Serum N1-methylnicotinamide is Associated with Left Ventricular Systolic Dysfunction in Chinese

Ming Liu,Chao Chen,Weiwei Tao,Zhuyuan Fang,Wenzheng Ju,Anxia He,Jihong Chu,Yun He,Meijuan Lu,Mulian Hua,Siqi Zhang

doi:10.1038/s41598-018-26956-7

Abstract

We previously reported that serum N1-methylnicotinamide (me-NAM), an indicator of nicotinamide N-methyltransferase (NNMT) activity, was associated with obesity, diabetes, and coronary artery disease in Chinese patients. However, whether NNMT might play a role in the development of heart failure remains to be elucidated. In this study, the associations between levels of serum me-NAM and left ventricular structure and function were investigated in Chinese patients. Serum me-NAM was measured by liquid chromatography-mass spectrometry in 265 subjects. M-mode, 2-dimensional and Doppler echocardiography were performed with the GE Vivid E9 system to assess left ventricular structure and function. Of note, the participants in the top tertile of me-NAM had the lowest left ventricular ejection fraction (LVEF), preload recruitable stroke work (PRSW), and highest prevalence of left ventricular systolic dysfunction (LVSD). Serum me-NAM was negatively correlated with LVEF and PRSW before and after adjusted for potential confounding variables (P ≤ 0.02). In multiple logistic regression analyses, the subjects in the top tertile of me-NAM had highest risks for LVSD (OR 6.80; 95% CI 1.26–36.72; P = 0.026), which was also observed in continuous analyses (OR 9.48; 95% CI 1.41–63.48; P = 0.02). In conclusion, serum me-NAM is negatively associated with LVEF and PRSW and accordingly positively associated with the prevalence of LVSD in Chinese patients.

Highlights

It was recently revealed that nicotinamide N-methyltransferase (NNMT) is a novel modulator of histone methylation and plays an important role in regulating cellular energy metabolism via NAD+ and polyamine flux pathways in animal studies[4]
Total/high-density lipoprotein (HDL) cholesterol ratio, and the prevalence of diabetes and proportion of antihyperglycemic treatment increased, while serum HDL cholesterol decreased across increasing tertiles of serum me-NAM (P ≤ 0.03, Table 1)
left ventricular mass index (LVMI), and LVIDd, and the prevalence of Left ventricular hypertrophy (LVH) and left ventricular systolic dysfunction (LVSD) significantly increased, while EF decreased across increasing tertiles of serum me-NAM (P ≤ 0.03, Table 1)

Summary

Introduction

It was recently revealed that nicotinamide N-methyltransferase (NNMT) is a novel modulator of histone methylation and plays an important role in regulating cellular energy metabolism via NAD+ and polyamine flux pathways in animal studies[4]. N1-methylnicotinamide (me-NAM) has been used as an indicator of NNMT activity because it can only be derived from the methylation reaction catabolized by NNMT in the liver[5]. Our recent epidemiological study revealed that serum me-NAM was associated with obesity and diabetes in Chinese population[11]. Our case-control study suggested that serum me-NAM was associated with the presence and severity of coronary artery disease in Chinese patients[12]. Diabetes and coronary artery disease were independent risk factors for the development of HF13–15, and left ventricular systolic dysfunction (LVSD) underlay most cases of HF but was often asymptomatic before its development[16], we hypothesize that increased serum me-NAM levels might be associated with LVSD. The present study aims to investigate the relationship between serum me-NAM levels and left ventricular structure and function in Chinese patients

Methods

Results

Conclusion