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Lipids in Health and Disease Jul 2023Apolipoproteins and lipoprotein(a) are associated with various cardiometabolic diseases, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND & AIMS
Apolipoproteins and lipoprotein(a) are associated with various cardiometabolic diseases, including insulin resistance, diabetes mellitus, hypertension, dyslipidemia, among others. This systematic review and meta-analysis was conducted to evaluate the association of these markers with metabolic syndrome (MetS).
METHODS
We ran a systematic search through PubMed, Scopus, Embase, Ovid/Medline, and Web of Science on March 15, 2023. No language or date restrictions were applied. The only synthesised effect measure reported was the odds ratio (OR) with its corresponding 95% confidence interval (95% CI). We utilised the random-effects model for the quantitative synthesis.
RESULTS
We analysed 50 studies (n = 150 519) with different definitions for MetS. Increased ApoB values were associated with MetS (OR = 2.8; 95% CI: 2.44-3.22; p < 0.01, I = 99%). Decreased ApoA1 values were associated with MetS (OR = 0.42; 95% CI: 0.38-0.47; p < 0.01, I = 99%). Increased values of the ApoB/ApoA1 ratio were associated with MetS (OR = 4.97; 95% CI: 3.83-6.44; p < 0.01, I = 97%). Decreased values of Lp(a) were associated with MetS (OR = 0.89; 95% CI: 0.82-0.96; p < 0.01; I = 92%).
CONCLUSIONS
Increased values of ApoB and ApoB/ApoA1 ratio are associated with MetS, while decreased values of ApoA1 and Lp(a) are associated with MetS. These findings suggest that these lipid markers may serve as potential indicators for identifying subjects at risk of developing MetS. However, further research is required to elucidate the underlying mechanisms of these associations.
Topics: Humans; Metabolic Syndrome; Lipoprotein(a); Apolipoproteins; Apolipoproteins B; Insulin Resistance
PubMed: 37420190
DOI: 10.1186/s12944-023-01860-w -
The American Journal of Clinical... Apr 2024Apolipoproteins (APOs) have emerged as significant players in lipid metabolism that affects the risk of chronic disease. However, the impact of circulating APO...
BACKGROUND
Apolipoproteins (APOs) have emerged as significant players in lipid metabolism that affects the risk of chronic disease. However, the impact of circulating APO concentrations on premature death remains undetermined.
OBJECTIVES
This study aimed to investigate the associations of serum APOs with all-cause, cardiovascular disease (CVD)-related, and cancer-related mortality.
METHODS
We included 340,737 participants who had serum APO measurements from the UK Biobank. Restricted cubic splines and multivariable Cox regression models were used to assess the associations between APOs and all-cause and cause-specific mortality by computing hazard ratios (HRs) and 95% confidence intervals (CIs). Based on 1-sample Mendelian randomization (MR) design, including 398,457 participants of White ancestry who had genotyping data from the UK Biobank, we performed instrumental variable analysis with 2-stage least squares regression to assess the association between genetically predicted APOs and mortality.
RESULTS
After adjusting for potential confounders including high-density and low-density lipoprotein particles, we observed nonlinear inverse relationships of APOA1 with all-cause, CVD-related, and cancer-related mortality (P-nonlinear < 0.001). By contrast, positive relationships were observed for APOB and all-cause (P-nonlinear < 0.001), CVD-related (P-linear < 0.001), and cancer-related (P-linear = 0.03) mortality. MR analysis showed consistent results, except that the association between APOB and cancer mortality was null. Furthermore, both observational and MR analyses found an inverse association between APOA1 and lung cancer-related mortality (HR comparing extreme deciles: 0.46; 95% CI: 0.26, 0.80; and HR: 0.78; 95% CI: 0.63, 0.97, respectively).
CONCLUSIONS
Our findings indicate that circulating APOA1 has potential beneficial effects on all-cause, CVD-related, and lung cancer-related death risk, whereas APOB may confer detrimental effects on all-cause and CVD-related death risk.
Topics: Humans; Mendelian Randomization Analysis; Risk Factors; Apolipoproteins; Cardiovascular Diseases; Apolipoproteins B; Lung Neoplasms
PubMed: 38211689
DOI: 10.1016/j.ajcnut.2024.01.002 -
BMC Musculoskeletal Disorders Nov 2023Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B...
BACKGROUND
Lipids are critical in bone metabolism, and several studies have highlighted their importance. This study aimed to investigate the relationship between apolipoprotein B (apo B) and bone mineral density (BMD) at different skeletal sites (lumbar spine, femoral neck, and total femur) and to compare the influence of apo B with other traditional lipid markers.
METHODS
The study included participants from the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2016 who had complete data for apo B and BMD at the three skeletal sites. We used weighted multivariate regression analysis, subgroup analysis, and interaction tests to examine associations. Restricted cubic spline (RCS) was used to examine the non-linear relationship.
RESULTS
A total of 4,258 adults were included in the study. Multivariate linear regression analysis showed that the relationship between apo B and BMD varied by skeletal site: a negative association was found with lumbar spine BMD [β = -0.054, 95%CI: (-0.073, -0.035)]. In contrast, a positive association was found with femoral neck BMD [β = 0.031, 95%CI: (0.011, 0.051)] and no significant association between apo B and total femur BMD.
CONCLUSIONS
Our findings suggest that apo B is associated with BMD in a site-specific manner.
Topics: Adult; Humans; Absorptiometry, Photon; Apolipoproteins B; Bone Density; Femur Neck; Lumbar Vertebrae; Nutrition Surveys
PubMed: 37919727
DOI: 10.1186/s12891-023-06990-x -
Journal of the American Heart... Aug 2023Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical... (Review)
Review
Concern continues about whether the measurement of apolipoprotein B (apoB) is adequately standardized, and therefore, whether apoB should be applied widely in clinical care. This concern is misplaced. Our objective is to explain why and what the term "standardization" means. To produce clinically valid results, a test must accurately, precisely, and selectively measure the marker of interest. That is, it must be standardized. Accuracy refers to how closely the result obtained with 1 method corresponds to the result obtained with the standard method, precision to how reproducible the result is on repeated testing, and selectivity to how susceptible the method is to error by inclusion of other classes of lipoprotein particles. Multiple expert groups have determined that the measurement of apoB is adequately standardized for clinical care, and that apoB can be measured inexpensively, using widely available automated methods, more accurately, precisely, and selectively than low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol. ApoB is a standard superior to low-density lipoprotein cholesterol and high-density lipoprotein cholesterol because it is a defined molecule, whereas the cholesterol markers are the mass of cholesterol within lipoprotein particles defined by their density, not by their molecular structure. Nevertheless, the standardization of apoB is being further improved by the application of mass spectrophotometric methods, whereas the limitations in the standardization and, therefore, the accurate, precise, and selective measurement of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol are unlikely to be overcome. We submit that greater accuracy, precision, and selectivity in measurement is a decisive advantage for apoB in the modern era of intensive lipid-lowering therapies.
Topics: Cholesterol, LDL; Cholesterol; Apolipoproteins B; Apolipoprotein B-100; Cholesterol, HDL; Lipoproteins; Apolipoprotein A-I
PubMed: 37489721
DOI: 10.1161/JAHA.123.030405 -
Current Opinion in Lipidology Dec 2023The triglyceride-rich apoB lipoprotein particles make up a minority of the apoB particles in plasma. They vary in size, in lipid, and in protein content. Most are small... (Review)
Review
PURPOSE OF REVIEW
The triglyceride-rich apoB lipoprotein particles make up a minority of the apoB particles in plasma. They vary in size, in lipid, and in protein content. Most are small enough to enter the arterial wall and therefore most are atherogenic. But how important a contribution TRL particles make to the total risk created by the apoB lipoproteins remains controversial. A recent Mendelian randomization analysis determined that the cardiovascular risk related to the cholesterol within these apoB particles--the TRL cholesterol--was greater than--and independent of--the risk related to apoB. If correct, these observations have major clinical significance.
RECENT FINDINGS
Accordingly, we have analyzed these results in detail. In our view, the independent strength of the association between TRL cholesterol and apoB with cardiovascular risk seems inconsistent with the biological connections between apoB and cholesterol as integral and highly correlated constituents of apoB particles. These results are also inconsistent with other lines of evidence such as the results of the fibrate randomized clinical trials. Moreover, we are also concerned with other aspects of the analysis.
SUMMARY
We do not regard the issue as settled. However, this enquiry has led us to a fuller understanding of the determinants of the cholesterol content of the TRL apoB particles and the complex processing of cholesterol amongst the plasma lipoproteins.
Topics: Humans; Cardiovascular Diseases; Risk Factors; Cholesterol; Lipoproteins; Triglycerides; Apolipoproteins B; Heart Disease Risk Factors
PubMed: 37773930
DOI: 10.1097/MOL.0000000000000905 -
BMC Medicine Jul 2023Asialoglycoprotein receptor 1 (ASGR1) is emerging as a potential drug target to reduce low-density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD) risk....
Genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and health outcomes: a drug-target Mendelian randomization study and a phenome-wide association study.
BACKGROUND
Asialoglycoprotein receptor 1 (ASGR1) is emerging as a potential drug target to reduce low-density lipoprotein (LDL)-cholesterol and coronary artery disease (CAD) risk. Here, we investigated genetically mimicked ASGR1 inhibitors on all-cause mortality and any possible adverse effects.
METHODS
We conducted a drug-target Mendelian randomization study to assess genetically mimicked effects of ASGR1 inhibitors on all-cause mortality and 25 a priori outcomes relevant to lipid traits, CAD, and possible adverse effects, i.e. liver function, cholelithiasis, adiposity and type 2 diabetes. We also performed a phenome-wide association study of 1951 health-related phenotypes to identify any novel effects. Associations found were compared with those for currently used lipid modifiers, assessed using colocalization, and replicated where possible.
RESULTS
Genetically mimicked ASGR1 inhibitors were associated with a longer lifespan (3.31 years per standard deviation reduction in LDL-cholesterol, 95% confidence interval 1.01 to 5.62). Genetically mimicked ASGR1 inhibitors were inversely associated with apolipoprotein B (apoB), triglycerides (TG) and CAD risk. Genetically mimicked ASGR1 inhibitors were positively associated with alkaline phosphatase, gamma glutamyltransferase, erythrocyte traits, insulin-like growth factor 1 (IGF-1) and C-reactive protein (CRP), but were inversely associated with albumin and calcium. Genetically mimicked ASGR1 inhibitors were not associated with cholelithiasis, adiposity or type 2 diabetes. Associations with apoB and TG were stronger for ASGR1 inhibitors compared with currently used lipid modifiers, and most non-lipid effects were specific to ASGR1 inhibitors. The probabilities for colocalization were > 0.80 for most of these associations, but were 0.42 for lifespan and 0.30 for CAD. These associations were replicated using alternative genetic instruments and other publicly available genetic summary statistics.
CONCLUSIONS
Genetically mimicked ASGR1 inhibitors reduced all-cause mortality. Beyond lipid-lowering, genetically mimicked ASGR1 inhibitors increased liver enzymes, erythrocyte traits, IGF-1 and CRP, but decreased albumin and calcium.
Topics: Humans; Apolipoproteins B; Asialoglycoprotein Receptor; Calcium; Cholelithiasis; Coronary Artery Disease; Diabetes Mellitus, Type 2; Genome-Wide Association Study; Insulin-Like Growth Factor I; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Risk Factors; Triglycerides
PubMed: 37400795
DOI: 10.1186/s12916-023-02903-w -
European Heart Journal Nov 2023The aims of this study were to investigate lipid parameters during the first 14-16 months of life, to identify influential factors, and to test whether high...
BACKGROUND AND AIMS
The aims of this study were to investigate lipid parameters during the first 14-16 months of life, to identify influential factors, and to test whether high concentrations at birth predict high concentrations at 2- and 14-16 months.
METHODS
The Copenhagen Baby Heart Study, including 13,354 umbilical cord blood samples and parallel venous blood samples from children and parents at birth (n = 444), 2 months (n = 364), and 14-16 months (n = 168), was used.
RESULTS
Concentrations of lipids, lipoproteins, and apolipoproteins in umbilical cord blood samples correlated highly with venous blood samples from newborns. Concentrations of low-density lipoprotein (LDL) cholesterol, non-high-density lipoprotein (HDL) cholesterol, apolipoprotein B, and lipoprotein(a) increased stepwise from birth to 2 months to 14-16 months. Linear mixed models showed that concentrations of LDL cholesterol, non-HDL cholesterol, and lipoprotein(a) above the 80th percentile at birth were associated with significantly higher concentrations at 2 and 14-16 months. Finally, lipid concentrations differed according to sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations.
CONCLUSIONS
Lipid parameters changed during the first 14-16 months of life, and sex, gestational age, birth weight, breastfeeding, and high parental concentrations influenced concentrations. Children with high concentrations of atherogenic lipid traits at birth had higher concentrations at 2 and 14-16 months. These findings increase our knowledge of how lipid traits develop over the first 14-16 months of life and may help in deciding the optimal child age for universal familial hypercholesterolaemia screening.
Topics: Child; Infant, Newborn; Humans; Birth Weight; Triglycerides; Lipids; Apolipoproteins; Cholesterol; Apolipoproteins B; Cholesterol, LDL; Lipoprotein(a); Cholesterol, HDL
PubMed: 37632410
DOI: 10.1093/eurheartj/ehad547 -
Environmental Science and Pollution... Nov 2023This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene,...
This study sought to examine hitherto unresearched relationships between serum terpenes and the prevalence of dyslipidemia. Serum terpenes such as limonene, α-pinene, and β-pinene from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) were used as independent variables in this cross-sectional study. Continuous lipid variables included total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), residual cholesterol (RC), and apolipoprotein B (Apo B). Binary lipid variables (elevated TC, ≥5.18 mmol/L; lowered HDL-C, <1.04 mmol/L in men, and <1.30 mmol/L in women; elevated non-HDL-C, ≥4.2 mmol/L; elevated TG, ≥1.7 mmol/L; elevated LDL-C, ≥3.37 mmol/L; elevated RC, ≥1.0 mmol/L; and elevated Apo B, ≥1.3 g/L) suggest dyslipidemia. The relationships between the mixture of serum terpenes with lipid variables were investigated using weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR). The study for TC, HDL-C, and non-HDL-C included a total of 1,528 people, whereas the analysis for TG, LDL-C, RC, and Apo B comprised 714 participants. The mean age of the overall participants was 47.69 years, and 48.77% were male. We found that tertiles of serum terpene were positively associated with binary (elevated TC, non-HDL-C, TG, LDL-C, RC, Apo B, and lowered HDL-C) and continuous (TC, non-HDL-C, TG, LDL-C, RC, and Apo B, but not HDL-C) serum lipid variables. WQS regression and BKMR analysis revealed that the mixture of serum terpenes was linked with the prevalence of dyslipidemia. According to our data, the prevalence of dyslipidemia was correlated with serum concentrations of three terpenes both separately and collectively.
Topics: Humans; Male; Female; Middle Aged; Cholesterol, LDL; Nutrition Surveys; Terpenes; Prevalence; Cross-Sectional Studies; Bayes Theorem; Cholesterol; Triglycerides; Cholesterol, HDL; Hypercholesterolemia; Dyslipidemias; Lipoproteins; Apolipoproteins B
PubMed: 37880399
DOI: 10.1007/s11356-023-30546-0 -
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 -
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