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Background: Low-density lipoprotein cholesterol (LDL-C) is the primary target of lipid-lowering therapy on the management of hypercholesterolemia in the United States and European guidelines, while apolipoprotein B (apoB) is the secondary target. The objective was to determine if elevated levels of apoB is superior to LDL-C in assessing residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment. Methods: This study included 131 participants with statin treatment. The generalized linear model and relative risk regression (generalized linear Poisson model with robust error variance) were used to analyze the association of the levels of apoB and LDL-C with the severity of coronary atherosclerosis and residual risk of coronary atherosclerotic heart disease. Results: Categorizing apoB and LDL-C based on tertiles, higher levels of apoB were significantly associated with the severity of coronary atherosclerosis (P trend = 0.012), whereas no such associations were found for elevated levels of LDL-C (P trend = 0.585). After multivariate adjustment, higher levels of apoB were significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level apoB (≤0.66 g/L), the multivariate adjusted RR and 95% CI of intermediate-level apoB (0.67–0.89 g/L) and high-level apoB (≥0.90 g/L) were 1.16 (1.01, 1.33) and 1.31 (1.08, 1.60), respectively (P trend = 0.011). There was a 45% increased residual risk of coronary atherosclerotic heart disease per unit increment in natural log-transformed apoB (P trend <0.05). However, higher levels of LDL-C were not significantly associated with residual risk of coronary atherosclerotic heart disease. When compared with low-level LDL-C (≤1.56 mmol/L), the multivariate adjusted RR and 95% CI of intermediate-level LDL-C (1.57–2.30 mmol/L) and high-level LDL-C (≥2.31 mmol/L) were 0.99 (0.84, 1.15) and 1.10 (0.86, 1.42), respectively (P trend = 0.437). Similar results were observed in the stratified analyses and sensitivity analyses. No significant interactions were detected for both apoB and LDL-C (all P interaction > 0.05). Conclusions: Elevated apoB are superior in assessing the residual risk of coronary atherosclerotic heart disease and severity of coronary atherosclerosis in participants with statin treatment. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia frequently coexists with hypertension in the population. Apolipoprotein B (ApoB) is increasingly considered a more potent predictor of cardiovascular disease (CVD). Abnormal levels of serum ApoB can potentially impact the mortality risk., Methods: The prospective cohort study employed data from the National Health and Nutrition Examination Survey (NHANES), which was performed between 2005 and 2016, with follow-ups extended until December 2019. Serum ApoB concentrations were quantified using nephelometry. In line with the NHANES descriptions and recommendations, the reference ranges for ApoB concentrations are 55-140 and 55-125 mg/dL for men and women, respectively. Participants were categorized into low, normal, and high ApoB levels. The low and high groups were combined into the abnormal group. In this study, all-cause mortality (ACM) and CVD mortality (CVM) were the endpoints. Survey-weighted cox hazards models were used for evaluating the correlation between serum ApoB levels and ACM and CVM. A generalized additive model (GAM) was employed to examine the dose-dependent relationship between ApoB levels and mortality risk., Results: After a median of 95 (interquartile range: 62-135) months of follow-up, 986 all-cause and 286 CVD deaths were recorded. The abnormal ApoB group exhibited a trend toward an elevated risk of ACM in relative to the normal group (HR 1.22, 95% CI: 0.96-1.53). The risk of CVM was elevated by 76% in the ApoB abnormal group (HR 1.76, 95% CI: 1.28-2.42). According to the GAM, there existed a nonlinear association between serum ApoB levels and ACM (P = 0.005) and CVM (P = 0.009)., Conclusions: In the US hypertensive population, serum Apo B levels were U-shaped and correlated with ACM and CVM risk, with the lowest risk at 100 mg/dL. Importantly, abnormal Apo B levels were related to an elevated risk of ACM and CVM. These risks were especially high at lower Apo B levels. The obtained findings emphasize the importance of maintaining appropriate Apo B levels to prevent adverse outcomes in hypertensive individuals., (© 2024. The Author(s).)

Abstract: In the absence of human immunodeficiency virus type 1 (HIV-1) Vif protein, the host antiviral deaminase apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (A3G) restricts the production of infectious HIV-1 by deamination of dC residues in the negative single-stranded DNA produced by reverse transcription. The Vif protein averts the lethal threat of deamination by precluding the packaging of A3G into assembling virions by mediating proteasomal degradation of A3G. In spite of this robust Vif activity, residual A3G molecules that escape degradation and incorporate into newly assembled virions are potentially deleterious to the virus. We hypothesized that virion-associated Vif inhibits A3G enzymatic activity and therefore prevents lethal mutagenesis of the newly synthesized viral DNA. Here, we show that (i) Vif-proficient HIV-1 particles released from H9 cells contain A3G with lower specific activity compared with Δvif-virus-associated A3G, (ii) encapsidated HIV-1 Vif inhibits the deamination activity of recombinant A3G, and (iii) purified HIV-1 Vif protein and the Vif-derived peptide Vif25–39 inhibit A3G activity in vitro at nanomolar concentrations in an uncompetitive manner. Our results manifest the potentiality of Vif to control the deamination threat in virions or in the pre-integration complexes following entry to target cells. Hence, virion-associated Vif could serve as a last line of defense, protecting the virus against A3G antiviral activity. [Copyright &y& Elsevier]

With the emergence of new lipid risk markers and a growing cardiometabolic risk burden in the United States, there is a need to better integrate residual risk into cardiovascular disease (CVD) risk stratification. In anticipation of the Adult Treatment Panel IV (ATP IV) guidelines from the National Cholesterol Education Program (NCEP), there exists controversy regarding the comparative performance of the 2 foremost markers, apolipoprotein B (apoB) and non–high-density lipoprotein cholesterol (non–HDL-C), as they relate to the current standard of risk assessment and treatment: low-density lipoprotein cholesterol (LDL-C). Although some emerging markers may demonstrate better performance compared with LDL-C, certain fundamental characteristics intrinsic to a beneficial biomarker must be met prior to routine use. Collectively, studies have found that non–HDL-C and apoB perform better than LDL-C in CVD risk prediction, both on- and off-treatment, as well as in subclinical CVD risk prediction. The performance of non–HDL-C compared with apoB, however, has been a point of ongoing debate. Although both offer the practical benefits of accuracy independent of triglyceride level and prandial state, non–HDL-C proves to be the better marker of choice at this time, given established cutpoints with safe and achievable goals, no additional cost, and quick time to result with an easy mathematical calculation. The purpose of this review is to assess the performance of these parameters in this context and to discuss the considerations of implementation into clinical practice. [ABSTRACT FROM AUTHOR]

Abstract: The hypertriglyceridemic waist phenotype, the National Cholesterol Education Program–Adult Treatment Panel III (NCEP-ATP III) criteria, and the International Diabetes Federation (IDF) criteria have been proposed as screening tools to identify subjects with features of the metabolic syndrome and therefore at increased cardiometabolic risk. The aim of the present study was to compare the ability of these 3 clinical approaches to identify individuals at increased cardiometabolic risk as suggested by the presence of deteriorated markers such as hyperinsulinemia, elevated apolipoprotein B levels, small low-density lipoprotein particles, high C-reactive protein concentrations, and low adiponectin levels. For that purpose, physical and cardiometabolic characteristics of a sample of 272 white men recruited for various metabolic investigations were studied. The hypertriglyceridemic waist phenotype was defined as having both a high waist circumference (≥90 cm) and increased fasting triglyceride levels (≥2.0 mmol/L). Having at least 3 of the 5 NCEP-ATP III criteria or waist circumference of at least 94 cm plus any 2 of the 4 additional IDF criteria was also used to identify individuals at increased cardiometabolic risk. A large proportion of men with the hypertriglyceridemic waist phenotype also met the NCEP-ATP III (82.7%) or IDF (89.2%) criteria. Men with the hypertriglyceridemic waist phenotype were characterized by alterations in their lipoprotein-lipid profile that included small low-density lipoprotein particles, increased apolipoprotein B and insulin levels, as well as reduced adiponectin concentrations, which were similar to individuals meeting the NCEP-ATP III or the IDF criteria. Moreover, the Framingham risk score of men meeting any of the 3 screening tools criteria was higher and was similar across the 3 approaches (4.2, 3.8, and 3.7, respectively). These results suggest that hypertriglyceridemic waist may be as discriminant as the NCEP-ATP III or the IDF criteria and could be used as an initial screening approach to identify individuals with deteriorated cardiometabolic risk markers. [Copyright &y& Elsevier]

The article reports on the signing of a $1.9 billion agreement between Genzyme and Isis Pharmaceuticals in the U.S. According to the author, the agreement is to in-license the cholesterol-lowering antisense drug mipomersen. He added that Genzyme will pay $325 million up front for the powerful drug mipomersen, an antisense treatment that slashes cholesterol levels. Moreover, mipomersen is a second-generation antisense phosphorothioate oligonucleotide inhibitor that is thought to act by binding mRNA encoding apolipoprotein B-100.

Serum uric acid (SUA) and apolipoprotein B (apoB) are markers of the risk of morbidity and mortality. However, no study has investigated their role, simultaneously with nutritional factors, on the risk of mortality. We calculated the dietary uricaemia score (DUS) and the dietary atherogenic score (DAS) and evaluated their associations with the risk of all-cause and cause-specific mortality. Data from the NHANES 1999-2010 study were used. Vital status through the 31 December 2011 was ascertained. Reduced rank regression models followed by stepwise linear regression analyses were applied on 39 macro/micronutrients to identify a dietary pattern most predictive of SUA (DUS) and apoB (DAS). Overall, 20,256 participants were included (mean age: 47.5 years; 48.7% men). DUS consists of 14 contributors (eight positive, six negative), whereas DAS consists of 23 contributors (six positive, 17 negative). An increasing risk of cause-specific mortality was found across the quartiles (Q) of DUS, i.e., participants with the highest score of DUS (Q4) had a greater risk of all-cause (hazard ratio (HR): 1.17, 95% confidence interval (CI): 1.07-1.30), cardiovascular disease (CVD) (HR: 1.36, 95%CI: 1.21-1.59) and cancer (HR: 1.06, 95%CI: 1.01-1.14) mortality compared with Q1. Similarly, participants at the highest DAS quartile had 25, 40 and 11% greater risk of all-cause, CVD and cancer mortality, respectively, compared with Q1. For the first time, we reported an underlying shared link between two atherosclerosis factors (SUA and apoB) and nutrients, as well as their joint adverse impact on all-cause and cause-specific mortality.

The article offers cardiovascular news briefs from the U.S. as of September 2012. A recommendation of low dose aspirin for adults with diabetes has been given by the American Diabetes Association. A study has been conducted to determine whether cardiovascular risk prediction can be improved by adding information or lipid related markers including apolipoprotein B and lipoprotein associated phospholipase A2. Air pollution has been considered as a risk factor for cardiovascular disease.

The article presents mipomersen as an antisense inhibitor of Apolipoprotein B (apo B) synthesis with potent effect on lipoprotein levels when administered without statin therapy. Untreated patients with mild-to-moderate hyperlipidemia were randomly administered with placebo or mipomersen over a 3 week period. The use of mipomersen as an additional therapy in statin-treated patients wit familial hyperlipidemia (FH) has been applied for registration with the U.S. Food & Drug Administration (FDA).

The article reports on the license and collaboration agreement of the U.S. Genzyme and Isis Pharmaceuticals in California. It states that the agreement is for Genzyme's mipomersen, a lipid-lowering drug. In addition, mipomersen cuts down the production rate of apoB-100 protein that is vital to transferring bad cholesterol. According to the author, Isis Pharmaceuticals receives $175 million for the license fee and another $50 million for its growth. Also, other expenses along the process are to be divided evenly.