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Circulation, Jun 04 2025, | https://doi.org/10.1161/CIRCULATIONAHA.125.073086
Burden of Cardiovascular Outcomes After SARS-CoV-2 Infection in South Korea and Japan: A Binational Population-Based Cohort Study
Sooji Lee *1,2, Seung Ha Hwang *2,3,4, Seoyoung Park *2,5, Yejun Son 2,5, Soeun Kim 2,5, Hyeon Jin Kim 2,5, Jaeyu Park 2,5, Hyesu Jo 2,6, Kyeongmin Lee 2,6, Jiyeon Oh 1,2, Min Seo Kim 7,8, Damiano Pizzol 9,10, Lee Smith 11, Jinseok Lee 3,4, Ho Geol Woo 12, Hayeon Lee †2,3,4, Dong Keon Yon †1,2,5,13,6,3
1Department of Medicine, Kyung Hee University, Seoul, South Korea. (S.L., J.O., D.K.Y.).
2Center for Digital Health, Medical Science Research Institute, Kyung Hee University, Seoul, South Korea. (S.L., S.H.H., S.P., Y.S., S.K., H.J.K., J.P., H.J., K.L., J.O., H.L., D.K.Y.).
3Department of Biomedical Engineering, Kyung Hee University, Yongin, South Korea. (S.H.H., J.L., H.L., D.K.Y.).
4Department of Electronics and Information Convergence Engineering, Kyung Hee University, Yongin, South Korea. (S.H.H., J.L., H.L.).
5Kyung Hee University Medical Center, Department of Precision Medicine, Kyung Hee University, Seoul, South Korea. (S.P., Y.S., S.K., H.J.K., J.P., D.K.Y.).
6College of Medicine, Department of Regulatory Science, Kyung Hee University, Yongin, South Korea. (H.J., K.L., D.K.Y.).
7Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge (M.S.K.).
8Cardiovascular Research Center, Massachusetts General Hospital, Boston (M.S.K.).
9Health Unit, Eni, Maputo, Mozambique (D.P.).
10Health Unit, Eni, San Donato Milanese, Italy (D.P.).
11Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom (L.S.).
12Department of Neurology, Kyung Hee University, Seoul, South Korea. (H.G.W.).
13Department of Pediatrics, Kyung Hee University, Seoul, South Korea. (D.K.Y.).
*S. Lee, S.H. Hwang, and S. Park contributed equally.
†H. Lee and D.K. Yon contributed equally.
Correspondence to: Dong Keon Yon, MD, PhD, Hayeon Lee, PhD
1Department of Medicine, Kyung Hee University, Seoul, South Korea. (S.L., J.O., D.K.Y.).
2Center for Digital Health, Medical Science Research Institute, Kyung Hee University, Seoul, South Korea. (S.L., S.H.H., S.P., Y.S., S.K., H.J.K., J.P., H.J., K.L., J.O., H.L., D.K.Y.).
3Department of Biomedical Engineering, Kyung Hee University, Yongin, South Korea. (S.H.H., J.L., H.L., D.K.Y.).
4Department of Electronics and Information Convergence Engineering, Kyung Hee University, Yongin, South Korea. (S.H.H., J.L., H.L.).
5Kyung Hee University Medical Center, Department of Precision Medicine, Kyung Hee University, Seoul, South Korea. (S.P., Y.S., S.K., H.J.K., J.P., D.K.Y.).
6College of Medicine, Department of Regulatory Science, Kyung Hee University, Yongin, South Korea. (H.J., K.L., D.K.Y.).
7Cardiovascular Disease Initiative, Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge (M.S.K.).
8Cardiovascular Research Center, Massachusetts General Hospital, Boston (M.S.K.).
9Health Unit, Eni, Maputo, Mozambique (D.P.).
10Health Unit, Eni, San Donato Milanese, Italy (D.P.).
11Centre for Health, Performance and Wellbeing, Anglia Ruskin University, Cambridge, United Kingdom (L.S.).
12Department of Neurology, Kyung Hee University, Seoul, South Korea. (H.G.W.).
13Department of Pediatrics, Kyung Hee University, Seoul, South Korea. (D.K.Y.).
*S. Lee, S.H. Hwang, and S. Park contributed equally.
†H. Lee and D.K. Yon contributed equally.
Correspondence to: Dong Keon Yon, MD, PhD, Hayeon Lee, PhD
Abstract
Background: Despite the significant global impact of the COVID-19 pandemic, limited studies have investigated the long-term cardiovascular sequelae of SARS-CoV-2 infection, particularly among Asian populations. This large-scale, population-based binational cohort study with long-term follow-up aimed to investigate the association between SARS-CoV-2 infection and the risk of cardiovascular events.
Methods: We used binational, large-scale, and population-based cohorts, including a Korean nationwide cohort (K-COV-N; discovery cohort; n=18 989 129) and a Japanese nationwide cohort (Japan Medical Data Center; validation cohort; n=12 218 680). Individuals aged 20 years or older were included from January 1, 2020, to December 31, 2022. We assessed the long-term risk of incident cardiovascular outcomes after SARS-CoV-2 infection. The primary outcome was the risk of cardiovascular diseases based on International Classification of Diseases, Tenth Revision code diagnosis. After propensity score-based overlap weighting, Cox proportional hazard models were used to estimate adjusted hazard ratios for cardiovascular outcomes. We assessed the time attenuation effect of cardiovascular outcomes after SARS-CoV-2 infection. Multiple subgroup analyses were conducted by 16 cardiovascular outcomes, COVID-19 severity, vaccination, and SARS-CoV-2 strain.
Results: In the overlap-weighted discovery cohort, 7 960 357 individuals were included (mean age, 48.52 years [SD, 9.33]; men, 4 283 878 [53.82%]). SARS-CoV-2 infection was associated with a long-term increased risk of overall cardiovascular outcomes (adjusted hazard ratio, 1.62 [95% CI, 1.60-1.64]), particularly ischemic heart disease (1.81 [95% CI, 1.77-1.84]), heart failure (1.79 [95% CI, 1.73-1.85]), cerebrovascular disorders (1.65 [95% CI, 1.60-1.69]), major adverse cardiovascular events (1.65 [95% CI, 1.60-1.70]), inflammatory heart diseases (1.53 [95% CI, 1.31-1.80]), dysrhythmia (1.44 [95% CI, 1.42-1.46]), and thrombotic disorders (1.42 [95% CI, 1.35-1.48]). The increased risk persisted up to 18 months, with the highest association observed for 1 to 6 months after infection. The risk of cardiovascular diseases was pronounced with COVID-19 severity; however, it decreased with the administration of complete vaccination and subsequent booster doses. A similar risk of cardiovascular outcomes existed across every SARS-CoV-2 era (pre-delta, delta, and omicron). Similar patterns were observed in the validation cohort. The absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low (2.12% versus 1.31% in the noninfected population), particularly stroke (0.24% versus 0.13%) and ischemic heart disease (0.73% versus 0.39%).
Conclusions: This binational study observed associations between SARS-CoV-2 infection and cardiovascular events during extended follow-up across viral eras. Complete vaccination was linked to lower cardiovascular events. However, the absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low, particularly for stroke and ischemic heart disease. Although these findings suggest ongoing vigilance and preventive measures remain crucial, they should be interpreted within the context of these low absolute risks when considering long-term cardiovascular complications.
Methods: We used binational, large-scale, and population-based cohorts, including a Korean nationwide cohort (K-COV-N; discovery cohort; n=18 989 129) and a Japanese nationwide cohort (Japan Medical Data Center; validation cohort; n=12 218 680). Individuals aged 20 years or older were included from January 1, 2020, to December 31, 2022. We assessed the long-term risk of incident cardiovascular outcomes after SARS-CoV-2 infection. The primary outcome was the risk of cardiovascular diseases based on International Classification of Diseases, Tenth Revision code diagnosis. After propensity score-based overlap weighting, Cox proportional hazard models were used to estimate adjusted hazard ratios for cardiovascular outcomes. We assessed the time attenuation effect of cardiovascular outcomes after SARS-CoV-2 infection. Multiple subgroup analyses were conducted by 16 cardiovascular outcomes, COVID-19 severity, vaccination, and SARS-CoV-2 strain.
Results: In the overlap-weighted discovery cohort, 7 960 357 individuals were included (mean age, 48.52 years [SD, 9.33]; men, 4 283 878 [53.82%]). SARS-CoV-2 infection was associated with a long-term increased risk of overall cardiovascular outcomes (adjusted hazard ratio, 1.62 [95% CI, 1.60-1.64]), particularly ischemic heart disease (1.81 [95% CI, 1.77-1.84]), heart failure (1.79 [95% CI, 1.73-1.85]), cerebrovascular disorders (1.65 [95% CI, 1.60-1.69]), major adverse cardiovascular events (1.65 [95% CI, 1.60-1.70]), inflammatory heart diseases (1.53 [95% CI, 1.31-1.80]), dysrhythmia (1.44 [95% CI, 1.42-1.46]), and thrombotic disorders (1.42 [95% CI, 1.35-1.48]). The increased risk persisted up to 18 months, with the highest association observed for 1 to 6 months after infection. The risk of cardiovascular diseases was pronounced with COVID-19 severity; however, it decreased with the administration of complete vaccination and subsequent booster doses. A similar risk of cardiovascular outcomes existed across every SARS-CoV-2 era (pre-delta, delta, and omicron). Similar patterns were observed in the validation cohort. The absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low (2.12% versus 1.31% in the noninfected population), particularly stroke (0.24% versus 0.13%) and ischemic heart disease (0.73% versus 0.39%).
Conclusions: This binational study observed associations between SARS-CoV-2 infection and cardiovascular events during extended follow-up across viral eras. Complete vaccination was linked to lower cardiovascular events. However, the absolute risk of cardiovascular disease events after SARS-CoV-2 infection remained remarkably low, particularly for stroke and ischemic heart disease. Although these findings suggest ongoing vigilance and preventive measures remain crucial, they should be interpreted within the context of these low absolute risks when considering long-term cardiovascular complications.
논문정보
- Research article
- 2025년 06월 (BRIC 등록일 2025-06-05)
- 국내(교신)+국외 연구진
- 의약학 > 의약학 기타
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