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Low serum level of apolipoprotein A1 may predict the severity of COVID-19: A retrospective study.
Zhu, Z, Yang, Y, Fan, L, Ye, S, Lou, K, Hua, X, Huang, Z, Shi, Q, Gao, G
Journal of clinical laboratory analysis. 2021;(8):e23911
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Abstract
BACKGROUND Dyslipidemia has been observed in patients with coronavirus disease 2019 (COVID-19). This study aimed to investigate blood lipid profiles in patients with COVID-19 and to explore their predictive values for COVID-19 severity. METHODS A total of 142 consecutive patients with COVID-19 were included in this single-center retrospective study. Blood lipid profile characteristics were investigated in patients with COVID-19 in comparison with 77 age- and gender-matched healthy subjects, their predictive values for COVID-19 severity were analyzed by using multivariable logistic regression analysis, and their prediction efficiencies were evaluated by using receiver operator characteristic (ROC) curves. RESULTS There were 125 and 17 cases in the non-severe and severe groups, respectively. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and apolipoprotein A1 (ApoA1) gradually decreased across the groups in the following order: healthy controls, non-severe group, and severe group. ApoA1 was identified as an independent risk factor for COVID-19 severity (adjusted odds ratio [OR]: 0.865, 95% confidence interval [CI]: 0.800-0.935, p < 0.001), along with interleukin-6 (IL-6) (adjusted OR: 1.097, 95% CI: 1.034-1.165, p = 0.002). ApoA1 exhibited the highest area under the ROC curve (AUC) among all single markers (AUC: 0.896, 95% CI: 0.834-0.941); moreover, the risk model established using ApoA1 and IL-6 enhanced prediction efficiency (AUC: 0.977, 95% CI: 0.932-0.995). CONCLUSION Blood lipid profiles in patients with COVID-19 are quite abnormal compared with those in healthy subjects, especially in severe cases. Serum ApoA1 may represent a good indicator for predicting the severity of COVID-19.
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HDL-C/apoA-I Ratio Is Associated with the Severity of Coronary Artery Stenosis in Diabetic Patients with Acute Coronary Syndrome.
Sun, L, Guo, M, Xu, C, Qiao, X, Hua, Y, Tuerhongjiang, G, Lou, B, Li, R, Bai, X, Zhou, J, et al
Disease markers. 2021;:6689056
Abstract
BACKGROUND Emerging evidence demonstrates that the lipid metabolism in acute coronary syndrome (ACS) patients with type 2 diabetes mellitus (T2DM) differs from nondiabetic patients. However, the distinct lipid profiles and their relationships with the severity of coronary artery stenosis and prognosis in patients with T2DM remain elusive. METHOD AND RESULT This single-center, prospective cohort study enrolled 468 patients diagnosed with ACS undergoing coronary angiography, consisting of 314 non-DM and 154 DM patients. The HDL-C/apoA-I ratio was significantly higher in DM patients with a multivessel (≥3 affected vessels) lesion than a single-vessel (1-2 affected vessels) lesion. Regression analyses showed that the HDL-C/apoA-I ratio was positively correlated to the number of stenotic coronary arteries in DM patients but not non-DM patients. However, Kaplan-Meier survival analysis revealed no significant difference in the major adverse cardiovascular event rate regarding different HDL-C/apoA-I levels in DM or non-DM ACS patients at the end of the 2-year follow-up. CONCLUSION A higher HDL-C/apoA-I ratio is associated with increased severity of coronary artery stenosis in DM patients with ACS but not with the rate of major adverse cardiovascular events at the end of the 2-year follow-up.
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Serum apolipoprotein B/apolipoprotein A1 ratio in relation to intervertebral disk herniation: a cross-sectional frequency-matched case-control study.
Chen, F, Wu, T, Bai, C, Guo, S, Huang, W, Pan, Y, Zhang, H, Wu, D, Fu, Q, Chen, Q, et al
Lipids in health and disease. 2021;(1):79
Abstract
STUDY DESIGN This was a cross-sectional frequency-matched case-control study. BACKGROUND AND AIM The serum lipid profile of lipoprotein(a) [Lp(a)] level and apolipoprotein B/apolipoprotein A1 ratio (Apo B/Apo A1) ratio were found to be more representative for serum lipid level and were recognized as the independent risk factors for various diseases. Although the blood levels of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) were found to be associated with symptomatic intervertebral disk herniation (IDH), no studies to date have evaluated the association of Apo AI, Apo B, Lp(a), and Apo B/Apo AI levels with symptomatic IDH. This study aimed to assess the link between blood lipid levels and symptomatic IDH. METHOD The study included 1839 Chinese patients. Of these, 918 patients were diagnosed with IDH and enrolled in the experimental group. A control group of 921 patients underwent a physical examination during the same period. The serum lipid levels of TC, TG, LDL-C, HDL-C, Lp(a), Apo B, and Apo B/Apo AI were examined and analyzed. The control group comprised randomly selected patients who met the baseline levels of the aforementioned lipid molecules. RESULTS Patients with IDH exhibited significantly higher TC, TG, LDL, Apo B, and Lp(a) levels than controls. The percentage of high TC, high TG, high LDL, high Apo B, and high Lp(a) were obviously higher in the IDH group than in the control group. However, hyperlipidemia had no relationship with the degenerated segment of the IDH (P = 0.201). The odds ratio (OR) for the incidence of IDH with elevated levels of LDL-C, TC, TG, Lp(a), Apo B, and Apo B/Apo AI was 1.583, 1.74, 1.62, 1.58, 1.49, and 1.39, respectively. The correlation analysis revealed the correlation between elevated LDL-C, TC, TG, Apo B, Lp(a), and incidence of IDH was significant (R2LDL = 0.017; R2TC = 0.004; R2TG = 0.015; R2Apo B = 0.004; R2Lp(a) = 0.021) (P < 0.05). CONCLUSION This study suggested that elevated levels of serum TC, TG, LDL, Apo B, Lp(a), and Apo B/Apo AI were associated with a higher risk of IDH. This study provided useful information to identify a population that might be at risk of developing IDH based on elevated lipid levels.
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Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: an intravascular optical coherence tomography study.
Deng, F, Li, D, Lei, L, Yang, Q, Li, Q, Wang, H, Deng, J, Zheng, Q, Jiang, W
Cardiovascular diabetology. 2021;(1):188
Abstract
BACKGROUND Apolipoprotein (Apo) A1 and Apo B are strongly associated with the risk of atherosclerotic cardiovascular disease (ASCVD). However, the relationship between the Apo B/A1 ratio and the morphology of coronary vulnerable plaques has not been fully elucidated in patients with ASCVD. METHODS A total of 320 patients with ASCVD undergoing percutaneous coronary intervention were enrolled and assigned into acute coronary syndrome (ACS) or chronic coronary syndrome (CCS) group. The morphology of culprit plaque was analyzed by intravascular optical coherence tomography. Association between the Apo B/A1 ratio and coronary vulnerable plaques were evaluated using logistic regression models and receiver operator characteristic (ROC) curve analyses. RESULTS The Apo B/A1 ratio was higher in ACS patients than CCS patients (0.77 ± 0.28 vs. 0.64 ± 0.22, P < 0.001) and it was also higher in patients with plaque rupture, erosion or thrombus than those without culprit plaques. The high Apo B/A1 ratio was associated with high percent of vulnerable plaques compared with low ratio group. The Apo B/A1 ratio was negatively related to fibrous cap thickness in lipid-rich plaque (r = - 0.228, P = 0.043). Univariate and multivariate logistic regression analyses revealed that the Apo B/A1 ratio was an independent factor of plaque rupture, erosion, and thrombus. The area under the ROC curve of the Apo B/A1 ratio for plaque rupture, erosion, and thrombus were 0.632, 0.624, and 0.670 respectively (P < 0.001 for all), which were higher than that of low-density lipoprotein cholesterol. CONCLUSIONS The Apo B/A1 ratio is an independent predictor for plaque rupture, erosion, and thrombus in patients with ASCVD.
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Apolipoprotein Mimetic Peptides: Potential New Therapies for Cardiovascular Diseases.
Wolska, A, Reimund, M, Sviridov, DO, Amar, MJ, Remaley, AT
Cells. 2021;(3)
Abstract
Since the seminal breakthrough of treating diabetic patients with insulin in the 1920s, there has been great interest in developing other proteins and their peptide mimetics as therapies for a wide variety of other medical disorders. Currently, there are at least 60 different peptides that have been approved for human use and over 150 peptides that are in various stages of clinical development. Peptides mimetic of the major proteins on lipoproteins, namely apolipoproteins, have also been developed first as tools for understanding apolipoprotein structure and more recently as potential therapeutics. In this review, we discuss the biochemistry, peptide mimetics design and clinical trials for peptides based on apoA-I, apoE and apoC-II. We primarily focus on applications of peptide mimetics related to cardiovascular diseases. We conclude with a discussion on the limitations of peptides as therapeutic agents and the challenges that need to be overcome before apolipoprotein mimetic peptides can be developed into new drugs.
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Risk stratification of ST-segment elevation myocardial infarction (STEMI) patients using machine learning based on lipid profiles.
Xue, Y, Shen, J, Hong, W, Zhou, W, Xiang, Z, Zhu, Y, Huang, C, Luo, S
Lipids in health and disease. 2021;(1):48
Abstract
BACKGROUND Numerous studies have revealed the relationship between lipid expression and increased cardiovascular risk in ST-segment elevation myocardial infarction (STEMI) patients. Nevertheless, few investigations have focused on the risk stratification of STEMI patients using machine learning algorithms. METHODS A total of 1355 STEMI patients who underwent percutaneous coronary intervention were enrolled in this study during 2015-2018. Unsupervised machine learning (consensus clustering) was applied to the present cohort to classify patients into different lipid expression phenogroups, without the guidance of clinical outcomes. Kaplan-Meier curves were implemented to show prognosis during a 904-day median follow-up (interquartile range: 587-1316). In the adjusted Cox model, the association of cluster membership with all adverse events including all-cause mortality, all-cause rehospitalization, and cardiac rehospitalization was evaluated. RESULTS All patients were classified into three phenogroups, 1, 2, and 3. Patients in phenogroup 1 with the highest Lp(a) and the lowest HDL-C and apoA1 were recognized as the statin-modified cardiovascular risk group. Patients in phenogroup 2 had the highest HDL-C and apoA1 and the lowest TG, TC, LDL-C and apoB. Conversely, patients in phenogroup 3 had the highest TG, TC, LDL-C and apoB and the lowest Lp(a). Additionally, phenogroup 1 had the worst prognosis. Furthermore, a multivariate Cox analysis revealed that patients in phenogroup 1 were at significantly higher risk for all adverse outcomes. CONCLUSION Machine learning-based cluster analysis indicated that STEMI patients with increased concentrations of Lp(a) and decreased concentrations of HDL-C and apoA1 are likely to have adverse clinical outcomes due to statin-modified cardiovascular risks. TRIAL REGISTRATION ChiCTR1900028516 ( http://www.chictr.org.cn/index.aspx ).
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The ratio of HDL-C to apoA-I interacts with free triiodothyronine to modulate coronary artery disease risk.
Li, L, Cai, G, Lu, W, Li, F, Yu, L, Xiao, J
BMC cardiovascular disorders. 2021;(1):504
Abstract
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.
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Interaction of lipid-free apolipoprotein A-I with cholesterol revealed by molecular modeling.
Baserova, VB, Dergunov, AD
Biochimica et biophysica acta. Proteins and proteomics. 2021;(5):140614
Abstract
We report the modeling of the interaction of differently self-associated lipid-free apoA-I with cholesterol monomer and tail-to-tail (TT) or face-to-face (FF) cholesterol dimer. Cholesterol dimerization is exploited to reconcile the existing experimental data on cholesterol binding to apoA-I with extremely low critical micelle concentration of cholesterol. Two crystal structures of 1-43 N-truncated apolipoprotein Δ(1-43)A-I tetramer (PDB ID 1AV1, structure B), 185-243 C-truncated apolipoprotein Δ(185-243)A-I dimer (PDB ID 3R2P, structure M) were analyzed. Cholesterol monomers bind to multiple binding sites in apoA-I monomer, dimer and tetramer with low, moderate and high energy (-10 to -28 kJ/mol with Schrödinger package), still insufficient to overcome the thermodynamic restriction by cholesterol micellization (-52.8 kJ/mol). The binding sites partially coincide with the putative cholesterol-binding motifs. However, apoA-I monomer and dimer existing in structure B, that contain nonoverlapping and non-interacting pairs of binding sites with high affinity for TT and FF cholesterol dimers, can bind in common 14 cholesterol molecules that correspond to existing values. ApoA-I monomer and dimer in structure M can bind in common 6 cholesterol molecules. The values of respective total energy of cholesterol binding up to 64.5 and 67.0 kJ/mol for both B and M structures exceed the free energy of cholesterol micellization. We hypothesize that cholesterol dimers may simultaneously interact with extracellular monomer and dimer of lipid-free apoA-I, that accumulate at acid pH in atheroma. The thermodynamically allowed apolipoprotein-cholesterol interaction outside the macrophage may represent a new mechanism of cholesterol transport by apoA-I from atheroma, in addition to ABCA1-mediated cholesterol efflux.
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The Beneficial Effects of Alpha Lipoic Acid Supplementation on Lp-PLA2 Mass and Its Distribution between HDL and apoB-Containing Lipoproteins in Type 2 Diabetic Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.
Baziar, N, Nasli-Esfahani, E, Djafarian, K, Qorbani, M, Hedayati, M, Mishani, MA, Faghfoori, Z, Ahmaripour, N, Hosseini, S
Oxidative medicine and cellular longevity. 2020;:5850865
Abstract
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a new specific vascular inflammation biomarker that is carried by the lipoproteins in the blood and plays a prominent role in the pathogenesis of atherosclerosis. Increased Lp-PLA2 levels and impaired Lp-PLA2 distribution across high-density lipoprotein (HDL) and non-HDL lipoproteins have been reported in diabetic patients, which is associated with the increase in cardiovascular disease (CVD) risk. This study is aimed at investigating the effect of alpha lipoic acid (ALA), as an antioxidant with potential cardioprotective properties, on the Lp-PLA2 mass and its distribution in diabetic patients. In a double-blind, randomized, placebo-controlled clinical trial, seventy diabetic patients were randomly allocated to ALA (1200 mg ALA as two 600 mg capsules/day) and placebo (two maltodextrin capsules/day) groups. The serum levels of total Lp-PLA2 mass, HDL-Lp-PLA2, oxidized low-density lipoproteins (ox-LDL), apolipoprotein A1 (apo A1), lipid profiles, fasting blood sugar (FBS), and insulin were measured, and apolipoprotein B- (apoB-) associated Lp-PLA2 and homeostasis model of assessment index (HOMA-IR) were calculated at the baseline and after 8 weeks of intervention. ALA significantly decreased the ox-LDL, total Lp-PLA2 mass, apoB-associated Lp-PLA2, and percent of apoB-associated Lp-PLA2 and triglyceride and increased the percent of HDL-Lp-PLA2 compared with the placebo group but had no significant effect on HDL-Lp-PLA2 mass, apo A1, lipid profiles, and glycemic indices. There was a positive correlation between the reduction in the ox-LDL level and total Lp-PLA2 mass in the ALA group. In conclusion, ALA may decrease the CVD risk by reducing the ox-LDL and Lp-PLA2 mass and improving the Lp-PLA2 distribution among lipoproteins in type 2 diabetic patients.
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Apolipoprotein B Level and the Apolipoprotein B/Apolipoprotein A-I Ratio as a Harbinger of Ischemic Stroke: A Prospective Observation in Taiwan.
Chou, YC, Chan, PC, Yang, T, You, SL, Bai, CH, Sun, CA
Cerebrovascular diseases (Basel, Switzerland). 2020;(5):487-494
Abstract
AIM: Prospective studies indicate that apolipoprotein (apo) measurements predict coronary heart disease risk. However, few population-based follow-up studies have addressed the predictive value of apo measurements in stroke risk. The aims of the present study were to analyze the predictive ability of apo measurements in the risk of ischemic stroke. METHODS Serum apo A-I and apo B levels and calculated apo B/apo A-I ratio were measured at baseline in 2002 in a cohort of 4,204 participants who were followed for a mean of 4.61 years for a stroke event. RESULTS After adjustment for potential confounders, a significantly stepwise increase in the incidence rate of stroke across quartiles of both apo B and the apo B/apo A-I ratio was evident in both genders and across age-groups. The predictive ability of apo B to detect ischemic stroke was comparable with that of the apo B/apo A-I ratio. Furthermore, both apo B and the apo B/apo A-I ratio were better predictors of the risk of ischemic stroke than total cholesterol (TC), low-density lipoprotein cholesterol, and the TC/high-density lipoprotein cholesterol ratio. CONCLUSIONS This cohort study demonstrates that apo B and the apo B/apo A-I ratio were a significant risk predictor of stroke. Furthermore, the predictive ability of apo B and the apo B/apo A-I ratio in stroke risk was better than routine clinical lipid measurements. Thus, measurements of apolipoproteins have superior clinical utility over traditional lipid measurements in identifying subjects at risk for ischemic stroke.