Glucose metabolism status modifies the relationship between lipoprotein(a) and carotid plaques in individuals with fatty liver disease

Abstract

Background and aimsGlucose and lipoprotein(a) [Lp(a)] have been recognized risk factors for atherosclerosis. The impact of both factors on fatty liver patients has not been studied. The aim of this study is to explore the role of high-level Lp(a) and different glucose metabolism statuses on carotid plaques in fatty liver patients.MethodsWe selected 4,335 fatty liver patients in this cross-sectional study. The diagnosis of fatty liver disease and carotid plaques was made by ultrasound. Participants were divided into four groups based on glucose metabolism status (normal glucose regulation [NGR], lower bound of impaired fasting glucose [IFG-L], higher bound of impaired fasting glucose [IFG-H], diabetes mellitus [DM]) and then categorized into 12 subgroups according to Lp(a) concentrations. The association between variables was estimated by odds ratio (OR).ResultsCarotid plaques were present in 1,613 (37.2%) fatty liver patients. Lp(a)≥30 mg/dL was associated with high risk of carotid plaques in those patients with IFG-L, IFG-H and DM (OR 1.934 [95% CI 1.033-3.618], 2.667 [1.378-5.162], 4.000 [2.219-7.210], respectively; p<0.05). Fatty liver patients with DM plus Lp(a)<10 mg/dL and 10≤Lp(a)<30 mg/dL were more vulnerable to carotid plaques (OR 1.563 [95% CI 1.090-2.241], 1.930 [1.279-2.914]), respectively, p<0.05).ConclusionsOur study first suggested that high-level Lp(a) may raise the risk of carotid plaques in fatty liver patients with not only diabetes but also IFG, manifesting that Lp(a) may be helpful for the early discovery of subclinical atherosclerosis in fatty liver patients with impaired glucose metabolism.

The complex role of lipoprotein(a) in the pathophysiology of non-alcoholic fatty liver disease: A systematic review

“…The specific characteristics and results of the selected studies are summarized in Table 1. In brief, in all studies participants' origins were from Asia [n=4 from China (12)(13)(14)(15), n=3 from Korea (7,10,11) and n=1 from Japan 8 ] with only one study where participants were recruited from a clinic in Italy. 16 In all studies, the association between Lp(a) and NAFLD was cross-sectional.…”

“…10 This observation comes in line with the results from another study in China launched in 2022 which suggested an interaction between glucose metabolism and Lp(a) in carotic plaques risk in NAFLD patients. 12 In a Korean study with more than 22,000 participants the mean Lp(a) levels was lower in subjects with NAFLD than in those free of NAFLD (70.0 vs 73.8 nmol/L, respectively). 7 Multi-adjusted analysis showed that participants assigned in 4 th Lp(a) quartile (highest Lp(a) level) had 19% lower odds of NAFLD.…”

“…The n=107 manuscripts were disregarded on the basis of Title/ Abstract because they were irrelevant or were Letters to the Editors or replies to Letters or reviews. Among the rest, n=18 manuscripts, n=9 manuscripts with n=9 studies were considered as relevant to the present work [7][8][9][10][11][12][13][14][15] (Figure 1).…”

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)‐Associated Cardiovascular Risk

“… 51 The latest evidence for other metabolic associations with plasma lipoprotein(a) include data showing that raised levels may increase the risk of carotid plaques (defined as focal carotid thickening of >1.2 mm) in patients with fatty liver disease, 52 including those with diabetes (4‐fold higher risk) or impaired glucose metabolism (prediabetes; 2‐ to 2.7‐fold higher risk); however, possible effects of lipoprotein(a) on CVD risk were not evaluated in these studies. 53 Data also showed that low plasma lipoprotein(a) may be associated with increased risk of fibrosis and cirrhosis in patients with fatty liver disease, 52 and that in patients with more advanced fatty liver disease (ie, steatohepatitis and fibrosis), lipoprotein(a) levels were lower compared with those with steatosis alone. 54 Potential explanations for the latter association include dysfunctional lipoprotein(a) particle assembly in the liver, or diminished apolipoprotein(a) production.…”

Association of fatty pancreas and subclinical atherosclerosis: A cross-sectional analysis

“…Carotid subclinical atherosclerosis was de ned as the presence of carotid plaque, i.e. an abnormal increase in CIMT (> 1.2 mm) 13 .…”