Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study

Yun-Hu Chen; Mo-Qing Yin; Li-Hua Fan; Xue-Chun Jiang; Hong-Feng Xu; Xing-Yu Zhu; Tao Zhang

doi:10.1016/j.heliyon.2024.e28619

Causal relationship between nutritional assessment phenotypes and heart failure: A Mendelian randomization study

Heliyon. 2024 Mar 26;10(7):e28619. doi: 10.1016/j.heliyon.2024.e28619. eCollection 2024 Apr 15.

Authors

Yun-Hu Chen¹, Mo-Qing Yin¹, Li-Hua Fan¹, Xue-Chun Jiang¹, Hong-Feng Xu¹, Xing-Yu Zhu², Tao Zhang³

Affiliations

¹ Cardiovascular Department, Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215400, China.
² Clinical Pharmacy Department, Taicang TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Suzhou, 215400, China.
³ Cardiovascular Department, Changzhou Hospital Affiliated to Nanjing University of Chinese Medicine, Changzhou, 213003, China.

Abstract

Introduction: Malnutrition is strongly associated with heart failure (HF); however, the causal link remains unclear. We used Mendelian randomization (MR) to infer causal associations between different nutritional assessment phenotypes and HF and to analyze whether these associations were mediated by common HF risk factors.

Methods: Two-sample bidirectional MR was used to infer causal associations between nutritional assessment phenotypes and HF. Mutual influences between different nutritional assessment phenotypes and potential correlations were estimated using multivariate MR methods. Two-step MR was used to quantify the mediating effects of common HF risk factors on the causal associations.

Results: Three phenotypes were positively associated with the development of HF: waist circumference (WC) (odds ratio [OR] = 1.74; 95% confidence interval [CI], 1.60-1.90; P = 3.95 × 10^-39), body mass index (BMI) (OR = 1.70; 95%CI, 1.60-1.80; P = 1.35 × 10^-73), and whole body fat mass (WBFM) (OR = 1.54; 95%CI, 1.44-1.65; P = 4.82 × 10^-37). Multivariate MR indicated that WBFM remained positively associated with HF after conditioning on BMI and WC (OR = 2.05; 95%CI, 1.27-3.31; P = 0.003). Three phenotypes were negatively correlated with the development of HF: usual walking pace (UWP) (OR = 0.40; 95%CI, 0.27-0.60; P = 8.41 × 10^-6), educational attainment (EA) (OR = 0.73; 95%CI, 0.67-0.79; P = 2.27 × 10^-13), and total cholesterol (TC) (OR = 0.90; 95%CI, 0.84-0.96; P = 4.22 × 10^-3). There was a bidirectional causality between HF and UWP (Effect estimate = -0.03; 95%CI, -0.05 to -0.01; P = 1.95 × 10^-3). Mediation analysis showed that common risk factors for HF (hypertension, coronary artery disease, cardiomyopathy, and valvular heart disease) mediated these causal associations (all P < 0.05).

Conclusions: BMI, WC, and WBFM are potential risk factors for HF, and the correlation between WBFM and HF was significantly stronger than that between BMI and WC, and HF. EA, UWP, and TC are potential protective factors against HF. Common risk factors for HF mediate these causal pathways. Early identification of potential risk or protective factors for HF patients from the dimension of nutritional status is expected to further improve patient outcomes.

Keywords: Causal association; Educational attainment; Heart failure; Mediation analysis; Mendelian randomization; Nutritional assessment; Risk factors.