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Frontiers in Endocrinology 2023Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the...
AIMS
Epidemiological evidence for the link of interleukin 1 (IL-1) and its inhibition with cardiovascular diseases (CVDs) remains controversial. We aim to investigate the cardiovascular effects of IL-1 receptor antagonist (IL-1Ra) and underlying mechanisms.
METHODS
Genetic variants identified from a genome-wide association study involving 30,931 individuals were used as instrumental variables for the serum IL-1Ra concentrations. Genetic associations with CVDs and cardiometabolic risk factors were obtained from international genetic consortia. Inverse-variance weighted method was utilized to derive effect estimates, while supplementary analyses employing various statistical approaches.
RESULTS
Genetically determined IL-1Ra level was associated with increased risk of coronary heart disease (CHD; OR, 1.07; 95% CI: 1.03-1.17) and myocardial infarction (OR, 1.13; 95% CI: 1.04-1.21). The main results remained consistent in supplementary analyses. Besides, IL-1Ra was associated with circulating levels of various lipoprotein lipids, apolipoproteins and fasting glucose. Interestingly, observed association pattern with CHD was reversed when adjusting for apolipoprotein B (OR, 0.84; 95%CI: 0.71-0.99) and slightly attenuated on accounting for other cardiometabolic risk factors. Appropriate lifestyle intervention was found to lower IL-1Ra concentration and mitigate the heightened CHD risk it posed.
CONCLUSION
Apolipoprotein B represents the key driver, and a potential target for reversal of the causal link between serum IL-1Ra and increased risk of CHD/MI. The combined therapy involving IL-1 inhibition and lipid-modifying treatment aimed at apolipoprotein B merit further exploration.
Topics: Humans; Interleukin 1 Receptor Antagonist Protein; Genome-Wide Association Study; Coronary Disease; Apolipoproteins B; Myocardial Infarction; Apolipoproteins; Interleukin-1; Receptors, Interleukin-1
PubMed: 37941911
DOI: 10.3389/fendo.2023.1278273 -
Clinica Chimica Acta; International... Aug 2023Triggering receptor expressed on myeloid cells 2 (TREM2) is a unique receptor expressed by macrophages in atherosclerotic plaque and is involved in the progression of...
BACKGROUND
Triggering receptor expressed on myeloid cells 2 (TREM2) is a unique receptor expressed by macrophages in atherosclerotic plaque and is involved in the progression of atherosclerosis. Whether serum soluble TREM2 (sTREM2) levels has a relationship with coronary heart disease (CHD) remains unclear.
METHODS
The cross-sectional study included 86 patients with CHD and 86 controls matched with age and sex. Demographic information, medication history, and laboratory data were collected. sTREM2 concentrations were detected by enzyme-linked immunosorbent assay. We compared the sTREM2 levels in two groups and constructed stepwise linear regression analysis for factors related to the sTREM2 level in patients with CHD; we further used the logistic regression model to evaluate the relationship between sTREM2 and CHD. The diagnostic value of sTREM2 and other biomarkers in CHD was evaluated by the receiver operating characteristic curve (ROC).
RESULTS
The serum level of sTREM2 in CHD patients is higher than that in controls. In CHD patients, the stepwise linear regression analysis found that sTREM2 levels were correlated with triglyceride (TG), high-density lipoprotein cholesterols (HDL-C), apolipoprotein B (ApoB) and smoking status. Logistic regression models showed that sTREM2 was associated independently with CHD after adjusted confounders. The ROC curve showed a sensitivity of 59.3% and specificity of 81.4% with an area under the curve of 0.781 (95% CI: 0.711-0.852) for the diagnosis of CHD with serum sTREM2 at a cut-off value of > 1104.894 pg/ml, indicating a higher diagnostic value than high sensitivity C reaction protein (hs-CRP) and apolipoprotein B (ApoB).
CONCLUSION
In this study, we provide evidence that sTREM2 levels are elevated in CHD patients and are associated with various cardiovascular risk factors. Additionally, sTREM2 demonstrates better diagnostic performance compared to traditional indicators in identifying CHD. These findings suggest that sTREM2 may serve as a potential biomarker for coronary heart disease.
Topics: Humans; Cross-Sectional Studies; Coronary Disease; Biomarkers; Atherosclerosis; C-Reactive Protein; Apolipoproteins B; Membrane Glycoproteins; Receptors, Immunologic
PubMed: 37536519
DOI: 10.1016/j.cca.2023.117499 -
Advances in Nutrition (Bethesda, Md.) Sep 2023Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits.... (Meta-Analysis)
Meta-Analysis Review
Cardiovascular disease (CVD) is the leading cause of death globally. Habitual consumption of tree nuts and peanuts is associated with cardioprotective benefits. Food-based dietary guidelines globally recommend nuts as a key component of a healthy diet. This systematic review and meta-analysis were conducted to examine the relationship between tree nut and peanut consumption and risk factors for CVD in randomized controlled trials (RCTs) (PROSPERO: CRD42022309156). MEDLINE, PubMed, CINAHL, and Cochrane Central databases were searched up to 26 September, 2021. All RCT studies that assessed the effects of tree nut or peanut consumption of any dose on CVD risk factors were included. Review Manager software was used to conduct a random effect meta-analysis for CVD outcomes from RCTs. Forest plots were generated for each outcome, between-study heterogeneity was estimated using the I test statistic and funnel plots and Egger's test for outcomes with ≥10 strata. The quality assessment used the Health Canada Quality Appraisal Tool, and the certainty of the evidence was assessed using grading of recommendations assessment, development, and evaluation (GRADE). A total of 153 articles describing 139 studies (81 parallel design and 58 cross-over design) were included in the systematic review, with 129 studies in the meta-analysis. The meta-analysis showed a significant decrease for low-density lipoprotein (LDL) cholesterol, total cholesterol (TC), triglycerides (TG), TC:high-density lipoprotein (HDL) cholesterol, LDL cholesterol:HDL cholesterol, and apolipoprotein B (apoB) following nut consumption. However, the quality of evidence was "low" for only 18 intervention studies. The certainty of the body of evidence for TC:HDL cholesterol, LDL cholesterol:HDL cholesterol, and apoB were "moderate" because of inconsistency, for TG were "low," and for LDL cholesterol and TC were "very low" because of inconsistency and the likelihood of publication bias. The findings of this review provide evidence of a combined effect of tree nuts and peanuts on a range of biomarkers to create an overall CVD risk reduction.
Topics: Humans; Cardiovascular Diseases; Nuts; Arachis; Cholesterol, LDL; Cholesterol, HDL; Randomized Controlled Trials as Topic; Cholesterol; Triglycerides; Apolipoproteins B
PubMed: 37149262
DOI: 10.1016/j.advnut.2023.05.004 -
Indian Heart Journal Mar 2024This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a... (Review)
Review
This review article describes the pathophysiological mechanisms linking Apolipoprotein B (Apo-B) and atherosclerosis, summarizes the existing evidence on Apo B as a predictor of atherosclerotic cardiovascular disease and recommendations of (inter)national treatment guidelines regarding Apo B in dyslipidemia management. A single Apo B molecule is present in every particle of very low-density lipoprotein, intermediate density lipoprotein, low density lipoprotein, and lipoprotein(a). This unique single Apo B per particle ratio makes plasma Apo B concentration a direct measure of the number of circulating atherogenic lipoproteins. This review of global evidence on Apo B as a biomarker for atherosclerosis confirms that Apo B is a single atherogenic lipid marker present in all lipids sub-fractions except HDL-C, and thus, Apo B integrates and extends the information from triglycerides and cholesterol, which could simplify and improve care for atherosclerotic cardiovascular disease.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Biomarkers; Cardiovascular Diseases; Cholesterol, HDL; Triglycerides
PubMed: 38599726
DOI: 10.1016/j.ihj.2023.12.001 -
Frontiers in Endocrinology 2023This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
This study aims to evaluate the effect of acupuncture on the emotion domain and metabolic parameters of Chinese women with polycystic ovarian syndrome (PCOS) by secondary analysis of a randomized clinical trial, conducted from 6 July 2012 to 7 October 2015.
METHOD
In this study, we investigated the effects of acupuncture (458 patients) and sham acupuncture (468 patients) on metabolic parameters, serum ions, and all quality-of-life scale scores related to PCOS. The quality of life of patients was evaluated using five relevant scales, operated by the research assistant, namely, PCOSQ, SF-36, and ChiQOL, as well as Zung-SAS and Zung-SDS. Metabolic parameters and serum ions were measured.
RESULTS
A reduction in acne score, AN, Hcy, and LDL-C, and an increase in the level of lipoprotein α, Apo A1, and Apo A1/Apo B were observed in the acupuncture group after 4 months' intervention after adjusting clomiphene and reproductive outcome (< 0.05). An increase in SF-36 total scores, RP and RE scores, ChiQOL total scores, and emotion domain scores was observed in the acupuncture group after 4 months' intervention, while PF and HT scores were decreased (adjusted < 0.05). Those same changes were observed in sham acupuncture. Meanwhile, the serum levels of Ca, K, and Cl were elevated in the acupuncture group after the interventions (adjusted < 0.005). There were no significant differences in HOMA-IR, MetS, FPG, FINS, HDL-C, TG, Apo B, and level of serum P, Mg, and Na. Also, no changes in BP, GH, VT, SF, physical form domain, and spirit domain were observed after treatment.
CONCLUSION
Acupuncture can improve not only the emotional changes in SF-36 scores and ChiQOL scores, but also lipid metabolism, implying that it may have a correlation between emotional change and lipid metabolism. Furthermore, acupuncture can also regulate the changes of serum Ca, K, and Cl.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT01573858.
Topics: Humans; Female; Apolipoprotein A-I; Polycystic Ovary Syndrome; Quality of Life; Acupuncture Therapy; Apolipoproteins B; Emotions
PubMed: 37711905
DOI: 10.3389/fendo.2023.1237260 -
Frontiers in Endocrinology 2023Previous studies have yielded conflicting findings regarding the association between circulating lipids and lipid-lowering drugs with urinary stones, and the causal...
BACKGROUND
Previous studies have yielded conflicting findings regarding the association between circulating lipids and lipid-lowering drugs with urinary stones, and the causal relationship between the two remains inconclusive.
OBJECTIVE
This study aimed to assess the causal relationship between circulating lipids (Triglycerides [TG], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], apolipoprotein A [APOA], apolipoprotein B [APOB] and Pure hypercholesterolaemia), lipid-lowering drugs (HMGCR [HMG-CoA reductase] inhibitors and PCSK9[Proprotein Convertase Subtilisin/Kexin Type 9] inhibitors) and the risk of urinary stones, using genetic data.
METHODS
Genetic instrumental variables (GIVs) for circulating lipids and lipid-lowering drugs were obtained from the UK Biobank and existing literature. Outcome data were extracted from a genetic association database with 3,625 urinary stone cases and 459,308 controls. Two-sample MR analysis, employing the TwoSampleMR software package in R 4.2.3, was conducted to assess the associations between multiple exposures. The primary outcome was determined using the inverse variance weighted (IVW) method for the causal relationship between exposure and outcome, while additional methods such as MR-Egger, weighted median, simple mode, and weighted mode were utilized as supplementary analyses. Robustness of the Mendelian Randomization (MR) analysis results was assessed through leave-one-out analysis and funnel plots.
RESULTS
The MR analysis revealed a significant association between elevated TG levels per 1 standard deviation and the occurrence of urinary stones (odds ratio [OR]: 1.002, 95% confidence interval [CI]: 1.000-1.003, P = 0.010). However, no significant association was observed between factors other than TG exposure and the risk of urinary stone occurrence across all methods(LDL-C: [OR], 1.001; 95% [CI], 1.000-1.003, P=0.132;HDL-C: [OR], 0.999; 95% [CI], 0.998-1.000, P=0.151;APOA:[OR] being 1.000 (95% [CI], 0.999-1.001, P=0.721;APOB: [OR] of 1.001 (95% [CI], 1.000-1.002, P=0.058;Pure hypercholesterolaemia: [OR] of 1.015 (95% [CI], 0.976-1.055, P=0.455) and lipid-lowering drugs (HMGCR inhibitors: [OR], 0.997; 95% [CI], 0.990-1.003, P=0.301 and PCSK9 inhibitors:[OR], 1.002; 95% [CI], 1.000-1.005, P=0.099).
CONCLUSION
Our findings provide conclusive evidence supporting a causal relationship between an increased risk of urinary stones and elevated serum TG levels. However, we did not find a significant association between urinary stone occurrence and the levels of LDL-C, HDL-C, APOA, APOB, Pure hypercholesterolaemia and lipid-lowering drugs.
Topics: Humans; Proprotein Convertase 9; Cholesterol, LDL; Risk Factors; Hypercholesterolemia; Mendelian Randomization Analysis; Hypolipidemic Agents; Triglycerides; Cholesterol, HDL; Apolipoproteins B; Urinary Calculi; Hyperlipoproteinemia Type II; Apolipoproteins A
PubMed: 38107516
DOI: 10.3389/fendo.2023.1301163 -
Pharmacological Research Sep 2023The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and...
The subendothelial retention of apolipoprotein B (apoB)-containing lipoproteins is a critical step in the initiation of pro-atherosclerotic processes. Recent genetic and clinical evidence strongly supports the concept that the lipid content of the particles is secondary to the number of circulating atherogenic particles that are trapped within the arterial lumen. Since each low-density lipoproteins (LDL) particle contains one apoB molecule, as do intermediate density lipoprotein (IDL) and very low-density lipoprotein (VLDL) particles, apoB level represents the total number of atherogenic lipoproteins, which is independent of particle density, and not affected by the heterogeneity of particle cholesterol content (clinically evaluated by LDL-cholesterol level). From this perspective, apoB is proposed as a better proxy to LDL-cholesterol for assessing atherosclerotic cardiovascular disease risk, especially in specific subgroups of patients, including subjects with diabetes mellitus, with multiple cardiometabolic risk factors (obesity, metabolic syndrome, insulin resistance, and hypertension) and with high triglyceride levels and very low LDL-cholesterol levels. Therefore, given the causal role of LDL-cholesterol in atherosclerotic cardiovascular disease (ASCVD) development, routine measurement of both LDL-cholesterol and apoB is of utmost importance to properly estimate global cardiovascular risk and to determine the 'residual' risk of ASCVD in patients receiving therapy, as well as to monitor therapeutic effectiveness.
Topics: Humans; Apolipoproteins B; Atherosclerosis; Cardiovascular Diseases; Cholesterol, LDL; Risk Assessment; Triglycerides
PubMed: 37517561
DOI: 10.1016/j.phrs.2023.106873 -
Frontiers in Endocrinology 2023The correlation between dyslipidemia and periodontitis is revealed through epidemiological studies. However, the results are affected by several confounding factors....
INTRODUCTION
The correlation between dyslipidemia and periodontitis is revealed through epidemiological studies. However, the results are affected by several confounding factors. This study aims to elucidate the genetic causal association between circulating lipid traits and periodontitis by two-sample Mendelian randomization (MR) analysis.
METHODS
After the different screening processes, two cohorts of circulating lipid traits from the UK Biobank were used as exposure data, including five circulating lipid traits. The Periodontitis cohort was selected from the GeneLifestyle Interactions in Dental Endpoints (GLIDE) consortium as outcome data. In univariable MR, the inverse variance weighted (IVW) was used in conjunction with six additional analytical methods to assess causality. The Cochran Q test, I statistic, MR-PRESSO, and MR-Egger intercept were used to quantify heterogeneity and pleiotropy. The multivariable MR-IVW (MVMR-IVW) and MVMR-robust were mainly used as analytical methods in the multiple MR analyses.
RESULTS
The IVW estimates showed that genetically predicted Apolipoprotein A1 (apo A1) [odds ratio (OR)=1.158, 95% confidence interval (CI)=1.007-1.331, -value=0.040] was potentially associated with the risk of periodontitis, but the statistical power of the results was low. Multivariable MR analysis did not reveal any significant causal relationship between apo A1 and periodontitis (OR=0.72, 95% CI=0.36-1.41, -value=0.34). In the validation cohort, there was also no significant causal relationship between apo A1 and periodontitis (OR=1.079, 95% CI=0.903-1.290, -value=0.401). Meanwhile, genetically predicted Apolipoprotein B (apo B), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) (all -values>0.05) were not significantly associated with the risk of periodontitis causal inference.
CONCLUSION
This MR analysis was unable to provide genetic evidence for the influence of these five circulating lipid traits on periodontitis. However, a more extensive study with a more comprehensive circulating lipid profile and periodontitis data is needed due to study limitations.
Topics: Humans; Apolipoprotein A-I; Mendelian Randomization Analysis; Apolipoproteins B; Cholesterol, HDL; Periodontitis
PubMed: 37583432
DOI: 10.3389/fendo.2023.1214232 -
Journal of Lipid Research Aug 2023Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high...
Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high apolipoprotein B (ApoB), and low low density lipoprotein (LDL) cholesterol to ApoB ratio. We investigated whether and to what extent hypertriglyceridemic hyperapoB associates with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). This prospective cohort study included 9,019 Chinese participants 40 years or older, from 2010 to 2015. Logistic regression models were used to examine the odds ratios (ORs) for the incidence and resolution of NAFLD associated with the hypertriglyceridemic hyperapoB lipoprotein phenotype and individual lipid and lipoprotein parameters. During a median 4.3 years of follow-up, compared with participants with optimal phenotype, the fully adjusted ORs (95% CIs) for participants with hypertriglyceridemic hyperapoB were 2.75 (1.91, 3.95) and 0.57 (0.33, 1.00) for incidence and resolution of NAFLD, respectively. These associations were consistent across subgroup participants with varied demographic, lifestyle, and metabolic status. Individually, each unit increase in HDL cholesterol (OR: 0.98; 95% CI: 0.97, 0.99), natural logarithm-transformed triglycerides (1.89; 1.52, 2.36), and ApoB (1.006; 1.002, 1.011) was independently associated with NAFLD incidence, and only triglycerides (0.77; 0.60, 0.99) was independently associated with NAFLD resolution. Our findings suggest that Chinese adults with hypertriglyceridemic hyperapoB have a higher risk of NAFLD incidence and a lower likelihood of NAFLD resolution. These associations were stable among adults with different demographic, lifestyle, and metabolic status, supporting hypertriglyceridemic hyperapoB as a valuable clinical marker for the prevention and control of NAFLD.
Topics: Humans; Non-alcoholic Fatty Liver Disease; Cohort Studies; Prospective Studies; Lipoproteins, LDL; Triglycerides; Cholesterol; Apolipoproteins B; Lipoproteins; Cholesterol, HDL
PubMed: 37481036
DOI: 10.1016/j.jlr.2023.100418 -
Arteriosclerosis, Thrombosis, and... May 2024Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl... (Review)
Review
Zebrafish have become a powerful model of mammalian lipoprotein metabolism and lipid cell biology. Most key proteins involved in lipid metabolism, including cholesteryl ester transfer protein, are conserved in zebrafish. Consequently, zebrafish exhibit a human-like lipoprotein profile. Zebrafish with mutations in genes linked to human metabolic diseases often mimic the human phenotype. Zebrafish larvae develop rapidly and externally around the maternally deposited yolk. Recent work revealed that any disturbance of lipoprotein formation leads to the accumulation of cytoplasmic lipid droplets and an opaque yolk, providing a visible phenotype to investigate disturbances of the lipoprotein pathway, already leading to discoveries in MTTP (microsomal triglyceride transfer protein) and ApoB (apolipoprotein B). By 5 days of development, the digestive system is functional, making it possible to study fluorescently labeled lipid uptake in the transparent larvae. These and other approaches enabled the first in vivo description of the STAB (stabilin) receptors, showing lipoprotein uptake in endothelial cells. Various zebrafish models have been developed to mimic human diseases by mutating genes known to influence lipoproteins (eg, , ). This review aims to discuss the most recent research in the zebrafish ApoB-containing lipoprotein and lipid metabolism field. We also summarize new insights into lipid processing within the yolk cell and how changes in lipid flux alter yolk opacity. This curious new finding, coupled with the development of several techniques, can be deployed to identify new players in lipoprotein research directly relevant to human disease.
Topics: Zebrafish; Animals; Lipid Metabolism; Apolipoproteins B; Humans; Disease Models, Animal; Phenotype; Zebrafish Proteins; Mutation
PubMed: 38482694
DOI: 10.1161/ATVBAHA.123.318287