clin Hemorheol Microcirc 47:53–58CrossRef
17.
go back to reference 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 368:1092–1100CrossRef 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 368:1092–1100CrossRef
18.
go back to reference Rodriguez CJ, Homma S (2003) Hypercoagulable states in patients with patent foramen ovale. Curr Hematol Rep 2:435–441PubMed Rodriguez CJ, Homma S (2003) Hypercoagulable states in patients with patent foramen ovale. Curr Hematol Rep 2:435–441PubMed
19.
go back to reference 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 11:179–182CrossRef 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 11:179–182CrossRef
20.
go back to reference 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 10:644–656CrossRef 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 10:644–656CrossRef
Metadata
Title
Correlations between serum homocysteine levels and RoPE score in patients with patent foramen ovale
Authors
Marco Zuin
Gianluca Rigatelli
Alberto Rigatelli
Federico Ronco
Luca Conte
Loris Roncon
Alberto Mazza
Publication date
01-05-2020
Publisher
Springer Japan
Keywords
Aneurysm
Aneurysm
Published in
Heart and Vessels / Issue 5/2020
Print ISSN: 0910-8327
Electronic ISSN: 1615-2573
DOI
https://doi.org/10.1007/s00380-019-01528-5

Other articles of this Issue 5/2020

Heart and Vessels 5/2020 Go to the issue