The intertwisted correlations among non-alcoholic fatty liver disease, atherosclerosis, and metabolic syndrome
The intertwisted correlations among non-alcoholic fatty liver disease, atherosclerosis, and metabolic syndrome
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非酒精性脂肪肝、动脉粥样硬化和代谢综合征之间的相互关联
DOI：
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发表时间：
2009
影响因子：
6.3
通讯作者：
M. Yoneda
中科院分区：
文献类型：
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作者：
Haruhisa Nakao;M. Yoneda
非酒精性脂肪性肝病是指从单纯性肝脂肪变性到非酒精性脂肪性肝炎(NASH)、fl脂肪性肝炎和fi肉芽肿性肝炎可进展为肝硬变和肝细胞癌的一系列疾病。NAFLD是肝功能异常最常见的原因。在不同的国家，NAFLD的患病率约占总人口的10%至30%，并被认为还在增加[1-3]。以前的研究表明，NAFLD与肥胖、2型糖尿病、血脂异常和胰岛素抵抗密切相关，这些都是代谢综合征的特征[4，5]。因此，NAFLD被认为是代谢综合征的肝脏表现[6，7]。代谢综合征是心血管疾病发展的危险因素，也是2型糖尿病的预测因子[8-10]。大量研究表明代谢综合征明显与心血管疾病有关[11]。鉴于多种证据表明NAFLD与心血管疾病有关，并可能在动脉粥样硬化的发展中发挥作用。近年来，NAFLD与心血管疾病的相关性的重要性受到关注，一些研究表明NAFLD与颈动脉内膜-中层厚度(IMT)有关，IMT是亚临床动脉粥样硬化的标志，与胰岛素抵抗、代谢综合征成分和心血管疾病的传统危险因素无关[12，13]。超声非侵入性测量颈动脉IMT与心血管疾病风险的增加直接相关。此外，颈动脉IMT已被证明是调整传统危险因素后心血管疾病的独立预测因子，也是美国心脏协会推荐的唯一纳入风险评估的非侵入性成像测试[14，15]。[12]报道称，在一项以医院为基础的病例对照研究中，非酒精性脂肪肝患者的颈动脉内中膜厚度明显大于年龄和性别匹配的非酒精性脂肪肝患者，与代谢综合征的经典危险因素无关。[12]在一项以医院为基础的病例对照研究中，非酒精性脂肪肝患者的颈动脉内中膜厚度(fi)明显大于非酒精性脂肪肝患者。NAFLD被认为是除与代谢综合征相关的颈动脉粥样硬化的一个强大的危险因素。此外，Targher et al.[16]显示非酒精性脂肪肝与2型糖尿病患者心血管事件发生率的增加独立相关。有趣的是，NAFLD患者的肝脏组织病理学的严重程度与早期颈动脉粥样硬化密切相关，与经典危险因素和代谢综合征的存在无关[17]。通过几项基于医院或人群的病例对照研究来研究NAFLD与颈动脉IMT的关系[18]。然而，尽管德国的一项研究调查了随机的大样本人群[19]，但也有一些研究检验了这种联系是在少数人群中进行的，或者主要利用了糖尿病患者。[20]在一项以医院为基础的病例对照研究中，对主要由非糖尿病患者组成但有心血管或代谢危险因素的大量人群进行了研究，证明肝脏脂肪变性与心脏动脉粥样硬化有关，与糖尿病患者的代谢综合征、心血管疾病、糖尿病和/或胰岛素抵抗无关，以及以前的报道。
Non-alcoholic fatty liver disease (NAFLD) refers to aspectrum of disorders from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), steatohepatitis withinflammation and fibrosis, which can progress to cirrhosis,and hepatocellular carcinoma. NAFLD is the most com-mon cause of abnormal liver function tests. The prevalenceof NAFLD is approximately between 10 and 30% of thegeneral population in various countries and considered tobe increasing [1–3]. Previous studies have shown thatNAFLD is strongly associated with obesity, type 2 diabetesmellitus, dyslipidemia and insulin resistance, which are allfeatures of the metabolic syndrome [4, 5]. Accordingly,NAFLD is considered the hepatic manifestation of themetabolic syndrome [6, 7]. The metabolic syndrome is arisk factor for the development of cardiovascular diseaseand a predictor of type 2 diabetes mellitus [8–10]. A largenumber of studies have demonstrated that metabolic syn-drome apparently associates with cardiovascular disease[11]. In view of several lines of evidence, NAFLD wouldrelate to cardiovascular disease and might play a role in thedevelopment of atherosclerosis.Recently, the importance of the association betweenNAFLD and cardiovascular disease has been focused, andseveral studies have revealed that NAFLD is related tocarotid artery intima-media thickness (IMT), a marker ofsubclinical atherosclerosis, independent of insulin resis-tance, metabolic syndrome components, and the traditionalrisk factors for cardiovascular disease [12, 13]. CarotidIMT, as measured noninvasively by ultrasonography, isdirectly associated with increased risk of cardiovasculardisease. In addition, carotid IMT has been shown to be anindependent predictor of cardiovascular disease afteradjustment for traditional risk factors, and the only non-invasive imaging test recommended by the American HeartAssociation for inclusion in the evaluation of risk [14, 15].Brea et al. [12] reported that patients with NAFLD havesignificantly greater carotid IMT than age and sex matchedpatients without NAFLD, independent of the classical riskfactor of the metabolic syndrome, in a hospital-based case–control study. NAFLD is suggested to be a strong riskfactor for carotid atherosclerosis beyond its associationwith metabolic syndrome. Furthermore, Targher et al. [16]showed that NAFLD is independently associated with anincreased incidence of cardiovascular events in type 2diabetic patients. Interestingly, the severity of liver histo-pathology among NAFLD patients is strongly associatedwith early carotid atherosclerosis, independent of classicalrisk factors and the presence of metabolic syndrome [17].The relation between NAFLD and carotid IMT wasinvestigated by several hospital-based or population-basedcase control studies [18]. However, some studies examinedthe association in a small population, or utilized mainlydiabetic individuals, although a German study investigateda random large population sample [19].In this issue of the Journal of Gastroenterology, Caralloet al. [20] studied a large population mainly consisting ofnondiabetic patients but with cardiovascular or metabolicrisk factors in a hospital-based case–control study, anddemonstrated that hepatic steatosis was associated withcardio atherosclerosis, independent of metabolic syndrome,cardiovascular diseases, diabetes mellitus, and/or insulinresistance, as well as previous reports in diabetic patients.