• Junxing Lv, Bin Zhang, Yunqing Ye, Zhe Li, Weiwei Wang, Qinghao Zhao, Qingrong Liu, Zhenyan Zhao, Haitong Zhang, Bincheng Wang, Zikai Yu, Zhenya Duan, Shuai Guo, Yanyan Zhao, Runlin Gao, Haiyan Xu, Yongjian Wu, and CHINA-VHD collaborators.
• Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, No.167 Beilishi Road, Xicheng District, Beijing, 100037, China.
• Bmc Med. 2023 Jul 17; 21 (1): 257257.

BackgroundValvular heart disease (VHD) can cause damage to extra-cardiac organs, and lead to multi-organ dysfunction. However, little is known about the cardio-renal-hepatic co-dysfunction, as well as its prognostic implications in patients with VHD. The study sought to develop a multi-biomarker index to assess heart, kidney, and liver function in an integrative fashion, and investigate the prognostic role of cardio-renal-hepatic function in VHD.MethodsUsing a large, contemporary, prospective cohort of 6004 patients with VHD, the study developed a multi-biomarker score for predicting all-cause mortality based on biomarkers reflecting heart, kidney, and liver function (N-terminal pro-B-type natriuretic peptide [NT-proBNP], creatinine, and albumin). The score was externally validated in another contemporary, prospective cohort of 3156 patients with VHD.ResultsDuring a median follow up of 731 (704-748) days, 594 (9.9%) deaths occurred. Increasing levels of NT-proBNP, creatinine, and albumin were independently and monotonically associated with mortality, and a weighted multi-biomarker index, named the cardio-renal-hepatic (CRH) score, was developed based on Cox regression coefficients of these biomarkers. The CRH score was a strong and independent predictor of mortality, with 1-point increase carrying over two times of mortality risk (overall adjusted hazard ratio [95% confidence interval]: 2.095 [1.891-2.320], P < 0.001). The score provided complementary prognostic information beyond conventional risk factors (C index: 0.78 vs 0.81; overall net reclassification improvement index [95% confidence interval]: 0.255 [0.204-0.299]; likelihood ratio test P < 0.001), and was identified as the most important predictor of mortality by the proportion of explainable log-likelihood ratio χ2 statistics, the best subset analysis, as well as the random survival forest analysis in most types of VHD. The predictive performance of the score was also demonstrated in patients under conservative treatment, with normal left ventricular systolic function, or with primary VHD. It achieved satisfactory discrimination (C index: 0.78 and 0.72) and calibration in both derivation and validation cohorts.ConclusionsA multi-biomarker index was developed to assess cardio-renal-hepatic function in patients with VHD. The cardio-renal-hepatic co-dysfunction is a powerful predictor of mortality and should be considered in clinical management decisions.© 2023. The Author(s).

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