Valvular calcification in liver cirrhosis: A comparison with non-cirrhotic cardiovascular controls

Abstract

BACKGROUND

Liver cirrhosis (LC) is associated with excess cardiovascular mortality; however, its relationship with ectopic valvular calcification remains unclear. Calcific aortic valve disease and mitral annular calcification (MAC) share common cardiometabolic drivers, such as age, obesity, diabetes, and dyslipidemia, yet their burden and determinants in cirrhosis particularly fatty LC are insufficiently defined. Clarifying these associations could inform screening and peri-transplant cardiovascular risk assessment. We hypothesized that fatty LC is independently associated with aortic valve calcification (AVC), that cirrhosis of any etiology is independently associated with MAC, and that multivariable models would demonstrate strong discrimination and calibration.

AIM

To determine the associations between cirrhosis etiologies and AVC and MAC, and to evaluate the performance of predictive models.

METHODS

In this single-center cross-sectional study, we enrolled 123 consecutive LC transplant candidates and 123 age- and sex-matched cardiovascular controls without LC or indications for valvular surgery. Semiquantitative echocardiographic calcium scores were obtained for the aortic valve and mitral annulus. Associations with AVC and MAC were assessed using univariate and multivariable logistic regression with Bonferroni correction. Model performance was evaluated using receiver operating characteristic area under the curve, precision-recall, and Hosmer-Lemeshow calibration.

RESULTS

The cohort [71.5% male; median age: 64 (interquartile range: 58-70) years] showed higher prevalence of AVC in patients with LC than in controls (P < 0.001) but lower prevalence of MAC (P < 0.001). Hypertension was less frequent in patients with cirrhosis (P < 0.001). Fatty LC was independently associated with AVC [model IIIa odds ratio (OR) = 3.873; 95% confidence interval (CI): 1.529-9.807; P = 0.004]. For MAC, LC of any etiology remained strongly associated (model IIIb: Fatty liver OR = 16.693; 95%CI: 3.843-72.512; P < 0.001; other etiologies OR = 12.719; 95%CI: 3.068-52.736; P < 0.001). Model discrimination and calibration were strong (area under the curve 0.834 and 0.917; Hosmer-Lemeshow P = 0.70 and 0.187, respectively).

CONCLUSION

LC especially of fatty etiology is independently associated with AVC, and cirrhosis of any cause is associated with MAC. The strong model performance supports their potential for cardiovascular risk stratification.

Keywords: Liver cirrhosis; Aortic valve calcification; Mitral annular calcification; Metabolic-associated fatty liver disease; Alcohol-related liver disease; Echocardiographic calcium scoring; Logistic regression; Risk stratification; Receiver operating characteristic analysis; Model calibration

Core Tip: In a single center observational study of 123 patients with liver cirrhosis (LC) and 123 age- and sex-matched cardiovascular controls, echocardiographic calcium scoring showed that LC - particularly metabolic associated fatty liver disease and alcohol related fatty liver disease - was independently linked to aortic valve calcification, while LC of any etiology strongly predicted mitral annular calcification. Fully adjusted models demonstrated strong discrimination and acceptable calibration, supporting their potential use for risk stratification in LC clinics. These models may help flag high-risk patients who warrant closer echocardiographic surveillance, pending external validation.