Cardiovascular and cerebrovascular diseases are frequently interconnected due to underlying pathology involving atherosclerosis and thromboembolism. The aim of this study was to investigate the impact of clinical interactions among cardiovascular and cerebrovascular diseases on patient outcomes using a large-scale nationwide claims-based dataset. Cardiovascular diseases were defined as myocardial infarction, heart failure, atrial fibrillation, and aortic dissection. Cerebrovascular diseases were defined as cerebral infarction, intracerebral hemorrhage, and subarachnoid hemorrhage. This retrospective study included 2,736,986 inpatient records (1,800,255 patients) at 911 hospitals from 2015 to 2016 from Japanese registry of all cardiac and vascular disease-diagnostic procedure combination dataset. Interactions among comorbidities and complications, rehospitalization, and clinical outcomes including in-hospital mortality were investigated. Among hospitalization records that involved cardiovascular disease, 5.9% (32,686 records) had cerebrovascular disease as a comorbidity and 2.1% (11,362 records) included an incident cerebrovascular complication after hospitalization. Cerebrovascular disease as a comorbidity or complication was associated with higher in-hospital mortality than no cerebrovascular disease (adjusted odds ratio (OR) [95% confidence interval]: 1.10 [1.06-1.14], 2.02 [1.91-2.13], respectively). Among 367,904 hospitalization records that involved cerebrovascular disease, 17.7% (63,647 records) had cardiovascular disease listed as comorbidity and 3.3% (11,834 records) as a complication. Only cardiovascular disease as a complication was associated with higher in-hospital mortality (adjusted OR [95% confidence interval]: 1.29 [1.22-1.37]). In addition, in-hospital mortality during rehospitalization due to the other disease was significantly higher than mortality during the hospitalization due to the first disease. In conclusion, substantial associations were observed between cardiovascular and cerebrovascular disease in a large-scale nationwide claims-based dataset; these associations had a significant impact on clinical outcomes. More intensive prevention and management of cardiovascular and cerebrovascular disease might be crucial., Competing Interests: Dr. Iihara reports personal fees and other funding from Megwell, personal fees from Daiichi Sankyo. Co. Ltd., personal fees from Otsuka Pharmaceutical, and grants from Idorsia Pharmaceuticals Japan outside of the submitted work. Dr. Komuro reports grants and personal fees from Daiichi Sankyo Company, Ltd., grants from Sumitomo Dainippon Pharma Co., Ltd., grants and personal fees from Takeda Pharmaceutical Company Ltd., grants from Mitsubishi Tanabe Pharma Corporation, grants from Teijin Pharma Ltd., grants from Idorsia Pharmaceuticals Ltd., grants from Otsuka Pharmaceutical Co., Ltd., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Ono Pharmaceutical Co., Ltd., grants from Toa Eiyo Ltd., and personal fees from AstraZeneca, and personal fees from Pfizer Japan Inc. outside of the submitted work. Dr. Matoba reports grants and personal fees from Bayer Yakuhin, Ltd., grants from Amgen, personal fees from Merck & Co., Inc., and personal fees from Abbott Vascular outside of the submitted work. Dr. Nishimura reports personal fees from Philips Japan, Ltd., personal fees from Tokyo Electric Power Company, personal fees from Terumo Company, and personal fees from H.U. group holdings outside of the submitted work. Dr. Nakayama reports personal fees from Pfizer Japan Inc, AstraZeneca K.K., Astellas Pharma Inc., Toppan Forms Co., InterSystems Corporation, Fujitsu Research Institute, Nikkei Business Publications, Inc., NIHON KOHDEN Co., FUKUDA DENSHI, Deloitte Tohmatsu Consulting LLC, and PwC Consulting LLC, outside of the submitted work. Dr. Toyoda reports personal fees from Daiichi-Sankyo, personal fees from Bayer Yakuhin, personal fees from Bristol-Myers-Squibb, personal fees from Outsuka Pharmaceutical Company Ltd., personal fees from Novartis Pharma Japan., and personal fees from Abbott Medical Japan Co., Ltd.,outside of the submitted work. Dr. Tsujita reports personal fees from Amgen K.K., grants and personal fees from Bayer Yakuhin, Ltd., grants and personal fees from Daiichi Sankyo Co., Ltd., personal fees from Kowa Pharmaceutical Co. Ltd., personal fees from Novartis Pharma K.K., grants and personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Pfizer Japan Inc., grants from AMI Co., Ltd., grants from Bristol-Myers K.K., grants from EA Pharma Co. Ltd., grants from Mochida Pharmaceutical Co., Ltd., grants from Nippon Boehringer Ingelheim, grants from Chugai Pharmaceutical Co., Ltd., grants from Edwards Lifesciences Corporation., grants from Johnson & Johnson K.K., grants from Ono Pharmaceutical Co., Ltd., grants from Takeda Pharmaceutical Co., Ltd., other funding from Abbott Japan Co., Ltd., other funding from Boston Scientific Japan K.K., other funding from Fides-one, Inc., other funding from ITI Co., Ltd., other funding from Kaneka Medix Co., Ltd., other funding from Nipro Corporation, other funding from Terumo Co., Ltd., other funding from Abbott Medical Co., Ltd., other funding from Cardinal Health Japan, other funding from Fides-one, Inc., other funding from Fukuda Denshi Co., Ltd., other funding from Japan Lifeline Co., Ltd., other funding from Medical Appliance Co., Ltd., and other funding from Medtronic Japan Co., Ltd. outside of the submitted work. Dr. Yasuda reports personal fees from Bristol-Meyers, grants and personal fees from Bayer, personal fees from Daiichi-Sankyo, grants and other funding from Takeda Pharmaceutical Company Ltd., grants from NEC, grants from Daiichi-Sankyo, grants and other funding from Abbott, other funding from Terumo Co., Ltd., other funding from Nihon Kohden, other funding from Medtronic, other funding from Japan Lifeline, other funding from Otsuka, other funding from Ono, other funding from Nippon Boehringer Ingelheim, other funding from Kowa, other funding from Zeon, other funding from Shionogi, other funding from Nippon-Shinyaku, other funding from Mochida, and other funding from Tesco outside of the submitted work. Dr. Miyamoto reports personal fees from Tokyo Marine, personal fees from Nichido Fire Insurance Co., Ltd., personal fees from Fujitsu Co., Ltd., personal fees from Softbank Co., Ltd., personal fees from Meiji Yasuda Life Insurance Company., and personal fees from Saraya Co., Ltd. outside of the submitted work. Dr. Ogawa reports personal fees from Towa Pharmaceutical Co., Ltd., personal fees from Bristol-Meyers Squibb Co., Ltd., personal fees from Pfizer Co., Ltd., personal fees from Toa Eiyo Co., Ltd., personal fees from Bayer Yakuhin Co., Ltd., and personal fees from Novartis Pharma Co., Ltd., personal fees from Takeda Pharmaceutical Co., LTD, personal fees from Daiichisankyo Co., Ltd., personal fees from Eisai Co., Ltd., personal fees from Teijin Co., Ltd. personal fees from Behringer Ingelheim Co., Ltd., Abbott Medical Japan Co., Ltd. outside of the submitted work. No other potential conflict of interest relevant to this article was reported. 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