Lee Sooji, Hwang Seung Ha, Park Seoyoung, Son Yejun, Kim Soeun, Kim Hyeon Jin, Park Jaeyu, Jo Hyesu, Lee Kyeongmin, Oh Jiyeon, Kim Min Seo, Pizzol Damiano, Smith Lee, Lee Jinseok, Woo Ho Geol, Lee Hayeon, Yon Dong Keon
Department of Medicine (S.L., J.O., D.K.Y.), Kyung Hee University, Seoul, South Korea.
Center for Digital Health, Medical Science Research Institute (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.), Kyung Hee University, Seoul, South Korea.
Circulation. 2025 Jul 8;152(1):11-23. doi: 10.1161/CIRCULATIONAHA.125.073086. Epub 2025 Jun 4.
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.
We used binational, large-scale, and population-based cohorts, including a Korean nationwide cohort (K-CONV-N [Korea Disease Control and Prevention Agency-COVID-19-National Health Insurance Service cohort]; 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 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.
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%).
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.
尽管新冠疫情对全球产生了重大影响，但针对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的长期心血管后遗症的研究有限，尤其是在亚洲人群中。这项大规模、基于人群的双边队列长期随访研究旨在调查SARS-CoV-2感染与心血管事件风险之间的关联。
我们使用了双边、大规模、基于人群的队列，包括韩国全国队列（韩国疾病控制与预防机构-新冠-国民健康保险服务队列；发现队列；n = 18989129）和日本全国队列（日本医疗数据中心；验证队列；n = 12218680）。纳入了2020年1月1日至2022年12月31日年龄在20岁及以上的个体。我们评估了SARS-CoV-2感染后发生心血管结局的长期风险。主要结局是基于编码诊断的心血管疾病风险。在基于倾向评分的重叠加权后，使用Cox比例风险模型估计心血管结局的调整后风险比。我们评估了SARS-CoV-2感染后心血管结局的时间衰减效应。通过16种心血管结局、新冠严重程度、疫苗接种和SARS-CoV-2毒株进行了多项亚组分析。
在重叠加权的发现队列中，纳入了7960357名个体（平均年龄48.52岁[标准差9.33]；男性4283878名[53.82%]）。SARS-CoV-2感染与总体心血管结局的长期风险增加相关（调整后风险比为1.62[95%置信区间为1.60 - 1.64]），尤其是缺血性心脏病（1.81[95%置信区间为1.77 - 1.84]）、心力衰竭（1.79[95%置信区间为1.73 - 1.85]）、脑血管疾病（1.65[95%置信区间为1.60 - 1.69]）、主要不良心血管事件（1.65[95%置信区间为1.60 - 1.70]）、炎症性心脏病（1.53[95%置信区间为1.31 - 1.80]）、心律失常（1.44[95%置信区间为1.42 - 1.46]）和血栓形成性疾病（1.42[95%置信区间为1.35 - 1.48]）。风险增加持续长达18个月，在感染后1至6个月观察到最高关联。心血管疾病风险在新冠严重程度方面较为显著；然而，随着全程接种疫苗及后续加强剂量的接种，风险降低。在每个SARS-CoV-2流行时期（德尔塔变异株出现前、德尔塔变异株、奥密克戎变异株），心血管结局的风险相似。在验证队列中观察到类似模式。SARS-CoV-2感染后心血管疾病事件的绝对风险仍然非常低（感染人群为2.12%，未感染人群为1.31%），尤其是中风（0.24%对0.13%）和缺血性心脏病（0.73%对0.39%）。
这项双边研究在跨病毒流行时期的长期随访中观察到SARS-CoV-2感染与心血管事件之间的关联。全程接种疫苗与较低的心血管事件相关。然而，SARS-CoV-2感染后心血管疾病事件的绝对风险仍然非常低，尤其是中风和缺血性心脏病。尽管这些发现表明持续保持警惕和采取预防措施仍然至关重要，但在考虑长期心血管并发症时，应在这些低绝对风险的背景下进行解读。
