ApoA1/HDL-C ratio as a predictor for coronary artery disease in patients with type 2 diabetes: a matched case-control study.

INTRODUCTION: This study investigated the possible relationship between the Apo lipoprotein A1 /high-density lipoprotein cholesterol (ApoA1/HDL-C) ratio and coronary artery disease (CAD) in patients with type 2 diabetes (T2D). METHODS: This was a matched case-control study of 482 patients with T2D in two groups of CAD and (n = 241) non-CAD (n = 241). The patients were classified into four quartiles according to the ApoA1/HDL-C ratio, and multivariate logistic regression analysis was performed to assess the relationship between ApoA1/HDL-C and CAD. ROC analysis was also conducted. RESULTS: This study showed that the ApoA1/HDL-C ratio has an independent association with CAD in individuals with T2D. The CAD group exhibited a significantly higher ApoA1/HDL-C ratio than those without CAD (p-value = 0.004). Moreover, the risk of CAD increased significantly across the ApoA1/HDL-C ratio quartiles, with the highest odds in the fourth quartile. The second quartile showed an odds ratio (OR) of 2.03 (p-value = 0.048) compared to the first. Moving to the third quartile, the OR increased to 2.23 (p-value = 0.023). The highest OR was noted in the fourth, reaching 3.41 (p-value = 0.001). Employing a cut-off value of 2.66 and an area under the curve (AUC) of 0.885, the ApoA1/HDL-C ratio predicts CAD among patients with T2D with a sensitivity of 75% and a specificity of 91% (p-value < 0.001). CONCLUSION: The current study revealed an independent association between ApoA1/HDL-C ratio and CAD in patients with T2D. This ratio can be a promising tool for predicting CAD during the follow-up of patients with T2D, aiding in identifying those at higher risk for CAD.

Imbalance of APOB Lipoproteins and Large HDL in Type 1 Diabetes Drives Atherosclerosis.

BACKGROUND: Individuals with type 1 diabetes (T1D) generally have normal or even higher HDL (high-density lipoprotein)-cholesterol levels than people without diabetes yet are at increased risk for atherosclerotic cardiovascular disease (CVD). Human HDL is a complex mixture of particles that can vary in cholesterol content by >2-fold. To investigate if specific HDL subspecies contribute to the increased atherosclerosis associated with T1D, we created mouse models of T1D that exhibit human-like HDL subspecies. We also measured HDL subspecies and their association with incident CVD in a cohort of people with T1D. METHODS: We generated LDL receptor-deficient (Ldlr-/-) mouse models of T1D expressing human APOA1 (apolipoprotein A1). Ldlr-/-APOA1Tg mice exhibited the main human HDL subspecies. We also generated Ldlr-/-APOA1Tg T1D mice expressing CETP (cholesteryl ester transfer protein), which had lower concentrations of large HDL subspecies versus mice not expressing CETP. HDL particle concentrations and sizes and proteins involved in lipoprotein metabolism were measured by calibrated differential ion mobility analysis and targeted mass spectrometry in the mouse models of T1D and in a cohort of individuals with T1D. Endothelial transcytosis was analyzed by total internal reflection fluorescence microscopy. RESULTS: Diabetic Ldlr-/-APOA1Tg mice were severely hyperglycemic and hyperlipidemic and had markedly elevated plasma APOB levels versus nondiabetic littermates but were protected from the proatherogenic effects of diabetes. Diabetic Ldlr-/-APOA1Tg mice expressing CETP lost the atheroprotective effect and had increased lesion necrotic core areas and APOB accumulation, despite having lower plasma APOB levels. The detrimental effects of low concentrations of larger HDL particles in diabetic mice expressing CETP were not explained by reduced cholesterol efflux. Instead, large HDL was more effective than small HDL in preventing endothelial transcytosis of LDL mediated by scavenger receptor class B type 1. Finally, in humans with T1D, increased concentrations of larger HDL particles relative to APOB100 negatively predicted incident CVD independently of HDL-cholesterol levels. CONCLUSIONS: Our results suggest that the balance between APOB lipoproteins and the larger HDL subspecies contributes to atherosclerosis progression and incident CVD in the setting of T1D and that larger HDLs exert atheroprotective effects on endothelial cells rather than by promoting macrophage cholesterol efflux.

Homocysteine concentration in coronary artery disease and severity of coronary lesions.

Our previous study reckons that the impact of the rs1801133 variant of 5,10-methylenetetrahydrofolate reductase (MTHFR) on coronary artery disease (CAD) is possibly mediated by cardiometabolic disorder. This study is performed to verify this hypothesis. Four hundred and thirty CAD patients and 216 CAD-free individuals were enrolled in this case-control study. The rs1801133 variant was genotyped by PCR-RFLP. Severity of coronary lesions was evaluated by number of stenotic coronary vessels and extent of coronary stenosis. The rs1801133 T allele significantly increased homocysteine levels in patients with CAD and CAD-free individuals. Individuals with the T allele of rs1801133 had an increased risk of developing CAD. In contrast, individuals with the TT genotype of rs1801133 were at high risk of multiple vessel lesions. The carriers of CT genotype had higher levels of systolic blood pressure (SBP), low-density lipoprotein cholesterol (LDL-C), and high-sensitivity C-reactive protein (hs-CRP), and lower levels of apolipoprotein A1 (APOA1) than those with CC genotype in male patients with CAD. The receiver operating characteristic (ROC) curve and precision-recall (PR) curve indicated that hyperhomocysteinemia was sensitive to predict the severity of CAD. Multivariate logistic regression revealed that homocysteine, rs1801133, age, smoking, weight, body mass index (BMI), lipoprotein(a) [Lp(a)], and hs-CRP were independent risk factors for CAD. The increased risk of CAD and severity of coronary lesions associated with rs1801133 in the Chinese Han population were attributed, at least partly, to high homocysteine levels. Hyperhomocysteinemia had a high predictive value for severe CAD or multiple vessel lesions.

The association between telomere length and blood lipids: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies suggest an association between telomere length (TL) and blood lipid (BL) levels. Nevertheless, the causal connections between these two traits remain unclear. We aimed to elucidate whether genetically predicted TL is associated with BL levels via Mendelian randomization (MR) and vice versa. Methods: We obtained genetic instruments associated with TL, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A-1 (ApoA-1) and apolipoprotein B (ApoB) from large-scale genome-wide association studies (GWASs). The causal relationships between TL and BL were investigated via bidirectional MR, multivariable MR and mediation analysis methods. The inverse variance weighted (IVW) method was employed as the principal methodology, complemented by several other estimators to enhance the robustness of the analysis. Results: In the forward MR analyses, we identified significant positive correlation between genetically predicted TL and the levels of TG (ß=0.04, 95% confidence interval [CI]: 0.01 to 0.06, p = 0.003). In the reverse MR analysis, TG (ß=0.02, 95% CI: 0.01 to 0.03, p = 0.004), LDL-C (ß=0.03, 95% CI: 0.01 to 0.04, p = 0.001) and ApoB (ß=0.03, 95% CI: 0.01 to 0.04, p = 9.71×10-5) were significantly positively associated with TL, although this relationship was not observed in the multivariate MR analysis. The mediation analysis via two-step MR showed no significant mediation effects acting through obesity-related phenotypes in analysis of TL with TG, while the effect of LDL-C on TL was partially mediated by body mass index (BMI) in the reverse direction, with mediated proportion of 12.83% (95% CI: 0.62% to 25.04%). Conclusions: Our study indicated that longer TL were associated with higher TG levels, while conversely, higher TG, LDL-C, and ApoB levels predicted longer TL, with BMI partially mediating these effects. Our findings present valuable insights into the development of preventive strategies and interventions that specifically target TL-related aging and age-related diseases.

Apolipoprotein A-I levels in the survival of patients with colorectal cancer: a retrospective study.

Background: Abnormal lipid levels have been associated with cancer incidence and progression. However, limited studies have investigated the relationship between apolipoprotein A-I (ApoA-I) and colorectal cancer (CRC). This study assessed the significance of ApoA-I levels in progression-free survival (PFS) and overall survival (OS) of patients with CRC. Methods: Survival curves were compared using Kaplan-Meier analysis, while the predictive values of various lipid indicators in CRC prognosis were evaluated based on receiver operating characteristic curves. The factors influencing PFS and OS in patients with CRC were analyzed using Cox proportional hazards regression models. Finally, the relationship between ApoA-I level and disease recurrence was investigated through logistic regression analysis. The optimal Apo-I level was determined through maximally selected rank statistics. Results: Using the optimal ApoA-I cutoff value (0.9 g/L), the 1,270 patients with CRC were categorized into low (< 0.9 g/L, 275 cases) and high (≥0.9 g/L, 995 cases) ApoA-I groups. Compared with other lipid indicators, ApoA-I demonstrated superior predictive accuracy. The high ApoA-I group exhibited significantly higher survival rates than the low ApoA-I group (PFS, 64.8% vs. 45.2%, P < 0.001; OS, 66.1% vs. 48.6%, P < 0.001). Each one-standard-deviation increase in ApoA-I level was related to a 12.0% decrease in PFS risk (hazard ratio [HR] 0.880; 95% confidence interval [CI], 0.801-0.968; P = 0.009) and an 11.2% decrease in OS risk (HR 0.888; 95%CI, 0.806-0.978; P = 0.015). Logistic regression analysis revealed that patients with low ApoA-I had a 32.5% increased risk of disease recurrence (odds ratio [OR] 0.675; 95%CI, 0.481-0.946; P = 0.0225) compared with those with high ApoA-I. PFS/OS nomograms based on ApoA-I demonstrated excellent prognostic prediction accuracy. Conclusions: Serum ApoA-I level may be a valuable and non-invasive tool for predicting PFS and OS in patients with CRC.

Establishment and validation of nomogram model for predicting major adverse cardiac events in patients with acute ST-segment elevation myocardial infarction based on glycosylated hemoglobin A1c to apolipoprotein A1 ratio: An observational study.

The objective of the current study is to assess the usefulness of HbA1cAp ratio in predicting in-hospital major adverse cardiac events (MACEs) among acute ST-segment elevation myocardial infarction (STEMI) patients that have undergone percutaneous coronary intervention (PCI). Further, the study aims to construct a ratio nomogram for prediction with this ratio. The training cohort comprised of 511 STEMI patients who underwent emergency PCI at the Huaibei Miners' General Hospital between January 2019 and May 2023. Simultaneously, 384 patients treated with the same strategy in First People's Hospital of Hefei formed the validation cohort during the study period. LASSO regression was used to screen predictors of nonzero coefficients, multivariate logistic regression was used to analyze the independent factors of in-hospital MACE in STEMI patients after PCI, and nomogram models and validation were established. The LASSO regression analysis demonstrated that systolic blood pressure, diastolic blood pressure, D-dimer, urea, and glycosylated hemoglobin A1c (HbA1c)/apolipoprotein A1 (ApoA1) were significant predictors with nonzero coefficients. Multivariate logistic regression analysis was further conducted to identify systolic blood pressure, D-dimer, urea, and HbA1c/ApoA1 as independent factors associated with in-hospital MACE after PCI in STEMI patients. Based on these findings, a nomogram model was developed and validated, with the C-index in the training set at 0.77 (95% CI: 0.723-0.817), and the C-index in the validation set at 0.788 (95% CI: 0.734-0.841), indicating excellent discrimination accuracy. The calibration curves and clinical decision curves also demonstrated the good performance of the nomogram models. In patients with STEMI who underwent PCI, it was noted that a higher HbA1c of the ApoA1 ratio is significantly associated with in-hospital MACE. In addition, a nomogram is constructed having considered the above-mentioned risk factors to provide predictive information on in-hospital MACE occurrence in these patients. In particular, this tool is of great value to the clinical practitioners in determination of patients with a high risk.

The indicative effects of apolipoproteins on organic erectile dysfunction: bridging Mendelian randomization and case-control study.

The existing research on the association between apolipoproteins (Apos) and erectile dysfunction (ED) primarily relies on observational studies and does not distinguish between organic and psychogenic causes when diagnosing ED. It is difficult to believe that Apos play a role in psychogenic ED. To address these issues, our study explored the causal relationship between lipoproteins and ED using Mendelian randomization (MR) analysis and differentiate between organic and psychogenic ED through the use of nocturnal penile tumescence and rigidity (NPTR) monitoring. Multivariate MR analysis revealed significant causal associations between high-density lipoprotein (HDL), Apo A1, and Apo B/A1 with ED (OR and 95% CI were 0.33 (0.14-0.78), 3.58 (1.52-8.43), and 0.30 (0.13-0.66)). we conducted statistical and analytical analyses on the data of 212 patients using multivariate analyses and receiver operating characteristic (ROC) curves. Patients with organic ED had significantly lower levels of HDL, Apo A1 and Apo A1/B, whereas patients with organic ED had considerably higher levels of Apo B and low-density lipoprotein (LDL). The diagnostic value of Apos in predicting the risk of organic ED was evaluated using ROC curves. The results indicated that Apo A1 and Apo A1/B demonstrated good predictive value. HDL, Apo A1, and Apo A1/B have been identified as risk factors for ED in our study. Furthermore, our research highlights the significance of Apo A1 and Apo A1/Apo B in the development of organic ED and suggests their potential use as indicators to assess the risks associated with organic ED.

A combined observational and Mendelian randomization investigation reveals NMR-measured analytes to be risk factors of major cardiovascular diseases.

Dyslipidaemias is the leading risk factor of several major cardiovascular diseases (CVDs), but there is still a lack of sufficient evidence supporting a causal role of lipoprotein subspecies in CVDs. In this study, we comprehensively investigated several lipoproteins and their subspecies, as well as other metabolites, in relation to coronary heart disease (CHD), heart failure (HF) and ischemic stroke (IS) longitudinally and by Mendelian randomization (MR) leveraging NMR-measured metabolomic data from 118,012 UK Biobank participants. We found that 123, 110 and 36 analytes were longitudinally associated with myocardial infarction, HF and IS (FDR < 0.05), respectively, and 25 of those were associated with all three outcomes. MR analysis suggested that genetically predicted levels of 70, 58 and 7 analytes were associated with CHD, HF and IS (FDR < 0.05), respectively. Two analytes, ApoB/ApoA1 and M-HDL-C were associated with all three CVD outcomes in the MR analyses, and the results for M-HDL-C were concordant in both observational and MR analyses. Our results implied that the apoB/apoA1 ratio and cholesterol in medium size HDL were particularly of importance to understand the shared pathophysiology of CHD, HF and IS and thus should be further investigated for the prevention of all three CVDs.

Abnormal maternal apolipoprotein levels during pregnancy are risk factors for preterm birth in women with dichorionic twin pregnancies: A retrospective study.

OBJECTIVE: In singleton-pregnant women, abnormal maternal apolipoprotein levels have been confirmed as a risk factor for preterm birth. However, there are currently no studies on the relationship of the related research in twin-pregnant women. METHODS: This single-center retrospective study included 743 dichorionic twin-pregnant women who delivered between January 2019 and December 2020. Twins delivered before 37 weeks gestation were categorized as the preterm group, while those delivered at or after 37 weeks gestation were classified as the term group. Maternal serum apolipoprotein A1 (ApoA1) levels, apolipoprotein B (ApoB) levels, and the ApoB/ApoA1 ratio were measured in the first trimester(6-14 weeks), the second trimester(18-28 weeks) and the third trimester(after 28 weeks). We conducted SPSS analysis to evaluate the correlation between ApoA1 levels, ApoB levels, the ApoB/ApoA1 ratio and preterm birth. RESULTS: Among the 743 included dichorionic twin-pregnant women, 53.57 % (398/743) delivered preterm. Compared with the term group, the ApoA1 levels in the third trimester were lower (p < 0.001), while the Apo B/ApoA1 ratio was higher in the second (p = 0.01) and third trimesters in the preterm group (p = 0.001). When preterm birth was categorized as iatrogenic and spontaneous preterm birth, the results were similar. In the analysis stratified by prepregnancy BMI, a higher risk of preterm birth was associated with low ApoA1 levels and a high Apo B/ApoA1 ratio in the second and third trimesters only among the subgroup of overweight/obese dichorionic twin-pregnant women. CONCLUSIONS: Low ApoA1 levels and a high Apo B/ApoA1 ratio during the second and third trimesters were associated with a high incidence of preterm birth for overweight/obese dichorionic twin-pregnant women.

Serum ApoB/ApoA1 ratio in patients with CHB and the occurrence of HBV related cirrhosis and HBV related hepatocellular carcinoma.

Clinical research has suggested that chronic HBV infection exerts a certain effect on the occurrence of cardiovascular disease by regulating cholesterol metabolism in liver cells. High serum apolipoprotein B/apolipoprotein A1 (ApoB/ApoA1) ratio plays a certain role in the above regulation, and it serves as a risk factor for cardiovascular disease. However, whether the ApoB/ApoA1 ratio is correlated with chronic HBV infection and its disease progression remains unclear. In accordance with the inclusion and exclusion criteria, all 378 participants administrated at Renmin Hospital of Wuhan University from March 2021 to March 2022, fell into Healthy Control (HC) group (50 participants), Hepatocellular carcinoma (HCC) group (107 patients), liver cirrhosis (LC) group (64 patients), chronic hepatitis B (CHB) group (62 patients), chronic hepatitis C (CHC) group (46 patients) and Hepatitis E Virus (HEV) group (49 patients). Serum ApoA1 and ApoB concentrations were measured at admission, and the ApoB/ApoA1 ratio was determined. The levels of laboratory parameters in the respective group were compared and ApoB/ApoA1 ratios in HCC patients and LC patients with different severity were further analyzed. ROC curves were plotted to analyze the early diagnostic ability of ApoB/ApoA1 ratio for HBV-associated HCC. Logistic regression and restricted cubic spline analysis were used to explore the correlation between ApoB/ApoA1 ratio and LC and HCC risk. A comparison was drawn in terms of ApoB/ApoA1 ratio between the groups, and the result was expressed in descending sequence: HEV group > CHB group > LC group > HCC group > CHC group > HC group, early-stage HCC < middle-stage HCC < advanced-stage HCC, Class A LC < Class B LC < Class C LC. Serum ApoB/ApoA1 ratio combined diagnosis with AFP exhibited the capability of increasing the detection efficacy and specificity of AFP for HCC and AFP-negative HCC. The incidence of LC and HCC in the respective logistic regression model showed a negative correlation with the serum ApoB/ApoA1 ratio in CHB patients (P < 0.05). After all confounding factors covered in this study were regulated, the result of the restricted cubic spline analysis suggested that in a certain range, serum ApoB/ApoA1 ratio showed an inverse correlation with the prevalence of LC or HCC in CHB patients. Serum ApoB/ApoA1 ratio in CHB patients may be conducive to identifying high-risk patients for HCC or LC, such that LC and HCC can be early diagnosed and treated.

Lipids, apolipoproteins and gestational diabetes mellitus: a Mendelian randomization study.

BACKGROUND: This study investigates the causal relationship between lipid traits and GDM in an effort to better understand the aetiology of GDM. METHODS: Employing a two-sample Mendelian Randomization (MR) framework, we used Single Nucleotide Polymorphisms (SNPs) as instrumental variables to examine the impact of lipids and apolipoproteins on GDM. The research comprised univariable and multivariable MR analyses, with a prime focus on individual and combined effects of lipid-related traits. Statistical techniques included the fixed-effect inverse variance weighted (IVW) method and supplementary methods such as MR-Egger for comprehensive assessment. RESULTS: Our findings revealed the following significant associations: apoA-I and HDL cholesterol were inversely correlated with GDM risk, while triglycerides showed a positive correlation. In multivariable analysis, apoA-I consistently exhibited a strong causal link with GDM, even after adjusting for other lipids and Body Mass Index (BMI). CONCLUSION: The study demonstrates a significant causal relationship between apoA-I and GDM risk.

Effects of Recombinant Human Lecithin Cholesterol Acyltransferase on Lipoprotein Metabolism in Humans.

BACKGROUND: LCAT (lecithin cholesterol acyl transferase) catalyzes the conversion of unesterified, or free cholesterol, to cholesteryl ester, which moves from the surface of HDL (high-density lipoprotein) into the neutral lipid core. As this iterative process continues, nascent lipid-poor HDL is converted to a series of larger, spherical cholesteryl ester-enriched HDL particles that can be cleared by the liver in a process that has been termed reverse cholesterol transport. METHODS: We conducted a randomized, placebocontrolled, crossover study in 5 volunteers with atherosclerotic cardiovascular disease, to examine the effects of an acute increase of recombinant human (rh) LCAT via intravenous administration (300-mg loading dose followed by 150 mg at 48 hours) on the in vivo metabolism of HDL APO (apolipoprotein)A1 and APOA2, and the APOB100-lipoproteins, very low density, intermediate density, and low-density lipoproteins. RESULTS: As expected, recombinant human LCAT treatment significantly increased HDL-cholesterol (34.9 mg/dL; P≤0.001), and this was mostly due to the increase in cholesteryl ester content (33.0 mg/dL; P=0.014). This change did not affect the fractional clearance or production rates of HDL-APOA1 and HDL-APOA2. There were also no significant changes in the metabolism of APOB100-lipoproteins. CONCLUSIONS: Our results suggest that an acute increase in LCAT activity drives greater flux of cholesteryl ester through the reverse cholesterol transport pathway without significantly altering the clearance and production of the main HDL proteins and without affecting the metabolism of APOB100-lipoproteins. Long-term elevations of LCAT might, therefore, have beneficial effects on total body cholesterol balance and atherogenesis.

No effect of liraglutide on high density lipoprotein apolipoprotein AI kinetics in patients with type 2 diabetes.

AIM: The catabolism of high density lipoprotein (HDL) apolipoprotein AI (apoAI) is accelerated in patients with type 2 diabetes (T2D), related to hypertriglyceridemia, insulin resistance and low plasma adiponectin levels. Since liraglutide is likely to partly correct these abnormalities, we hypothesized that it might have a beneficial effect on HDL apoAI kinetics in patients with T2D. METHODS: An in vivo kinetic study of HDL apoAI was performed in 10 patients with T2D before and after 6 months of treatment with 1.2 mg/day of liraglutide, using a bolus of l-[1-13C]leucine followed by a 16-hour constant infusion. RESULTS: Liraglutide reduced BMI (34.9 ± 4.7 vs 36.6 ± 4.9 kg/m2, P = 0.012), HbA1c (7.1 ± 1.1 vs 9.6 ± 2.6%, P = 0.003), HOMA-IR (5.5 ± 1.9 vs 11.6 ± 11.2, P = 0.003), fasting triglycerides (1.76 ± 0.37 vs 2.48 ± 0.69 mmol/l, P < 0.001) and triglycerides during kinetics (2.34 ± 0.81 vs 2.66 ± 0.65 mmol/l, P = 0.053). Plasma HDL cholesterol and adiponectin concentrations were unchanged (respectively 0.97 ± 0.26 vs 0.97 ± 0.19 mmol/l, P = 1; 3169 ± 1561 vs 2618 ± 1651 µg/l, P = 0.160), similar to triglyceride content in HDL (5.13 ± 1.73 vs 5.39 ± 1.07%, P = 0.386). Liraglutide modified neither HDL apoAI fractional catabolic rate (0.35 ± 0.11 vs 0.38 ± 0.11 pool/day, P = 0.375), nor its production rate (0.44 ± 0.13 vs 0.49 ± 0.15 g/l/day, P = 0.375), nor its plasma concentration (1.26 ± 0.19 vs 1.29 ± 0.14 g/l, P = 0.386). CONCLUSION: Six months of treatment with 1.2 mg/day of liraglutide had no effect on the kinetics of HDL apoAI in patients with T2D. The lack of decrease in triglyceride content in HDL related to an only moderate decrease in triglyceridemia, probably greatly explains these results. Insufficient improvement of insulin sensitivity and adiponectinemia may also be implied.

Association of cardiac biomarkers with long-term cardiovascular events in a community cohort.

MATERIALS AND METHODS: The study assessed major adverse cardiac events (MACE) (myocardial infarction, coronary artery bypass graft, percutaneous intervention, stroke, and death. Cox proportional hazards models assessed apolipoprotein AI (ApoA1), apolipoprotein B (ApoB), ceramide score, cystatin C, galectin-3 (Gal3), LDL-C, Non-HDL-C, total cholesterol (TC), N-terminal B-type natriuretic peptide (NT proBNP), high-sensitivity cardiac troponin (HscTnI) and soluble interleukin 1 receptor-like 1. In adjusted models, Ceramide score was defined by from N-palmitoyl-sphingosine [Cer(16:0)], N-stearoyl-sphingosine [Cer(18:0)], N-nervonoyl-sphingosine [Cer(24:1)] and N-lignoceroyl-sphingosine [Cer(24:0)]. Multi-biomarker models were compared with C-statistics and Integrated Discrimination Index (IDI). RESULTS: A total of 1131 patients were included. Adjusted NT proBNP per 1 SD resulted in a 31% increased risk of MACE/death (HR = 1.31) and a 31% increased risk for stroke/MI (HR = 1.31). Adjusted Ceramide per 1 SD showed a 13% increased risk of MACE/death (HR = 1.13) and a 29% increased risk for stroke/MI (HR = 1.29). These markers added to clinical factors for both MACE/death (p = 0.003) and stroke/MI (p = 0.034). HscTnI was not a predictor of outcomes when added to the models. DISCUSSION: Ceramide score and NT proBNP improve the prediction of MACE and stroke/MI in a community primary prevention cohort.

In a community cohort, where a wide range of biomarkers were evaluated, Ceramide score provided additive value over traditional cardiac risk factors alone for predicting stroke/MI. NT ProBNP provided additive value in prediction of MACE/death. Other biomarkers failed to improve the discrimination of these models.

The neutrophil-to-apolipoprotein A1 ratio is associated with adverse outcomes in patients with acute decompensated heart failure at different glucose metabolic states: a retrospective cohort study.

BACKGROUND: The present study was performed to assess the association between the neutrophil-to-apolipoprotein A1 ratio (NAR) and outcomes in patients with acute decompensated heart failure (ADHF) at different glucose metabolism states. METHODS: We recruited 1233 patients with ADHF who were admitted to Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University from December 2014 to October 2019. The endpoints were defined as composites of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke and exacerbation of chronic heart failure. The restricted cubic spline was used to determine the best cutoff of NAR, and patients were divided into low and high NAR groups. Kaplan-Meier plots and multivariable Cox proportional hazard models were used to investigate the association between NAR and the risk of adverse outcomes. RESULTS: During the five-year follow-up period, the composite outcome occurred in 692 participants (56.1%). After adjusting for potential confounding factors, a higher NAR was associated with a higher incidence of composite outcomes in the total cohort (Model 1: HR = 1.42, 95% CI = 1.22-1.65, P<0.001; Model 2: HR = 1.29, 95% CI = 1.10-1.51, P = 0.002; Model 3: HR = 1.20, 95% CI = 1.01-1.42, P = 0.036). At different glucose metabolic states, a high NAR was associated with a high risk of composite outcomes in patients with diabetes mellitus (DM) (Model 1: HR = 1.54, 95% CI = 1.25-1.90, P<0.001; Model 2: HR = 1.40, 95% CI = 1.13-1.74, P = 0.002; Model 3: HR = 1.31, 95% CI = 1.04-1.66, P = 0.022), and the above association was not found in patients with prediabetes mellitus (Pre-DM) or normal glucose regulation (NGR) (both P>0.05). CONCLUSIONS: The NAR has predictive value for adverse outcomes of ADHF with DM, which implies that the NAR could be a potential indicator for the management of ADHF.

Apolipoprotein A1 Infusions and Cardiovascular Outcomes after Acute Myocardial Infarction.

BACKGROUND: Cardiovascular events frequently recur after acute myocardial infarction, and low cholesterol efflux - a process mediated by apolipoprotein A1, which is the main protein in high-density lipoprotein - has been associated with an increased risk of cardiovascular events. CSL112 is human apolipoprotein A1 derived from plasma that increases cholesterol efflux capacity. Whether infusions of CSL112 can reduce the risk of recurrent cardiovascular events after acute myocardial infarction is unclear. METHODS: We conducted an international, double-blind, placebo-controlled trial involving patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors. Patients were randomly assigned to receive either four weekly infusions of 6 g of CSL112 or matching placebo, with the first infusion administered within 5 days after the first medical contact for the acute myocardial infarction. The primary end point was a composite of myocardial infarction, stroke, or death from cardiovascular causes from randomization through 90 days of follow-up. RESULTS: A total of 18,219 patients were included in the trial (9112 in the CSL112 group and 9107 in the placebo group). There was no significant difference between the groups in the risk of a primary end-point event at 90 days of follow-up (439 patients [4.8%] in the CSL112 group vs. 472 patients [5.2%] in the placebo group; hazard ratio, 0.93; 95% confidence interval [CI], 0.81 to 1.05; P = 0.24), at 180 days of follow-up (622 patients [6.9%] vs. 683 patients [7.6%]; hazard ratio, 0.91; 95% CI, 0.81 to 1.01), or at 365 days of follow-up (885 patients [9.8%] vs. 944 patients [10.5%]; hazard ratio, 0.93; 95% CI, 0.85 to 1.02). The percentage of patients with adverse events was similar in the two groups; a higher number of hypersensitivity events was reported in the CSL112 group. CONCLUSIONS: Among patients with acute myocardial infarction, multivessel coronary artery disease, and additional cardiovascular risk factors, four weekly infusions of CSL112 did not result in a lower risk of myocardial infarction, stroke, or death from cardiovascular causes than placebo through 90 days. (Funded by CSL Behring; AEGIS-II ClinicalTrials.gov number, NCT03473223.).

Impaired Cholesterol Uptake Capacity in Patients with Hypertriglyceridemia and Diabetes Mellitus.

BACKGROUND: Although low high-density lipoprotein cholesterol (HDL-C) levels are a common metabolic abnormality associated with insulin resistance, their role in cardiovascular risk stratification remains controversial. Recently, we developed a simple, high-throughput, cell-free assay system to evaluate the "cholesterol uptake capacity (CUC)" as a novel concept for HDL functionality. In this study, we assessed the CUC in patients with hypertriglyceridemia and diabetes mellitus. METHODS: The CUC was measured using cryopreserved serum samples from 285 patients who underwent coronary angiography or percutaneous coronary intervention between December 2014 and May 2019 at Kobe University Hospital. RESULTS: The CUC was significantly lower in diabetic patients (n = 125) than in nondiabetic patients (93.0 vs 100.7 arbitrary units (A.U.), P = 0.002). Patients with serum triglyceride (TG) levels >150 mg/dL (n = 94) also had a significantly lower CUC (91.8 vs 100.0 A.U., P = 0.004). Furthermore, the CUC showed a significant inverse correlation with TG, hemoglobin A1c (Hb A1c), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Finally, the HDL-C/Apolipoprotein A1 (ApoA1) ratio, calculated as a surrogate index of HDL particle size, was significantly positively correlated with the CUC (r2 = 0.49, P < 0.001), but inversely correlated with TG levels (r2 = -0.30, P < 0.001). CONCLUSIONS: The CUC decreased in patients with hypertriglyceridemia and diabetes mellitus, and HDL particle size was a factor defining the CUC and inversely correlated with TG levels, suggesting that impaired CUC in insulin-resistant states was partially due to the shift in HDL towards smaller particles. These findings provide a better understanding of the mechanisms underlying impaired HDL functionality.

Causal association of blood lipids with all-cause and cause-specific mortality risk: a Mendelian randomization study.

Dyslipidemia has long been implicated in elevating mortality risk; yet, the precise associations between lipid traits and mortality remained undisclosed. Our study aimed to explore the causal effects of lipid traits on both all-cause and cause-specific mortality. One-sample Mendelian randomization (MR) with linear and nonlinear assumptions was conducted in a cohort of 407,951 European participants from the UK Biobank. Six lipid traits, consisting of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglycerides, apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and lipoprotein(a), were included to investigate the causal associations with mortality. Two-sample MR was performed to replicate the association between each lipid trait and all-cause mortality. Univariable MR results showed that genetically predicted higher ApoA1 was significantly associated with a decreased all-cause mortality risk (HR[95% CI]:0.93 [0.89-0.97], P value = 0.001), which was validated by the two-sample MR analysis. Higher lipoprotein(a) was associated with an increased risk of all-cause mortality (1.03 [1.01-1.04], P value = 0.002). Multivariable MR confirmed the direct causal effects of ApoA1 and lipoprotein(a) on all-cause mortality. Meanwhile, nonlinear MR found no evidence for nonlinearity between lipids and all-cause mortality. Our examination into cause-specific mortality revealed a suggestive inverse association between ApoA1 and cancer mortality, a significant positive association between lipoprotein(a) and cardiovascular disease mortality, and a suggestive positive association between lipoprotein(a) and digestive disease mortality. High LDL-C was associated with an increased risk of cardiovascular disease mortality but a decreased risk of neurodegenerative disease mortality. The findings suggest that implementing interventions to raise ApoA1 and decrease lipoprotein(a) levels may improve overall health outcomes and mitigate cancer and digestive disease mortality.

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.