Pastori Daniele, Baratta Francesco, Novo Marta, Cocomello Nicholas, Violi Francesco, Angelico Francesco, Del Ben Maria
I Clinica Medica, Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Viale del Policlinico 155, 00161 Rome, Italy.
Department of Anatomical, Histological, Forensic Medicine and Orthopedics Sciences, Sapienza University of Rome, 00161 Rome, Italy.
J Clin Med. 2018 Oct 23;7(11):378. doi: 10.3390/jcm7110378.
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 < 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) ( = 0.002) and gamma-glutamyl transpeptidase (GGT) ( < 0.001). Furthermore, levels of RLP-C and Hamaguchi score, were significantly correlated ( = 0.193, < 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 = 0.040). Age (hazard ratio (HR) 1.039, 95% confidence interval (CI), 1.005⁻1.074, = 0.024), previous cardiovascular events (HR 2.210, 95% CI, 1.052⁻4.643, = 0.036), female sex (HR 0.454, 95% CI, 0.208⁻0.989, = 0.047) and RLP-C above the median (HR 2.202, 95% CI, 1.132⁻4.285, = 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.
非酒精性脂肪性肝病（NAFLD）的特征是致动脉粥样硬化性血脂异常和心血管风险增加。残粒脂蛋白胆固醇（RLP-C）正成为一种新的心血管危险因素，但其在NAFLD患者中的预测价值尚不清楚。我们研究了影响RLP-C水平的因素，以及其与NAFLD患者主要心血管和脑血管不良事件（MACCE）的关联。开展了一项前瞻性观察性队列研究，纳入798例未经选择的患有心脏代谢疾病的患者，通过超声筛查是否存在NAFLD。空腹RLP-C（mg/dL）计算为总胆固醇-（高密度脂蛋白（HDL）+低密度脂蛋白（LDL））。随访研究的主要终点是MACCE的复合终点。与无NAFLD的患者相比，NAFLD患者（79.2%）的空腹RLP-C中位数更高（分别为27.0与20.0mg/dL，P<0.001）。代谢综合征、NAFLD、年龄高于中位数和女性性别与空腹RLP-C高于中位数独立相关。在NAFLD患者中，RLP-C值与肝病严重程度相关，如RLP-C值在天冬氨酸转氨酶（AST）三分位数（P = 0.002）和γ-谷氨酰转肽酶（GGT）（P<0.001）中呈上升趋势所示。此外，RLP-C水平与浜口评分显著相关（r = 0.193，P<0.001）。在中位随访32个月（四分位间距：14.2⁻51.7，1700人年）期间，596例NAFLD患者中记录到41例MACCE（2.41%/年）。RLP-C高于中位数的NAFLD患者的事件发生率高于低于中位数的患者（对数秩检验P = 0.040）。年龄（风险比（HR）1.039，95%置信区间（CI），1.005⁻1.074，P = 0.024）、既往心血管事件（HR 2.210，95%CI，1.052⁻4.643，P = 0.036）、女性性别（HR 0.454，95%CI，0.208⁻0.989，P = 0.047）和RLP-C高于中位数（HR 2.202，95%CI，1.132⁻4.285，P = 0.020）与MACCE相关。总之，我们发现NAFLD与循环中较高的RLP-C独立相关，并且高RLP-C水平可预测NAFLD患者的MACCE。
