Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study
Background RING finger protein 213 (RNF213) p.R4810K is an established risk factor for moyamoya disease and intracranial artery stenosis in East Asian people. Recent evidence suggests its potential association with extracranial cardiovascular diseases, including pulmonary hypertension. We hypothesiz...
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Wiley
2025-02-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.036333 |
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| author | Kotaro Noda Yorito Hattori Tatsuya Nishii Hiroki Horinouchi Yuriko Nakaoku Soshiro Ogata Yasunobu Inagaki Ryotaro Asano Takeshi Yoshimoto Kunihiro Nishimura Takeshi Ogo Yoshikazu Nakaoka Masafumi Ihara |
| author_facet | Kotaro Noda Yorito Hattori Tatsuya Nishii Hiroki Horinouchi Yuriko Nakaoku Soshiro Ogata Yasunobu Inagaki Ryotaro Asano Takeshi Yoshimoto Kunihiro Nishimura Takeshi Ogo Yoshikazu Nakaoka Masafumi Ihara |
| author_sort | Kotaro Noda |
| collection | DOAJ |
| description | Background RING finger protein 213 (RNF213) p.R4810K is an established risk factor for moyamoya disease and intracranial artery stenosis in East Asian people. Recent evidence suggests its potential association with extracranial cardiovascular diseases, including pulmonary hypertension. We hypothesized that insidious abnormal cardiac functions are detected in RNF213 p.R4810K carriers with cerebrovascular diseases. Methods and Results We investigated patients registered in the National Cerebral and Cardiovascular Center Genome Registry between May 2017 and August 2021 who underwent echocardiography. All patients had cerebrovascular diseases. Patients with a medical history of chronic heart or pulmonary diseases were excluded. RNF213 p.R4810K was genotyped in all the patients. Of 2089 patients registered in the registry, 71 carriers and 1241 noncarriers were eligible for our analyses. The carriage of RNF213 p.R4810K emerged as a significant predictor for longer right ventricular outflow tract acceleration time in multivariable linear regression analysis (β=8.33 [95% CI, 0.92–15.74]; P=0.028). Additionally, the carriers showed increased odds of having right ventricular outflow tract acceleration time values ≥150 milliseconds (odds ratio, 2.22 [95% CI, 1.18–4.18]; P=0.014) in multivariable logistic regression analysis. Conclusions A longer right ventricular outflow tract acceleration time may reflect an increased pulmonary vascular bed induced by abnormal vascular collateral networks and dilation of capillary vessels in peripheral pulmonary arteries in the preclinical stage of RNF213‐related pulmonary hypertension. Thus, the right ventricular outflow tract acceleration time marker in RNF213 p.R4810K carriers suggests a biphasic course from the presymptomatic to symptomatic phase. Furthermore, vascular neurologists should carefully examine multiple organs because RNF213‐related vasculopathy covers systemic cardiovascular diseases. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000050750. |
| format | Article |
| id | doaj-art-6ed36083d989451ab8d58c6b95ca9256 |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-6ed36083d989451ab8d58c6b95ca92562025-02-04T11:00:01ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802025-02-0114310.1161/JAHA.124.036333Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort StudyKotaro Noda0Yorito Hattori1Tatsuya Nishii2Hiroki Horinouchi3Yuriko Nakaoku4Soshiro Ogata5Yasunobu Inagaki6Ryotaro Asano7Takeshi Yoshimoto8Kunihiro Nishimura9Takeshi Ogo10Yoshikazu Nakaoka11Masafumi Ihara12Department of Neurology National Cerebral and Cardiovascular Center Suita JapanDepartment of Neurology National Cerebral and Cardiovascular Center Suita JapanDepartment of Radiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Radiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Neurology National Cerebral and Cardiovascular Center Suita JapanDivision of Pulmonary Circulation, Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita JapanDepartment of Neurology National Cerebral and Cardiovascular Center Suita JapanDepartment of Preventive Medicine and Epidemiology National Cerebral and Cardiovascular Center Suita JapanDivision of Pulmonary Circulation, Department of Cardiovascular Medicine National Cerebral and Cardiovascular Center Suita JapanDepartment of Vascular Physiology National Cerebral and Cardiovascular Center Suita JapanDepartment of Neurology National Cerebral and Cardiovascular Center Suita JapanBackground RING finger protein 213 (RNF213) p.R4810K is an established risk factor for moyamoya disease and intracranial artery stenosis in East Asian people. Recent evidence suggests its potential association with extracranial cardiovascular diseases, including pulmonary hypertension. We hypothesized that insidious abnormal cardiac functions are detected in RNF213 p.R4810K carriers with cerebrovascular diseases. Methods and Results We investigated patients registered in the National Cerebral and Cardiovascular Center Genome Registry between May 2017 and August 2021 who underwent echocardiography. All patients had cerebrovascular diseases. Patients with a medical history of chronic heart or pulmonary diseases were excluded. RNF213 p.R4810K was genotyped in all the patients. Of 2089 patients registered in the registry, 71 carriers and 1241 noncarriers were eligible for our analyses. The carriage of RNF213 p.R4810K emerged as a significant predictor for longer right ventricular outflow tract acceleration time in multivariable linear regression analysis (β=8.33 [95% CI, 0.92–15.74]; P=0.028). Additionally, the carriers showed increased odds of having right ventricular outflow tract acceleration time values ≥150 milliseconds (odds ratio, 2.22 [95% CI, 1.18–4.18]; P=0.014) in multivariable logistic regression analysis. Conclusions A longer right ventricular outflow tract acceleration time may reflect an increased pulmonary vascular bed induced by abnormal vascular collateral networks and dilation of capillary vessels in peripheral pulmonary arteries in the preclinical stage of RNF213‐related pulmonary hypertension. Thus, the right ventricular outflow tract acceleration time marker in RNF213 p.R4810K carriers suggests a biphasic course from the presymptomatic to symptomatic phase. Furthermore, vascular neurologists should carefully examine multiple organs because RNF213‐related vasculopathy covers systemic cardiovascular diseases. Registration URL: https://www.umin.ac.jp; Unique identifier: UMIN000050750.https://www.ahajournals.org/doi/10.1161/JAHA.124.036333echocardiographypulmonary hypertensionright ventricular outflow tract acceleration timeRNF213 p.R4810Kstroke |
| spellingShingle | Kotaro Noda Yorito Hattori Tatsuya Nishii Hiroki Horinouchi Yuriko Nakaoku Soshiro Ogata Yasunobu Inagaki Ryotaro Asano Takeshi Yoshimoto Kunihiro Nishimura Takeshi Ogo Yoshikazu Nakaoka Masafumi Ihara Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease echocardiography pulmonary hypertension right ventricular outflow tract acceleration time RNF213 p.R4810K stroke |
| title | Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study |
| title_full | Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study |
| title_fullStr | Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study |
| title_full_unstemmed | Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study |
| title_short | Relationship Between RNF213 p.R4810K and Echocardiographic Findings in Patients with Cerebrovascular Diseases: A Multicenter Prospective Cohort Study |
| title_sort | relationship between rnf213 p r4810k and echocardiographic findings in patients with cerebrovascular diseases a multicenter prospective cohort study |
| topic | echocardiography pulmonary hypertension right ventricular outflow tract acceleration time RNF213 p.R4810K stroke |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.036333 |
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