Remnant Lipoprotein Cholesterol and Cardiovascular and Cerebrovascular Events in Patients with Non-Alcoholic Fatty Liver Disease

Daniele Pastori; Francesco Baratta; Marta Novo; Nicholas Cocomello; Francesco Violi; Francesco Angelico; Maria Del Ben

doi:10.3390/jcm7110378

Remnant Lipoprotein Cholesterol and Cardiovascular and Cerebrovascular Events in Patients with Non-Alcoholic Fatty Liver Disease

J Clin Med. 2018 Oct 23;7(11):378. doi: 10.3390/jcm7110378.

Authors

Daniele Pastori¹, Francesco Baratta^{2

3}, Marta Novo^{4

5}, Nicholas Cocomello⁶, Francesco Violi⁷, Francesco Angelico⁸, Maria Del Ben⁹

Affiliations

¹ I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. daniele.pastori@uniroma1.it.
² I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. francesco.baratta@uniroma1.it.
³ Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy. francesco.baratta@uniroma1.it.
⁴ I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. marta.novo@uniroma1.it.
⁵ Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy. marta.novo@uniroma1.it.
⁶ I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. nicholas.cocomello@gmail.com.
⁷ I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. francesco.violi@uniroma1.it.
⁸ Department of Public Health and Infectious Diseases, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. francesco.angelico@uniroma1.it.
⁹ I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy. maria.delben@uniroma1.it.

Abstract

: Non-alcoholic fatty liver disease (NAFLD) is characterized by an atherogenic dyslipidaemia and an increased cardiovascular risk. Remnant lipoprotein cholesterol (RLP-C) is emerging as a novel cardiovascular risk factor, but its predictive value in patients with NAFLD is unknown. We investigated factors affecting RLP-C levels, and the association with major adverse cardiovascular and cerebrovascular events (MACCE) in NAFLD. A prospective observational cohort study was carried out including 798 unselected patients with cardio-metabolic diseases screened by ultrasound for the presence of NAFLD. Fasting RLP-C (mg/dL) was calculated as total cholesterol-(HDL (high-density lipoprotein) + LDL (low-density-lipoprotein)). Primary endpoint of the follow-up study was a combined endpoint of MACCE. Patients with NAFLD (79.2%) had higher median fasting RLP-C in comparison to those without (27.0 vs. 20.0 mg/ dL, respectively p < 0.001). Metabolic syndrome, NAFLD, age above median, and female sex were independently associated to fasting RLP-C above the median. In patients with NAFLD, values of RLP-C were associated with liver disease severity, as shown by the increasing value of RLP-C across tertiles of aspartate aminotransferase (AST) (p = 0.002) and gamma-glutamyl transpeptidase (GGT) (p < 0.001). Furthermore, levels of RLP-C and Hamaguchi score, were significantly correlated (r = 0.193, p < 0.001). During a median follow-up of 32 months (interquartile range: 14.2⁻51.7, 1700 person-years), 41 MACCE (2.41%/year) were registered in 596 NAFLD patients. The rate of events was higher in NAFLD patients with RLP-C above the median compared to those below (log-rank test p = 0.040). Age (hazard ratio (HR) 1.039, 95% confidence interval (CI), 1.005⁻1.074, p = 0.024), previous cardiovascular events (HR 2.210, 95% CI, 1.052⁻4.643, p = 0.036), female sex (HR 0.454, 95% CI, 0.208⁻0.989, p = 0.047) and RLP-C above the median (HR 2.202, 95% CI, 1.132⁻4.285, p = 0.020) were associated with MACCE. In conclusion, we found that NAFLD was independently associated with higher circulating RLP-C, and that high RLP-C levels were predictive of MACCE in patients with NAFLD.

Keywords: NAFLD; cardiovascular events; cholesterol remnants.