Effects of moderate ethanol exposure on risk factors for cardiovascular disease and colorectal cancer in adult Wistar rats.

While past studies have provided evidence linking excessive alcohol consumption to increased risk for cardiovascular diseases (CVDs) and colorectal cancer (CRC), existing data on the effects of moderate alcohol use on these conditions have produced mixed results. The purpose of this study was to investigate the effects of moderate alcohol consumption on risk factors associated with the development of CVDs and CRC in adult rats. Twenty-four, 14-month-old, non-deprived male Wistar rats were randomly assigned to either an ethanol group, which consisted of voluntary access to a 20% (v/v) ethanol solution on alternate days, or a water control group (n = 12/group) for 13 weeks. Blood samples were collected to analyze levels of albumin, glucose, adiponectin, lipids, oxidized low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), apolipoprotein A1 (apoA1), C-reactive protein (CRP), high-mobility group box 1 protein (HMGB-1), tumor necrosis factor-alpha (TNF-α), thyroxine, thyroid-stimulating hormone, 8-oxo-2'-deoxyguanosine (8-oxo-dG), liver function enzymes, and antioxidant capacity. Colonic gene expression related to colon carcinogenesis was also assessed. Ethanol-treated rats were found to have significantly higher HDL-C and apoA1 levels compared to controls. Moderate alcohol consumption led to significantly lower CRP levels and a trend for decrease in HMGB-1, TNF-α, and 8-oxo-dG levels. In the ethanol-exposed group, colonic gene expression of superoxide dismutase was upregulated while aldehyde dehydrogenase 2 showed a trend for increase compared to the control group. These results indicate that adopting a moderate approach to alcohol consumption could potentially improve health biomarkers related to CVD and CRC by increasing HDL-C levels and antioxidant activity and reducing DNA damage and inflammatory activity.

Associations of apolipoproteinA1, high density lipoprotein cholesterol with hemoglobin glycation index and triglyceride-glucose index in Chinese adults with coronary artery disease.

AIMS: Scarce data explored the associations of apolipoproteins with hemoglobin glycation index (HGI) and triglyceride-glucose (TyG) index. This study determined associations of serum apolipoproteinA1 (ApoA1) and high density lipoprotein cholesterol (HDL-C) with HGI and TyG index in coronary artery disease (CAD) patients. METHODS: A total of 10,803 CAD patients were included in this cross-sectional pilot study. Serum concentrations of ApoA1 and HDL-C were measured. Analyses of covariance were used to compare the mean differences in glucose metabolism indices (e.g., HGI, TyG index, hemoglobin glycation [HbA1c], fasting blood glucose [FBG]) among the quartiles of ApoA1, HDL-C and HDL-C/ApoA1 ratio. RESULTS: In multivariate analysis, higher ApoA1, HDL-C and HDL-C/ApoA1 ratio were associated with significantly lower HGI (Quartile [Q]4 vs. Q1: -0.032 % vs. 0.017 % for ApoA1; -0.072 % vs. 0.079 % for HDL-C; -0.083 % vs. 0.085 % for HDL-C/ApoA1 ratio). Intermediate ApoA1 level was inversely associated with TyG index (Q2 vs. Q1: 296.278 vs. 306.794). The mean TyG index were significantly decreased with increased HDL-C and HDL-C/ApoA1 ratio (Q4 vs. Q1: 298.584 vs. 309.221 for HDL-C; 300.405 vs. 315.218 for HDL-C/ApoA1 ratio). Moreover, the inverse associations of ApoA1, HDL-C and HDL-C/ApoA1 ratio with HbA1c and FBG also were observed. In path analysis, the associations of HDL-C and HDL-C/ApoA1 ratio with TyG index were mediated by obesity. CONCLUSION: This study provided further support for the hypoglycemic effects of ApoA1 and HDL-C in patients with CAD. Replication of these findings is warranted in further longitudinal studies in different populations.

Efficacy and Safety of Pemafibrate Versus Bezafibrate to Treat Patients with Hypertriglyceridemia: A Randomized Crossover Study.

AIM: Pemafibrate is a highly selective agonist for peroxisome proliferator-activated receptor (PPAR)-α, a key regulator of lipid and glucose metabolism. We compared the efficacy and safety of pemafibrate with those of bezafibrate, a nonselective PPAR-α agonist. METHODS: In this randomized crossover study, 60 patients with hypertriglyceridemia (fasting triglyceride [TG] ≥ 150 mg/dL) were treated with pemafibrate of 0.2 mg/day or bezafibrate of 400 mg/day for 24 weeks. The primary endpoint was percent change (%Change) from baseline in TG levels, while the secondary endpoints were %Change in high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (Apo A-I) levels. RESULTS: The %Change in TG and Apo A-I levels was significantly greater with pemafibrate than with bezafibrate (-46.1% vs. -34.7%, p＜0.001; 9.2% vs. 5.7%, p =0.018, respectively). %Change in HDL-C levels was not significantly different between the two treatments. %Change in liver enzyme levels was markedly decreased with pemafibrate than with bezafibrate. Creatinine levels significantly increased in both treatments; however, its %Change was significantly lower with pemafibrate than with bezafibrate (5.72% vs. 15.5%, p＜0.001). The incidence of adverse events (AEs) or serious AEs did not differ between the two treatments; however, the number of patients with elevated creatinine levels (≥ 0.5 mg/dL and/or 25% from baseline) was significantly higher in the bezafibrate group than in the pemafibrate group (14/60 vs. 3/60, p =0.004) [corrected]. CONCLUSION: Compared with bezafibrate, pemafibrate is more effective in decreasing TG levels and increasing Apo A-I levels and is safer regarding liver and renal function.

Sex-Dependent Mediation of Leptin in the Association of Perilipin Polymorphisms with BMI and Plasma Lipid Levels in Children.

Variations in the perilipin (PLIN) gene have been suggested to be associated with obesity and its related alterations, but a different nutritional status seems to contribute to differences in these associations. In our study, we examined the association of several polymorphisms at the PLIN locus with obesity and lipid profile in children, and then analyzed the mediation of plasma leptin levels on these associations. The single-nucleotide polymorphisms (SNPs) rs894160, rs1052700, and rs2304795 in PLIN1, and rs35568725 in PLIN2, were analyzed by RT-PCR in 1264 children aged 6-8 years. Our results showed a contrasting association of PLIN1 rs1052700 with apolipoprotein (Apo) A-I levels in boys and girls, with genotype TT carriers showing significantly higher Apo A-I levels in boys and significantly lower Apo A-I levels in girls. Significant associations of the SNP PLIN2 rs35568725 with high-density lipoprotein cholesterol (HDL-cholesterol), Apo A-I, and non-esterified fatty acids (NEFA) were observed in boys but not in girls. The associations of the SNPs studied with body mass index (BMI), NEFA, and Apo A-I in boys and girls were different depending on leptin concentration. In conclusion, we describe the mediation of plasma leptin levels in the association of SNPs in PLIN1 and PLIN2 with BMI, Apo A-I, and NEFA. Different leptin levels by sex may contribute to explain the sex-dependent association of the PLIN SNPs with these variables.

Cross-sectional and longitudinal associations of apolipoprotein A1 and B with glycosylated hemoglobin in Chinese adults.

Apolipoproteins exert a key role on glucose metabolism; however, scarce data have examined the relationship between apolipoproteins and glycated haemoglobin (HbA1c) in Chinese adults. This study determined the cross-sectional and longitudinal associations of serum Apolipoprotein A1 (ApoA1), Apolipoprotein B (ApoB) and the ApoB/A1 ratio with HbA1c in Chinese adults. A total of 1448 subjects (584 men and 864 women) aged 54.8 years were included in a baseline survey, and the concentrations of Apo and HbA1c were measured. A total of 826 participants were followed up approximately once after 3.94 ± 0.62 years. In cross-sectional analysis, serum ApoA1 was inversely associated with HbA1c, while ApoB and the ApoB/A1 ratio were positively associated with HbA1c. After further adjusting for the potential covariates, a higher ApoA1 was associated with lower HbA1c (Quartile 4 [Q4] vs. Q1 = 5.673% vs. 5.796%, P-trend = 0.014). In contrast, positive association of ApoB concentration and the ApoB/A1 ratio with HbA1c level were showed (Q4 vs. Q1 = 5.805% vs. 5.589% for ApoB; Q4 vs. Q1 = 5.841% vs. 5.582% for ApoB/A1 ratio). The longitudinal results showed no significant associations of ApoA1, ApoB levels and the ApoB/A1 ratio with HbA1c changes (all P-trends > 0.05). Path analysis suggested that body mass index did not have mediating effect on Apo-HbA1c association. Our findings revealed that higher ApoA1, lower ApoB concentrations and the ApoB/A1 ratio were associated with lower HbA1c level in Chinese adults.

Decreased serum apolipoprotein A1 level predicts poor prognosis of patients with de novo myelodysplastic syndromes.

BACKGROUND: Myelodysplastic syndromes (MDS) is a group of heterogeneous myeloid clonal diseases originating from hematopoietic stem cells. It has been demonstrated that apolipoproteins A1(ApoA1) are associated with disease risk in many cancer types. However, there still lacks evidence regarding the link between ApoA1 and MDS. This study was designed to investigate the prognostic value of pretreatment ApoA1 levels in MDS patients. METHODS: We retrospectively analyzed a cohort of 228 MDS patients to explore the prognostic value of the serum ApoA1 levels at diagnosis. Patients were divided into the high ApoA1 group and the low ApoA1 group. The prognostic significance was determined by univariate and multivariate Cox hazard models. RESULTS: MDS patients with low ApoA1 levels had significantly shorter overall survival (OS, P < 0.0001) along with a higher frequency of TP53 mutation (P = 0.002). Based on univariate analysis, age (≥ 60 years), gender (male), lower levels of hemoglobin (< 10 g/dl), HDL (≤0.91 mmol/L), higher bone marrow blast percentage (> 5%), higher IPSS-R scores and poorer karyotype were significantly associated with decreased OS. However, low ApoA1 level did not influence leukemia-free survival (LFS, P = 0.367). Multivariate Cox proportional hazards regression analysis indicated that low ApoA1 level (≤ 1.02 g/L) was also an independent adverse prognostic factor for OS in MDS (P = 0.034). CONCLUSIONS: Decreased ApoA1 level predicts a poor prognosis of MDS patients and thus provides a novel evaluation factor for them that is independent of the IPSS-R system.

Evaluation of S100A12 and Apo-A1 plasma level potency in untreated new relapsing-remitting multiple sclerosis patients and their family members.

Multiple sclerosis is an inflammatory disease of the spinal cord and brain. Receptor for advanced glycation end products and Apolipoprotein A1 (Apo-AI) have been recommended to have a pathogenic role in the neuroinflammatory disorder as multiple sclerosis. The purpose of this research was to measure the plasma levels of S100A12 and Apo-A1 in the first-degree family of relapsing-remitting multiple sclerosis (RRMS) patients. Plasma levels of S100A12 & Apo-A1 were evaluated via enzyme-linked immunosorbent assay in the thirty-five new cases of untreated patients with deterministic RRMS according to the McDonald criteria, twenty-four healthy controls, and twenty-six first-degree members of untreated RRMS patients (called them as high-risk group). The main findings of this study were as follows: the plasma level of S100A12 was significantly lower in the new cases of untreated RRMS (P ≤ 0.05; 0.045) and high-risk (P ≤ 0.05; 0.001) groups. Although the plasma protein level of Apo-A1 was reduced significantly in the high-risk group (P < 0.05, P = 0.003) as compared to the healthy control group, there was no significant difference in the untreated RRMS patients (P = 0.379). The plasma level of vitamin D3 in both RRMS patients and high-risk groups displayed significance reduction, although, there was no significant association between vitamin D and S100A12 & Apo-A1 levels. Given the role of S100A12 and Apo-A1 in the inflammatory process performed in the first-degree family members of the RRMS patients, which revealed a significant decrease in this group, we concluded that they can be considered as one of the contributing factors in the pathogenesis of MS, though more research is needed before assuming them as predictive biomarkers.

Serum apolipoprotein B to apolipoprotein A-I ratio is an independent predictor of liver metastasis from locally advanced rectal cancer in patients receiving neoadjuvant chemoradiotherapy plus surgery.

BACKGROUND: The ratio of serum apolipoprotein B (apoB) to apolipoprotein A-I (apoAI) had been reported as a prognostic factor in colorectal cancer. This retrospective study aimed to assess the implication of apoB-to-apoAI ratio in predicting liver metastasis from rectal cancer (RC). METHODS: The clinical data of 599 locally advanced RC patients treated with chemoradiotherapy followed by surgery were reviewed. Serum apoAI, apoB and apoB-to-apoAI ratio were analyzed for their correlation with the liver-metastasis-free, other-metastasis-free and overall survivals, together with the pretreatment and postsurgical pathoclinical features of the patients. Univariate and multivariate survival analyses were realized through the Kaplan-Meier approach and Cox model, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for independent predictors. RESULTS: Carbohydrate antigen 19 - 9 ≥ 26.3 U/ml, apoB-to-apoAI ratio ≥ 0.63, tumor regression grade 5 - 3, pT4 and pN + stage emerged as independent predictors of poorer liver-metastasis-free survival. The hazard ratios were 1.656 (95% CI, 1.094-2.506), 1.919 (95% CI, 1.174-3.145), 1.686 (95% CI, 1.053-2.703), 1.890 (95% CI, 1.110-3.226) and 2.012 (95% CI, 1.314-2.077), respectively. Except apoB-to-apoAI ratio, the other 4 factors were also independent predictors of poorer other-metastasis-free and overall survivals. And the independent predictors of poorer overall survival also included age ≥ 67 years old, distance to anal verge < 5 cm. CONCLUSIONS: Serum apoB-to-apoAI ratio could be used as a biomarker for prediction of liver metastasis risk in locally advanced RC.

Predictive value of preoperative platelet-to-albumin ratio and apolipoprotein B-to-apolipoprotein A1 ratio for osteosarcoma in children and adolescents: a retrospective study of 118 cases.

BACKGROUND: This retrospective study investigated biomarkers that can reflect coagulation, inflammation, and lipid abnormalities: platelet-to-albumin ratio (PAR), platelet-to lymphocyte ratio (PLR), low-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (LDL-C/HDL-C), apolipoprotein B-to-apolipoprotein ratio (ApoB/ApoA1) whether may be viable prognostic predictors in children and adolescents with osteosarcoma. METHODS: The retrospective review has enrolled a total of 118 children and adolescent patients diagnosed with osteosarcoma. Analyses with a receiver operating characteristic (ROC) curve were performed to evaluate the optimal cut-off values and to compare the area under curves (AUC). Kaplan-Meier curves were used to visualize survival outcome and a Cox proportional hazards model were used to confirm independent prognostic factors. RESULTS: Osteosarcoma patients in high PAR group (> 4.41) and high ApoB/ApoA1 group (> 0.82) experienced significantly shorter overall survival compared with those in low PAR group (≤ 4.41) and low ApoB/ApoA1 group (≤ 0.82). In univariate and multivariable analyses, preoperative PAR and ApoB/ApoA1 were identified as independent prognostic factors for OS in children and adolescents with osteosarcoma. CONCLUSION: Preoperative PAR and ApoB/ApoA1 can be used as promising predictors in children and adolescents with osteosarcoma to help clinicians recognize patients with an increased risk of poor prognosis.

Hsa_circRNA_102682 is closely related to lipid metabolism in gestational diabetes mellitus.

OBJECTIVE: To explore the relationship between circular RNA (circRNA) in gestational diabetes mellitus (GDM) and the metabolic profile at the molecular level, and find a biological marker that can predict GDM early. METHODS: A retrospective case-control study was conducted using data and samples from women treated at a hospital in China between January 10 2018 and February 20 2019. Reverse transcription polymerase chain reaction (qRT-PCR) was used to evaluate the expression level of hsa_circRNA_102682 in serum and analyze its correlation with lipid metabolism parameters. RESULTS: Advanced age and higher pre-pregnancy body mass index (BMI) during pregnancy are risk factors for GDM. The expression level of hsa_circ_102682 was lower among the cases than the controls (p=.000). The levels of triglyceride, apolipoprotein A1 (APOA1), APOB, and high-density lipoprotein cholesterol (HDL-C) were different between the controls and cases (p<.05). Hsa_circRNA_102682 was significantly correlated with triglycerides, APOA1, APOB, 1-h blood glucose in the serum of GDM patients, and the correlation coefficients were 0.319, 0.314, 0.286, and 0.311, respectively (p<.05). The area under the receiver operating characteristic curve is 0.684 (95% confidence interval 0.611-0.756, p=.0001). CONCLUSIONS: Hsa_circRNA_102682 may regulate lipid metabolism, participate in the pathogenesis of GDM. It can be used as a marker to predict GDM.

Serum apolipoprotein A1 rather than apolipoprotein B is associated with hypertension prevalence in Chinese people with coronary artery disease.

OBJECTIVE: Studies on the association of apolipoprotein A1 (ApoA1) and apolipoprotein B (ApoB) with hypertension (HTN) prevalence in patients with coronary artery disease (CAD) are limited. This cross-sectional study aimed to investigate this association in Chinese people in Wuhan, China. METHODS: Serum ApoA1 and ApoB levels were measured by immunoturbidimetry assay. Logistic regression analysis was used to estimate the associations of ApoA1 and ApoB level and ApoB/A1 ratio with HTN prevalence. RESULTS: We included 5192 individuals (3060 men, mean age 61 years; 4412 HTN cases) in this study. After adjusting for covariates, serum ApoA1 but not ApoB level or ApoB/A1 ratio was inversely associated with HTN prevalence. HTN prevalence was reduced with the fifth versus first quintile of ApoA1 level [odds ratio = 0.78 (95% confidence interval 0.62-0.98)]. In stratified analyses based on sex, the probability of HTN with the fifth versus first ApoA1 level was 0.71 (0.53-0.96) for men. The probability of HTN with the fifth versus first quintile of ApoB/A1 ratio was 1.54 (1.11-2.13) after adjustment. With quintiles 2-5 versus of ApoB level, the probability of HTN did not differ in both men and women. On path analyses, the association of ApoA1 level and ApoB/A1 ratio with HTN was mediated by BMI (ß coefficients: -0.179 to 0.133). CONCLUSION: In general, high serum ApoA1 level may be associated with a reduced probability of HTN prevalence in patients with CAD in China, and this association may be mediated by BMI.

Higher blood high density lipoprotein and apolipoprotein A1 levels are associated with reduced risk of developing amyotrophic lateral sclerosis.

BACKGROUND: Premorbid body mass index, physical activity, diabetes and cardiovascular disease have been associated with an altered risk of developing amyotrophic lateral sclerosis (ALS). There is evidence of shared genetic risk between ALS and lipid metabolism. A very large prospective longitudinal population cohort permits the study of a range of metabolic parameters and the risk of subsequent diagnosis of ALS. METHODS: The risk of subsequent ALS diagnosis in those enrolled prospectively to the UK Biobank (n=502 409) was examined in relation to baseline levels of blood high and low density lipoprotein (HDL, LDL), total cholesterol, total cholesterol:HDL ratio, apolipoproteins A1 and B (apoA1, apoB), triglycerides, glycated haemoglobin A1c (HbA1c) and creatinine, plus self-reported exercise and body mass index. RESULTS: Controlling for age and sex, higher HDL (HR 0.84, 95% CI 0.73 to 0.96, p=0.010) and apoA1 (HR 0.83, 95% CI 0.72 to 0.94, p=0.005) were associated with a reduced risk of ALS. Higher total cholesterol:HDL was associated with an increased risk of ALS (HR 1.17, 95% CI 1.05 to 1.31, p=0.006). In models incorporating multiple metabolic markers, higher LDL or apoB was associated with an increased risk of ALS, in addition to a lower risk with higher HDL or apoA. Coronary artery disease, cerebrovascular disease and increasing age were also associated with an increased risk of ALS. CONCLUSIONS: The association of HDL, apoA1 and LDL levels with risk of ALS contributes to an increasing body of evidence that the premorbid metabolic landscape may play a role in pathogenesis. Understanding the molecular basis for these changes will inform presymptomatic biomarker development and therapeutic targeting.

The association of apolipoproteins with later-life all-cause and cardiovascular mortality: a population-based study stratified by age.

Midlife lipid levels are important predictors of cardiovascular diseases, yet their association with mortality in older adults is less clear. We aimed to (1) identify lipid profiles based on cholesterol, triglycerides, and apolipoproteins using cluster analysis, and (2) investigate how lipid profiles and lipid levels at different ages are associated with later-life all-cause and cardiovascular mortality. We used data from 98,270 individuals in the Swedish AMORIS cohort who had blood measurements between 1985-1996 and were followed until 2012. Over the follow-up (mean 18.0 years), 30,730 (31.3%) individuals died. Three lipid profiles were identified. Compared with reference profile, a high lipid profile (low ApoA-I and high total cholesterol (TC), triglycerides, ApoB, and ApoB/ApoA-I ratio) at ages 39-59 or 60-79 was associated with higher all-cause mortality. A high lipid profile at ≥ 80 years, however, did not confer higher mortality. For the specific markers, high TC (≥ 7.25 mmol/L) was associated with higher all-cause mortality in ages 39-59 but lower mortality in ages 60-79 and ≥ 80. Low ApoA-I (< 1.28 g/L) and high ApoB/ApoA-I ratio (≥ 1.18), on the other hand, were associated with higher cardiovascular mortality regardless of age at lipid measurement, highlighting their potential relevance for survival in both young and older individuals.

Apolipoprotein B/A1 Ratio Is Associated with Severity of Coronary Artery Stenosis in CAD Patients but Not in Non-CAD Patients Undergoing Percutaneous Coronary Intervention.

BACKGROUND AND AIMS: Lipid metabolism plays important roles in atherosclerosis. Several studies have found that lipoprotein is associated with coronary artery disease (CAD) and hyperlipidemia. Although the roles of the apolipoprotein B/A1 ratio (ApoB/A1) were originally thought to be atherosclerotic, few studies have focused on the specific relationship between ApoB/A1 and severity of coronary artery stenosis with or without the presence of CAD. METHODS: A total of 6956 consecutive patients aged 21-98 years with suspected CAD who had undergone coronary angiography were enrolled. The severity of coronary lesions was evaluated using the Gensini score (GS). The relationships between ApoB/A1 and severity of coronary artery stenosis were evaluated. RESULTS: A total of 1795 non-CAD patients and 5161 CAD patients were included in the observational analysis. Patients with CAD had higher ApoB/A1 than individuals without CAD (0.67 (0.53-0.82) vs. 0.61 (0.49-0.75), p < 0.001). In CAD patients, the higher the ApoB/A1 was, the higher the proportion of patients with MI, triple-vessel lesions, and higher Gensini scores. ApoB/A1 was significantly positively correlated with HbA1c and Gensini scores in CAD patients but not in non-CAD patients (all p < 0.001). Logistic analyses showed that ApoB/A1 could be a risk factor for multivessel disease (OR: 2.768, 95% CI: 1.868-4.103, p < 0.001). ApoB/A1 was found to be significantly positively correlated with the Gensini score in CAD patients. CONCLUSIONS: ApoB/A1 is highly associated with the presence and severity of coronary artery stenosis in patients with CAD but not in non-CAD patients.

Long-term risk of a major cardiovascular event by apoB, apoA-1, and the apoB/apoA-1 ratio-Experience from the Swedish AMORIS cohort: A cohort study.

BACKGROUND: Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop. METHODS AND FINDINGS: In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study. CONCLUSIONS: An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines.

Serum apolipoprotein A-I potentiates the therapeutic efficacy of lysocin E against Staphylococcus aureus.

Lysocin E is a lipopeptide with antibiotic activity against methicillin-resistant Staphylococcus aureus. For unclear reasons, the antibacterial activity of lysocin E in a mouse systemic infection model is higher than expected from in vitro results, and the in vitro activity is enhanced by addition of bovine serum. Here, we confirm that serum from various species, including humans, increases lysocin E antimicrobial activity, and identify apolipoprotein A-I (ApoA-I) as an enhancing factor. ApoA-I increases the antibacterial activity of lysocin E when added in vitro, and the antibiotic displays reduced activity in ApoA-I gene knockout mice. Binding of ApoA-I to lysocin E is enhanced by lipid II, a cell-wall synthesis precursor found in the bacterial membrane. Thus, the antimicrobial activity of lysocin E is potentiated through interactions with host serum proteins and microbial components.

Effect of renal function on high-density lipoprotein particles in patients with coronary heart disease.

BACKGROUND: Although renal insufficiency and dyslipidemia are known to be closely associated, the effect of kidney function on the size and clinical value of high-density lipoprotein (HDL) particles remains largely unknown, especially in patients with coronary heart disease. METHODS: A total of 419 coronary heart disease patients and 105 non-coronary heart disease patients were included. HDL particle size, represented by HDL-C/apoA-I, was compared between groups stratified by estimated glomerular filtration rate (eGFR) and Gensini scores using standard Student's t test and one-way ANOVA. Pearson's correlation test was performed to analyze the association between eGFR and HDL-C/apoA-I in patients with coronary heart disease. The relationship between HDL particle size and the occurrence of coronary heart disease was explored using Univariate logistic regression analysis. RESULTS: In patients with coronary heart disease, between-group analysis revealed that HDL-C/apoA-I increased as eGFR declined, and significance appeared as eGFR declined to under 60 ml/min·1.73 m2 (P < 0.001), and Pearson's correlation test also confirmed an inverse correlation between eGFR and HDL-C/apoA-I levels in coronary heart disease patients. When stratified by Gensini scores, in coronary heart disease patients with eGFR ≥ 90 mL/(min·1.73 m2), those with higher Gensini scores had smaller HDL-C/apoA-I. However, with or without kidney insufficiency, smaller HDL-C/apoA-I was associated with a higher occurrence of coronary heart disease (P < 0.05). CONCLUSION: With the presence of renal insufficiency, HDL-C/apoA1 was higher in patients with coronary heart disease. Lower HDL-C/apoA1 was still associated with a higher occurrence of coronary heart disease, but the original association between lower HDL-C/apoA1 and more severe coronary artery stenosis was lost in patients with renal insufficiency.

Preprocedural Lp(a) level and ApoB/ApoA-Ι ratio and the risk for contrast-induced acute kidney injury in patients undergoing emergency PCI.

BACKGROUND: High serum Lipoprotein(a) (Lp(a)) level and Apolipoprotein B/Apolipoprotein AΙ (ApoB/ApoA-Ι) ratio are risk factors for cardiovascular disease and kidney disease and have been found to be correlated with the prevalence and prognosis of various kidney diseases. However, it is not clear whether the serum Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI are correlated with the prevalence of contrast-induced acute kidney injury (CI-AKI). METHODS: A total of 931 participants undergoing emergency PCI from July 2018 to July 2020 were included. According to whether the serum creatinine concentration was higher than the baseline concentration (by ≥25% or ≥ 0.5 mg/dL) 48-72 h after contrast exposure, these participants were divided into a CI-AKI group (n = 174) and a non-CI-AKI group (n = 757). Serum Lp(a), ApoA-Ι and ApoB concentration were detected in the patients when they were admitted to hospital, and the ApoB/ApoA-Ι ratio was calculated. Logistic regression and restricted cubic spline analyses were used to explore the correlation between the Lp(a) concentration or the ApoB/ApoA-Ι ratio and the risk of CI-AKI. RESULTS: Among the 931 participants undergoing emergency PCI, 174 (18.69%) participants developed CI-AKI. Compared with the non-CI-AKI group, the Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI in the CI-AKI group were significantly higher (P < 0.05). The incidence of CI-AKI was positively associated with the serum Lp(a) level and ApoB/ApoA-Ι ratio pre-PCI in each logistic regression model (P < 0.05). After adjusting for all the risk factors included in this study, restricted cubic spline analyses found that the Lp(a) level and the ApoB/ApoA-Ι ratio before PCI, within certain ranges, were positively associated with the prevalence of CI-AKI. CONCLUSION: High Lp(a) levels and high ApoB/ApoA-Ι ratios before PCI are potential risk factors for CI-AKI.

The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk.

OBJECTIVE: In the present work, research was carried out to explore the correlation between the high-density lipoprotein cholesterol (HDL-C)/apolipoprotein A-I (apoA-I) ratio and serum free triiodothyronine (FT3) and their interaction on the risk of coronary artery disease (CAD). METHODS: A total of 1686 patients who underwent selective coronary angiography were enrolled in the present study, including 1279 patients with CAD and 407 controls. The subjects were divided into three groups according to tertiles of the HDL-C/apoA-I ratio. Binary logistic regression analysis was used to evaluate the interaction of the HDL-C/apoA-I ratio and FT3 level with the risk of CAD. RESULTS: The group with the highest HDL-C/apoA-I ratio had the lowest levels of FT3. Multiple linear regression analysis showed that the HDL-C/apoA-I ratio was negatively associated with FT3 after adjusting for age, sex, body mass index (BMI), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), FT4 and TSH. A logistic regression model showed that a high HDL-C/apoA-I ratio (> 0.89 mmol/g) and high FT3 levels (> 4.5 pmol/l) were protective factors for CAD. Patients with a lower HDL-C/apoA-I ratio (≤ 0.89 mmol/g) and lower FT3 level (≤ 4.5 pmol/l) had an increased risk of CAD (OR = 2.441, P = 0.000, S = 1.13, AP = 0.068, AP* = 0.116, RERI = 0.168). CONCLUSIONS: The HDL-C/apoA-I ratio was negatively associated with FT3, and there was a significant interaction between the HDL-C/apoA-I ratio and FT3 with the risk of CAD.

Serum apolipoprotein A-I depletion is causative to silica nanoparticles-induced cardiovascular damage.

The rapid development of nanotechnology has greatly benefited modern science and engineering and also led to an increased environmental exposure to nanoparticles (NPs). While recent research has established a correlation between the exposure of NPs and cardiovascular diseases, the intrinsic mechanisms of such a connection remain unclear. Inhaled NPs can penetrate the air-blood barrier from the lung to systemic circulation, thereby intruding the cardiovascular system and generating cardiotoxic effects. In this study, on-site cardiovascular damage was observed in mice upon respiratory exposure of silica nanoparticles (SiNPs), and the corresponding mechanism was investigated by focusing on the interaction of SiNPs and their encountered biomacromolecules en route. SiNPs were found to collect a significant amount of apolipoprotein A-I (Apo A-I) from the blood, in particular when the SiNPs were preadsorbed with pulmonary surfactants. While the adsorbed Apo A-I ameliorated the cytotoxic and proinflammatory effects of SiNPs, the protein was eliminated from the blood upon clearance of the NPs. However, supplementation of Apo A-I mimic peptide mitigated the atherosclerotic lesion induced by SiNPs. In addition, we found a further declined plasma Apo A-I level in clinical silicosis patients than coronary heart disease patients, suggesting clearance of SiNPs sequestered Apo A-I to compromise the coronal protein's regular biological functions. Together, this study has provided evidence that the protein corona of SiNPs acquired in the blood depletes Apo A-I, a biomarker for prediction of cardiovascular diseases, which gives rise to unexpected toxic effects of the nanoparticles.