Remnant Lipoprotein Cholesterol as a Factor Related to Adult Fatty Liver Disease

Context Dyslipidemia is related to fatty liver disease (FLD), whose relationship with remnant lipoprotein cholesterol (RLP-C), a component of blood lipids, remains unclear. Objective To clarify the correlation between RLP-C and the occurrence and severity of FLD and establish an FLD discriminant model based on health check indicators. Methods Retrospective study of participants who underwent health check-up in the First Affiliated Hospital of China Medical University (Shenyang, China) between January and December 2019. We categorized participants according to liver ultrasound results and analyzed the correlation between RLP-C and occurrence of FLD (n = 38 885) through logistic regression, restricted cubic spline, and receiver operating characteristic curve. We categorized the severity of FLD according to the control attenuation parameter and analyzed the correlation between RLP-C and FLD severity through multiple logistic regression; only males were included (n = 564). Results The adjusted OR (aOR) per SD between RLP-C and FLD was 2.33 (95% CI 2.21-2.46, P < .001), indicating a dose–response relationship (P < .0001). The optimal cut-off value of RLP-C was 0.45 mmol/L and the area under the curve (AUC) was 0.79. The AUC of the 8-variable model was 0.89 in both the training and the validation sets. FLD severity was related to the level of RLP-C (aOR per SD = 1.29, 95% CI 1.07-1.55, P = .008). Conclusion RLP-C has a strong positive correlation with FLD occurrence and FLD severity. These results may help clinicians identify and implement interventions in individuals with high FLD risk and reduce FLD prevalence.

Dysbetalipoproteinemia: differentiating multifactorial remnant cholesterol disease from genetic apoE deficiency

Background Dysbetalipoproteinemia (DBL) is characterized by the accumulation of remnant lipoprotein particles and associated with an increased risk of cardiovascular and peripheral vascular disease (PVD). DBL is thought to be mainly caused by the presence of an E2/E2 genotype of the apolipoprotein E (APOE) gene, in addition to environmental factors. However, there exists considerable variability in the phenotype of these patients. Objective The objectives were to verify the proportion of DBL subjects diagnosed using the gold standard Fredrickson criteria who did not carry E2/E2 and to compare the clinical characteristics of DBL patients with vs without E2/E2. Methods A total of 12 432 patients with lipoprotein ultracentrifugation as well as APOE genotype or apoE phenotype data were included in the present retrospective study. Results Among the 12 432 patients, 4% (n=524) were positive for Fredrickson criteria (F+), and only 38% (n=197) of the F+ individuals were E2/E2. The F+ E2/E2 group had significantly higher remnant cholesterol concentration (3.44 vs 1.89 mmol/L) and had higher frequency of DBL-related xanthomas (24% vs 2%) and floating beta (95% vs 11%) than the F+ non-E2/E2 group (p<0.0001). The F+ E2/E2 group had an independent higher risk of PVD (OR 11.12 (95% CI 1.87-66.05) p=0.008) events compared to the F+ non-E2/E2 group. Conclusion In the largest cohort of DBL worldwide, we demonstrated that the presence of E2/E2 was associated with a more severe DBL phenotype. We suggest that two dysbetalipoproteinemia phenotypes should be distinguished: the multifactorial remnant cholesterol disease and the genetic apoE deficiency disease.

Associations between remnant lipoprotein cholesterol and central systolic blood pressure in a Chinese community-based population: a cross-sectional study

Background The lipid profile is reportedly related to peripheral blood pressure or pulse wave velocity. However, no studies have investigated the associations between lipid parameters, especially remnant lipoprotein cholesterol (RLP-C), and central systolic blood pressure (cSBP). Methods This study used baseline data of a community-based cohort in Beijing, China. Participants who had been treated with anti-hypertensive or lipid-lowering agents were excluded. RLP-C is equal to total cholesterol (TC) minus the sum of low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). An Omron HEM-9000AI device was used to measure non-invasive cSBP. The associations between blood lipid profile and non-invasive cSBP were evaluated using multivariable regression models. Results The 5173 included participants were 55.0 ± 8.5 years old; 35.7% (1845) of participants were men. Increased cSBP was significantly associated with increased TC, LDL-C, non-high-density lipoprotein cholesterol (non-HDL-C), triglyceride (TG), and RLP-C but with decreased HDL-C, even after adjusting for possible covariates. When simultaneously entering individual pairs of RLP-C and other blood lipid parameters into the multivariable regression model, RLP-C remained significantly associated with cSBP, even after adjusting for other lipids. Compared with participants who had RLP-C levels in the first quartile (Q1), cSBP for those with RLP-C in Q4 was increased to 4.57 (95% confidence interval [CI]: 3.08–6.06) mmHg after adjusting for LDL-C, 4.50 (95%CI: 2.98–6.02) mmHg after adjusting for TC, 3.91 (95%CI: 1.92–5.89) mmHg after adjusting for TG, 5.15 (95%CI: 3.67–6.63) mmHg after adjusting for HDL-C, and 4.10 (95%CI: 2.36–5.84) mmHg after adjusting for non-HDL-C. Conclusions Increased blood RLP-C level was significantly associated with higher cSBP in a Chinese population, independently of other lipids, which indicates its importance in individual cardiovascular risk assessment.

Small Dense Low‐Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study

Background Elevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Methods and Results Plasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C. Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42; P <0.0001) was in the model. These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non–high‐density lipoprotein cholesterol, in contrast to LDL triglycerides. Conclusions sdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.

SUN-022 Metformin-Fish Oil Adjunct Therapy Improves apoB-Remnant Lipoprotein and Triglyceride Levels in Women with Polycystic Ovary Syndrome

Background: Polycystic ovary syndrome (PCOS) is highly associated with the metabolic syndrome (MetS): obesity, insulin resistance and atherogenic dyslipidemia. Women with PCOS-MetS are at higher risk of developing ischemic cardiovascular disease (CVD) and Type-2 Diabetes. First-line intervention in PCOS-MetS includes targeting diet and lifestyle, and metformin is commonly prescribed to treat insulin resistance, however these interventions have shown limited effectiveness to improve dyslipidemia. At present there are limited safe and efficious options to target atherogenic dyslipidemia in young women with PCOS. Fish oil (FO) and Icosapentyl ethyl supplementation have been shown to reduce fasting TG, apoB and to improve ischemic CVD outcomes. The efficacy of FO or as an adjunct therapy to metformin to improve ApoB-remnant lipemia in PCOS-MetS is unknown. The aim of this pilot study was to determine the effect of metformin, FO and FO-metformin combination treatment on fasting and non-fasting plasma TG and apoB-remnant lipoprotein metabolism in patients with PCOS-MetS. Methods: Participants diagnosed with PCOS aged 18-30yrs received dietary counselling and were randomly assigned to receive FO (n=8), metformin (n=7) or FO-metformin (n=12) treatment for 12 wks. Plasma lipids (TG and cholesterol), ApoB48 and ApoB100 lipoprotein metabolism were assessed in the fasting and non-fasting state using a standardized high-fat meal test. Results: At baseline, the fasting plasma TG, ApoB48 and ApoB100 was 238.0 ± 21.0 mg/dL, 9.00 ± 1.12 ug/ml and 290 ± 18.00 mg/dL. FO and FO-metformin decreased fasting plasma TG by 10% and 30% compared to the metformin treatment group (7%). Fasting ApoB48 was reduced 45%, 16% and 19% in FO-metformin, FO and metformin treatment groups, respectively. Non-fasting plasma TG and apoB48 lipoprotein area under the curve were reduced by 30% in the FO-metformin treatment group. Conclusion: These pilot findings demonstrate FO-metformin adjunct therapy may have greater efficacy to improve atherogenic apoB-dyslipidemia compared to metformin or FO alone in high-risk patients with PCOS-MetS. A larger clinical trial is warranted to determine the long term effects of FO-metformin intervention on apoB-dyslipidemia and atherosclerotic cardiovascular disease indices.