Association Among C-Reactive Protein, Fatty Liver Disease, and Cardiovascular Risk

Abstract

Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a marker of coronary heart disease and other chronic diseases, has not been investigated in NAFLD. We tested the relationship between uCRP and NAFLD in middle-aged asymptomatic subjects, independently of other metabolic disturbances associated with metabolic syndrome and cardiovascular risk. We compared 310 subjects with steatosis visible on ultrasound (cases) with 630 and without (controls). Body mass index (BMI), blood pressure and serum levels of uCRP, glucose, lipids, and lipoproteins were measured in all subjects. Differences between groups and the impact of serum uCRP levels were tested by univariate and multivariate logistic regression analysis. Cases were statistically different from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P < 0.001). Cases were significantly older (P < 0.001), and had significantly higher values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis, variables significantly associated with cases were glucose (OR, 4.09; 95% CI, 2.98-5.61), BMI (OR 5.54; 95% CI, 4.09-7.49), and uCRP (OR 7.06; 95% CI, 4.51-11.02). By multivariate analysis, uCRP levels were associated with hepatic steatosis (OR 5.83; 95% CI, 3.07-11.06). Cardiovascular risk was also higher in subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an increased concentration of uCRP independently of other metabolic disturbances; this suggests an increased risk of cardiovascular diseases and could be used as a marker of chronic inflammation.

Synergistic effect of fatty liver and smoking on metabolicsyndrome

“…Third, the smoking data was collected by binary criteria in this study so the effects of smoking on metabolic syndrome components might be underestimated [35] . In summary, fatty liver and smoking were closely related to insulin resistance [1][2][3][4][5][6][7][8][9][11][12][13][14]16,[21][22][23]25,32] , and our study provided evidence that fatty liver and smoking had a synergistic effect on metabolic syndrome and its components, especially for triglyceride and HDL-C levels. We suggested that smoking cessation would have the great benefit of reducing the risk of metabolic syndrome, especially for subjects with fatty liver.…”

“…While these studies provided evidence that smoking increased plasma TG and decreased HDL-C levels, most of these studies did not control potential confounding factors. Fatty liver also increased the risk of dyslipidemia such as hypertriglyceridemia and decreased HDL-C [3] . In our study, after controlling for confounding factors such as age, gender, drinking habit, and physical activity, the ORs for hypertriglyceridemia in subjects remained high: group 2 [fatty liver (-)/smoking (+)] 2.4 (95% CI: 1.8-3.…”

“…The association between fatty liver and metabolic syndrome was broadly discussed in previous studies [1][2][3][4][5][6][7][8][9] . Fatty liver is often associated with central obesity, type 2 diabetes mellitus, dyslipidemia, and hypertension.…”

“…Two studies based on Asian populations showed that Japanese subjects [1] with fatty liver had 5-to 9-fold risk of developing metabolic syndrome and Chinese subjects [6] had a 5.2-fold risk of developing metabolic syndrome. Lizardi-Cervera et al [3] found that the constellation of metabolic disturbances observed in subjects with fatty liver increased the risk of cardiovascular disease compared to those without fatty liver (OR, 4.7 vs 2.8). Fatty liver and metabolic syndrome are becoming important public health issues worldwide.…”

Non‐alcoholic fatty liver disease is associated with cardiovascular disease risk markers

“…Fasting adiponectin is inversely correlated with hepatic fat content in healthy non-diabetic subjects (31,33) but non-significantly in patients with type 2 diabetes mellitus (n = 10) (31). TNF-a, IL-6 and CRP may contribute to the inflammatory CVD milieu, predisposing to atherosclerosis and CVD (34)(35)(36). On the contrary, studies in both humans and animals (23,37) have revealed both anti-inflammatory (23) and antithrombotic (37) properties of adiponectin, enabling a protective association between adiponectin and CVD (38).…”