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The American Journal of Cardiology Aug 2023The present study aimed to examine the association between discordant apolipoprotein B (Apo B) with low-density lipoprotein cholesterol (LDL-C) or non-high-density...
The present study aimed to examine the association between discordant apolipoprotein B (Apo B) with low-density lipoprotein cholesterol (LDL-C) or non-high-density lipoprotein cholesterol (non-HDL-C) and cardiovascular disease (CVD) risk in the Chinese population and to determine whether adding information on Apo B to LDL-C and HDL-C improves CVD risk prediction. This study collected data from the China Health and Nutrition Survey from 2009 to 2015. Discordant Apo B with LDL-C and non-HDL-C were defined based on residual differences and medians. Logistic regression was used to examine the association between discordant Apo B with LDL-C or non-HDL-C and CVD risk. Areas under the receiver operating characteristic curve and categorical net reclassification improvement were utilized to assess the incremental predictive value of Apo B levels for CVD risk. A total of 7,117 participants were included, the mean age was 50.8 ± 14.3 years, 53.6% were female. During the 6-year follow-up, 207 CVD cases were identified. Participants with discordant high Apo B relative to LDL-C or non-HDL-C were at higher risk of CVD than those with the concordant group (odds ratio 1.38, 95% confidence interval 1.01 to 1.87; odds ratio 1.40, 95% confidence interval 1.01 to 1.94, respectively). However, Apo B had no significant contribution to the predictive value of the China atherosclerotic CVD (ASCVD) risk score (areas under the receiver operating characteristic curve 0.788 for China ASCVD score alone vs 0.790 for China ASCVD score plus Apo B). In conclusion, Apo B has the strongest association with CVD risk in healthy Chinese participants than LDL-C and non-HDL-C. However, it has minimal value in CVD risk assessment and discrimination.
Topics: Humans; Female; Adult; Middle Aged; Aged; Male; Cardiovascular Diseases; Cholesterol, LDL; Prospective Studies; Risk Factors; Cholesterol, HDL; Apolipoproteins; Apolipoproteins B; Cholesterol; Lipoproteins; Heart Disease Risk Factors
PubMed: 37352662
DOI: 10.1016/j.amjcard.2023.05.052 -
Frontiers in Endocrinology 2023Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to...
BACKGROUND
Previous findings have indicated that elevated low-density lipoprotein cholesterol (LDL-C) and remnant cholesterol (RC) are associated with hypertension. We aim to explore whether higher RC levels may be associated with hypertension beyond LDL-C in the general US adult population.
METHODS
This study included 10,842 adults from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Weighted multivariable logistic regression models were used to estimate the odds ratios (ORs) of hypertension for LDL-C and RC. We also performed analyses examining the association between hypertension and LDL-C vs. RC concordant/discordant groups.
RESULTS
A total of 4,963 (41.54%, weighted) individuals had hypertension. The weighted median levels were LDL-C: 118mg/dL, RC: 20mg/dL. At lower LDL-C clinical cut-point, the proportion of discordantly high RC dramatically increased. After multivariable adjustment, log RC was associated with higher prevalence of hypertension [OR 2.54, 95% confidence interval (CI) 2.17-2.99]. Participants with the highest tertile of RC were more likely to have hypertension (OR 2.18; 95% CI 1.89-2.52) compared with those with the lowest tertile of RC. This association remained marked after including body mass index (BMI), LDL-C, high-density lipoprotein cholesterol (HDL-C) or triglycerides. The association between LDL-C and hypertension was absent after adjusting for BMI, RC or triglycerides. Compared with low LDL-C/low RC group, the discordant low LDL-C/high RC group was associated with hypertension (OR 2.04; 95% CI 1.72-2.42), whereas the high LDL-C/low RC group was not, regardless of BMI, HDL-C or triglycerides. Similar results were observed when examining discordance among different clinical cut-points, except for the cut-point of LDL-C 70 mg/dL and RC 13 mg/dL. To better understand the association, we performed an additional analysis, which showed that among participants with apolipoprotein B < median (92mg/dL), those with discordant RC ≥ median (20mg/dL) had significantly higher odds of having hypertension (OR 1.73; 95% CI 1.38-2.17).
CONCLUSION
RC was associated with hypertension beyond LDL-C in the general US adult population. This association went beyond increased triglycerides levels, and lipoproteins other than apoB may be involved.
Topics: Adult; Humans; Cholesterol, LDL; Nutrition Surveys; Cholesterol; Cholesterol, HDL; Triglycerides; Hypertension; Apolipoproteins B; Hyperlipidemias
PubMed: 37842298
DOI: 10.3389/fendo.2023.1260764 -
Ecotoxicology and Environmental Safety Dec 2023Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a...
Neonicotinoid insecticides (NNIs) are widely used in agriculture, horticulture, forestry, and household environment, but their potential impact on human health remains a subject of concern. This study aimed to investigate the relationship between NNIs and their metabolites in urine with serum lipid profiles in adults using data from the National Health and Nutrition Examination Survey (NHANES) 2015-2016. The study included 1192 participants aged over 20 years with urinary NNIs levels, serum lipid parameter levels and potential confounders. Urinary concentrations of NNIs, including imidacloprid, acetamiprid, clothianidin, thiacloprid, N-desmethyl-acetamiprid, and 5-hydroxy-imidacloprid, were quantified. Serum lipids profiles, such as total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (Apo-B), were assessed. Considering the effects of lipid-lowering medications, the censored normal regression model was used to explore the associations between urinary NNIs and TC, TG, HDL-C, LDL-C and Apo-B levels. The results revealed a significant increase of 9.0 mg/dL (95%CI: 2.0, 16.1) in TC levels among participants with detectable N-desmethyl-acetamiprid compared to those with undetectable levels. Stratified analysis indicated that the association between N-desmethyl-acetamiprid and HDL-C levels was more pronounced among participants aged ≥ 46 years compared to those aged between 20 and 45 years with undetectable N-desmethyl-acetamiprid (p=0.044). Additionally, there were marginal effect modification of BMI on the association between N-desmethyl-acetamiprid and LDL-C (p=0.097) and Apo-B (p=0.052) levels. Specifically, participants with BMI ≥ 25 kg/m² and detectable N-desmethyl-acetamiprid tended to have higher LDL-C and Apo-B levels compared to those with BMI < 25 kg/m² and undetectable N-desmethyl-acetamiprid. However, no significant associations were observed between other NNIs and lipid profiles in the present study. To validate these findings, further longitudinal studies with larger sample sizes should be conducted, particularly within populations characterized by a high detection rate of NNIs.
Topics: Adult; Humans; Young Adult; Middle Aged; Insecticides; Nutrition Surveys; Cholesterol, LDL; Cross-Sectional Studies; Neonicotinoids; Triglycerides; Cholesterol, HDL; Apolipoproteins B
PubMed: 37992647
DOI: 10.1016/j.ecoenv.2023.115724 -
European Heart Journal Mar 2024RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3)...
BACKGROUND AND AIMS
RNA-based, antibody-based, and genome editing-based therapies are currently under investigation to determine if the inhibition of angiopoietin-like protein-3 (ANGPTL3) could reduce lipoprotein-lipid levels and atherosclerotic cardiovascular disease (ASCVD) risk. Mendelian randomisation (MR) was used to determine whether genetic variations influencing ANGPTL3 liver gene expression, blood levels, and protein structure could causally influence triglyceride and apolipoprotein B (apoB) levels as well as coronary artery disease (CAD), ischaemic stroke (IS), and other cardiometabolic diseases.
METHODS
RNA sequencing of 246 explanted liver samples and genome-wide genotyping was performed to identify single-nucleotide polymorphisms (SNPs) associated with liver expression of ANGPTL3. Genome-wide summary statistics of plasma protein levels of ANGPTL3 from the deCODE study (n = 35 359) were used. A total of 647 carriers of ANGPTL3 protein-truncating variants (PTVs) associated with lower plasma triglyceride levels were identified in the UK Biobank. Two-sample MR using SNPs that influence ANGPTL3 liver expression or ANGPTL3 plasma protein levels as exposure and cardiometabolic diseases as outcomes was performed (CAD, IS, heart failure, non-alcoholic fatty liver disease, acute pancreatitis, and type 2 diabetes). The impact of rare PTVs influencing plasma triglyceride levels on apoB levels and CAD was also investigated in the UK Biobank.
RESULTS
In two-sample MR studies, common genetic variants influencing ANGPTL3 hepatic or blood expression levels of ANGPTL3 had a very strong effect on plasma triglyceride levels, a more modest effect on low-density lipoprotein cholesterol, a weaker effect on apoB levels, and no effect on CAD or other cardiometabolic diseases. In the UK Biobank, the carriers of rare ANGPTL3 PTVs providing lifelong reductions in median plasma triglyceride levels [-0.37 (interquartile range 0.41) mmol/L] had slightly lower apoB levels (-0.06 ± 0.32 g/L) and similar CAD event rates compared with non-carriers (10.2% vs. 10.9% in carriers vs. non-carriers, P = .60).
CONCLUSIONS
PTVs influencing ANGPTL3 protein structure as well as common genetic variants influencing ANGPTL3 hepatic expression and/or blood protein levels exhibit a strong effect on circulating plasma triglyceride levels, a weak effect on circulating apoB levels, and no effect on ASCVD. Near-complete inhibition of ANGPTL3 function in patients with very elevated apoB levels may be required to reduce ASCVD risk.
Topics: Humans; Acute Disease; Brain Ischemia; Diabetes Mellitus, Type 2; Pancreatitis; Stroke; Atherosclerosis; Coronary Artery Disease; Angiopoietin-Like Protein 3; Antibodies; Apolipoproteins B; Triglycerides
PubMed: 38243829
DOI: 10.1093/eurheartj/ehad845 -
Nutrition Reviews Jun 2024Genetic predisposition and dietary factors can impact cardiovascular disease (CVD) risk. Two important markers in assessing CVD risk are apolipoprotein (apo) B and... (Review)
Review
Genetic predisposition and dietary factors can impact cardiovascular disease (CVD) risk. Two important markers in assessing CVD risk are apolipoprotein (apo) B and apolipoprotein A1 plasma levels. These markers are measured as a ratio, with a high apoB:apoA1 ratio associated with increased CVD risk. Dietary and lifestyle recommendations are the cornerstone of managing primary and secondary CVD risk-mitigation strategies. One way to assess the impact of various dietary and lifestyle interventions on CVD risk is to evaluate the changes in CVD risk markers, such as apoB, apoA1, and apoB:apoA1 ratio. Various human studies have demonstrated the impact of dietary, macronutrient, and micronutrient interventions on apoB and apoA1 status. This review aims to elucidate dietary, macronutrient, micronutrient, and nutrigenetic considerations for impacting apoB and apoA1 levels. A low-carbohydrate, high-saturated-fat diet, low fiber intake, low vitamin and mineral intake, and zinc and iron deficiency are associated with an elevated apoB:apoA1 ratio. The Mediterranean diet, vegan diet, fermented dairy products, lower sugar intake, higher protein intake, higher polyunsaturated fat intake, and an omega-3-rich diet are associated with a decreased apoB:apoA1 ratio. Micronutrients associated with a decreased apoB:apoA1 ratio include vitamin D sufficiency, increased serum vitamin C, and magnesium. Variants in the APOE, APOA1, and FADS2 genes may alter the apoB:apoA1 ratio in response to various dietary interventions. When accounting for factors that may favorably alter the apoB:apoA1 ratio, researchers should consider a healthy diet sufficient in polyunsaturated fats, vitamins, minerals, trace minerals, and lower excess sugars.
Topics: Humans; Micronutrients; Cardiovascular Diseases; Diet; Nutrients; Biomarkers; Apolipoprotein A-I; Heart Disease Risk Factors; Apolipoproteins B; Nutrigenomics; Risk Factors
PubMed: 37615981
DOI: 10.1093/nutrit/nuad102 -
The American Journal of the Medical... Nov 2023Apolipoprotein B (apoB) is a crucial component that directly reflects the number of atherogenic lipoprotein particles and is closely related to atherosclerosis. However,...
BACKGROUND
Apolipoprotein B (apoB) is a crucial component that directly reflects the number of atherogenic lipoprotein particles and is closely related to atherosclerosis. However, there was an inconsistency among previous studies in its relationship with mortality. Using nationally representative data, we aimed to investigate the association of apoB with cardiovascular and all-cause mortality.
METHODS
We retrospectively included participants from the National Health and Nutrition Examination Survey (2007-2014), and mortality was ascertained through December 31, 2015. Hazard ratios (HRs) with 95% confidence intervals (CIs) of apoB in quartiles (Q1-Q4) for mortality risk were calculated using multivariable-adjusted Cox proportional hazards models, and restricted cubic spline regressions were performed to test dose relationships.
RESULTS
We enrolled 10,375 participants with a mean age of 46.3 years, of which 47.88% were men. During a mean follow-up time of 69.2 months, 533 (5.14%) and 91 (0.88%) deaths were due to all causes and cardiovascular disease, respectively. After adjusting for confounders, per SD, increment of apoB was associated with an elevated risk of cardiovascular mortality (HR, 1.13; 95% CI, 1.03-1.24). The risk of all-cause mortality was significantly reduced in the third quartile (Q3) of apoB (HR, 0.71; 95% CI, 0.56-0.91) compared with the reference quartile (Q1). Moreover, spline analyses showed that the relationship of apoB with all-cause mortality was U-shaped, and the threshold value was 108 mg/dL.
CONCLUSIONS
ApoB was linearly associated with increased risk of cardiovascular mortality and non-linearly associated with all-cause mortality in a U-shaped manner, independently of other cardiovascular risk factors.
Topics: Male; Humans; Adult; Middle Aged; Female; Nutrition Surveys; Retrospective Studies; Apolipoproteins B; Cardiovascular Diseases; Proportional Hazards Models; Atherosclerosis
PubMed: 37611866
DOI: 10.1016/j.amjms.2023.07.012 -
Journal of Lipid Research Feb 2024Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of...
Angiopoietin-like protein (ANGPTL) complexes 3/8 and 4/8 are established inhibitors of LPL and novel therapeutic targets for dyslipidemia. However, the effects of regular exercise on ANGPTL3/8 and ANGPTL4/8 are unknown. We characterized ANGPTL3/8 and ANGPTL4/8 and their relationship with in vivo measurements of lipase activities and cardiometabolic traits before and after a 5-month endurance exercise training intervention in 642 adults from the HERITAGE (HEalth, RIsk factors, exercise Training And GEnetics) Family Study. At baseline, higher levels of both ANGPTL3/8 and ANGPTL4/8 were associated with a worse lipid, lipoprotein, and cardiometabolic profile, with only ANGPTL3/8 associated with postheparin LPL and HL activities. ANGPTL3/8 significantly decreased with exercise training, which corresponded with increases in LPL activity and decreases in HL activity, plasma triglycerides, apoB, visceral fat, and fasting insulin (all P < 5.1 × 10). Exercise-induced changes in ANGPTL4/8 were directly correlated to concomitant changes in total cholesterol, LDL-C, apoB, and HDL-triglycerides and inversely related to change in insulin sensitivity index (all P < 7.0 × 10). In conclusion, exercise-induced decreases in ANGPTL3/8 and ANGPTL4/8 were related to concomitant improvements in lipase activity, lipid profile, and cardiometabolic risk factors. These findings reveal the ANGPTL3-4-8 model as a potential molecular mechanism contributing to adaptations in lipid metabolism in response to exercise training.
Topics: Adult; Humans; Angiopoietin-like Proteins; Angiopoietin-Like Protein 3; Triglycerides; Lipase; Exercise; Cardiovascular Diseases; Apolipoproteins B; Lipoprotein Lipase; Angiopoietin-Like Protein 4
PubMed: 38160757
DOI: 10.1016/j.jlr.2023.100495 -
Current Opinion in Cardiology Jan 2024Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present... (Review)
Review
PURPOSE OF REVIEW
Some experts and consensus groups continue to argue that apolipoprotein B (apoB) should not be introduced broadly into clinical care. But, too often, the present approach to clinical care is not succeeding. An important reason for this failure, we believe, is that the conventional approach limits what the expert clinician can accomplish and is too complex, confusing, and contradictory for primary care physicians to apply effectively in their practise.
RECENT FINDINGS
There are four major reasons that apoB should be measured routinely in clinical care. First, apoB is a more accurate marker of cardiovascular risk than LDL-C or non-HDL-C. Second, the measurement of apoB is standardized whereas the measurements of LDL-C and non-HDL-C are not. Third, with apoB and a conventional lipid panel, all the lipid phenotypes can be simply and accurately distinguished. This will improve the care of the expert. Fourth, apoB, as the single measure to evaluate the success of therapy, would simplify the process of care for primary care physicians.
SUMMARY
By introducing apoB broadly into clinical care, the process of care will be improved for both the expert and the primary care physician, and this will improve the outcomes of care.
Topics: Humans; Apolipoproteins B; Cholesterol; Cholesterol, HDL; Cholesterol, LDL; Lipoproteins; Cardiovascular Diseases
PubMed: 37934698
DOI: 10.1097/HCO.0000000000001100 -
Lipids in Health and Disease Oct 2023Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a...
BACKGROUND
Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder. The primary objective of this study was to identify the major pathogenic mutations in a Chinese family with FH.
METHODS
Whole-genome sequencing (WGS) was used to identify variants of FH-related genes, including low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9). Bioinformatics software was used to predict signal peptides, transmembrane structures, and spatial construction information of the mutated sequences. Western blotting was performed on the mutant protein to determine the presence of the major structural domains of the LDLR. The PCSK9 and APOB genes were screened and analyzed. Moreover, the proband and his brother were treated with a PCSK9 inhibitor for 1 year, and the effect of the treatment on lipid levels was assessed.
RESULTS
WGS revealed two potentially pathogenic mutations in the LDLR gene. One was a novel mutation, c.497delinsGGATCCCCCAGCTGCATCCCCCAG (p. Ala166fs), and the other was a known pathogenic mutation, c.2054C>T (p. Pro685Leu). Bioinformatics prediction and in vitro experiments revealed that the novel mutation could not be expressed on the cell membrane. Numerous gene variants were identified in the APOB gene that may have a significant impact on the family members with FH. Thus, it is suggested that the severe manifestation of FH in the proband primarily resulted from the cumulative genetic effects of variants in both LDLR and APOB. However, a subsequent study indicated that treatment with a PCSK9 inhibitor (Evolocumab) did not significantly reduce the blood lipid levels in the proband or his brother.
CONCLUSIONS
The cumulative effect of LDLR and APOB variants was the primary cause of elevated blood lipid levels in this family. However, PCSK9 inhibitor therapy did not appear to be beneficial for the proband. This study emphasizes the importance of genetic testing in determining the most suitable treatment options for patients with FH.
Topics: Humans; Male; Apolipoproteins B; East Asian People; Hyperlipoproteinemia Type II; Lipids; Mutation; Proprotein Convertase 9; Receptors, LDL; Genetic Testing
PubMed: 37853441
DOI: 10.1186/s12944-023-01935-8 -
Journal of Clinical Lipidology 2023Proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibodies (mAbs) reduce fasting and post fat load cholesterol in non-HDL and intermediate density... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Proprotein convertase subtilisin kexin type 9 (PCSK9) monoclonal antibodies (mAbs) reduce fasting and post fat load cholesterol in non-HDL and intermediate density lipoprotein (IDL) in familial dysbetalipoproteinemia (FD). However, the effect of PCSK9 mAbs on the distribution and composition of atherogenic lipoproteins in patients with FD is unknown.
OBJECTIVE
To evaluate the effect of the PCSK9 mAb evolocumab added to standard lipid-lowering therapy in patients with FD on fasting and post fat load lipoprotein distribution and composition.
METHODS
Randomized placebo-controlled double-blind crossover trial comparing evolocumab (140 mg subcutaneous every 2 weeks) with placebo during two 12-week treatment periods. Patients received an oral fat load at the start and end of each treatment period. Apolipoproteins (apo) were measured with ultracentrifugation, gradient gel electrophoresis, retinyl palmitate and SDS-PAGE.
RESULTS
PCSK9 mAbs significantly reduced particle number of all atherogenic lipoproteins, with a stronger effect on smaller lipoproteins than on larger lipoproteins (e.g. IDL-apoB 49%, 95%confidence interval (CI) 41-59 and very low-density lipoprotein (VLDL)-apoB 33%, 95%CI 16-50). Furthermore, PCSK9 mAbs lowered cholesterol more than triglyceride (TG) in VLDL, IDL and low-density lipoprotein (LDL) (e.g. VLDL-C 48%, 95%CI 29-63%; and VLDL-TG 20%, 95%CI 6.3-41%). PCSK9 mAbs did not affect the post fat load response of chylomicrons.
CONCLUSION
PCSK9 mAbs added to standard lipid-lowering therapy in FD patients significantly reduced lipoprotein particle number, in particular the smaller and more cholesterol-rich lipoproteins (i.e. IDL and LDL). PCSK9 mAbs did not affect chylomicron metabolism. It seems likely that the observed effects are achieved by increased hepatic lipoprotein clearance, but the specific working mechanism of PCSK9 mAbs in FD patients remains to be elucidated.
Topics: Humans; Proprotein Convertase 9; Hyperlipoproteinemia Type III; Lipoproteins; Lipoproteins, VLDL; Cholesterol; Antibodies, Monoclonal; Apolipoproteins B; Lipoproteins, LDL
PubMed: 37517914
DOI: 10.1016/j.jacl.2023.07.004