Ratio Of Apo Research Articles

Abstract 4143289: Contemporary and Genomic Cardiovascular Risk Factors Have Explanatory Power Similar to Traditional Risk Factors for Incident Myocardial Infarction

Background: Modifiable cardiovascular risk factors (CRF) have been proposed to be responsible for 80-90% of the risk for incident coronary artery disease (CAD). However, these studies were conducted prior to the era of preventive medications, novel biomarkers, and genetic risk scores. The relative contributions of traditional and contemporary CRF in light of secular trends in worsening cardiometabolic health globally have not been assessed. Hypothesis: Including genetic risk scores and contemporary biomarkers will enhance discrimination and explainability of myocardial infarction (MI) incidence prediction. Methods: The UKBiobank was used to identify traditional CRF (hypertension, diabetes, dyslipidemia, smoking, waist-to-hip ratio (WHR), diet, exercise, alcohol intake and socioeconomic deprivation), and contemporary/genetic CRF (lipoprotein(a), high-sensitivity C-reactive protein [hsCRP], familial hypercholesterolemia [FH] variants, and polygenic risk score for CAD [PRS CAD ]). Incident MI was defined as first-time MI diagnosis or coronary revascularization. Base model discrimination was assessed using C-statistics from Cox proportional hazards models. Percent contribution of each risk factor was calculated by explanatory power lost via Nagelkerke R 2 after removal of the CRF from the full model. Population attributable risks (PAR) were additionally assessed for each model and CRF individually. Results: Over a median [IQR] follow-up of 11.0 [9.6, 12.5] years, 17409/299707 (5.8%) of participants developed incident CAD. C-statistics sequentially increased from base model to traditional CRF to contemporary/genetic CRF model with PAR of 84.3% (95% CI 82.4%-86.5%) ( Table 1 ). Among CRFs, hypertension (C 0.74, R 2 loss 15.2%, PAR 32.5%) and PRS CAD (C 0.72, R 2 loss 12.4%, PAR 38.4%) most strongly explained MI incidence by all 3 indices. Based on discriminability, ApoB:ApoA1 ratio (C 0.71, R 2 loss 3.4%), presence of diabetes (C 0.71, R 2 loss 2.2%), and log(hsCRP) (C 0.71, R 2 loss 1.82%) were subsequently prioritized. PAR analyses included prevalence in prioritization where WHR, presence of diabetes, and log(lipoprotein(a)) levels rose higher. Conclusions: The addition of genetic risk factors and contemporary biomarkers to explanatory models for CAD shows previously underappreciated importance of contemporary CRFs such as PRS, hsCRP, and lipoprotein(a) alongside traditional CRFs such as hypertension, dyslipidemia and presence of diabetes.

Impaired Cholesterol Uptake Capacity in Patients with Hypertriglyceridemia and Diabetes Mellitus.

Although low high-density lipoprotein cholesterol (HDL-C) levels are a common metabolic abnormality associated with insulin resistance, their role in cardiovascular risk stratification remains controversial. Recently, we developed a simple, high-throughput, cell-free assay system to evaluate the "cholesterol uptake capacity (CUC)" as a novel concept for HDL functionality. In this study, we assessed the CUC in patients with hypertriglyceridemia and diabetes mellitus. The CUC was measured using cryopreserved serum samples from 285 patients who underwent coronary angiography or percutaneous coronary intervention between December 2014 and May 2019 at Kobe University Hospital. The CUC was significantly lower in diabetic patients (n = 125) than in nondiabetic patients (93.0 vs 100.7 arbitrary units (A.U.), P = 0.002). Patients with serum triglyceride (TG) levels >150 mg/dL (n = 94) also had a significantly lower CUC (91.8 vs 100.0 A.U., P = 0.004). Furthermore, the CUC showed a significant inverse correlation with TG, hemoglobin A1c (Hb A1c), homeostasis model assessment of insulin resistance (HOMA-IR), and body mass index (BMI). Finally, the HDL-C/Apolipoprotein A1 (ApoA1) ratio, calculated as a surrogate index of HDL particle size, was significantly positively correlated with the CUC (r2 = 0.49, P < 0.001), but inversely correlated with TG levels (r2 = -0.30, P < 0.001). The CUC decreased in patients with hypertriglyceridemia and diabetes mellitus, and HDL particle size was a factor defining the CUC and inversely correlated with TG levels, suggesting that impaired CUC in insulin-resistant states was partially due to the shift in HDL towards smaller particles. These findings provide a better understanding of the mechanisms underlying impaired HDL functionality.

Targeting the vivid facets of apolipoproteins as a cardiovascular risk factor in rheumatoid arthritis.

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

Predictive value of ApoB/ApoA-I for recurrence within 1 year after first incident stroke.

ApoB/ApoA-I ratio is a reliable indicator of cholesterol balance, particularly in the prediction of ischemic events risk. The aim of this study was to investigate the prognostic value of ApoB/ApoA-I for stroke recurrence within 1 year after the first incident. We retrospectively included patients who were first diagnosed with acute (<7 days after onset) ischemic stroke. Blood samples were collected on admission, and serum ApoB and ApoA-I concentrations were measured. We analyzed the relationship between ApoB/ApoA-I ratio and ischemic stroke recurrence within 1 year. A total of 722 patients with acute ischemic stroke were included, of whom 102 experienced stroke recurrence within 1 year, with a recurrence rate of 14.1%. Serum ApoB/ApoA-I concentrations on admission were higher in patients with stroke recurrence at 1 year compared with those with a good prognosis (P < 0.001). The Kaplan-Meier survival curve revealed a significant difference in cumulative stroke recurrence rates across ApoB/ApoA-I tertiles (log-rank P-value < 0.001). A positive correlation between the ApoB/ApoA-I ratio and the risk of stroke recurrence within 1 year was demonstrated using Cox regression analysis, which remained significant after adjusting for traditional risk factors [hazard ratio (HR) 4.007, 95% confidence interval (CI) 1.661-9.666]. This relationship was particularly strong in patients with LAA stroke (HR 4.955, 95% CI 1.591-15.434). Subgroup analysis further revealed that a high ApoB/ApoA-I ratio was strongly associated with stroke recurrence regardless of whether patients had high or low LDL-C levels. ApoB/ApoA-I ratio, measured during the acute phase of the first stroke, was positively correlated with the risk of stroke recurrence within 1 year.

Causal role of lipid metabolome on the risk of ischemic stroke, its etiological subtypes, and long-term outcome: A Mendelian randomization study

Background and aimsThe lipid profile is consistently associated with coronary artery disease (CAD) and ischemic stroke (IS). However, the lipoprotein subfractions have not been deeply explored in stroke subtypes, especially in IS outcome. MethodsWe performed two-sample Mendelian randomization (MR) analysis using 92 lipid traits measured by nuclear magnetic resonance in 115,000 subjects from the UK Biobank. Data for genetic associations with IS, its subtypes, and long-term outcome (LTO) were obtained from three cohorts of European ancestry: GIGASTROKE (73,652 cases, 1,234,808 controls), GODS (n = 1791) and GISCOME (n = 6165). Results obtained using CARDIoGRAMPlusC4D were used to identify differences with CAD. ResultsGenetically determined low concentration of medium high-density lipoprotein (HDL) particles (odds ratio (OR) = 0.92, 95% CI 0.88–0.96; p = 3.6 × 10−4) and its cholesterol content (OR = 0.92, 95% CI 0.88–0.96; p = 1.9 × 10−4) showed causal associations with an increased risk of stroke. Genetic predisposition to high apolipoprotein (apo)B to apoA-I ratio was causally associated with an increased risk of IS (OR = 1.12, 95% CI 1.06–1.18, p = 1.1 × 10−4), and a highly suggestive association was found between non-esterified cholesterol in low-density lipoprotein (LDL) and increased risk of atherothrombotic stroke (LAS) (OR = 1.35, 95% CI 1.10–1.66; p = 4.0 × 10−3). Low cholesterol in small and medium LDL was suggestively associated with poor LTO. ConclusionsOur results support that low medium HDL concentration was causally associated with an increased stroke risk, while high levels of non-esterified cholesterol in LDL were suggestively associated with an increased risk of LAS and with a better LTO.

A-216 Measuring Inflammation and Cardiovascular Markers at Benchtop NMR using Diffusion and Relaxation Edited Experiments

Abstract Background Metabolic phenotyping is an established tool in systems medicine that captures a profile of one’s individual health status and reflects the interaction between genes and external stressors. It uses analytical platforms such as NMR or MS to acquire molecular profiles, and modelling to extract actionable knowledge. Applying these techniques to a cohort of Australians infected by SARS-CoV-2 revealed a strong alteration in regions of 1D NMR spectra associated with lipoproteins and glycoproteins, and referred as Supramolecular Phospholipid Composite SPC (δ = 3.2 ppm) and Glyc (δ = 2.07 ppm). The latter is an established marker of inflammation. These results were later confirmed using larger cohorts from Spain (n = 525) and the UK (n = 1022). The urgent need for very rapid testing, at the early stage of the pandemic, prompted the development of bespoke NMR experiments able to measure this lipoproteins/glycoproteins signature without requiring complex modelling. Methods Physico-chemical properties of lipoprotein particles, such as diffusion, transverse and longitudinal relaxation rates, differ from low molecular weight metabolites. Therefore, an edited experiment JEDI (PGPE) was designed that combines diffusion, relaxation and scalar coupling editing blocks to produce a lipoprotein profile devoid of chemical noise (overlapping peaks) and where peaks give quantitative results. Results The SPC peak was further broken down into 3 sub-regions that are related to the main subfraction HDL and LDL (choline headgroups of phospholipids). Interestingly the ratio of SPC3/SPC2 highly correlates with the Apo-B100/Apo-A1 ratio, an established cardiovascular risk marker that is increased in patients with COVID19. Longitudinal data suggest this latter remains elevated even 30 days after onset in some patients. Furthermore, the edited experiment performs equally well at low field using a benchtop NMR. Conclusion Translation of a spectral signature relevant for monitoring COVID patients from high to low field NMR is possible using sophisticated editing techniques.

Dietary, macronutrient, micronutrient, and nutrigenetic factors impacting cardiovascular risk markers apolipoprotein B and apolipoprotein A1: a narrative 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.

The Value of the Apolipoprotein B/Apolipoprotein A1 Ratio in Predicting the Rapid Progression of Non-Culprit Coronary Lesions in Acute Coronary Syndrome in Patients with Diabetes Mellitus after Percutaneous Coronary Intervention.

This study aims to assess the predictive value of the apolipoprotein B (ApoB) /apolipoprotein A1 (ApoA1) ratio in acute coronary syndrome (ACS) in patients with diabetes mellitus (DM) for the rapid progression (RP) of non-culprit coronary lesions (NCCLs) after percutaneous coronary intervention (PCI) and observe the effect of the ApoB/ApoA1 ratio on major adverse cardiac events (MACE).A total of 175 patients with DM presenting with ACS who received a PCI and an average 13-month follow-up coronary angiography (CAG) were enrolled from January 2015 to December 2020. According to the CAG, the patients were divided into the RP group and the non-RP group. MACE was defined as a composite of death from cardiac causes, cardiac arrest, myocardial infarction, or rehospitalization from unstable or progressive angina at the end of a 24-month follow-up.The low-density lipoprotein cholesterol (LDL-C), ApoB, ApoB/ApoA1 ratio, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratio levels at baseline were significantly higher in the RP group than in the non-RP group. The ApoA1 level at baseline in the non-RP group was significantly higher than in the RP group. The predictive significance of the ApoB/ApoA1 ratio (area under the curve (AUC) = 0.712) for the RP of NCCLs was significantly higher than those of ApoA1, ApoB, LDL-C/HDL-C ratio (AUC = 0.628, AUC = 0.640, and AUC = 0.620, respectively). A higher ApoB/ApoA1 ratio and the RP of NCCLs were significantly associated with the occurrence of MACE.The ApoB/ApoA1 ratio was an effective clinical indicator for the RP of NCCLs after PCI in patients with DM presenting with ACS. The high ApoB/ApoA1 ratio and the RP of NCCLs were two risks for MACE.

Plasma lipoprotein subclass variation in middle-aged and older adults: Sex-stratified distributions and associations with health status and cardiometabolic risk factors

Circulating lipids and lipoproteins mediate cardiovascular risk, however routine plasma lipid biochemistry provides limited information on pro-atherogenic remnant particles. We analysed plasma lipoprotein subclasses including very low-density and intermediate-density lipoprotein (VLDL and IDL); and assessed their associations with health and cardiometabolic risk. From 1,976 community-dwelling adults aged 45-67 years, 114/1071 women (10.6%) and 153/905 men (16.9%) were categorised as very healthy. Fasting plasma lipoprotein profiles comprising 112 parameters were measured using 1H nuclear magnetic resonance (NMR) spectroscopy, and associations with health status and cardiometabolic risk factors examined. HDL cholesterol was higher, and IDL and VLDL cholesterol and triglycerides lower, in very healthy women compared to other women, and women compared to men. IDL and VLDL cholesterol and triglyceride were lower in very healthy men compared to other men. HDL cholesterol and apolipoprotein (apo) A-I were inversely, and IDL and VLDL cholesterol, apoB-100, and apoB-100/apoA-I ratio directly associated with body mass index (BMI) in women and men. In women, LDL, IDL and VLDL cholesterol increased with age. Women with diabetes and cardiovascular disease had higher cholesterol, triglycerides, phospholipids and free cholesterol across IDL and VLDL fractions, with similar trends for men with diabetes. Lipoprotein subclasses and density fractions, and their lipid and apolipoprotein constituents, are differentially distributed by sex, health status and BMI. Very healthy women and men are distinguished by favorable lipoprotein profiles, particularly lower concentrations of VLDL and IDL, providing reference intervals for comparison with general populations and adults with cardiometabolic risk factors.

408-P: Associations between Apolipoprotein B (apoB): Apolipoprotein A1 (apoA1) Ratio and Metabolic and Kidney Disease in Youth with Type 1 Diabetes

ApoA1 is a major protein component of high-density lipoprotein (HDL) and apoB the main protein component of low-density lipoprotein (LDL). The ratio between apoB and apoA1 (ApoB:ApoA1) is often used to measure cardiovascular disease (CVD) risk in adults, yet little is known about its relationship with insulin resistance, central adiposity and early kidney disease, important CVD risk factors, in youth with T1D. In a study of 50 youth with type 1 diabetes, glomerular filtration rate (GFR) and renal plasma flow (RPF) were assessed using iohexol and p-aminohippurate clearance, and urine albumin-to-creatinine ratio (UACR) was also measured. Central adiposity was assessed using DXA and insulin sensitivity was estimated (eIS). Intraglomerular pressure was estimated using the Gomez equations. The study participants were 16±3.0 years old, 50% were female, and their average HbA1c was 8.7±1.3%. They had an average T1D duration of 5.7±2.6 years, with UACR levels of 6[5-14] mg/g and GFR of 189±40 ml/min. Concentrations of apoA1 and apoB were quantified by targeted nuclear magnetic resonance spectroscopy. ApoA1 (185±35 vs. 150±36 mg/dl, p=0.001) and apoB (108±29 vs. 90±27 mg/dl, p=0.03) were higher in girls vs. boys, but the apoB:apoA1 ratio was similar between the sexes (p=0.59). ApoB correlated with PGLO (r: 0.42, p=0.01), log UACR (r: 0.33, p=0.02), and trunk mass (r: 0.34, p=0.02), whereas ApoB:ApoA1 correlated with GFR (r: 0.44, p=0.002), PGLO (r: 0.48, p=0.01), log UACR (r: 0.38, p=0.008), trunk mass (r: 0.45, p=0.001), BMI (r: 0.40, p=0.004) and inversely with eIS (-0.44, p=0.001). The ratio of apoB to apoA1 associated with markers of metabolic and kidney disease in youth with T1D. Further research is needed to fully understand the mechanisms behind these associations and to identify potential strategies for preventing or mitigating cardiovascular disease in young persons with T1D. Disclosure L.Remmers: None. C.Birznieks: None. D.Carrasco: None. S.Gross: None. J.K.Snell-bergeon: None. L.A.Hall: None. K.J.Nadeau: None. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. K.L.Tommerdahl: None.

Association of lipid parameters with insulin resistance in the Kazakh population.

Insulin resistance (IR) is a consequence of chronic adipose tissue inflammation and underlies the pathogenesis of several diseases, such as type 2 diabetes mellitus, cardiovascular diseases and metabolic syndrome. In this study, we examined the association between dyslipidaemia and IR; directly comparing conventional lipid ratios and apoB/apoA1 ratios for strength and independence as risk factors for IR in a Kazakh population. The design of this study was a case-control study. There were 507 participants in the study. We examined each participant's plasma total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A1. IR was determined using an IR homeostasis model assessment (HOMA-IR). To assess the risk of an atherogenic blood lipid profile, atherogenicity coefficients were calculated: Bad cholesterol to good cholesterol ratio ((TC-HDL)/HDL); TG to HDL ratio (TRG/HDL); apoB to apoA1 ratio (apoB/apoA1). In this study, high waist circumference and BMI were more common in men. The group with IR had significantly higher waist circumference (cm) (p = 0.0001) and BMI (kg/m2) (p = 0.04) than the group without IR. The risk of IR was significantly associated with the apoB/apoA1 ratio (p = 0.03). Analysis of the association between HOMA-IR and apoB/apoA1 ratio increased the risk of IR at apoB/apoA1 ratios of 0.71 to 0.85 and above 0.86 by a factor of 1.93 and 1.84, respectively. HOMA-IR levels were weakly significantly correlated with TG levels (rS = 0.3; p = 0.0001) and very weakly positively correlated with apoB levels (rS = 0.1; p = 0.002) and apoB/apoA1 (rS = 0.1; p = 0.001), there was a weak negative correlation with apoA1 levels (rS = -0.1; p = 0.02). Logistic regression analysis showed that the risk of developing IR was significantly lower in men than in women, adjusted OR (95% CI) = 0.75 (0.49-1.0) p = 0.02. In our study, IR was more common in Kazakh women than in Kazakh men. IR was also associated with apoB and TG levels. Thus, we suggest that analysis of TG, apoB and apoB/apoA1 ratio may be recommended as early predictors of IR risk in the Kazakh population (Tab. 3, Ref. 22). Text in PDF www.elis.sk Keywords: insulin resistance, dyslipidaemia, apolipoproteins, triglycerides, lipids.

THE RELATIONSHIP BETWEEN APOB AND APOA1 WITH INSULINEMIC STATUS IN PREDIABETIC SUBJECTS

The present study was mainly aimed at exploring the causal association of the atherogenic (ApoB) and antiatherogenic apolipoproteins (ApoA1) and their ratio in the basic defects of pancreatic β cell dysfunction and insulin resistance in type 2 Diabetes Mellitus (T2DM). An intermediate stage towards diabetes, the prediabetic stage, was chosen to explore the association. Following a standardized selection process, 131 subjects were purposefully recruited for the study, including 18 with impaired fasting glucose (IFG), 56 with impaired glucose tolerance (IGT), and 57 with type 2 diabetes (T2DM). Fifty-nine healthy subjects served as controls. Glucose, lipid and insulin were estimated by glucose-oxidase, enzymatic colorimetric assay and enzyme linked immunosorbent assay (ELISA) respectively. Serum ApoB and ApoA1 were estimated by immuno-nephelometric method. Appropriate statistical tools were used to calculate statistical differences using Statistical Package for Social studies (SPSS) for Windows V12. Absolute insulin (mIU) levels were significantly higher in the IGT and T2DM groups compared to controls (p 0.001 and p = 0.001, respectively). HOMA%B (meanSD) was significantly lower in T2DM groups (p=&lt;0.001) and higher in IGT compared to the controls although it is significantly lower in IFG compared to the controls but mean value is about 90%. HOMA%S was significantly lower in IGT and T2DM group (p=0.001 and 0.002 respectively). ApoA1 levels were significantly higher only in the T2DM group (p = 0.027), whereas ApoB levels were higher in both the IGT and T2DM groups (p = 0.026-0.001).. Neither ApoB nor ApoA1 showed any significant difference in the IFG group as compared to control. ApoB-ApoA1 ratio did not show significant difference among the groups. ApoB showed significant positive correlation with both fasting and postprandial glucose (p=0.006 and 0.040 respectively). In IGT group ApoB was positively correlated with absolute insulin (p=0.025) and HOMA%B (p=0.049) and negatively with HOMA%S (p=0.026). ApoB, but not ApoA1 or the ApoB and ApoA1 ratio, seem to have a causal association with insulin resistance, and elevation of ApoB is also modulated by obesity and atherogenic lipids. Bioresearch Commu. 9(1): 1170-1176, 2023 (January)

Cardiovascular Risk Factors before Onset of Rheumatoid Arthritis Are Associated with Cardiovascular Events after Disease Onset: A Case-Control Study.

The increased comorbidity and mortality in rheumatoid arthritis (RA) patients are largely due to cardiovascular disease (CVD). Previously, we demonstrated increased frequencies of risk factors for CVD (elevated body mass index (BMI), elevated apoliprotein (Apo) B:ApoA1 ratio, and smoking) in pre-RA individuals compared with matched controls. Assess the impact of traditional CV risk factors present before the onset of RA on the risk of CV events (CVE) after diagnosis in comparison with matched controls. A case-control study including 521 pre-symptomatic individuals and 1566 controls identified within the Health Surveys of the Medical Biobank was performed. CVD risk factors were hypertension, elevated ApoB:A1 ratio, BMI, diabetes, and smoking. Information on comorbidities was requested from the Swedish National Patient Register and Cause of Death Register. Pre-RA individuals had a higher risk of future CVE compared with matched controls (HR [95% CI] 1.70 [1.31-2.21]), which remained after adjustments for risk factors for CVD (HR [95% CI] 1.73 [1.27-2.35]). Most risk factors were associated with CVE after diagnosis, and a combination resulted in a higher risk in RA compared with controls; two risk factors, HR [95% CI] 2.70 [1.19-6.13] vs. 1.26 [0.75-2.13]; and three to four risk factors, HR [95% CI] 6.32 [2.92-13.68] vs. 3.77 [2.34-6.00]. Risk factors for CVD present in pre-RA individuals were associated with future CVE, and even after adjustments for these risk factors and treatments after RA onset, pre-RA individuals had a higher risk of CVE compared with controls. These findings further highlight the importance of the early assessment of risk for CVD.

Sugar-Sweetened Beverage Consumption and Plasma Lipoprotein Cholesterol, Apolipoprotein, and Lipoprotein Particle Size Concentrations in US Adults

Prospective cohort studies have found a relation between sugar-sweetened beverage (SSB) consumption (sodas and fruit drinks) and dyslipidemia. There is limited evidence linking SSB consumption to emerging features of dyslipidemia, which can be characterized by variation in lipoprotein particle size, remnant-like particle (RLP), and apolipoprotein concentrations. To examine the association between SSB consumption and plasma lipoprotein cholesterol, apolipoprotein, and lipoprotein particle size concentrations among US adults. We examined participants from the Framingham Offspring Study (FOS; 1987-1995, n = 3047) and the Women's Health Study (1992, n = 26,218). Concentrations of plasma LDL cholesterol, apolipoprotein B (apoB), HDL cholesterol, apolipoprotein A1 (apoA1), triglyceride (TG), and non-HDL cholesterol, as well as total cholesterol:HDL cholesterol ratio and apoB:apoA1 ratio, were quantified in both cohorts; concentrations of apolipoprotein E, apolipoprotein C3, RLP-TG, and RLP cholesterol (RLP-C) were measured in the FOS only. Lipoprotein particle sizes were calculated from nuclear magnetic resonance signals for lipoprotein particle subclass concentrations (TG-rich lipoprotein particles [TRL-Ps]: very large, large, medium, small, and very small; LDL particles [LDL-Ps]: large, medium, and small; HDL particles [HDL-Ps]: large, medium, and small). SSB consumption was estimated from food frequency questionnaire data. We examined the associations between SSB consumption and all lipoprotein and apoprotein measures in linear regression models, adjusting for confounding factors such as lifestyle, diet, and traditional lipoprotein risk factors. SSB consumption was positively associated with LDL cholesterol, apoB, TG, RLP-TG, RLP-C, and non-HDL cholesterol concentrations and total cholesterol:HDL cholesterol and apoB:apoA1 ratios; and negatively associated with HDL cholesterol and apoA1 concentrations (P-trend range: <0.0001 to 0.008). After adjustment for traditional lipoprotein risk factors, SSB consumers had smaller LDL-P and HDL-P sizes; lower concentrations of large LDL-Ps and medium HDL-Ps; and higher concentrations of small LDL-Ps, small HDL-Ps, and large TRL-Ps (P-trend range: <0.0001 to 0.001). Higher SSB consumption was associated with multiple emerging features of dyslipidemia that have been linked to higher cardiometabolic risk in US adults.

Predictive value of the apolipoprotein B/A1 ratio in intracerebral hemorrhage outcomes.

Background and AimsThe apolipoprotein B (apoB)/apolipoprotein A1 (apoA1) ratio is a key indicator in predicting future cardiovascular outcomes. However, it is still unclear whether the ratio of apoB/apoA1 is a better predictor of the outcomes after intracerebral hemorrhage (ICH). Therefore, we aimed to assess the relationships between the ratio of apoB/apoA1 and functional outcomes, all‐cause mortality, and stroke recurrence in ICH patients.MethodsTwo hundred and sixteen Chinese ICH patients participated in this study from December 2018 to December 2019. Laboratory routine tests including hematology analysis, coagulation tests, and lipid levels were examined. The clinical outcomes included functional outcomes evaluated by the modified Rankin Scale score (mRS), all‐cause death, and stroke recurrence 1 year after discharge. Associations between the apoB/apoA1 ratio and the outcomes were evaluated using logistic regression analysis. Based on multivariate analysis, we constructed a nomogram. Univariate survival analysis was performed by the Kaplan–Meier method and log‐rank test. All the patients were classified into two groups by the median value of the apoB/apoA1 ratio: B1 < 0.8 and B2 ≥ 0.8.ResultsOf the 216 patients, 107 had an apoB/apoA1 ratio ≥ 0.8. Eighty‐five patients had poor functional outcomes (mRS ≥ 3), and 32 patients had severe functional outcomes (mRS ≥ 4). During the 1‐year follow‐up, a total of 18 patients died, and 13 patients had apoB/apoA1 ratio levels ≥0.8 during the 1‐year follow‐up period. Moreover, 16 recurrent strokes were recorded. Adjustments for age, sex, smoking, alcohol, body mass index, lipid levels, and hematoma site and volume showed that a high apoB/apoA1 ratio was significantly related to adverse functional outcomes and all‐cause mortality. The ORs for B2 versus B1 were 3.76 (95% CI: 1.37 to 10.40, p = 0.010), 22.74 (95% CI: 1.08 to 474.65, p = 0.044), and 7.23 (95% CI: 1.28 to 40.88, p = 0.025) for poor functional outcomes with mRS ≥ 3, mRS ≥ 4, and all‐cause mortality, respectively.ConclusionAn increased apoB/apoA1 ratio at admission was independently related to poor functional outcome and all‐cause mortality in ICH patients at the 1‐year follow‐up.

Antihyperlipidemic and Hepatoprotective Properties of Vitamin B6 Supplementation in Rats with High-Fat Diet-Induced Hyperlipidemia.

The incidence and mortality of hyperlipidemia are increasing year by year, showing a younger trend. At present, the treatment of hyperlipidemia is mainly dependent on western medicine, but its side effects on liver and kidney function are common in clinics. Therefore, it is necessary to study the treatment of hyperlipidemia by augmenting effective dietary nutrition supplements. Vitamin B6 (VitB6), as an essential cofactor for enzymes, participates in lipid metabolism. The effects of VitB6 on hyperlipidemia, however, have not been reported until now. The present study was to investigate the influence of VitB6 on hepatic lipid metabolism in hyperlipidaemia rats induced by a High-Fat Diet (HFD). Male Sprague-Dawley rats were kept on HFD for two weeks to establish the hyperlipidemia model. The rats in low-dosage and high-dosage groups were received 2.00 and 3.00 mg/kg/- day of VitB6 for eight weeks, respectively. The results showed that both doses of VitB6 reduced HFD-induced hepatic Low-Density Lipoprotein Cholesterol (LDL-C); decreased blood cholesterol (TC), triglycerides, LDL-C, atherogenic index (AI), Atherogenic Index of Plasma (AIP), apolipoprotein B (ApoB) and ApoB/apolipoprotein A-1(ApoA1) ratio; increased liver High-Density Lipoprotein Cholesterol (HDL-C) and serum ApoA1; reduced hepatic steatosis and triglyceride accumulation, lowered fat storage, and recovered heart/body and brain/body ratio to a normal level. In addition, VitB6 supplementation markedly decreased HMGR level, increased the mRNA abundance of LDLR and CYP7A1, and protein expression of SIRT1, following the downregulation of SREBP-1 and PPARγ protein expression in the liver of hyperlipidemia rats. In summary, oral VitB6 supplementation can ameliorate HFD-induced hepatic lipid accumulation and dyslipidemia in SD rats by inhibiting fatty acid and cholesterol synthesis, promoting fatty acid decomposition and cholesterol transport.

Increased apolipoprotein-B:A1 ratio predicts cardiometabolic risk in patients with juvenile onset SLE.

BackgroundCardiovascular disease is a leading cause of mortality in patients with juvenile-onset systemic lupus erythematosus (JSLE). Traditional factors for cardiovascular risk (CVR) prediction are less robust in younger patients. More reliable CVR biomarkers are needed for JSLE patient stratification and to identify therapeutic approaches to reduce cardiovascular morbidity and mortality in JSLE.MethodsSerum metabolomic analysis (including >200 lipoprotein measures) was performed on a discovery (n=31, median age 19) and validation (n=31, median age 19) cohort of JSLE patients. Data was analysed using cluster, receiver operating characteristic analysis and logistic regression. RNA-sequencing assessed gene expression in matched patient samples.FindingsHierarchical clustering of lipoprotein measures identified and validated two unique JSLE groups. Group-1 had an atherogenic and Group-2 had an atheroprotective lipoprotien profile. Apolipoprotein(Apo)B:ApoA1 distinguished the two groups with high specificity (96.2%) and sensitivity (96.7%). JSLE patients with high ApoB:ApoA1 ratio had increased CD8+ T-cell frequencies and a CD8+ T-cell transcriptomic profile enriched in genes associated with atherogenic processes including interferon signaling. These metabolic and immune signatures overlapped statistically significantly with lipid biomarkers associated with sub-clinical atherosclerosis in adult SLE patients and with genes overexpressed in T-cells from human atherosclerotic plaque respectively. Finally, baseline ApoB:ApoA1 ratio correlated positively with SLE disease activity index (r=0.43, p=0.0009) and negatively with Lupus Low Disease Activity State (r=-0.43, p=0.0009) over 5-year follow-up.InterpretationMulti-omic analysis identified high ApoB:ApoA1 as a potential biomarker of increased cardiometabolic risk and worse clinical outcomes in JSLE. ApoB:ApoA1 could help identify patients that require increased disease monitoring, lipid modification or lifestyle changes.FundingLupus UK, The Rosetrees Trust, British Heart Foundation, UCL & Birkbeck MRC Doctoral Training Programme and Versus Arthritis.

HDL, apo a1 and long-term cardio-metabolic prognosis in statin-treated patients with suspected stable angina pectoris: a prospective cohort study

Abstract Background Reduced serum levels of high density lipoprotein cholesterol (HDL-C) is a hallmark of the metabolic syndrome. Epidemiologic studies have reported an inverse correlation between HDL- C and cardiovascular disease (CVD) risk. However, recent works suggest that the association is strongest in healthy individuals. Changes in particle number and functional properties of HDL may more closely reflect CVD prognosis in patients with pre-existent disease. The majority of such patients receive statin treatment, which affects both HDL-C levels, and particle composition. Hence, serum apoA1 and the HDL-C:apoA1 ratio have been proposed as more sensitive indicators of cardio-metabolic prognosis. Purpose We studied the associations of serum HDL-C, apoA1 and the HDL-C: apoA1 ratio to long term risk of CVD mortality and incident type 2 diabetes (T2D) patients with suspected stable angina pectoris (SAP). Methods A total of 41064 patients underwent elective coronary angiography in 2000–2004 and were followed-up for CVD mortality throughout 2016. In a subgroup of 2519 participants without verified or possible diabetes at baseline, the associations to incident type 2 diabetes (T2D) were evaluated throughout 2014. Information on clinical endpoints was obtained through national health registries. Risk estimates are reported per 1 SD increment of (log transformed) biomarkers and were calculated by cox or logistic regression. We explored risk classification by calculating the continuous net reclassification improvement (NRI). Results At inclusion, median (25th-75th percentiles) age was 62 (55–70) years, 28% were women 76% had obstructive coronary artery disease and 80% received statins. During median (25th-75th percentiles) 13.9 (12.0–15.3) years of follow-up, 14.1% of the participants died from CVD. After multivariate adjustment (age, gender, body mass index, HbA1c, triglycerides, statin treatment, fasting status) HDL and apoA1, but not the HDL: apoA1 ratio, significantly predicted CVD mortality. The hazard ratio (HR) and 95% confidence interval (CI) was: 0.86 (0.78–0.94), 0.88 (0.80–0.98) and 0.96 (0.86–1.03) for HDL-C, apoA1 and the HDL-C:apoA1 ratio, respectively. HDL-C was the only of the evaluated biomarkers providing a significant NRI (95% CI) of 0.14 (0.04–0.19). In the subset evaluated for incdent T2D, HDL-C provided multivariate adjusted odds ratios (OR; 95% CI) and NRI (95% CI) of 0.69 (0.58–0.82) and 0.34 (0.21–0.47) for new onset TSD. The corresponding OR (95% CI) and NRI (95% CI) for apoA1 were: 0.85 (0.73–0.99) and 0.20 (0.06–0.33), respectively. The HDL:apo A1 ratio provided an OR (95% CI) of 0.66 (0.55–0.80) and NRI (95% CI) of 0.24 (0.11–0.37) for T2D. No significant effect modifications according to statin treatment were found (P≥0.22). Conclusion Among patients with suspected SAP, of which the majority received statins, HDL-C was non-inferior to apoA1 and the HDL:apoA1 ratio in predicting long term risk of CVD mortality and T2D. Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Department of Heart Disease, Haukeland University Hospital; Department of Clinical Science, University of Bergen

Baseline white blood cell count-to-apolipoprotein A1 ratio as a novel predictor of long-term adverse outcomes in patients who underwent percutaneous coronary intervention: a retrospective cohort study

BackgroundPrevious studies suggested that baseline white blood cell count and apolipoprotein A1 levels were associated with clinical outcomes in patients with coronary heart disease (CAD) who underwent percutaneous coronary intervention (PCI). However, the ratio of baseline white blood cell count-to-apolipoprotein A1 level (WAR) and CAD after PCI have not been investigated. The present study investigated the effects of baseline WAR on long-term outcomes after PCI in patients with CAD.MethodsA total of 6050 patients with CAD who underwent PCI were included in the study. Of these, 372 patients were excluded because no baseline white blood cell counts or apolipoprotein A1 (ApoA1) data was available or because of malignancies or other diseases. Finally, 5678 patients were enrolled in the present study and were divided into 3 groups according to WAR value: lower group - WAR< 5.25 (n = 1889); median group - 5.25 ≤ WAR≤7.15 (n = 1892); and higher group - WAR≥7.15 (n = 1897). The primary endpoint was long-term mortality, including all-cause mortality (ACM) and cardiac mortality (CM), after PCI. The average follow-up time was 35.9 ± 22.6 months.ResultsA total of 293 patients developed ACM, including 85 (4.5%) patients in the lower group, 90 (4.8%) patients in the median group, and 118 (6.2%) patients in the higher group. The risk of ACM, cardiac mortality (CM), major adverse cardiovascular and cerebrovascular events (MACCEs), and major adverse cardiovascular events (MACEs) increased 62.6% (hazard risk [HR] =1.626, 95%CI: 1.214–2.179, P = 0.001), 45.5% (HR = 1.455, 95%CI: 1.051–2.014, P = 0.024), 21.2% (HR = 1.212, 95%CI: 1.011–1.454, P = 0.038), and 23.8% (HR = 1.238, 95%CI: 1.025–1.495, P = 0.027), respectively, as determined by multivariate Cox regression analyses comparing the patients in the higher group to patients in the lower group. Patients with a WAR≥4.635 had 92.3, 81.3, 58.1 and 58.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, compared to the patients with WAR< 4.635. Every 1 unit increase in WAR was associated with 3.4, 3.2, 2.0 and 2.2% increased risks of ACM, CM, MACCEs and MACEs, respectively, at the 10-year follow-up.ConclusionThe present study indicated that baseline WAR is a novel and an independent predictor of adverse long-term outcomes in CAD patients who underwent PCI.

Prediction of Subclinical Coronary Atherosclerosis in Patients with High and Very High Cardiovascular Risk

Objective To develop a diagnostic rule for detection of patients (pts) with high probability of subclinical atherosclerosis among those with high or very high cardiovascular (CV) risk.Materials and Methods This cross-sectional study enrolled 52 pts (32 men [62 %]), aged 40 to 65 years [mean age 54.6±8.0]) with high or very high CV risk (5-9 and ≥10 % by The Systematic Coronary Risk Estimation Scale [SCORE], respectively). All participants underwent cardiac computed tomography (CT) angiography and calcium scoring. Traditional risk factors (RFs) (family history of premature CVD, smoking, overweight / obesity and abdominal obesity, hypertension, type 2 diabetes mellitus, lipids parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides) and lipids-related markers (apolipoprotein A1, apolipoprotein B, ApoB / ApoA1 ratio), biomarkers of inflammation (high-sensitivity C-reactive protein [hs CRP], fibrinogen), indicator carbohydrate metabolism (glucose), ankle-brachial index, stress-test, carotid plaques according to ultrasound were evaluated in all pts. Psychological RFs were evaluated using Hospital Anxiety and Depression Scale and DS-14 for type D personality.Results All pts were divided into 2 groups according to the CT angiography results: pts in the main group (n=21) had any non-obstructive lesions or calcium score &gt;0, pts in the control group (n=31) had intact coronary arteries. The groups did not differ in age or gender. 26 multiple linear logistic models for any subclinical atherosclerosis were developed based on obtained diagnostic features. Taking into account R-square = 0.344 (p=0.0008), the best fitting model was follows: subclinical coronary atherosclerosis= -1.576 + 0.234 x SCORE ≥5 % + 0.541 x hs CRP &gt;2 g / l +0.015 x heart rate (bpm) +0.311 family history of premature CVD. The developed algorithm had sensitivity of 63 % and specificity of 80 %.Conclusion The created diagnostic model diagnostic model suggests the presence of subclinical coronary atherosclerosis in patients with high / very high CV risk with a high degree of probability. This easy-to-use method can be used in routine clinical practice to improve risk stratification and management choices in high-risk pts.