Measurement Of Apolipoprotein Research Articles

Efficacy and Safety of Lerodalcibep in Patients With or at High Risk of Cardiovascular Disease

Recent changes in national and international lipid guidelines for reducing cardiovascular events recommend additional drugs, greater reductions, and lower targets for low-density lipoprotein cholesterol (LDL-C) if not attained with statins. The achievement of these targets with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has not yet been evaluated in a randomized clinical trial. To evaluate the 52-week safety and efficacy of lerodalcibep, a small anti-PCSK9-binding protein, in patients with cardiovascular disease (CVD) or who are at very high or high risk of CVD and requiring addition LDL-C-lowering treatment. This was a randomized, double-blind, placebo-controlled phase 3 trial. The trial was conducted at 66 clinics in 11 countries between April 23, 2021, and November 15, 2023. Individuals 18 years and older taking maximally tolerated statin therapy with LDL-C of 70 mg/dL or greater with CVD or 100 mg/dL or greater if at high risk of CVD were included. Patients were randomized 2:1 to monthly 1.2-mL subcutaneous lerodalcibep, 300 mg, or placebo for 52 weeks. The safety analysis included all randomized patients. The co-primary efficacy end points were percent change from baseline in LDL-C at week 52 and the mean of weeks 50 and 52. Secondary efficacy outcomes included additional lipid apolipoprotein measures and achievement of guideline-recommended LDL-C targets. Of 922 randomized participants (mean [range] age, 64.5 [27-87] years; 414 [44.9%] female; mean [SD] baseline LDL-C, 116.2 [43.5] mg/dL), 811 (88%) completed the trial. The mean (SE) placebo-adjusted reduction in LDL-C with lerodalcibep by modified intention-to-treat (mITT) analysis was 56.2% (2.2%) at week 52 and 62.7% (1.9%) for the mean of weeks 50 and 52; 49.7% (2.4%) and 55.3% (2.2%) by ITT with imputation using a washout model, and 60.3% (2.3%) and 65.9% (1.9%) by per-protocol analysis at week 52 and the mean of weeks 50 and 52, respectively (P < .001 for all). With lerodalcibep, 555 of 615 participants (90%) achieved both a reduction in LDL-C of 50% or greater and recommended LDL-C targets during the study. Treatment-emergent adverse events were similar between lerodalcibep and placebo, except for injection site reactions. These occurred in 42 of 613 participants receiving lerodalcibep (6.9%) compared to 1 of 307 receiving placebo (0.3%), were graded mild or moderate, and did not result in higher discontinuation of treatment, at 26 of 613 (4.2%) and 14 of 307 (4.6%), respectively. Sporadic in vitro antidrug antibodies were detected, which had no impact on free PCSK9 or LDL-C-lowering efficacy. In this trial, lerodalcibep, a novel anti-PCSK9 small binding protein, dosed monthly and stable at ambient temperatures significantly reduced LDL-C in patients with CVD or at high risk of atherosclerotic cardiovascular disease with a safety profile similar to placebo. These results support long-term use of lerodalcibep in patients with CVD or at high risk of CVD who are unable to achieve adequate LDL-C reduction while receiving maximal tolerated statins alone. ClinicalTrials.gov Identifier: NCT04806893.

Associations of an HDL apolipoproteomic index with cardiometabolic risk factors before and after exercise training in the HERITAGE Family Study

Background and aimsPrevious studies have derived and validated an HDL apolipoproteomic score (pCAD) that predicts coronary artery disease (CAD) risk. However, the associations between pCAD and markers of cardiometabolic health in healthy adults are not known, nor are the effects of regular exercise on pCAD. MethodsA total of 641 physically inactive adults free of cardiovascular disease from the HERITAGE Family Study completed 20 weeks of exercise training. The pCAD index (range 0–100) was calculated using measurements of apolipoproteins A-I, C–I, C-II, C-III, and C-IV from ApoA-I-tagged serum (higher index = higher CAD risk). The associations between pCAD index and cardiometabolic traits at baseline and their training responses were assessed with Spearman correlation and general linear models. A Bonferroni correction of p < 8.9 × 10−04 was used to determine statistical significance. ResultsThe mean ± SD baseline pCAD index was 29 ± 32, with 106 (16.5 %) participants classified as high CAD risk. At baseline, pCAD index was positively associated with blood pressure, systemic inflammation, and body composition. HDL size, VO2max, and HDL-C were negatively associated with pCAD index at baseline. Of those classified as high CAD risk at baseline, 52 (49 %) were reclassified as normal risk after training. Following training, pCAD index changes were inversely correlated (p < 1.4 × 10−04) with changes in HDL-C, HDL size, and LDL size. ConclusionsA higher pCAD index was associated with a worse cardiometabolic profile at baseline but improved with regular exercise. The results from this study highlight the potential role of HDL apolipoproteins as therapeutic targets for lifestyle interventions, particularly in high-risk individuals.

Plasma Lipid Profile and Apolipoproteins in Patients with Coronary Artery Diseases and Healthy Persons, in Sana'a City, Yemen

Background: Cardiovascular disease (CVD) is the primary cause of all disease loads and accounts for almost half of all fatalities. The early detection of coronary artery disease (CAD) has drawn a lot of attention because it is anticipated that the global burden of cardiovascular disease will rise by almost 75% by 2020. They are easily oxidized, which causes an increase in affinity for arterial proteoglycans and a decrease in affinity for LDL receptors. It demonstrates significant CAD importance.&#x0D; Objective: The measurement of plasma lipid profiles and apolipoproteins (ApoA-1, ApoB, and Apo B/A-1 ratio) in healthy individuals and patients suffering from coronary artery disease.&#x0D; Methods: In this cross-sectional comparative study, 90 Yemeni subjects aged 45 to 70 years were divided into three groups: Group I: 30 cases as CAD positive (CAD+). Group II: 30 cases CAD negative (CAD -). Group III: 30 healthy person was as control. A standardized questionnaire was administered to collect demographic and clinical data from participants. Venous blood (10 ml) was collected from each individual and divided into two portions. The first portion was 5 ml in plain tubes, ApoA-1 and Apo B vacuum tubes for freezing at -20°C until analysis. 5ml in a plain tube for measuring fasting blood glucose, and lipid profile.&#x0D; Results: ApoB and Apo B/A ratios were significantly higher in CAD+ and CAD− subjects compared to controls. In addition, ApoB and Apo B/A ratios were significantly higher in CAD+ subjects compared to CAD- subjects. (P. value =0.002). In contrast, Apo A-1 was significant in CAD+ compared to CAD- and controls, and not significantly different between CAD and controls P. value = (0.001, 0.032). Furthermore, FBS and LDL-c were significantly higher in CAD+ compared to CAD subjects (P value = 0.05). In contrast, HDL-c was significantly lower in CAD+ compared to CAD and controls, with no significant difference between CAD and controls (P value=0.038, 0.004, 0.70). However, TG was not substantially different between CAD- and controls, but it was significantly greater in CAD+ compared to controls (P. value =0.002, 0.09, 0.31). Nevertheless, there was no difference in TC between study groups (P. value = 0.08, 0.12, 0.98).&#x0D; Conclusions: The degree of CAD is significantly positively correlated with WHR. More important than overall obesity, abdominal obesity is a risk factor for coronary heart disease (CHD). A significant positive connection has been observed between the Apo B/Apo A ratio and CAD. One thing to think about as a CAD risk factor is Apo B.

Lipoprotein Characteristics and Incident Coronary Heart Disease: Prospective Cohort of Nearly 90 000 Individuals in UK Biobank.

Background Associations of coronary heart disease (CHD) with plasma lipids are well described, but the associations with characteristics of lipoproteins (which transport lipids) remain unclear. Methods and Results UK Biobank is a prospective study of 0.5 million adults. Analyses were restricted to 89 422 participants with plasma lipoprotein and apolipoprotein measures from Nightingale nuclear magnetic resonance spectroscopy and without CHD at baseline. CHD risk was positively associated with concentrations of very-low-density lipoproteins, intermediate-density lipoproteins, and low-density lipoproteins (LDL), and inversely associated with high-density lipoproteins. Hazard ratios (99% CIs) per SD were 1.22 (1.17-1.28), 1.16 (1.11-1.21), 1.20 (1.15-1.25), and 0.90 (0.86-0.95), respectively. Larger subclasses of very-low-density lipoproteins were less strongly associated with CHD risk, but associations did not materially vary by size of LDL or high-density lipoprotein. Given lipoprotein particle concentrations, lipid composition (including cholesterol) was not strongly related to CHD risk, except for triglyceride in LDL particles. Apolipoprotein B was highly correlated with LDL concentration (r=0.99), but after adjustment for apolipoprotein B, concentrations of very-low-density lipoprotein and high-density lipoprotein particles remained strongly related to CHD risk. Conclusions This large-scale study reliably quantifies the associations of nuclear magnetic resonance-defined lipoprotein characteristics with CHD risk. CHD risk was most strongly related to particle concentrations, and separate measurements of lipoprotein concentrations may be of greater value than the measurement by apolipoprotein B, which was largely determined by LDL concentration alone. Furthermore, there was strong evidence of positive association with mean triglyceride molecules per LDL particle but little evidence of associations with total triglycerides or other lipid and lipoprotein fractions after accounting for lipoprotein concentrations.

Standardization of Apolipoprotein B, LDL-Cholesterol, and Non-HDL-Cholesterol.

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.

Obesity Indices Could Predict High Apolipoprotein B/Apolipoprotein A1 Ratio in Non-menopausal Indonesian Adult Females

Previous researches have demonstrated associations between high obesity indices with increased risk of metabolic and cardiovascular disorders. It has also been established that abnormalities of lipoprotein metabolism have an important role in atherogenesis and that non-menopausal females are protected from atherosclerotic cardiovascular events relative to menopausal females and males. This study aimed to investigate the relationship between obesity indices such as body mass index (BMI), waist circumference (WC), body fat percentage (BF), and visceral fat (VF) with apolipoprotein B/apolipoprotein A1 ratio in non-menopausal Indonesian adult females. A total of 75 non-menopausal Indonesian adult females were included as subjects in this cross-sectional study. Measured indices included BMI, WC, BF, and VF. Measurement of apolipoprotein B and A1 were performed by immunoturbidimetry, followed by calculation of the ratio. A cut-off value of 0.8 was used to define high apolipoprotein B/apolipoprotein A1 ratio. Apolipoprotein B/Apolipoprotein A1 ratio was significantly correlated with BMI (r=0.384, p=0.001), WC (r=0.363, p=0.001), BF (r=0.385, p=0.001), VF (r=0.380, p=0.001). The area under curve of BF (0.754) was slightly larger than BMI (0.722), VF (0.721), and WC (0.686) in predicting high apolipoprotein B/apolipoprotein A1 ratio. A positive significant correlation was observed between obesity indices with the apolipoprotein B/apolipoprotein A1 ratio. Obesity indices could be used to predict high apolipoprotein B/apolipoprotein A1 ratio.

Quantitative protein mass-spectrometry requires a standardized pre-analytical phase.

Quantitative protein mass-spectrometry (QPMS) in blood depends on tryptic digestion of proteins and subsequent measurement of representing peptides. Whether serum and plasma can be used interchangeably and whether in-vitro anticoagulants affect the recovery is unknown. In our laboratory serum samples are the preferred matrix for QPMS measurement of multiple apolipoproteins. In this study, we investigated the effect of different matrices on apolipoprotein quantification by mass spectrometry. Blood samples were collected from 44 healthy donors in Beckton Dickinson blood tubes simultaneously for serum (with/without gel) and plasma (heparin, citrate or EDTA). Nine apolipoproteins were quantified according to standard operating procedure using value-assigned native serum calibrators for quantitation. Tryptic digestion kinetics were investigated in the different matrices by following formation of peptides for each apolipoprotein in time, up to 22h. In citrate plasma recovery of apolipoproteins showed an overall reduction with a bias of-14.6%. For heparin plasma only-0.3% bias was found compared to serum, whereas for EDTA-plasma reduction was more pronounced (-5.3% bias) and variable with >14% reduction for peptides of apoA-I, A-II and C-III. Digestion kinetics revealed that especially slow forming peptides showed reduced formation in EDTA-plasma. Plasma anticoagulants affect QPMS test results. Heparin plasma showed comparable results to serum. Reduced concentrations in citrate plasma can be explained by dilution, whereas reduced recovery in EDTA-plasma is dependent on altered proteolytic digestion efficiency. The results highlight the importance of a standardized pre-analytical phase for accurate QPMS applications in clinical chemistry.

Diagnosis of remnant hyperlipidaemia.

In recent years, there has been interest for the development of simplified diagnosis algorithms of dysbetalipoproteinemia (DBL) in order to avoid the complex testing associated with the Fredrickson criteria (reference method). The purpose of this review is to present recent advances in the field of DBL with a focus on screening and diagnosis. Recently, two different multi-step algorithms for the diagnosis of DBL have been published and their performance has been compared to the Fredrickson criteria. Furthermore, a recent large study demonstrated that only a minority (38%) of DBL patients are carriers of the E2/E2 genotype and that these individuals presented a more severe phenotype. The current literature supports the fact that the DBL phenotype is more heterogeneous and complex than previously thought. Indeed, DBL patients can present with either mild or more severe phenotypes that can be distinguished as multifactorial remnant cholesterol disease and genetic apolipoprotein B deficiency. Measurement of apolipoprotein B as well as APOE gene testing are both essential elements in the diagnosis of DBL.

487-P: Posttranslational Modifications of Apolipoproteins C-I, C-II, and C-III and Peripheral Artery Disease in Multiethnic Study of Atherosclerosis (MESA)

Apolipoproteins (apo) C-I, C-II and C-III in circulation are in several post-translational forms with distinct effects on lipoprotein metabolism. ApoC-I and apoC-II exist as dominant native and minor truncated (C-I’; C-II’) forms; apoC-III appears as unglycosylated (C-III0a) , or glycosylated with zero (C-III0b) , one (C-III1, most abundant) or two (C-III2) sialic acids. The association of these proteoforms with peripheral artery disease (PAD) in a general population is unstudied. Total apoC-I, C-II and C-III concentrations and relative amounts of their proteoforms were measured in baseline plasma of 5,681 MESA participants. The ankle-brachial index (ABI) was assessed at baseline, 3 and years. Prevalent PAD was defined as baseline ABI ≤ 0.9. Incident PAD was follow-up ABI ≤ 0.9 or a hospital-based diagnosis of PAD to include revascularization. After adjustment for baseline characteristics, lipid lowering therapy and plasma lipids, low baseline ABI was associated with low C-III0b to C-III1 ratio (C-III0b/III1, p=0.01) and high C-III2 to C-III1 ratio (C-III2/III1, p&amp;lt;0.01) . Prevalent PAD (n=226) was only associated with C-III2/III1 (OR 1.16, 95% CI: 1.01-1.33, p=0.03) . Lower ABI at follow-up was associated with lower C-III0b/III1 and higher C-III2/III1 at baseline (p&amp;lt;0.both) . Incident PAD (n=244) was associated with C-III2/III1 (HR 1.22, 1.06-1.41, p=0.01) . Total apoC-I, C-II and C-III concentrations, or apoC-I and C-II truncations were not associated with ABI at baseline and follow-up, or with cross-sectional and prospective PAD determinations. ApoC-I and apoC-II and their truncations do not appear linked with PAD. In contrast, we find different associations of apoC-III0b and apoC-III2 with prevalent and incident PAD that are independent of other risk factors, including plasma lipids. Our data provide further support that proteoforms may have unique properties not captured by “total” apolipoprotein measures. Disclosure P.Reaven: Research Support; AstraZeneca, Dexcom, Inc. J.Koska: None. S.Hansen: None. Y.Hu: None. J.Furtado: Research Support; Eli Lilly and Company, Pfizer Inc. S.Sinari: None. D.Billheimer: None. D.Nedelkov: None. M.Budoff: Research Support; Amarin Corporation, Novo Nordisk, Speaker's Bureau; Boehringer Ingelheim International GmbH, Lilly. R.Mcclelland: None. Funding National Institutes of Health (R01-HL138969)

M264 Towards an SI-traceable LC-MRM-MS based candidate reference measurement procedure for multiplex measurement of serum apolipoproteins (A), A-I, B, C-I, C-II, C-III and E

M264 Towards an SI-traceable LC-MRM-MS based candidate reference measurement procedure for multiplex measurement of serum apolipoproteins (A), A-I, B, C-I, C-II, C-III and E

Elevated Apolipoprotein B/A-1 Ratio is Associated With an Increased Risk of Aortic Stenosis: Experience From the AMORIS Cohort

Lipoproteins are associated with acquired aortic valve stenosis (AS). This study investigated whether an elevated apolipoprotein (apo)B/apoA-1 ratio was associated with an increased risk of AS and if this association was influenced by a history of a major adverse cardiovascular event (MACE) defined as stroke, myocardial infarction or revascularisation. A study was undertaken of 131,816 individuals, aged ≥30 years, from the Swedish Apolipoprotein MOrtality RISk (AMORIS) cohort, with measurements of apolipoproteins B and A-1 at health examinations during 1985-1996. There were fewer women and the average age was 4 years older in the highest apoB/apoA-1 quintile compared with the lowest. Being overweight, having reduced renal function and diabetes mellitus were more frequent. Low-density lipoprotein cholesterol, triglyceride and apolipoprotein B levels were higher in the top apoB/apoA-1 quintile. During follow-up through 2011, non-rheumatic aortic valve disease was diagnosed in 2,999 individuals (2.3%). Using ICD-10 codes from 1997, AS was identified in 1,887 patients. An elevated apoB/apoA-1 ratio was associated with an increased incidence of aortic valve disease after multivariable adjustment [hazard ratio (HR) (95% CI) for the fifth vs first quintile of 1.28 (1.09-1.50)]. Restricting the analyses to incident AS during 1997-2011 yielded an HR of 1.41 (1.15-1.72). This increased incidence was primarily seen in women and individuals aged ≥65 years. History of MACE did not influence these associations. An elevated apoB/apoA-1 ratio was associated with an increased incidence of AS, particularly in women and individuals aged ≥65 years, regardless of previous MACE.

Measurement of apolipoprotein B levels helps in the identification of patients at risk for hypertriglyceridemic pancreatitis

BackgroundSevere hypertriglyceridemia (HTG) is a common cause of acute pancreatitis, although even moderate HTG may elevate this risk. Identifying patients who are prone to hypertriglyceridemic pancreatitis (HTGP) can facilitate early, preventative interventions. ObjectiveTo examine advanced lipoprotein profile (ALP) of hypertriglyceridemic patients with and without HTGP to identify lipid and lipoprotein parameters which may help improve risk stratification. MethodsThis was a retrospective cohort study of adult patients with serum triglycerides (TGs) ≥ 500 mg/dL who underwent ALP testing. Chart reviews were conducted to identify those who developed HTGP or not. Comparisons of lipid profiles of patients with and without HTGP were performed using chi-square or rank-sum tests. ROC curves were generated to identify lipid and lipoprotein parameters which helped improve prediction of HTGP beyond serum TG levels. ResultsFifty-eight subjects were included in the analysis. Twenty had at least one documented episode of HTGP. Among patients with HTGP, median serum TG concentrations were 2832 mg/dL vs. 978 mg/dL in the non-pancreatitis group (p < 0.001). Chylomicron TG/total TG, chylomicron TG/VLDL TG, chylomicron TG/apoB, total TG/total Cholesterol, and total TG/apoB were significantly higher among the pancreatitis group. Total serum TG/apoB had the best discriminant value for predicting HTGP with an AUC-ROC of 0.87 (p < 0.001). A cutoff of >10.6 was associated with a sensitivity of 90% and specificity of 75%. ConclusionMeasurement of serum apoB levels and calculation of serum TG/apoB ratio may help identify hypertriglyceridemic patients at risk for HTGP.

The extended lipid panel assay: a clinically-deployed high-throughput nuclear magnetic resonance method for the simultaneous measurement of lipids and Apolipoprotein B

BackgroundStandard lipid panel assays employing chemical/enzymatic methods measure total cholesterol (TC), triglycerides (TG), and high-density lipoprotein cholesterol (HDL-C), from which are calculated estimates of low-density lipoprotein cholesterol (LDL-C). These lipid measures are used universally to guide management of atherosclerotic cardiovascular disease risk. Apolipoprotein B (apoB) is generally acknowledged to be superior to LDL-C for lipid-lowering therapeutic decision-making, but apoB immunoassays are performed relatively infrequently due to the added analytic cost. The aim of this study was to develop and validate the performance of a rapid, high-throughput, reagent-less assay producing an “Extended Lipid Panel” (ELP) that includes apoB, using the Vantera® nuclear magnetic resonance (NMR) analyzer platform already deployed clinically for lipoprotein particle and other testing.MethodsPartial least squares regression models, using as input a defined region of proton NMR spectra of plasma or serum, were created to simultaneously quantify TC, TG, HDL-C, and apoB. Large training sets (n > ~ 1000) of patient sera analyzed independently for lipids and apoB by chemical methods were employed to ensure prediction models reflect the wide lipid compositional diversity of the population. The analytical performance of the NMR ELP assay was comprehensively evaluated.ResultsExcellent agreement was demonstrated between chemically-measured and ELP assay values of TC, TG, HDL-C and apoB with correlation coefficients ranging from 0.980 to 0.997. Within-run precision studies measured using low, medium, and high level serum pools gave coefficients of variation for the 4 analytes ranging from 1.0 to 3.8% for the low, 1.0 to 1.7% for the medium, and 0.9 to 1.3% for the high pools. Corresponding values for within-lab precision over 20 days were 1.4 to 3.6%, 1.2 to 2.3%, and 1.0 to 1.9%, respectively. Independent testing at three sites over 5 days produced highly consistent assay results. No major interference was observed from 38 endogenous or exogenous substances tested.ConclusionsExtensive assay performance evaluations validate that the NMR ELP assay is efficient, robust, and substantially equivalent to standard chemistry assays for the clinical measurement of lipids and apoB. Routine reporting of apoB alongside standard lipid measures could facilitate more widespread utilization of apoB for clinical decision-making.

Apolipoprotein B Level and the Apolipoprotein B/Apolipoprotein A-I Ratio as a Harbinger of Ischemic Stroke: A Prospective Observation in Taiwan

Aim: Prospective studies indicate that apolipoprotein (apo) measurements predict coronary heart disease risk. However, few population-based follow-up studies have addressed the predictive value of apo measurements in stroke risk. The aims of the present study were to analyze the predictive ability of apo measurements in the risk of ischemic stroke. Methods: Serum apo A-I and apo B levels and calculated apo B/apo A-I ratio were measured at baseline in 2002 in a cohort of 4,204 participants who were followed for a mean of 4.61 years for a stroke event. Results: After adjustment for potential confounders, a significantly stepwise increase in the incidence rate of stroke across quartiles of both apo B and the apo B/apo A-I ratio was evident in both genders and across age-groups. The predictive ability of apo B to detect ischemic stroke was comparable with that of the apo B/apo A-I ratio. Furthermore, both apo B and the apo B/apo A-I ratio were better predictors of the risk of ischemic stroke than total cholesterol (TC), low-density lipoprotein cholesterol, and the TC/high-density lipoprotein cholesterol ratio. Conclusions: This cohort study demonstrates that apo B and the apo B/apo A-I ratio were a significant risk predictor of stroke. Furthermore, the predictive ability of apo B and the apo B/apo A-I ratio in stroke risk was better than routine clinical lipid measurements. Thus, measurements of apolipoproteins have superior clinical utility over traditional lipid measurements in identifying subjects at risk for ischemic stroke.

High-Sensitivity C-Reactive Protein Discordance With Atherogenic Lipid Measures and Incidence of Atherosclerotic Cardiovascular Disease in Primary Prevention: The ARIC Study.

BackgroundInflammation is an independent causal risk factor for atherosclerotic cardiovascular diseases (ASCVDs). However, whether hsCRP (high‐sensitivity C‐reactive protein) is prognostic across various levels of atherogenic lipid measures such as low‐density lipoprotein cholesterol, non–high‐density lipoprotein cholesterol, apolipoprotein B and total cholesterol/high‐density lipoprotein cholesterol in primary prevention is unknown.Methods and ResultsWe studied 9748 ARIC (Atherosclerosis Risk in Communities) study participants who were free of ASCVD at baseline (visit 4, 1996–1998) and had measurements of lipids, apolipoprotein B, and hsCRP. We used multivariable adjusted Cox models to estimate the risk of incident ASCVD events associated with hsCRP levels (less than/greater than or equal to median) in individuals where triple lipid measures combined (low‐density lipoprotein cholesterol + non–high‐density lipoprotein cholesterol + apolipoprotein B) or quadruple measures combined [triple + total cholesterol/high‐density lipoprotein cholesterol] were less than versus greater than or equal to median cut points. Mean age of participants was 62.6±5.6 years; 59% women, 22% black. There were 1574 ASCVD events over median (interquartile range) follow‐up of 18.4 (12.8–19.5) years, and discordance between hsCRP and lipid measures was prevalent in 50% of the population. hsCRP greater than or equal to median (2.4 mg/L), compared with less than median, was associated with an increased risk of ASCVD in individuals with less than median levels of the triple (adjusted hazard ratio, 1.33; 95% CI, 1.09–1.60) and quadruple (adjusted hazard ratio,1.47; 95% CI, 1.18–1.85) lipid measures. Such increased risk was consistent among individuals with low (<7.5%) or high (≥7.5%) estimated risk by the pooled cohort equation. There were no interactions by sex, diabetes mellitus, or statin use.ConclusionsOur findings suggest that inflammation is independently associated with ASCVD regardless of atherogenic lipid levels and pooled cohort equation risk score in individuals without known ASCVD.

Estimation of non-high-density lipoprotein cholesterol and its correlation as a surrogate measure of apolipoprotein B in patients with metabolic syndrome

Background: The primary target of therapy for dyslipidemia according to the present lipid guidelines is low-density lipoprotein cholesterol (LDL-C). Its main drawback is it is a derived value and erroneous values may be obtained if triglyceride values are high. Hence, direct measurement of apolipoprotein B (Apo-B), which is present in all atherogenic particles (very-LDL, intermediate-density lipoprotein, and LDL) would be ideal and is a superior indicator of cardiovascular risk. However, current limitations of Apo-B estimation are lack of standardization and lack of technical expertise and cost factor. To overcome these limitations, there is a need to test a particular lipid value from the standard lipid test, which can be used as a surrogate measure of Apo-B. As non-high-density lipoprotein cholesterol (HDL-C) is a measure of the cholesterol content of all Apo-B-containing lipoproteins, it may represent a simple and inexpensive surrogate to Apo-B in select patient subgroups. Hence, this study was undertaken to estimate non-HDL-C and LDL-C from the standard lipid test and also measure Apo-B levels in patients with metabolic syndrome using appropriate statistical methods, correlation and concordance between non-HDL-C versus Apo-B and LDL-C versus Apo-B were analyzed. Methodology: This was a cross-sectional study carried out in Bangalore on 135 patients of metabolic syndrome fulfilling the International Diabetes Federation criteria, from January 2019 to March 2019. Detailed history and examination was undertaken. Fasting blood glucose, Apo-B-100, and lipid profile were obtained in the fasting state venous blood sample. Results: A significant positive correlation was noted between non-HDL-C levels and Apo-B values with a correlation coefficient of 0.883 and area under the curve (AUC) of 0.972. In contrast, the correlation between LDL-C and Apo-B-100 showed a correlation coefficient of 0.815 and AUC of 0.949. Similarly, the concordance/discordance analysis of the same parameters showed concordance across the range of corresponding non-HDL-C and Apo-B quintiles except in the middle quintile where the values were discordant. Concordance was >50% across 80% of the range of values between LDL-C and non-HDL-C. Conclusion: This study showed that there is a good correlation between non-HDL-C levels and Apo-B values with less discordance. Hence, non-HDL-C can be used as a simple and cost-effective alternative (surrogate) to Apo-B estimation.

Brain imaging measurements of fibrillar amyloid-β burden, paired helical filament tau burden, and atrophy in cognitively unimpaired persons with two, one, and no copies of the APOE ε4 allele

IntroductionWe previously characterized associations between brain imaging measurements of amyloid-β (Aβ) plaque burden and apolipoprotein E (APOE) ε4 gene dose in a small number of cognitively unimpaired late-middle-aged APOE ε4 homozygotes (HMs), heterozygotes (HTs), and noncarriers (NCs). We now characterize cross-sectional Aβ plaque, tau tangle, and cortical atrophy (neurodegeneration) measurements, classifications, and associations with age in a larger number of unimpaired HMs, HTs, and NCs over a wider age range. MethodsWe analyzed 11C Pittsburgh compound B (Aβ) positron emission tomography (PET), flortaucipir (tau) PET, and volumetric magnetic resonance imaging data from 164 study participants of age 47–86 years, including 26 APOE ε4 HMs, 48 HTs, and 90 NCs matched for age and sex. ResultsAβ PET measurements rose, plateaued at the respective ages of 68 and 76, and then declined with age in unimpaired HM and HT groups. Compared with NCs, these two groups began to have significantly higher Aβ PET measurements at ages 62 and 70, respectively, and no longer had significantly higher measurements by ages 71 and 78, respectively. They began to have significantly higher entorhinal cortex tau PET measurements at ages 66 and 70, respectively, and no longer had significantly higher measurements by ages 74 and 78, respectively. Brain atrophy measurements tended to decline slowly with age in all three genetic groups. Their elevated tau PET measurements were attributable to those with positive Aβ PET scans. 41.0%, 18.0%, and 5.0% of the 47- to 70-year-old HMs, HTs, and NCs and 25.0%, 79.0%, and 38.0% of the 71- to 86-year-old HMs, HTs, and NCs had positive Aβ PET scans, and the long-term recall memory scores are significantly higher in the older HMs than in HT and NC groups, suggesting resistance to Aβ deposition in those HMs who remained unimpaired at older ages. ConclusionsThis study provides information about Aβ plaque burden, tau tangle burden, and neurodegeneration in cognitively unimpaired persons at three levels of genetic risk for AD. Unimpaired APOE ε4 HMs can be studied before their 70s to evaluate the understanding of factors, processes, and interventions involved in the predisposition to and prevention of AD, and after their 70s, to discover factors, processes, and interventions involved in the resilience or resistance to and prevention of AD.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Dyslipidemia Profiles in Patients with Peripheral Artery Disease.

This review of the literature aims to discuss the evidence linking different lipid and apolipoprotein measures to peripheral artery disease. Measures of atherogenic dyslipidemia, including elevations in total cholesterol and total cholesterol/high-density lipoprotein cholesterol as well as low levels of high-density lipoprotein cholesterol, are strongly associated with future risk of peripheral artery disease. Compared to coronary artery disease, there are fewer data showing an association between low-density lipoprotein cholesterol and future risk of peripheral artery disease. Novel lipid measures, including nuclear magnetic resonance-derived lipoproteins and oxidized lipids, may lead to better assessments of future peripheral artery disease risk. These data highlight the important differences between lipid risk factors for peripheral and coronary artery disease. Improved understanding of these distinctions may lead to new therapeutic options for patients with peripheral artery disease.

Utility of apolipoprotein measurements in predicting incident type 2 diabetes: A Chinese cohort study

There is conflicting data regarding the utility of measuring apolipoproteins in addition to traditional lipid measures in risk assessment of cardiometabolic diseases. The aim of this study was to determine whether apolipoprotein measurements can improve the ability to predict the future development of type 2 diabetes beyond what is possible based on traditional type 2 diabetes risk factors and clinical routine lipid measurements. A total of 4,223 Chinese adults without diabetes were followed for a mean duration of 5.42 years. The hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to analyze the longitudinal associations of apolipoprotein B (apo B), apolipoprotein A-I (apo A-I), and the apo B/apo A-I ratio with the risk of type 2 diabetes. Further, the analysis of the area under receiver operating characteristics curves (AUC) was performed to test the predictive value of apolipoprotein measurements. After adjusting for potential confounders, the HRs of diabetes consistently showed an increasing trend across both the apo B and the apo B/apo A-I ratio quartiles (p for trend=0.004). In analyses of AUC, the predictive ability for type 2 diabetes risk for the apo B and the apo B/apo A-I ratio was superior to that of routine lipid and lipoprotein measurements. Apolipoprotein measurements significantly predict diabetes risk in an Asian population. Furthermore, the predictive ability of apo B alone to detect diabetes was comparable with that of the apo B/apo A-I ratio and better than the routine lipid measurements.