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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 -
Frontiers in Endocrinology 2023To investigate the relationship between function of thyroid, lipids, and cholelithiasis and to identify whether lipids mediate the causal relationship between function...
OBJECTIVE
To investigate the relationship between function of thyroid, lipids, and cholelithiasis and to identify whether lipids mediate the causal relationship between function of thyroid and cholelithiasis.
METHODS
A Mendelian randomization (MR) study of two samples was performed to determine the association of thyroid function with cholelithiasis. A two-step MR was also performed to identify whether lipid metabolism traits mediate the effects of thyroid function on cholelithiasis. A method of inverse variance weighted (IVW), weighted median method, maximum likelihood, MR-Egger, MR-robust adjusted profile score (MR-RAPS) method, and MR pleiotropy residual sum and outlier test (MR-PRESSO) methods were utilized to obtain MR estimates.
RESULTS
The IVW method revealed that FT4 levels were correlated with an elevated risk of cholelithiasis (OR: 1.149, 95% CI: 1.082-1.283, = 0.014). Apolipoprotein B (OR: 1.255, 95% CI: 1.027-1.535, = 0.027) and low-density lipoprotein cholesterol (LDL-C) (OR: 1.354, 95% CI: 1.060-1.731, = 0.016) were also correlated with an elevated risk of cholelithiasis. The IVW method demonstrated that FT4 levels were correlated with the elevated risk of apolipoprotein B (OR: 1.087, 95% CI: 1.019-1.159, = 0.015) and LDL-C (OR: 1.084, 95% CI: 1.018-1.153, = 0.012). Thyroid function and the risk of cholelithiasis are mediated by LDL-C and apolipoprotein B. LDL-C and apolipoprotein B had 17.4% and 13.5% of the mediatory effects, respectively.
CONCLUSIONS
We demonstrated that FT4, LDL-C, and apolipoprotein B had significant causal effects on cholelithiasis, with evidence that LDL-C and apolipoprotein B mediated the effects of FT4 on cholelithiasis risk. Patients with high FT4 levels should be given special attention because they may delay or limit the long-term impact on cholelithiasis risk.
Topics: Humans; Mendelian Randomization Analysis; Cholesterol, LDL; Thyroid Gland; Apolipoproteins B; Causality
PubMed: 37065749
DOI: 10.3389/fendo.2023.1166740 -
Journal of Medical Primatology Dec 2022Owl monkeys (Aotus infulatus) are frequently affected by heart diseases and, as in humans, dyslipidemia is one of the predisposing factors for adverse cardiovascular...
BACKGROUND
Owl monkeys (Aotus infulatus) are frequently affected by heart diseases and, as in humans, dyslipidemia is one of the predisposing factors for adverse cardiovascular events. In view of this, the study of the lipid profile and plasma apolipoproteins can contribute to the clinical management of this neotropical primate species.
METHODS
Lipid profile as well as A-1 and B apolipoprotein values were analyzed in 60 owl monkeys, studying their relationship with body biometry and the presence of cardiac alterations.
RESULTS
Animals suspected of having heart disease did not show significant differences (p < .05) in terms of biometry or in relation to lipid profile and apolipoproteins A-1 and B values; however, higher values of LDL and ApoB and ApoB/ApoA-1 were observed in this group.
CONCLUSIONS
This study is the first to describe the lipid profile and apolipoprotein values in owl monkeys, and further work will be needed to better elucidate the worthiness of LDL, ApoB, and the ApoB/ApoA-1 ratio in this primate species.
Topics: Animals; Aotidae; Apolipoprotein A-I; Apolipoproteins; Apolipoproteins B
PubMed: 35916434
DOI: 10.1111/jmp.12607 -
Journal of Diabetes Research 2019Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase... (Review)
Review
PURPOSE
Nontraditional cardiovascular risk factors as apolipoprotein A (ApoA), apolipoprotein B (ApoB), and the proprotein convertase subtilisin/kexin type 9 (PCSK9) increase the prevalence of cardiovascular mortality in chronic kidney disease (CKD) or in end-stage renal disease (ESRD) through quantitative alterations. This review is aimed at establishing the biomarker (ApoA, ApoB, and PCSK9) level variations in uremic patients, to identify the studies showing the association between these biomarkers and the development of cardiovascular events and to depict the therapeutic options to reduce cardiovascular risk in CKD and ESRD patients.
METHODS
We searched the electronic database of PubMed, Scopus, EBSCO, and Cochrane CENTRAL for studies evaluating apolipoproteins and PCSK9 in CKD and ESRD. Randomized controlled trials, observational studies (including case-control, prospective or retrospective cohort), and reviews/meta-analysis were included if reference was made to those keys and cardiovascular outcomes in CKD/ESRD.
RESULTS
18 studies met inclusion criteria. Serum ApoA-I has been significantly associated with the development of new cardiovascular event and with cardiovascular mortality in ESRD patients. ApoA-IV level was independently associated with maximum carotid intima-media thickness (cIMT) and was a predictor for sudden cardiac death. The ApoB/ApoA-I ratio represents a strong predictor for coronary artery calcifications, cardiovascular mortality, and myocardial infarction in CKD/ESRD. Plasma levels of PCSK9 were not associated with cardiovascular events in CKD patients.
CONCLUSIONS
Although the "dyslipidemic status" in CKD/ESRD is not clearly depicted, due to different research findings, ApoA-I, ApoA-IV, and ApoB/ApoA-I ratio could be predictors of cardiovascular risk. Serum PCSK9 levels were not associated with the cardiovascular events in patients with CKD/ESRD. Probably in the future, the treatment of dyslipidemia in CKD/ESRD will be aimed at discovering new effective therapies on the action of these biomarkers.
Topics: Apolipoproteins A; Apolipoproteins B; Cardiovascular Diseases; Humans; Kidney Failure, Chronic; Proprotein Convertase 9; Renal Insufficiency, Chronic; Risk Factors
PubMed: 31915710
DOI: 10.1155/2019/6906278 -
Circulation Research Feb 2023Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid...
BACKGROUND
Recognition of the importance of conventional lipid measures and the advent of novel lipid-lowering medications have prompted the need for more comprehensive lipid panels to guide use of emerging treatments for the prevention of coronary heart disease (CHD). This report assessed the relevance of 13 apolipoproteins measured using a single mass-spectrometry assay for risk of CHD in the PROCARDIS case-control study of CHD (941 cases/975 controls).
METHODS
The associations of apolipoproteins with CHD were assessed after adjustment for established risk factors and correction for statin use. Apolipoproteins were grouped into 4 lipid-related classes [lipoprotein(a), low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides] and their associations with CHD were adjusted for established CHD risk factors and conventional lipids. Analyses of these apolipoproteins in a subset of the ASCOT trial (Anglo-Scandinavian Cardiac Outcomes Trial) were used to assess their within-person variability and to estimate a correction for statin use. The findings in the PROCARDIS study were compared with those for incident cardiovascular disease in the Bruneck prospective study (n=688), including new measurements of Apo(a).
RESULTS
Triglyceride-carrying apolipoproteins (ApoC1, ApoC3, and ApoE) were most strongly associated with the risk of CHD (2- to 3-fold higher odds ratios for top versus bottom quintile) independent of conventional lipid measures. Likewise, ApoB was independently associated with a 2-fold higher odds ratios of CHD. Lipoprotein(a) was measured using peptides from the Apo(a)-kringle repeat and Apo(a)-constant regions, but neither of these associations differed from the association with conventionally measured lipoprotein(a). Among HDL-related apolipoproteins, ApoA4 and ApoM were inversely related to CHD, independent of conventional lipid measures. The disease associations with all apolipoproteins were directionally consistent in the PROCARDIS and Bruneck studies, with the exception of ApoM.
CONCLUSIONS
Apolipoproteins were associated with CHD independent of conventional risk factors and lipids, suggesting apolipoproteins could help to identify patients with residual lipid-related risk and guide personalized approaches to CHD risk reduction.
Topics: Humans; Prospective Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Case-Control Studies; Proteomics; Apolipoproteins; Risk Factors; Coronary Disease; Triglycerides; Cholesterol, HDL; Lipoprotein(a); Apolipoproteins B; Apolipoprotein A-I
PubMed: 36691918
DOI: 10.1161/CIRCRESAHA.122.321690 -
The Journal of Clinical Endocrinology... Aug 2022Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of...
BACKGROUND
Lipoprotein(a) (Lp(a)) is a significant cardiovascular risk factor. Knowing the mechanisms that regulate its concentration can facilitate the development of Lp(a)-lowering drugs. This study analyzes the relationship between triglycerides (TGs) and Lp(a) concentrations, cross-sectionally and longitudinally, and the influence of the number and composition of TG-rich lipoproteins, and the APOE genotype.
METHODS
Data from Aragon Workers Health Study (AWHS) (n = 5467), National Health and Nutrition Examination Survey III phase 2 (n = 3860), and Hospital Universitario Miguel Servet (HUMS) (n = 2079) were used for cross-sectional TG and Lp(a) relationship. Lp(a) intrasubject variation was studied in AWHS participants and HUMS patients with repeated measurements. TG-rich lipoproteins were quantified by nuclear magnetic resonance in a subsample from AWHS. Apolipoproteins B and E were quantified by Luminex in very low-density lipoprotein (VLDL) isolated by ultracentrifugation, from HUMS samples. APOE genotyping was carried in AWHS and HUMS participants. Regression models adjusted for age and sex were used to study the association.
RESULTS
The 3 studies showed an inverse relationship between TG and Lp(a). Increased VLDL number, size, and TG content were associated with significantly lower Lp(a). There was an inverse association between the apoE concentration in VLDL and Lp(a). No significant association was observed for apolipoprotein (apo)B. Subjects carrying the apoE2/E2 genotype had significantly lower levels of Lp(a).
CONCLUSION
Our results show an inverse relationship Lp(a)-TG. Subjects with larger VLDL size have lower Lp(a), and lower values of Lp(a) were present in patients with apoE-rich VLDL and apoE2/E2 subjects. Our results suggest that bigger VLDLs and VLDLs enriched in apoE are inversely involved in Lp(a) plasma concentration.
Topics: Apolipoprotein E2; Apolipoproteins B; Apolipoproteins E; Cross-Sectional Studies; Humans; Lipoprotein(a); Lipoproteins, VLDL; Nutrition Surveys; Triglycerides
PubMed: 35789387
DOI: 10.1210/clinem/dgac412 -
Journal of Atherosclerosis and... Oct 2021Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride... (Review)
Review
Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder caused by biallelic pathogenic mutations in the MTTP gene. Deficiency of microsomal triglyceride transfer protein (MTTP) abrogates the assembly of apolipoprotein (apo) B-containing lipoprotein in the intestine and liver, resulting in malabsorption of fat and fat-soluble vitamins and severe hypolipidemia. Patients with ABL typically manifest steatorrhea, vomiting, and failure to thrive in infancy. The deficiency of fat-soluble vitamins progressively develops into a variety of symptoms later in life, including hematological (acanthocytosis, anemia, bleeding tendency, etc.), neuromuscular (spinocerebellar ataxia, peripheral neuropathy, myopathy, etc.), and ophthalmological symptoms (e.g., retinitis pigmentosa). If left untreated, the disease can be debilitating and even lethal by the third decade of life due to the development of severe complications, such as blindness, neuromyopathy, and respiratory failure. High dose vitamin supplementation is the mainstay for treatment and may prevent, delay, or alleviate the complications and improve the prognosis, enabling some patients to live to the eighth decade of life. However, it cannot fully prevent or restore impaired function. Novel therapeutic modalities that improve quality of life and prognosis are awaited. The aim of this review is to 1) summarize the pathogenesis, clinical signs and symptoms, diagnosis, and management of ABL, and 2) propose diagnostic criteria that define eligibility to receive financial support from the Japanese government for patients with ABL as a rare and intractable disease. In addition, our diagnostic criteria and the entry criterion of low-density lipoprotein cholesterol (LDL-C) <15 mg/dL and apoB <15 mg/dL can be useful in universal or opportunistic screening for the disease. Registry research on ABL is currently ongoing to better understand the disease burden and unmet needs of this life-threatening disease with few therapeutic options.
Topics: Abetalipoproteinemia; Apolipoproteins B; Cholesterol, LDL; Cost of Illness; Disease Management; Humans; Prognosis
PubMed: 33994405
DOI: 10.5551/jat.RV17056 -
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 -
Current Opinion in Endocrinology,... Apr 2021This review summarizes the evidence that apolipoprotein B (apoB) integrates the conventional lipid markers - total cholesterol, triglycerides, LDL-cholesterol, and... (Review)
Review
PURPOSE OF REVIEW
This review summarizes the evidence that apolipoprotein B (apoB) integrates the conventional lipid markers - total cholesterol, triglycerides, LDL-cholesterol, and non-HDL-cholesterol - into a single index that accurately and simply quantitates the atherogenic risk due to the apoB lipoprotein particles.
RECENT FINDINGS
Marked hypertriglyceridemia remains the essential signal for hyperchylomicronemia and potential pancreatitis. However, with the exception of Lp(a) and the abnormal cholesterol-enriched remnant particles that are the hallmark of type III hyperlipoproteinemia, recent evidence from discordance analyses and Mendelian randomization indicate that apoB integrates the risk due to the atherogenic lipoprotein particles because all LDL particles are, within the limits of our ability to measure any differences, equally atherogenic and all, except the largest VLDL particles are, within the limits of our ability to measure any differences, equally atherogenic.
SUMMARY
Measuring apoB as well as the conventional lipids is essential for accurate diagnosis. For almost all follow-up, however, apoB is all that need be measured. ApoB is the Rosetta Stone of lipidology because dyslipoproteinemia cannot be understood unless apoB is measured.
Topics: Apolipoproteins B; Cholesterol, LDL; Dyslipidemias; Humans; Hypertriglyceridemia; Lipoproteins; Triglycerides
PubMed: 33229928
DOI: 10.1097/MED.0000000000000596 -
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