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. 2016 Feb 2;7(5):5728-37.
doi: 10.18632/oncotarget.6799.

Increased Levels of Low-Density Lipoprotein Cholesterol Within the Normal Range as a Risk Factor for Nonalcoholic Fatty Liver Disease

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Free PMC article

Increased Levels of Low-Density Lipoprotein Cholesterol Within the Normal Range as a Risk Factor for Nonalcoholic Fatty Liver Disease

Dan-Qin Sun et al. Oncotarget. .
Free PMC article

Abstract

Objectives: Dyslipidemia exists within the setting of NAFLD and the relationship of a normal level of low-density lipoprotein cholesterol (LDL-c) with NAFLD is largely unknown. This large population-based study aimed to investigate the association between LDL-c levels within the normal range and the incidence of NAFLD.

Methods: A total of 60527 subjects from 2 medical centers who had undergone liver ultrasonography were initially enrolled into this study. NAFLD was defined by ultrasonographic detection of steatosis in the absence of other liver disease. Subjects were divided into 4 groups (Q1 to Q4) by normal LDL-c quartiles : Q1: ≤ 2.00, Q2: 2.10-2.35, Q3: 2.36-2.68 and Q4: 2.69-3.12 mmol/L. The odds ratios (OR), hazard ratio (HR) and 95% confidence intervals (CIs) for NAFLD were calculated across each quartile of LDL-c, using the Q1 as reference.

Results: The prevalence rates of NAFLD in a cross-sectional population from Q1 to Q4 were 19.34%, 25.86%, 35.65% and 42.08%, respectively. The OR for NAFLD in the cross-sectional population were 1.31 (95% CI 1.14-1.54), 1.73 (95% CI 1.46-2.04), and 1.82 (95% CI 1.49-2.23), respectively, after adjusting for known confounding variables. The HR for NAFLD in the longitudinal population were 1.23 (95% CI 1.12-1.35), 1.57 (95% CI 1.44-1.72) and 2.02 (95% CI 1.86-2.21), compared with Q1. Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD.

Conclusions: Increased levels of LDL-c within the normal range may play a significant role in the prevalence and incidence of NAFLD, independent of other confounding factors.

Keywords: low-density lipoprotein cholesterol; non-alcoholic fatty liver disease; risk factor.

Conflict of interest statement

CONFLICTS OF INTEREST

The authors report no declarations of interest.

Figures

Figure 1
Figure 1. Study flow diagram
A total of 27374 participants were enrolled initially, while 19675 participants were included in the cross-sectional population. A total of 33153 participants were enrolled initially, while 20433 participants were included in the longitudinal population.
Figure 2
Figure 2. Forest plots of odds ratios (OR) (95% confidence interval [CI]) for quartiles of LDL-c in the cross-sectional population
Confounding variables contained age, sex, body mass index, systolic blood pressure, fasting plasmaglucose, albumin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, total cholesterol, triglyceride, high-density lipoprotein cholesterol, and uric acid. Increasing trends of OR for NAFLD with the increases in normal LDL-c levels are shown. Q1: ≤ 2.00 mmol/L, Q2: 2.10-2.35 mmol/L, Q3: 2.36-2.68 mmol/L and Q4: 2.69-3.12 mmol/L.
Figure 3
Figure 3. Kaplan-Meier curves reflecting cumulative incidence rate of NAFLD in the longitudinal population according to quartiles of normal LDL-c level
Subjects with higher LDL-c level within the normal range had an increased cumulative incidence rate of NAFLD. P value for trend is computed from Cox analysis.
Figure 4
Figure 4. Unadjusted and adjusted odds ratios (OR) and hazard ratios (HR) for NAFLD
A. and B. showed the OR and HR of LDL-c in the cross-sectional population and longitudinal population, respectively. Model 1 is a univariate analysis. Model 2 is adjusted for sex, age, body mass index. Model 3 is adjusted for sex, age, body mass index, systolic blood pressure, fasting plasma glucose, albumin, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, serum uric acid, total cholesterol, triglyceride, high-density lipoprotein cholesterol and uric acid. Q1: ≤ 2.00 mmol/L, Q2: 2.10-2.35 mmol/L, Q3: 2.36-2.68 mmol/L and Q4: 2.69-3.12 mmol/L.

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