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PloS One 2024Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with...
BACKGROUND
Early life factors may predict cardiovascular disease (CVD), but the pathways are still unclear. There is emerging evidence of an association of early life factors with apolipoproteins, which are linked to CVD. The study objective was to assess the associations between birth variables and adult apolipoproteins (apoA1 and apoB, and their ratio) in a population-based cohort.
METHODS
The LifeGene Study is a prospective cohort comprising index participants randomly sampled from the general population. Blood samples were collected between 2009 and 2016. In this sub-study, we used birth variables, obtained from a national registry for all participants born 1973 or later, including birth weight and gestational age, while adult CVD risk factors included age, sex, body mass index (BMI), lipids, and smoking history. We employed univariate and multivariate general linear regression to explore associations between birth variables, lipid levels and other adult CVD risk factors. The outcomes included non-fasting apoA1 and apoB and their ratio, as well as total cholesterol and triglycerides. A total of 10,093 participants with both birth information and lipoprotein levels at screening were included. Of these, nearly 42.5% were men (n = 4292) and 57.5% were women (n = 5801).
RESULTS
The mean (standard deviation) age of men was 30.2 (5.7) years, and for women 28.9 (5.8) years. There was an increase of 0.022 g/L in apoA1 levels per 1 kg increase in birth weight (p = 0.005) after adjusting for age, sex, BMI, gestational age, and smoking history. Similarly, there was a decrease of 0.023 g/L in apoB levels per 1 kg increase in birth weight (p<0.001) after adjusting for the same variables. There were inverse associations of birth weight with the apoB/apoA1 ratio. No independent association was found with total cholesterol, but with triglyceride levels (ẞ-coefficient (95% Confidence Interval); -0.067 (-0.114, -0.021); p-value 0.005).
CONCLUSIONS
Lower birth weight was associated with an adverse adult apolipoprotein pattern, i.e., a higher apoB/apoA1 ratio, indicating increased risk of future CVD manifestations. The study highlights the need of preconception care and pregnancy interventions that aim at improving maternal and child outcomes with long-term impacts for prevention of cardiovascular disease by influencing lipid levels.
Topics: Male; Adult; Pregnancy; Child; Humans; Female; Birth Weight; Prospective Studies; Cardiovascular Diseases; Apolipoproteins B; Apolipoproteins; Triglycerides; Cholesterol; Apolipoprotein A-I
PubMed: 38427666
DOI: 10.1371/journal.pone.0299725 -
Lipids in Health and Disease Feb 2024Dyslipidemia is significantly more common in those with concurrent chronic kidney disease (CKD) and chronic heart failure (CHF). Sacubitril/valsartan has showcased its...
BACKGROUND AND OBJECTIVE
Dyslipidemia is significantly more common in those with concurrent chronic kidney disease (CKD) and chronic heart failure (CHF). Sacubitril/valsartan has showcased its influence on both cardiac and renal functions, extending its influence to the modulation of lipid metabolism pathways. This study aimed to examine how sacubitril/valsartan affects lipid metabolism within the context of CKD and CHF.
METHODS
This study adopted a retrospective design, focusing on a single center and involving participants who were subjected to treatment with sacubitril/valsartan and valsartan. The investigation assessed the treatment duration, with a particular emphasis on recording blood lipid indicators, including triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein A (ApoA), and apolipoprotein B (ApoB). Furthermore, cardiac and renal functions, blood pressure, potassium levels, and other factors influencing the blood lipids were analyzed in both groups at identical time points.
RESULTS
After 16 weeks of observation, the sacubitril/valsartan group exhibited lower TG levels compared to the valsartan group. Noteworthy was the fact that individuals undergoing sacubitril/valsartan treatment experienced an average reduction of 0.84 mmol/L in TG levels, in stark contrast to the valsartan group, which registered a decline of 0.27 mmol/L (P < 0.001). The sacubitril/valsartan group exhibited elevated levels of HDL-C and ApoA in comparison to the valsartan group (P = 0.023, P = 0.030). While TC, LDL-C, and ApoB decreased compared to baseline, the differences between groups were not statistical significance. Regarding cardiac indicators, there was an observed enhancement in the left ventricular ejection fraction (LVEF) within the sacubitril/valsartan group when compared to the baseline, and it was noticeably higher than that of the valsartan group. Spearman correlation analysis and multiple linear regression analysis revealed that medication, body mass index(BMI), and hemoglobin A1c (HbA1c) had a direct influencing effect on TG levels.
CONCLUSION
Sacubitril/valsartan demonstrated improvements in lipid metabolism and cardiac indicators in patients with CKD and CHF. Specifically, it presented promising benefits in reducing TG levels. In addition, both BMI and HbA1c emerged as influential factors contributing to alterations in TG levels, independent of the administration of sacubitril/valsartan.
Topics: Humans; Retrospective Studies; Stroke Volume; Cholesterol, LDL; Glycated Hemoglobin; Lipid Metabolism; Tetrazoles; Ventricular Function, Left; Valsartan; Heart Failure; Biphenyl Compounds; Renal Insufficiency, Chronic; Drug Combinations; Apolipoproteins A; Apolipoproteins B; Apolipoproteins; Aminobutyrates
PubMed: 38419057
DOI: 10.1186/s12944-024-02051-x -
Communications Biology Feb 2024Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein...
Apolipoprotein B-100 (APOB) is a component of fat- and cholesterol-transporting molecules in the bloodstream. It is the main lipoprotein in low-density lipoprotein cholesterol (LDL) and has been implicated in conditions that end healthspan (the interval between birth and onset of chronic disease). However, APOB's direct relationship with healthspan remains uncertain. With Mendelian randomization, we show that higher levels of APOB and LDL shorten healthspan in humans. Multivariable Mendelian randomization of APOB and LDL on healthspan suggests that the predominant trait accounting for the relationship is APOB. In addition, we provide preliminary evidence that APOB increases risk for Alzheimer's disease, a condition that ends healthspan. If these relationships are causal, they suggest that interventions to improve healthspan in aging populations could include strategies targeting APOB. Ultimately, given that more than 44 million people currently suffer from Alzheimer's disease worldwide, such interventions are needed.
Topics: Humans; Alzheimer Disease; Mendelian Randomization Analysis; Apolipoproteins B; Cholesterol, LDL; Phenotype
PubMed: 38402277
DOI: 10.1038/s42003-024-05887-2 -
Genes Jan 2024Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be regulated by 17 circadian...
Circadian Rhythm Alteration of the Core Clock Genes and the Lipid Metabolism Genes Induced by High-Fat Diet (HFD) in the Liver Tissue of the Chinese Soft-Shelled Turtle ().
Physiology disorders of the liver, as it is an important tissue in lipid metabolism, can cause fatty liver disease. The mechanism might be regulated by 17 circadian clock genes and 18 fat metabolism genes, together with a high-fat diet (HFD). Due to their rich nutritional and medicinal value, Chinese soft-shelled turtles () are very popular among the Chinese people. In the study, we aimed to investigate the influence of an HFD on the daily expression of both the core clock genes and the lipid metabolism genes in the liver tissue of the turtles. The two diets were formulated with 7.98% lipid (the CON group) and 13.86% lipid (the HFD group) to feed 180 juvenile turtles, which were randomly divided into two groups with three replicates per group and 30 turtles in each replicate for six weeks, and the diet experiment was administrated with a photophase regimen of a 24 h light/dark (12L:12D) cycle. At the end of the experiment, the liver tissue samples were collected from nine turtles per group every 3 h (zeitgeber time: ZT 0, 3, 6, 9, 12, 15, 18, 21 and 24) for 24 h to investigate the daily expression and correlation analysis of these genes. The results showed that 11 core clock genes [i.e., circadian locomotor output cycles kaput (), brain and muscle arnt-like protein 1 and 2 (1/2), timeless (, cryptochrome 1 (2), period2 (2), nuclear factor IL-3 gene (3), nuclear receptor subfamily 1, treatment D, member 1 and 2 (1/2) and retinoic acid related orphan receptor α/β/γ (/)] exhibited circadian oscillation, but 6 genes did not, including neuronal PAS domain protein 2 (2), 1, 1, basic helix-loop-helix family, member E40 (40), and D-binding protein (), and 16 lipid metabolism genes including fatty acid synthase (), diacylglycerol acyltransferase 1 (1), 3-hydroxy-3-methylglutaryl-CoA reductase (), Low-density lipoprotein receptor-related protein 1-like (1), Lipin 1 (1), Carnitine palmitoyltransferase 1A (1a), Peroxisome proliferator activation receptor α, β and γ (//), Sirtuin 1 (1), (1), Apolipoprotein B (), Pyruvate Dehydrogenase kinase 4 (4), Acyl-CoA synthase long-chain1 (1), Liver X receptors α () and Retinoid X receptor, α () also demonstrated circadian oscillations, but 2 genes did not, and in the liver tissues of the CON group. However, in the HFD group, the circadian rhythms' expressional patterns were disrupted for the eight core clock genes, , 2, 2, 3, 11/2 and /, and the peak expression of 1/2 and showed delayed or advanced phases. Furthermore, four genes (1, 1, and ) displayed no diurnal rhythm in the CON group; instead, significant circadian rhythms appeared in the HFD group. Meanwhile, the HFD disrupted the circadian rhythm expressions of seven fat metabolism genes (, 1a, 1, 1, , 4 and 1). Meanwhile, the other nine genes in the HFD group also showed advanced or delayed expression peaks compared to the CON group. Most importantly of all, there were remarkably positive or negative correlations between the core clock genes and the lipid metabolism genes, and their correlation relationships were altered by the HFD. To sum up, circadian rhythm alterations of the core clock genes and the lipid metabolism genes were induced by the high-fat diet (HFD) in the liver tissues of . This result provides experimental and theoretical data for the mass breeding and production of in our country.
Topics: Animals; Apolipoproteins B; ARNTL Transcription Factors; Circadian Rhythm; Diet, High-Fat; Lipid Metabolism; Lipids; Liver; Sirtuin 1; Turtles; CLOCK Proteins
PubMed: 38397147
DOI: 10.3390/genes15020157 -
Journal of Cardiovascular Development... Jan 2024The prevention of cardiovascular (CV) disease is mandatory from childhood onwards. Among biochemical markers related to the clinical cardiovascular outcome, LDL...
RATIONALE
The prevention of cardiovascular (CV) disease is mandatory from childhood onwards. Among biochemical markers related to the clinical cardiovascular outcome, LDL cholesterol (LDL-C), non-HDL-C and apolipoprotein B (ApoB) are recognized as main target parameters. Emphasis on ApoB concentrations is growing, as representative of any class of atherogenic lipoprotein. This consideration allows checking of subjects under 18 years of age when the CV risk occurs. The aim of this study is to evaluate ApoB levels in a sample of Italian hyperlipidemic children and adolescents, and their siblings, to test any relationship with their lipid profile.
METHODS
A retrospective study, including 1877 children and adolescents (aged 0-18 years), was performed. Clinical and biochemical data were selected from a database, including the lipid profile, ApoB analysis and anthropometric parameters of any proband. Participants had been checked as potentially hyperlipidemia affected, the suspicion raised by familial CV risk or because the dyslipidemia was already known. Data from the first visit at the University Hospitals in Rome and Turin were collected. Patients affected by secondary hyperlipidemia or obesity were excluded. Blood test analysis was performed in fasting conditions by automated commercial kits. Participants were classified according to gender, age (stratified in subgroups: 0-5, 6-10, 11-14, and 15-18 years old) and anthropometric parameters, referred to as weight in Kg and height in cm, and BMI calculated. Lipid profile results were stratified in relation to acceptable, borderline, or increased levels, as indicated by NCEP, and any potential relation with ApoB established. Statistics were performed by Epi-Info 7 programs to evaluate the variance analysis. Either parent could sign the informed consent.
RESULTS
Among the whole sample n.1010 and n.867 participants were females and males, respectively. TC values acceptable (≤170 mg/dL), borderline (171-200 mg/dL) and elevated (≥201 mg/dL) were found in 411 (22%), 585 (31%) and 881 (47%) participants, respectively. The LDL-C cut-off considered was 110 mg/dL (90° percentile). Mean ApoB progressively increased from 65 to 110 mg/dL according to TC levels and resulted in significant correlation when any age subgroup and gender was considered. The highest ApoB values, TC and LDL-C related, were found in the youngest subgroup, regardless of gender.
CONCLUSION
ApoB results increase progressively and in parallel with TC and LDL-C and represent a further parameter to distinguish between normal and hyperlipidemic subjects. Serum levels are close to 70 mg/dL and to 100 mg/dL in the former and latter group, respectively.
PubMed: 38392258
DOI: 10.3390/jcdd11020044 -
Frontiers in Endocrinology 2024The effect of hypolipidemic drugs on male erectile function is still controversial. This Mendelian randomization (MR) study aimed to explore the potential impact of...
OBJECTIVE
The effect of hypolipidemic drugs on male erectile function is still controversial. This Mendelian randomization (MR) study aimed to explore the potential impact of lipid-lowering drug targets on ED.
METHODS
We collected seven genetic variants encoding lipid-lowering drug targets (LDLR, HMGCR, NPC1L1, PCSK9, APOB, APOC3 and LPL) from published genome-wide association study (GWAS) statistics, and performed drug target MR analysis. The risk of ED was defined as the primary outcome, sex hormone levels and other diseases as the secondary outcomes. Mediation analyses were performed to explore potential mediating factors.
RESULTS
The results showed that LDLR, LPL agonists and APOC3 inhibitors were significantly associated with a reduced risk of ED occurrence. APOB inhibitors were associated with an increased risk of ED occurrence. In terms of sex hormone levels, LDLR and LPL agonists were significantly associated with increased TT levels, and HMGCR was associated with decreased TT and BT levels significantly. In terms of male-related disease, MR results showed that LDLR agonists and PCSK9 inhibitors were significantly associated with an elevated risk of PH; HMGCR, NPC1L1 inhibitors were associated with a reduced risk of PCa; and LDLR agonists were significantly associated with a reduced risk of AS and MI; in addition, HMGCR inhibitors were associated with a reduced risk of PCa.
CONCLUSION
After performing drug-targeted MR analysis, we found that that there was a causal relationship between lipid-lowering drug targets and ED. APOC3, APOB, LDLR and LPL may be new candidate drug targets for the treatment of ED.
Topics: Male; Humans; Proprotein Convertase 9; Erectile Dysfunction; Genome-Wide Association Study; Reproductive Health; Cholesterol, LDL; Hypolipidemic Agents; Apolipoproteins B; Gonadal Steroid Hormones
PubMed: 38390206
DOI: 10.3389/fendo.2024.1362499 -
Journal of Korean Medical Science Feb 2024Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have...
BACKGROUND
Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort.
METHODS
We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age: 38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment.
RESULTS
Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV%) and forced vital capacity (FVC%) after controlling for covariates ( < 0.001). However, FEV/FVC ratio was not significantly different among the four quartiles ( = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV% < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094-1.351), 1.293 (1.156-1.448), and 1.481 (1.311-1.672) ( for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090-1.348), 1.283 (1.147-1.436), and 1.502 (1.331-1.695) with increasing quartiles ( for trend < 0.001). However, the aORs for FEV/FVC < LLN were not significantly different among groups ( for trend = 0.273).
CONCLUSION
High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.
Topics: Adult; Humans; Male; Apolipoprotein A-I; Apolipoproteins B; Cohort Studies; Forced Expiratory Volume; Lung; Spirometry; Vital Capacity; Lung Diseases
PubMed: 38374625
DOI: 10.3346/jkms.2024.39.e51 -
Scientific Reports Feb 2024This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a...
This study aimed to investigate the association of lipid profile in early pregnancy and the risk of congenital heart disease (CHD) in offspring. This study was a prospective cohort design based on the Fujian Birth Cohort Study in China. We recruited pregnant women at ≤ 14 weeks of gestation between 2019 and 2022, and all participants in this study filled out the questionnaire about periconceptional exposure. Simultaneously, we collected participants' fasting blood samples to measure their lipid profile by automatic biochemical analyzer. The outcome was defined as offspring with CHD. A multivariable logistic regression model was used to calculate adjusted odds ratio (AOR) risk estimates, which indicate the associations between maternal lipid profiles and CHD in offspring. Restricted cubic splines were used to estimate their nonlinear relationship. A total of 21,425 pregnant women with an average gestational age of 11.3 (± 1.40) weeks were included in the analysis. The higher triglyceride (AOR 1.201, 95% CI [1.036, 1.394]), low-density lipoprotein (AOR 1.216, 95% CI [1.048, 1.410]), apolipoprotein B (Apo B) (AOR 2.107, 95% CI [1.179, 3.763]) levels were correlated with increased odds of CHD in offspring, while high-density lipoprotein (OR 0.672, 95% CI [0.490, 0.920]) related with decreased odds of CHD in offspring. The restricted cubic spline suggested a nonlinear relationship between total cholesterol (TC) levels and the risk of CHD in offspring (P = 0.0048), but no significant nonlinear relationships were found in other lipid profile. Apolipoprotein A was not related to the risk of CHD in offspring as either a continuous variable or a hierarchical variable. Elevated lipid profile in early pregnancy levels are associated with an increased risk of CHD in offspring. Additionally, there is a non-linear relationship between TC levels and the risk of CHD in offspring.
Topics: Humans; Female; Pregnancy; Infant; Prospective Studies; Risk Factors; Cohort Studies; Heart Defects, Congenital; Apolipoproteins B
PubMed: 38351050
DOI: 10.1038/s41598-024-53876-6 -
The Journal of Biological Chemistry Mar 2024Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers...
Hyperlipidemia predisposes individuals to cardiometabolic diseases, the most common cause of global mortality. Microsomal triglyceride transfer protein (MTP) transfers multiple lipids and is essential for the assembly of apolipoprotein B-containing lipoproteins. MTP inhibition lowers plasma lipids but causes lipid retention in the liver and intestine. Previous studies suggested two lipid transfer domains in MTP and that specific inhibition of triglyceride (TG) and not phospholipid (PL) transfer can lower plasma lipids without significant tissue lipid accumulation. However, how MTP transfers different lipids and the domains involved in these activities are unknown. Here, we tested a hypothesis that two different β-sandwich domains in MTP transfer TG and PL. Mutagenesis of charged amino acids in β2-sandwich had no effect on PL transfer activity indicating that they are not critical. In contrast, amino acids with bulky hydrophobic side chains in β1-sandwich were critical for both TG and PL transfer activities. Substitutions of these residues with smaller hydrophobic side chains or positive charges reduced, whereas negatively charged side chains severely attenuated MTP lipid transfer activities. These studies point to a common lipid transfer domain for TG and PL in MTP that is enriched with bulky hydrophobic amino acids. Furthermore, we observed a strong correlation in different MTP mutants with respect to loss of both the lipid transfer activities, again implicating a common binding site for TG and PL in MTP. We propose that targeting of areas other than the identified common lipid transfer domain might reduce plasma lipids without causing cellular lipid retention.
Topics: Humans; Amino Acids; Apolipoproteins B; Carrier Proteins; Phospholipids; Triglycerides; Hydrophobic and Hydrophilic Interactions; Protein Domains; Mutation; Structure-Activity Relationship; Binding Sites
PubMed: 38325741
DOI: 10.1016/j.jbc.2024.105726 -
Medical Science Monitor : International... Feb 2024BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more...
BACKGROUND Hypertriglyceridemia-induced acute pancreatitis (HTG-AP), representing 10% of all acute pancreatitis cases, is characterized by younger onset age and more severe progression, often leading to higher ICU admission rates. This condition poses a significant challenge due to its rapid progression and the potential for severe complications, including multiple organ failure. HTG-AP is distinct from other forms of pancreatitis, such as those caused by cholelithiasis or alcohol, in terms of clinical presentation and outcomes. It's essential to identify early markers that can predict the severity of HTG-AP to improve patient management and outcomes. MATERIAL AND METHODS This study divided 127 HTG-AP patients into mild acute pancreatitis (MAP, n=71) and moderate-to-severe acute pancreatitis (MSAP/SAP, n=56) groups. Blood biological indicators within the first 24 hours of admission were analyzed. Risk factors for HTG-AP progression were determined using binary logistic regression and ROC curves. RESULTS Elevated levels of HCT, NLR, TBI, DBI, AST, Cre, and AMS were noted in the MSAP/SAP group, with lower levels of LYM, Na⁺, Ca²⁺, ApoA, and ApoB compared to the MAP group (p<0.05). NEUT%, Ca²⁺, ApoA, and ApoB were significantly linked with HTG-AP severity. Their combined ROC analysis yielded an area of 0.81, with a sensitivity of 61.8% and specificity of 90%. CONCLUSIONS NEUT%, Ca²⁺, ApoA, and ApoB are significant risk factors for progressing to MSAP/SAP in HTG-AP. Their combined assessment provides a reliable predictive measure for early intervention in patients at risk of severe progression.
Topics: Humans; Pancreatitis; Calcium; Neutrophils; Acute Disease; Retrospective Studies; Hypertriglyceridemia; Apolipoproteins; Apolipoproteins A; Apolipoproteins B
PubMed: 38321725
DOI: 10.12659/MSM.942832