The Role of Remnant Cholesterol/High-Density Lipoprotein Cholesterol Ratio in Nonalcoholic Fatty Liver Disease among Non-Obese Individuals with Normal LDL-c Levels

doi:10.21203/rs.3.rs-4270985/v1

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Research Article

The Role of Remnant Cholesterol/High-Density Lipoprotein Cholesterol Ratio in Nonalcoholic Fatty Liver Disease among Non-Obese Individuals with Normal LDL-c Levels

https://doi.org/10.21203/rs.3.rs-4270985/v1

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Background

The ratio of RC to high-density lipoprotein cholesterol (RC/HDL-c) is demonstrated to be a dependable indicator of the risk of metabolic illness. Nevertheless, there is a dearth of studies investigating the significance of the RC/HDL-c ratio in nonalcoholic fatty liver disease (NAFLD) patients who are non-obese (NOB) and possess regular low-density lipoprotein cholesterol (LDL-c) levels.

Methods

The current paper was a longitudinal investigation that encompassed a sample of 178474 Chinese individuals, both women and men, who had an average age of 41.13 years. The individuals in this paper received comprehensive physical evaluations at a wellness screening facility located within Wenzhou People's Hospital. The definition of NAFLD is established through the utilization of ultrasound imaging to identify the presence of steatosis. We utilized univariate and multivariate Cox proportional hazard analysis to determine the link between NAFLD and RC/HDL-c level. Additionally, we utilized the receiver operating characteristic curve to ascertain the TC/HDL-c threshold for the NAFLD estimation.

Results

Following the adjustment for possible confounding variables encompassing blood urea nitrogen (BUN), sex, age, aspartate aminotransferase (AST), albuminous protein (ALB), alanine aminotransferase(ALT), creatinine (CR), gamma-glutamyl transpeptidase(GGT), globulin (GLB), glucose (GLU), body mass index (BMI), LDL-c, total bilirubin (TB), total cholesterol (TC), serum uric acid (SUA), TG, HDL-c, a non-linear connection was observed between the RC/HDL-c and NAFLD ratio. Notably, this relationship exhibited an inflection point (IF) at a value of 1.33. The observed effect sizes (ES) and corresponding confidence intervals, situated on both IF sides, were determined to be 1.64 (95% CI: 1.53 to 1.76) and 0.59 (95% CI: 0.53 to 0.64), respectively. The AUC values for the RC/HDL-c ratios (0.707) exhibited a significant increase compared to the AUC values for RC (0.665) and HDL-c (0.699) (P < 0.05). Furthermore, the determined threshold for identifying the NAFLD was determined to be 0.715.

Conclusion

we found a non-linear pattern exhibited by the relation between the RC/HDL-c and NAFLD ratio. A positive connection was found between RC/HDL-c ratio being < 1.33 and the NAFLD existence. Conversely, a negative connection was found between the RC/HDL-c ratio being > 1.33 and the NAFLD occurrence.

HDL-C

NAFLD

Predictive value

Nonalcoholic fatty liver disease (NAFLD) is the predominant form of chronic liver disease (CLD) globally, which is distinguished by an anomalous buildup of lipids in the liver [1]. Cirrhosis, hepatocellular carcinoma, and nonalcoholic steatohepatitis (Nash) are all potential complications of NAFLD [2] [3], which also affect the cardiovascular, endocrine, respiratory, and renal organs [4] [5] [6]. NAFLD is highly frequent worldwide, impacting around 30.1% of the whole population. It is a prevalent and persistent liver condition that is global [7]. Because of the widespread occurrence and harmfulness of NAFLD, early detection and intervention of NAFLD is essential, and we hope to identify NAFLD early through simple, non-invasive indicators.

There is a strong correlation between dyslipidemia and NAFLD [8] [9].NAFLD is distinguished by heightened levels of triglycerides, elevated LDL-c concentrations, and hindered HDL-c values. During fasting, RC refers to a group of lipoproteins that have a high concentration of triglycerides, specifically very low-density lipoproteins and intermediate-density lipoprotein [10]. Prior clinical research has additionally verified that RC is linked to the incidence of cardiovascular incidents, diabetes, hypertension, and NAFLD [11–14]. Our aim in this investigation was to discover if RC/HDL-c can evaluate the NAFLD risk in non-obese (NOB) and people with appropriate LDL-c levels and to assess its ability to predict NAFLD.

Research population

In this work, data from a longitudinal cohort study are retrieved from the Dryad database and analyzed secondary to Sun et al.'s original publication [15]. 339101 participants were enrolled in the Medical Health Screening Programme. Accordingly, 183903 subjects were involved and chosen based on the exclusion criteria: (1) Alcohol abuse (2) administrating antidiabetics, antihyperlipidemics, and antihypertensive agents, agents (3) Additional identified factors contributing to CLD (4)LDL-c > 3.12 mmol/L(5) BMI > 25 kg/m² (6) Missing triglyceride (TG) data, BMI, LDL-c, HDL-c, and TC. (7)Those who had no RC and HDL-c records (8) Those with the RC/HDL-c ratio values that fall outside the range of averages ± three standard deviations(SD) [16]. The study encompassed 178474 NOB Chinese individuals with normal levels of LDL-c who were treated at Wenzhou People's Hospital between January 2010 and December 2014 (Fig. 1). Since ethical permission for the original longitudinal cohort research was already acquired from Wenzhou Municipal People's Hospital, Obtaining ethical clearance for this experiment was unnecessary.

Data source

The data presented by Sun et al. can be freely accessed and downloaded as raw data from the Data-Dryad database (https://datadryad.org/stash). Article Title: Correlation between LDL-c and the normal range and NAFLD in the NOP Chinese population: a cross-sectional and longitudinal research. The factors present in the database file were sex, age, gamma-glutamyl transpeptidase(GGT), albuminous protein(ALB), aspartate aminotransferase (AST), alanine aminotransferase(ALT), glucose(GLU), globulin(GLB), creatinine(CR), blood urea nitrogen(BUN), total bilirubin(TB), serum uric acid(SUA), HDL-c, total cholesterol (TC), TG, LDL-c, BMI. The formula for determining BMI:

$$\text{B}\text{M}\text{I} =\frac{\text{w}\text{e}\text{i}\text{g}\text{h}\text{t} \left(\text{k}\text{g}\right)}{\text{h}\text{e}\text{i}\text{g}\text{h}\text{t} \left(\text{m}2\right)}$$

Ultrasonographic NAFLD Diagnosis

The NAFLD diagnosis was created in accordance with the 2010 criteria established by the Chinese Society of Hepatolog [17]. Five diagnostic criteria are associated with NAFLD. (1) In the hepatic region, near-field echoes exhibit diffuse enhancement while far-field echoes gradually diminish in strength. (2) Liver cavity structure is unclear. (3) The liver has a little to moderate enlargement, which is defined by its rounded edges. (4) The signal of blood flow in the liver is diminished. (5) The liver's right lobe and the diaphragm are blurred or incomplete. To determine RC, LDL-c and HDL-c were deducted from T [13]. The RC/HDL-c ratio was determined by dividing the plasma RC concentration (mmol/L) by the HDL-c concentration (mmol/L).

Statistical analysis

In order to determine the correlation between RC/HDL-c and the occurrence of NAFLD, all participants were split into four distinct values: Q1(≤0.33)、Q2༈0.34–0.55༉、Q3༈0.56–0.85༉and Q4༈≥0.86༉. Mean ± SD was deployed to express continuous variables that followed a normal distribution, while frequencies or percentages were used to represent categorical variables (CV). The statistical tests used to assess differences in means and percentages between groups were One-way ANOVA (under the assumption of a normal distribution), Kruskal-Wallis H test (on the assumption of a skewed distribution), and chi-square test (for CV). In addition, a univariate linear regression model was deployed to determine the connections between RC/HDL-c and NAFLD. The Cox proportional hazards model was deployed to examine the link between the RC/HDL-c and NAFLD. This model allowed for the evaluation of the NAFLD risk, resulting in the obtaining of both the P-value with a 95% confidence interval (CI) and the odds ratio (OR). The investigation utilized three models: model 1 represented the original, unaltered model; Model 2 was modified just for age and sex; and Model 3 was corrected for the main other indicators ( ALT, GGT, AST, ALB, TB, GLU, BUN, SUA, CR, TG, BMI, GLB) in addition to the same parameters as model 2. Furthermore, the Generalized Additive Model was employed to identify non-linear relationships (NLR). The likelihood of RC, RC/HDL-c, and HDL-c on the NAFLD diagnosis was examined using ROC curves. All analyses were conducted utilizing the statistical software R (http://www.R-project.org, The R Foundation) and EmpowerStats (http://www.empowerstats.com, X&Y Solutions, Inc., Boston, MA). A p-value of < 0.05 indicated statistical significance.

Baseline Features

In the observational investigation, 178474 individuals participated. The participants were 51.08 years old on average, with 89374 (50.08%) being female. In total, 25209 participants (14.12%) were identified as having NAFLD based on the findings of pelvic ultrasound. Table 1 demonstrates the clinical and biochemical characteristics of the participants in the research, categorized based on the quartiles of their RC/HDL-c ratios. Variations in baseline information were found to be statistically significant among the RC/HDL-c ratio quartiles. The primary findings were as follows: (1) In the population with a greater RC/HDL-c ratio, males were approximately twice as high as females (66.61% vs. 33.39%. (2) The anthropometric parameters of the group with an elevated ratio of RC/HDL-c showed a significant elevation in contrast to those of the control group. (3) Except for HDL-c, other biochemical indexes such as blood lipid, glucose metabolism, and liver enzymes were significantly increased in the great RC/HDL-c group. (4) The occurrence of NAFLD increased gradually between the RC/HDL-c ratio quartiles (5.98% vs. 8.3% vs. 13.16% vs. 28.61%).

Table 1

Baseline Features
RC/HDL-c		Q1		Q2		Q3		Q4		P-value
Number		43628		44427		45016		45403
Age(years, mean ± sd)		38.29 ± 13.41		39.95 ± 13.89		41.56 ± 14.09		44.57 ± 14.07		< 0.001
GGT(IU/L, mean ± sd)		23.30 ± 23.71		25.55 ± 24.72		29.04 ± 30.24		39.83 ± 43.54		< 0.001
ALT(U/L, mean ± sd)		18.14 ± 18.72		19.09 ± 18.16		20.56 ± 17.23		24.56 ± 18.25		< 0.001
AST(U/L, mean ± sd)		21.83 ± 12.25		22.23 ± 11.39		22.77 ± 11.28		24.52 ± 10.71		< 0.001
BUN(mmol/L, mean ± sd)		4.27 ± 1.25		4.31 ± 1.22		4.42 ± 1.30		4.64 ± 2.85		< 0.001
GLB(g/L, mean ± sd)		29.26 ± 3.90		29.40 ± 3.83		29.39 ± 3.88		29.57 ± 3.84		< 0.001
ALB(g/L, mean ± sd)		44.47 ± 2.94		44.50 ± 2.87		44.63 ± 2.83		44.94 ± 2.72		< 0.001
CR(mmol/L, mean ± sd)		76.68 ± 20.03		77.31 ± 17.97		79.39 ± 23.92		81.42 ± 26.44		< 0.001
TB(µmol/L, mean ± sd)		12.59 ± 5.15		12.41 ± 5.05		12.24 ± 5.03		12.08 ± 4.85		< 0.001
GLU(mmol/L, mean ± sd)		5.04 ± 0.69		5.10 ± 0.76		5.16 ± 0.80		5.33 ± 1.09		< 0.001
HDL-c(mmol/L, mean ± sd)		1.64 ± 0.36		1.57 ± 0.33		1.42 ± 0.28		1.16 ± 0.23		< 0.001
TC (mmol/L, mean ± sd)	4.07 ± 0.65		4.49 ± 0.68		4.71 ± 0.69		5.01 ± 0.76		< 0.001
SUA(µmol/L, mean ± sd)	260.14 ± 81.94		268.24 ± 83.51		285.05 ± 86.57		320.23 ± 91.13		< 0.001
TG(mmol/L, mean ± sd)	0.92 ± 0.38		1.05 ± 0.47		1.27 ± 0.63		2.14 ± 1.59		< 0.001
LDL-c(mmol/L, mean ± sd)		2.11 ± 0.47		2.22 ± 0.46		2.31 ± 0.45		2.38 ± 0.45		< 0.001
BMI (kg/m2, mean ± sd)		20.81 ± 2.11		21.08 ± 2.10		21.55 ± 2.06		22.33 ± 1.89		< 0.001
RC(mmol/L, mean ± sd)		0.32 ± 0.17		0.70 ± 0.17		0.98 ± 0.21		1.46 ± 0.44		< 0.001
RC/HDL-c		0.20 ± 0.09		0.45 ± 0.06		0.69 ± 0.09		1.30 ± 0.50		< 0.001
Sex										-
Female		26857 (61.56%)		25560 (57.53%)		21799 (48.43%)		15158 (33.39%)
Male		16771 (38.44%)		18867 (42.47%)		23217 (51.57%)		30245 (66.61%)
NAFLD										-
None		41021 (94.02%)		40738 (91.70%)		39094 (86.84%)		32412 (71.39%)
Yes		2607 (5.98%)		3689 (8.30%)		5922 (13.16%)		12991 (28.61%)
GGT stands for gamma-glutamyl transpeptidase, RC stands for remnant cholesterol, ALB refers to albuminous protein, AST denotes aspartate aminotransferase, and ALT signifies alanine aminotransferase. The abbreviations TB, GLB, LDL-c, CR, BUN, and GLU refer to the following parameters: total bilirubin, globulin, low-density lipoprotein cholesterol, creatinine, blood urea nitrogen, and glucose, respectively. SUA refers to serum uric acid, TG stands for triglyceride, and TC represents total cholesterol. HDL-c, which stands for high-density lipoprotein cholesterol, is a biomarker used to assess the levels of cholesterol carried by high-density lipoproteins in the bloodstream. BMI, an acronym for body mass index, is a numerical figure calculated based on a person's weight and height measurements, commonly employed to evaluate body composition and identify potential weight-related health risks. NAFLD, short for nonalcoholic fatty liver disease, refers to a medical condition caused by the fat buildup in the liver, unrelated to excessive alcohol consumption.

Univariate analysis (UVA)

Table 2 displays the UVA findings. The findings from the UVA demonstrated correlations between various factors, including age, sex, TB, ALT, BMI, HDL-c, ALB, GGT, TG, RC GLB, CR, BUN, AST, TC, GLU, SUA, LDL-c, and RC/HDL-c, with NAFLD. UVA showed that age, gender, ALT, GGT, ALB, AST, TB, GLB, BUN, CR, SUA, GLU, TC, TG, BMI, RC, RC/HDL-c, and LDL-c exhibited positive link to NAFLD. The HDL-c level displayed an adverse link with NAFLD.

Table 2

Findings of UVA
	Statistics	OR (95% CI)	P-value
Sex
Male	89100 (49.92%)	4.18 (4.05, 4.32)	< 0.0001
Female	89374 (50.08%)	1.0
Age	41.13 ± 14.06	1.03 (1.03, 1.03)	< 0.0001
GGT	29.25 ± 32.00	1.02 (1.02, 1.02)	< 0.0001
ALB	44.63 ± 2.85	1.07 (1.06, 1.07)	< 0.0001
GLB	29.39 ± 3.87	1.01 (1.01, 1.01)	< 0.0001
AST	22.80 ± 11.41	1.03 (1.03, 1.03)	< 0.0001
CR	78.67 ± 22.32	1.01 (1.01, 1.02)	< 0.0001
BUN	4.41 ± 1.79	1.17 (1.16, 1.18)	< 0.0001
SUA	283.13 ± 88.90	1.01 (1.01, 1.01)	< 0.0001
ALT	20.51 ± 18.17	1.04 (1.03, 1.04)	< 0.0001
TB	12.35 ± 5.05	1.01 (1.01, 1.01)	< 0.0001
GLU	5.15 ± 0.85	1.69 (1.66, 1.71)	< 0.0001
TC	4.54 ± 0.79	1.64 (1.61, 1.67)	< 0.0001
TG	1.34 ± 1.02	2.71 (2.66, 2.75)	< 0.0001
HDL-c	1.45 ± 0.36	0.11 (0.10, 0.11)	< 0.0001
LDL-c	2.25 ± 0.47	2.54 (2.46, 2.61)	< 0.0001
BMI	21.43 ± 2.13	2.08 (2.06, 2.11)	< 0.0001
RC/HDL-c	0.66 ± 0.49	4.01 (3.91, 4.12)	< 0.0001
RC	0.87 ± 0.50	3.21 (3.13, 3.29)	< 0.0001

Results of the link of RC/HDL-c with NAFLD

To investigate the potential link between the RC to HDL-c ratio and the NAFLD risk, we developed two multivariate logistic regression models (Table 3). The unadjusted correlation coefficient between the RC/HDL-c ratio and the NAFLD probability was 4.01 (95% CI 3.91–4.12). Following the adjustment for sex and age, the RC/HDL-c ratio was found to be strongly correlated to a greater NAFLD risk (least adjusted model: OR 3.12, 95% CI 3.04–3.21). In a subsequent model that was fully adjusted, the link between the ratio of RC/HDL-c and NAFLD remained consistent (completely adjusted model: OR 1.56, 95% CI 1.50–1.72). In order to conduct sensitivity analysis, we treated RC/HDL-c as a CV (quartile), and a similar pattern was detected.

Table 3

Correlation between RC/HDL-c and NAFLD in several models
Variable	Crude model (OR, 95%CI, P)	Minimally adjusted model (OR, 95%CI, P)	Fully adjusted model (OR, 95%CI, P)
RC/HDL-c (quartile)	4.01 (3.91, 4.12) < 0.0001	3.12 (3.04, 3.21) < 0.0001	1.56 (1.50, 1.72) < 0.0001
Q1	1.0	1.0	1.0
Q2	1.43 (1.36, 1.51) < 0.0001	1.34 (1.27, 1.41) < 0.0001	1.16 (1.07, 1.26) 0.0002
Q3	2.39 (2.28, 2.51) < 0.0001	2.01 (1.91, 2.11) < 0.0001	1.40 (1.28, 1.52) < 0.0001
Q4	6.33 (6.06, 6.62) < 0.0001	4.55 (4.35, 4.77) < 0.0001	1.79 (1.59, 2.02) < 0.0001
Crude model: we did not account for additional variables
Minimally adjusted model: we made adjustments for age and sex
Fully adjusted model: we made adjustments for sex, age, ALB, SUA, GLU, AST, ALT, GGT, BUN, CR, GLB, TB, TG, BMI

The subgroup results in analyses.

This research aim was to examine the relationships of the RC/HDL-c ratio with the likelihood of developing NAFLD in subgroups by gender, age, GGT, TC, TG, HDL-c, BMI, and LDL-c. We detected a link between all subgroups and RC/HDL-c ratio regarding NAFLD likelihood (Table 4).

Table 4

ES of RC/HDL-c on NAFLD in predetermined and investigational subgroups
Characteristic	ES (95% CI)		P for interaction
Sex			< 0.0001
Female	2.21 (2.00, 2.44)
Male	1.86 (1.78, 1.94)
Age			< 0.0001
<37	2.04 (1.87, 2.23)
≥37	1.88 (1.79, 1.96)
GGT			< 0.0001
1–16	2.08 (1.78, 2.42)
17–25	2.06 (1.91, 2.22)
>25	1.82 (1.74, 1.90)
TC			< 0.0001
2.00–3.00	2.43 (1.85, 3.19)
4.00–4.00	2.14 (1.98, 2.32)
5.00–16.00	1.96 (1.87, 2.06)
TG			< 0.0001
0.16–0.86		0.82 (0.63, 1.07)
0.87–1.33	1.08 (0.95, 1.23)
1.34–43.23	1.47 (1.41, 1.53)
HDL-c			< 0.0001
0.08–1.25	1.72 (1.65, 1.80)
1.26–1.56	2.15 (1.95, 2.37)
1.57–5.38	2.26 (1.88, 2.72)
LDL-c			< 0.0001
0.41–2.04	2.05 (1.92, 2.19)
2.05–2.48	2.14 (2.00, 2.29)
2.49–3.12	2.01 (1.89, 2.13)
BMI			< 0.0001
12.48–20.44	2.98 (2.48, 3.57)
20.45–22.63	2.27 (2.12, 2.44)
22.64–24.99	2.00 (1.91, 2.08)

NLR analyses

In the current investigation, an examination was conducted to analyze the NLR between RC/HDL-c and NAFLD, as RC/HDL-c was considered to be a continuous variable (Fig. 2). After controlling for GGT, sex, age, ALB, GLU, ALT, SUA, GLB, TB, BUN, AST, CR, TG, and BMI, an NLR between them was found. The inflection point (IP) was determined to be 1.33, employing a two-piecewise linear regression model. A positive connection was found between the RC/HDL-c ratio and NAFLD on the lower portion of the IP. The ES, 95% CI, and p-value were determined to be 1.64, 1.53 to 1.76, and < 0.001, respectively. Furthermore, an inverse relationship was observed to the right of the IP. In addition, the ES, 95% CI, and P values were determined to be 0.59, 0.53 to 0.65, and < 0.001, respectively (Table 5).

Table 5

Findings of two-piecewise linear regression model
IP of RC/HDL-c	Effect size (OR)	95%CI P value
<1.33	1.64	1.53 to 1.76 <0.001
≥1.33	0.59	0.53 to 0.65 <0.001
Effect: NAFLD Cause: RC/HDL-c
Adjusted: age, sex, GGT, ALT, AST, ALB, GLB, TB, BUN, CR, SUA, GLU, TG, BMI

NAFLD risk assessment according to the TC/HDL-c ratio

A ROC curve analysis was deployed to measure and contrast the prognostic capabilities of various variables (Fig. 3). The outcomes revealed that the area under the curve (AUC) for the RC/HDL-c ratio exhibited significantly superior performance compared to the AUCs for both RC and HDL-c values. The ROC area and 95% CI for the RC/HDL-c ratios, and for RC and HDL-c individually, were calculated to be 0.707 (0.704–0.711), 0.665 (0.661–0.668), and 0.699 (0.695–0.702), respectively. The study determined that an RC/HDL-c ratio cut-off value of 0.715 was found to be optimal for identifying NAFLD. This cut-off value emerged with a sensitivity of 62.5% and a specificity of 69%.

This is the initial retrospective cross-sectional paper based on our knowledge to establish the predictive value of the RC/HDL-c ratio in detecting NAFLD in NOB Chinese people characterized by normal LDL-c levels. According to the fact that the AUC area of RC/HDL-c is larger than that of additional lipid indicators, including RC and HDL-c, RC/HDL-c shows better NAFLD predictive ability in individuals with NOB and normal LDL-c levels. By utilizing a two-segment linear regression model, we could construct an NLR of RC/HDL-c with NAFLD. RC/HDL-c was strong with NAFLD when analyzed on the IP's left side (OR: 1.64) and had a negative link with NAFLD when analyzed on the IP's right side (OR: 0.59). As far as we know, we are the initial group to document an NLR between RC/HDL-c and NAFLD. Therefore, our study may help identify high-risk groups so that targeted preventive measures can be taken. More importantly, the RC/HDL-c ratio could be easily calculated and obtained. This novel measure has the potential to be an efficient monitoring instrument for the avoidance and management of NAFLD likelihood in the general population.

Both obese and NOB NAFLD have a shared pathophysiological mechanism, which involves the buildup of free fatty acids(FA) inside the live [18]. RC is the measure of cholesterol found in VLDL and chylomicron remnants [19]. RC is considered to be a promising biomarker for evaluating the risk of cardiovascular disease relative to other lipid marker [20]. In addition, cardiovascular disease is a prevalent factor contributing to mortality among patients with NAFL [21]. Many research investigations revealed that NAFLD patients with great RC levels show a higher likelihood of cardiovascular disease-related mortality [22]. Furthermore, certain investigations have discovered that heightened RC levels are closely connected to a greater occurrence of diabetes problems and hypertension [11] [12]. This suggests that measuring RC in NAFLD patients is of great value. HDL-c is a lipid characteristic that helps prevent the development of atherosclerosis. Previously, many papers have demonstrated a strong link between HDL-c and various metabolic disorder [23]. Currently, only a few research studies exist on the RC/HDL-c ratio [24]. Some investigations revealed that the RC/HDL-c ratio is linked to the occurrence of intracranial atherosclerosis and diabetic complication [25] [26]. Can simultaneous identification of RC and HDL-c enhance the discriminatory capacity of NAFLD? Our research demonstrated that the simultaneous detection of RC and HDL-c significantly enhanced the capacity to detect NAFLD, surpassing the effectiveness of other traditional lipid markers. Most of the participants in the previous study were obese [27], and our research is the first to measure the relation between RC and HDL-c and NAFLD in NOB and normal LDL-c populations. Therefore, the RC/HDL-c ratio is a promising metabolic indicator that deserves increased attention from researchers.

At present, one of the possible mechanisms leading to NAFLD in non-obese patients is that visceral adipose tissue (VAT) is more likely to cause NAFLD than total body fat [28]. The VAT function in the pathophysiology of insulin resistance is significant [29]. Free FA and VAT-secreted cytokines are transported into the liver via the portal venous system, which is considered to be the driver of NAFLD development [30]. Multiple studies have demonstrated a strong correlation of VAT with NAFLD [31] [32].

The present observational research possesses multiple strengths: (1) The research has a substantial sample size, and after rigorous statistical adjustment, the final conclusion can be regarded as relatively objective. (2) Herein, all subjects have received a physical examination, and the findings of this investigation are highly applicable to the overall population. (3) The present research presents the initial proof that the RC/HDL-c ratio is autonomously linked to NAFLD in the overall NOP population with regular lipid levels.

This research is subject to several limitations. Firstly, despite attempts to mitigate the influence of any confounding factors, it is possible that residual and unmeasured confounding variables were not fully accounted for. Secondly, the outcomes of the current research may not be generalizable to populations beyond the specific NOB population with normal blood lipids from which the participants were selected. Thirdly, due to constraints imposed by the original data, it was not possible to enhance the understanding of the association between NAFLD and other indicators such as dietary habits, smoking, alcohol consumption, white blood cells, neutrophils, lymphocytes, and platelets. Fourthly, we determined that NAFLD is diagnosed by ultrasonography, with liver biopsy being considered the most reliable method for diagnosing NAFLD.

This study represents the initial investigation into the link between the ratio of RC/HDL-c and NAFLD in individuals with NOB body mass index and normal LDL-c levels. Following the adjustment for various risk factors, it was determined that the RC/HDL-c ratio independently contributes to the susceptibility to NAFLD. Consequently, the RC/HDL-c ratio serves as a convenient and easily accessible parameter for assessing the likelihood of diagnosing NAFLD in NOB individuals.

effect sizes

Remnant Cholesterol

NOB

non-obese

GGT

gamma-glutamyl transpeptidase

ALT

alanine aminotransferase

AST

aspartate aminotransferase

total protein

ALB

albuminous protein

GLB

globulin

total bilirubin

BUN

blood urea nitrogen

creatinine

SUA

serum uric acid

GLU

glucose

total cholesterol

triglyceride

HDL-c

high-density lipoprotein cholesterol

LDL-c

low-density lipoprotein cholesterol

BMI

body mass index

NAFLD

non-alcoholic fatty liver disease

hazard ratio

UVA

univariate analysis

AUC

area under the curve

ULR

univariate linear regression.

Ethics approval and consent to participate

Ethical approval for the initial longitudinal cohort study was obtained from Wenzhou Municipal People's Hospital; therefore, ethical approval was not required for this study.

Consent for publication

Not applicable

Availability of data and materials

The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no conflict of interest.

Funding

Clinical study of integrated abdominal aortic coated stent for the treatment of abdominal aortic aneurysm. Number： PKX2023-S14.

Authors' contributions

LX contributed to the conception and design of the study. Acquisition of data: LX, SBZ, YLW. Analysis and interpretation of data: LX. ZDF verified the data. Drafting of the manuscript: SBZ. Review and/or revision of the manuscript: ZDF. Administration or material support: YLW. Final approval of manuscript: All authors.

Acknowledgements

Thanks to Professor Fang for his guidance and suggestions on this study！

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No competing interests reported.

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The Role of Remnant Cholesterol/High-Density Lipoprotein Cholesterol Ratio in Nonalcoholic Fatty Liver Disease among Non-Obese Individuals with Normal LDL-c Levels

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Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Research population

Data source

Ultrasonographic NAFLD Diagnosis

Statistical analysis

Results

Baseline Features

Univariate analysis (UVA)

Results of the link of RC/HDL-c with NAFLD

NLR analyses

NAFLD risk assessment according to the TC/HDL-c ratio

Discussion

Conclusion

Abbreviations

Declarations

References

Additional Declarations

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