apoB Ratio Research Articles

ApoB100 remodeling and stiffened cholesteryl ester core raise LDL aggregation in familial hypercholesterolemia patients

Patients with familial hypercholesterolemia (FH) exhibit a significant residual cardiovascular risk. A new cardiovascular risk factor is the susceptibility of individual LDL particles to aggregation. This study examined LDL aggregation and its relationship with LDL lipid composition and biophysical properties in patients with FH compared to controls. LDL aggregation was measured as the change in particle size, assessed by dynamic light scattering, after exposure to sphingomyelinase, which breaks down sphingomyelin in the LDL phospholipid layer. Dynamic light scattering and transmission electron microscopy showed that LDL in FH patients exhibited smaller size and greater susceptibility to aggregation. Biochemical analyses revealed a higher cholesteryl ester (CE)/ApoB100 ratio in LDL from FH patients. Differential scanning calorimetry showed that LDL from FH patients had higher transition temperatures, indicating a more ordered CE core. Fourier transform infrared spectroscopy revealed fewer flexible α-helices (1658 cm⁻1) and more stable α-helices (1651 cm⁻1) in ApoB100 of LDL from FH patients. These structural changes correlated with higher CE content and increased LDL aggregation. In conclusion, a more ordered CE core in smaller LDL particles, combined with a higher proportion of stable α-helices in ApoB100, promotes LDL aggregation in FH patients. These findings suggest new potential therapeutic targets within LDL to reduce cardiovascular risk in FH patients.

Triglyceride-rich lipoprotein, remnant cholesterol, and apolipoproteins CII, CIII, and E in patients with schizophrenia

Patients with schizophrenia show a disproportionally increased risk of cardiovascular disease. Hypertriglyceridemia is prevalent in this population; however, how this relates to levels of remnant cholesterol, triglyceride (TG)-rich lipoprotein (TRL) particle size and composition, TG turnover, and apolipoprotein (apo) and angiopoietin-like protein (ANGPTL) concentrations is unknown. Fasting levels of cholesterol (total [TC], LDL-C, HDL-C, non-HDL-C and remnant cholesterol) and TG were determined in 110 patients diagnosed with schizophrenia, and 46 healthy controls. TRL particle size, concentration and composition, and β-hydroxybutyrate (TG turnover marker) were assessed by NMR. Levels of apoCII, apoCIII, apoE, ANGPTL3, ANGPTL4, and ANGPTL8 were measured by ELISA, and apoCII, apoCIII and apoE were further evaluated in HDL and non-HDL fractions. Patients with schizophrenia had significantly elevated TG, TG:apoB ratio, non-HDL-C, remnant cholesterol, non-HDL-apoCII and non-HDL-apoCIII, and HDL-apoE (all P < 0.05), lower HDL-C and apoA-I (all P < 0.001), and comparable apoB, TC, TC:apoB ratio, LDL-C, β-hydroxybutyrate, ANGPTL3, ANGPTL4 and ANGPTL8 to healthy controls. Patients had a 12.0- and 2.5-fold increase in the concentration of large and medium TRL particles respectively, but similar cholesterol:TG ratio within each particle. Plasma TG, remnant cholesterol, and large and medium TRL particle concentrations correlated strongly with apoCII, apoCIII, and apoE in the non-HDL fraction, and with apoCIII and apoE in the HDL fraction in patients with schizophrenia. Differences in TG, HDL-C, TRL particle concentrations, apoCIII, and apoE persisted after adjustment for conventional risk factors. These results are consistent with impaired TRL lipolysis and clearance in patients with schizophrenia which may be responsive to targeting apoCIII.

Heterogeneity of diabetic dyslipidemia, data from the NHANES (2011-2016).

Epidemiologic studies have demonstrated that diabetes amplifies the effects of dyslipidemia as a risk factor for cardiovascular disease (CVD). A better understanding of lipid profiles is important for lipid-lowering treatment and reducing cardiovascular risk in populations with diabetes. To describe the dyslipidemia patterns in patient with and without diabetes in the adult US population. Data from National Health and Nutrition Examination Survey (NHANES) 2011 to 2016 was analyzed. Surprisingly, 49.9% of the people with diabetes have both normal triglycerides (TGs) and normal high-density lipoprotein cholesterol (HDL-C). 33.4% of the people with diabetes have elevated TGs and 36.1% of them have low HDL-C. Only 19.3% of them have both elevated TGs and low HDL-C. Among people without diabetes, 67.5% have normal TGs and normal HDL-C, 28.0% have elevated TGs, 23.9% have low HDL-C and 8.8% have both elevated TGs and low HDL-C. The differences in the proportions of individuals with both elevated TGs and low HDL-C between the diabetic group and the nondiabetic group were more obvious in females: 7.7% in women without diabetes and 22.7% in women with diabetes. The proportion of individuals in the TG↑HDL-C↓group in the population with diabetes exhibited a decreasing trend in age groups > 30 years old, and the 30 to 40 years group of individuals with diabetes had the highest proportion of atherogenic dyslipidemia. The low-density lipoprotein cholesterol (LDL-C) to apoB ratio is generally lower in people with diabetes, with the lowest level in the TG↑HDL-C↓group. Dyslipidemia patterns in diabetes patients are highly heterogeneous. Deep phenotyping sub-groups of dyslipidemia is warranted to identify higher-risk patients for evaluation of non-LDL-C therapies. This explained at least partially of the difficult search for novel therapies in the post-LDL-C era.

Evaluation of Serum ApoA1 and ApoB Levels in the First-degree Relatives of Patients with Essential Hypertension at a Tertiary Care Centre in Eastern India: A Cross-sectional Study

Introduction: An altered serum lipid profile and lipoprotein levels are major modifiable risk factors for hypertension. Apolipoprotein A1 and B100 (ApoA1 and ApoB100) are the chief structural proteins of High-density Lipoprotein Cholesterol (HDL-C) and Low-density Lipoprotein Cholesterol (LDL-C), respectively. The level of ApoB in the serum represents overall atherogenicity, whereas the level of ApoA1 can indicate total antiatherogenicity. Aim: To evaluate the serum levels of ApoA1 and ApoB in the first-degree relatives of individuals with essential hypertension. Materials and Methods: This cross-sectional observational study was conducted in the Clinical Biochemistry laboratory in association with the Department of General Medicine at SCB Medical College and Hospital, Cuttack, Odisha, India, from February 2018 to March 2019. It consisted of 165 participants: group I included hypertensive patients (n=55); group II included first-degree relatives of the above hypertensive patients (n=55); and group III included non hypertensive healthy age-matched controls (n=55). The waist-hip ratio, Blood Pressure (BP), fasting plasma glucose, serum cholesterol, triglycerides, HDL-C, LDL-C, ApoA1, ApoB, and the ApoB/ApoA1 ratio were all measured. Statistical analysis was performed using Statistical Package for Social Sciences (SPSS) software version 25.0. Results: The mean age of subjects in groups I, II, and III was 49±8.3, 38±5.2, and 37±5.4 years, respectively, with males constituting 56% and females 44% of the total participants. The ApoA1 levels were lowest in group I (104.9±16.3 mg/dL) and highest in group III (117.4±7.3 mg/dL). The serum ApoB levels and the ratio of ApoB/ApoA1 were highest in group I (104.2±14.1; 1.1±0.64 mg/dL) and lowest in group III (60.9±18.2; 0.5±0.15 mg/dL). A highly significant negative correlation (r=- 0.40, p&lt;0.01) was found between Systolic Blood Pressure (SBP) and ApoA1. A significant correlation (r=0.26, p=0.04) was observed between SBP and the ApoB/ApoA1 ratio in group III. Conclusion: Serum ApoB levels and the ratio of ApoB/ ApoA1 were significantly elevated in the first-degree relatives of hypertensive patients, thus emphasising the importance of screening individuals with a positive family history of hypertension.

The non-HDL-C to APOB ratio as a predictor of inaccurate LDL-C measurement in patients with chronic intrahepatic cholestasis and jaundice: a retrospective study.

Cholestasis is characterized by the accumulation of bile in the liver or biliary system due to obstruction or impaired flow, necessitating lipid profiling to assess lipid metabolism abnormalities. Intrahepatic cholestasis, being the most significant type of cholestasis, further complicates the assessment of lipid abnormalities. However, the accuracy of low-density lipoprotein cholesterol (LDL-C) measurement in intrahepatic cholestasis patients remains uncertain. This study aimed to evaluate the consistency of the homogeneous assay and the Friedewald formula in detecting LDL-C levels and identify factors influencing LDL-C test results in intrahepatic patients with cholestasis. Retrospective analysis of laboratory data was conducted on intrahepatic cholestatic patients. Correlations between LDL-C values obtained using the homogeneous method (LDL-C(D)) and the Friedewald formula (LDL-C(F)), as well as associations between high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A1 (ApoA1), LDL-C(D) and LDL-C(F), and apolipoprotein B (ApoB), were analyzed. Logistic regression analyses were employed to identify diagnostic indicators for inaccurate LDL-C measurements in intrahepatic cholestatic patients. Compared to patients with intrahepatic cholestasis without jaundice, the correlation between LDL-C(F) and LDL-C(D) was weaker in those with jaundice. Additionally, HDL-C exhibited a strong correlation with ApoA1 in both jaundice and non-jaundice cholestasis cases. Elevated non-HDL-C to APOB ratio (NH-C/B Ratio) levels (>4.5) were identified as a reliable predictor of inaccurate LDL-C measurements in patients with chronic intrahepatic cholestasis accompanied by jaundice. LDL-C measurement reliability is moderately weaker in patients with intrahepatic cholestasis accompanied by jaundice. Elevated levels of the NH-C/B ratio serve as a significant predictor of inaccurate LDL-C measurements in this chronic patient population, highlighting its clinical relevance for diagnostic assessments.

FRI100 Lipoprotein X In Graft Vs. Host Disease Affecting Liver

Abstract Disclosure: D. Vedamurthy: None. C. Vitali: None. M. Cuchel: None. D. Soffer: None. D. Rader: None. Introduction: Lipoprotein-X (LpX) is an abnormal lipoprotein rich in phospholipid and unesterified cholesterol (UC) found in patients with cholestatic liver disease, lecithin-cholesterol acyl transferase (LCAT) deficiency, and after lipid emulsion infusion. LpX has been detected in patients with graft-versus-host disease (GVHD) of the liver. Cholestasis leads to the accumulation of bile salts and UC in the circulation, promoting the formation of LpX. This condition is often not well-recognized, partly because the detection of LpX is technically challenging and requires specialized laboratory assays. Case Description: A 66-year lady with acute myeloblastic leukemia (AML) underwent an allogeneic matched unrelated donor stem cell transplant (SCT) which was complicated by graft-versus-host disease (GVHD) affecting the liver, eyes, lungs, and skin. Past medical history includes hypertension. Family history was significant for coronary artery disease in the mother. She is a reformed smoker. Her post-transplant course was highly complicated with infections, GVHD affecting the liver, eyes, lungs, and skin, and vascular events including myocardial infarction and stroke. Laboratory testing revealed abnormal liver enzymes (ALT=268, AST=173, ALKP =402 U/L), and a markedly abnormal lipid profile (TC=500, Non-HDL-C=358, TG= 345 mg/dL). Her thyroid panel and viscosity were normal, but apolipoprotein B levels were discordantly low (77mg/dL). The ratio of ApoB: Non-HDL cholesterol was abnormally low (0.215). She was started on ezetimibe, evolocumab, and omega-3 fatty acids by her neurovascular team for cardiovascular risk reduction. A physical exam revealed a thin, frail woman with mild oral and nail GVHD changes. The rest of the exam was notable for the abdomen showing chronic patchy hyperpigmentation with sclerodermatous changes anteriorly and posteriorly. She had no significant focal neurologic deficits. Her lipid levels were improved with therapy, but TC, non-HDL-C, UC, and triglycerides levels were still elevated (TC=353, non-HDL=258, UC=163, TG=414 mg/dL), UC: TC ratio was high (0.46). FPLC separation of TRL-depleted plasma revealed the presence of LpX. LpX is not very atherogenic, and we recommended continuing current medical therapy as the serum viscosity was within normal limits. Conclusion: The presence of LpX should be suspected in the setting of GVHD accompanied by markedly elevated TC. LpX may cause hyperviscosity, which can induce end-organ ischemia. While the direct assessment of LpX is challenging and requires specialized techniques, ApoB and non-HDL-C levels are available in most clinical laboratories, and a very low ApoB: Non-HDL-C ratio in GVHD patients may indicate the presence of LpX. The treatment goal is to resolve the underlying causes of cholestasis. If hyperviscosity is present, Lp-X can be acutely treated by plasma exchange or lipoprotein apheresis. Presentation: Friday, June 16, 2023

Hypertriglyceridemic hyperapoB and the development and resolution of nonalcoholic fatty liver disease: a cohort study

Hypertriglyceridemic hyperapoB is an adverse lipoprotein phenotype characterized by low high density lipoprotein (HDL) cholesterol, high triglycerides, high apolipoprotein B (ApoB), and low low density lipoprotein (LDL) cholesterol to ApoB ratio. We investigated whether and to what extent hypertriglyceridemic hyperapoB associates with the incidence and resolution of nonalcoholic fatty liver disease (NAFLD). This prospective cohort study included 9,019 Chinese participants 40 years or older, from 2010 to 2015. Logistic regression models were used to examine the odds ratios (ORs) for the incidence and resolution of NAFLD associated with the hypertriglyceridemic hyperapoB lipoprotein phenotype and individual lipid and lipoprotein parameters. During a median 4.3 years of follow-up, compared with participants with optimal phenotype, the fully adjusted ORs (95% CIs) for participants with hypertriglyceridemic hyperapoB were 2.75 (1.91, 3.95) and 0.57 (0.33, 1.00) for incidence and resolution of NAFLD, respectively. These associations were consistent across subgroup participants with varied demographic, lifestyle, and metabolic status. Individually, each unit increase in HDL cholesterol (OR: 0.98; 95% CI: 0.97, 0.99), natural logarithm-transformed triglycerides (1.89; 1.52, 2.36), and ApoB (1.006; 1.002, 1.011) was independently associated with NAFLD incidence, and only triglycerides (0.77; 0.60, 0.99) was independently associated with NAFLD resolution. Our findings suggest that Chinese adults with hypertriglyceridemic hyperapoB have a higher risk of NAFLD incidence and a lower likelihood of NAFLD resolution. These associations were stable among adults with different demographic, lifestyle, and metabolic status, supporting hypertriglyceridemic hyperapoB as a valuable clinical marker for the prevention and control of NAFLD.

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.

Quantification of LDL-Cholesterol Corrected for Molar Concentration of Lipoprotein(a).

Cholesterol in lipoprotein(a) [Lp(a)-C] is commonly estimated as 30% of the measured Lp(a) mass. However, difficulties in the accurate measurement of Lp(a) mass, along with the inaccuracy of the 30% assumption, produce erroneous values when LDL-C is corrected for Lp(a) [LDL-CLp(a)corr]. Our aim was to develop a new formula for LDL-CLp(a)corr to reduce this error. We developed a new formula to calculate Lp(a)-C from the molar measurement of Lp(a), which is Lp(a) nmol/L × 0.077 = Lp(a)-C mg/dL. The calculated Lp(a)-C is subtracted from LDL-C to obtain LDL-CLp(a)corr. The results obtained with our novel formula versus the conventional formula were compared in 440 samples from 239 participants enrolled in the BANTING study. With the conventional formula, approximately 7% of samples with low LDL-C resulted in negative LDL-CLp(a)corr values. With the new formula, no negative LDL-CLp(a)corr values occurred. Among groups with the highest Lp(a)/apoB ratio (p < 0.001) and smaller apolipoprotein(a) isoform size (p < 0.006), LDL-CLp(a)corr was significantly underestimated by the conventional formula, which may result in theundertreatment of some patients. The new formula provides more reliable estimates of LDL-CLp(a)corr than the conventional formula. ClinicalTrials.gov NCT02739984.

Abstract 12400: The LDL-C / ApoB Ratio Predicts Future Cardiovascular Events in Cardiovascular Disease Patients With Nonalcoholic Fatty Liver Disease as Well as in Those Without Nonalcoholic Fatty Liver Disease

Introduction: A low LDL-C / apoB ratio reflects small LDL particle size and is associated with insulin resistance. Non-alcoholic fatty liver disease (NALFD) is an important feature of the insulin resistance syndrome and confers an increased cardiovascular risk. The impact of the LDL-C / apoB ratio on the risk of cardiovascular events in patients with NAFLD is unclear. Hypothesis: We hypothesize that the LDL-C/apoB ratio predicts cardiovascular events in patients with NAFLD. Methods: We enrolled a large high risk cohort of 1515 patients with established cardiovascular disease (1272 patients with angiographically proven stable CAD and 243 patients with sonographically proven peripheral artery disease). NAFLD was diagnosed using the validated fatty liver index. Prospectively, cardiovascular events were recorded over a mean follow-up period of 7.6±4.9 years. Results: At baseline, the LDL-C / apoB ratio was significantly lower in patients with NAFLD (n=709) than in subjects who did not have NAFLD (1.34±0.29 vs. 1.39±0.26 mg/dl; p=0.001). During follow-up, 755 patients suffered cardiovascular events. The event rate was higher in patients with than in those without NAFLD (53.6 vs. 47.6%; p=0.020). The LDL-C/ApoB ratio significantly predicted cardiovascular events in the total study cohort, with a standardized adjusted hazard ratio (HR) of 0.86 [0.80-0.94]; p&lt;0.001 and both in patients with NAFLD (HR 0.87 [0.78-0.97]; p=0.013) and in subjects who did not have NAFLD (HR 0.87 [0.77-0.97]; p=0.013, respectively). Conclusions: We conclude that in subjects with established cardiovascular disease the LDL-C / apoB ratio predicts cardiovascular events both among patients with NAFLD and in those who do not have NAFLD.

Interplay of Atherogenic Particle Number and Particle Size and the Risk of Coronary Heart Disease.

We examined the interplay of apolipoprotein B (apoB) and LDL particle size, approximated by the LDL-cholesterol (LDL-C)/apoB ratio, on the risk of new-onset coronary heart disease (CHD). Participants without cardiovascular disease from the UK Biobank (UKB; n = 308 182), the Women's Health Study (WHS; n = 26 204), and the Framingham Heart Study (FHS; n = 2839) were included. Multivariable Cox models were used to assess the relationship between apoB and LDL-C/apoB ratio and incidence of CHD (14 994 events). Our analyses were adjusted for age, sex (except WHS), HDL-cholesterol (HDL-C), systolic blood pressure, antihypertensive treatment, diabetes, and smoking. In all 3 studies, there was a strong positive correlation between apoB and LDL-C (correlation coefficients r = 0.80 or higher) and a weak inverse correlation of apoB with LDL-C/apoB ratio (-0.28 ≤ r ≤ -0.14). For all 3 cohorts, CHD risk was higher for higher levels of apoB. Upon multivariable adjustment, the association between apoB and new-onset CHD remained robust and statistically significant in all 3 cohorts with hazard ratios per 1 SD (95% CI): 1.24 (1.22-1.27), 1.33 (1.20-1.47), and 1.24 (1.09-1.42) for UKB, WHS, and FHS, respectively. However, the association between LDL-C/apoB and CHD was statistically significant only in the FHS cohort: 0.78 (0.64-0.94). Our analysis confirms that apoB is a strong risk factor for CHD. However, given the null association in 2 of the 3 studies, we cannot confirm that cholesterol-depleted LDL particles are substantially more atherogenic than cholesterol-replete particles. These results lend further support to routine measurement of apoB in clinical care.

Identification of Dysbetalipoproteinemia by an Enhanced Sampson-NIH Equation for Very Low-Density Lipoprotein-Cholesterol.

Dysbetalipoproteinemia (hyperlipoproteinemia type III, HLP3) is a genetic disorder that results in the accumulation of cholesterol on highly atherogenic remnant particles. Traditionally, the diagnosis of HLP3 depended upon lipoprotein gel electrophoresis or density gradient ultracentrifugation. Because these two methods are not performed by most clinical laboratories, we describe here two new equations for estimating the cholesterol content of VLDL (VLDL-C), which can then be used for the diagnosis of HLP3. Using results from the beta-quantification (BQ) reference method on a large cohort of dyslipidemic patients (N = 24,713), we identified 115 patients with HLP3 based on having a VLDL-C to plasma TG ratio greater than 0.3 and plasma TG between 150 and 1,000 mg/dl. Next, we developed two new methods for identifying HLP3 and compared them to BQ and a previously described dual lipid apoB ratio method. The first method uses results from the standard lipid panel and the Sampson-NIH equation 1 for estimating VLDL-C ( S -VLDL-C), which is then divided by plasma TG to calculate the VLDL-C/TG ratio. The second method is similar, but the Sampson-NIH equation 1 is modified or enhanced ( eS -VLDL-C) by including apoB as an independent variable for predicting VLDL-C. At a cut-point of 0.194, the first method showed a modest ability for identifying HLP3 (sensitivity = 73.9%; specificity = 82.6%; and area under the curve (AUC) = 0.8685) but was comparable to the existing dual lipid apoB ratio method. The second method based on eS -VLDL-C showed much better sensitivity (96.5%) and specificity (94.5%) at a cut-point of 0.209. It also had an excellent AUC score of 0.9912 and was superior to the two other methods in test classification. In summary, we describe two new methods for the diagnosis of HLP3. The first one just utilizes the results of the standard lipid panel and the Sampson-NIH equation 1 for estimating (VLDL-C) ( S -VLDL-C) and can potentially be used as a screening test. The second method ( eS -VLDL-C), in which the Sampson-NIH equation 1 is modified to include apoB, is nearly as accurate as the BQ reference method. Because apoB is widely available at most clinical laboratories, the second method should improve both the accessibility and the accuracy of the HLP3 diagnosis.

1096-P: The LDL-C/apoB Ratio Predicts Future Cardiovascular Events in Cardiovascular Disease Patients with Nonalcoholic Fatty Liver Disease as Well as in Those without Nonalcoholic Fatty Liver Disease

A low LDL-C / apoB ratio reflects small LDL particle size and is associated with insulin resistance. Nonalcoholic fatty liver disease (NALFD) is an important feature of the insulin resistance syndrome and confers an increased cardiovascular risk. The impact of the LDL-C / apoB ratio on the risk of cardiovascular events in patients with NAFLD is unclear and is addressed in the present study. We enrolled a large high risk cohohort of 1515 patients with established cardiovascular disease (1272 patients with angiographically proven stable CAD and 243 patients with sonographically proven peripheral artery disease) . NAFLD was diagnosed using the validated fatty liver index. Prospectively, cardiovascular events were recorded over a mean follow-up period of 7.6±4.9 years. At baseline, the LDL-C / apoB ratio was significantly lower in patients with NAFLD (n=709) than in subjects who did not have NAFLD (1.34±0.29 vs. 1.39±0.26 mg/dl; p=0.001) . During follow-up, 755 patients suffered cardiovascular events. The event rate was higher in patients with than in those without NAFLD (53.6 vs. 47.6%; p=0.020) . The LDL-C/ApoB ratio significantly predicted cardiovascular events in the total study cohort, with a standardized adjusted hazard ratio (HR) of 0.86 [0.80-0.94]; p&amp;lt;0.0 and both in patients with NAFLD (HR 0.87 [0.78-0.97]; p=0.013) and in subjects who did not have NAFLD (HR 0.87 [0.77-0.97]; p=0.013, respectively) . We conclude that in subjects with established cardiovascular disease the LDL-C / apoB ratio predicts cardiovascular events both among patients with NAFLD and in those who do not have NAFLD. Disclosure M.Maechler: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.

An adverse lipoprotein phenotype—hypertriglyceridaemic hyperapolipoprotein B—and the long-term risk of type 2 diabetes: a prospective, longitudinal, observational cohort study

This study examines the risk of new-onset diabetes in patients with hypertriglyceridaemic hyperapolipoprotein B (high triglycerides, high apolipoprotein B [apoB], low LDL cholesterol to apoB ratio, and low HDL cholesterol). The aim was to establish whether this lipoprotein phenotype identified a substantial group at high risk of developing diabetes over the next 20 years. In this prospective, longitudinal, observational cohort study, we used data from the Framingham Offspring cohort (recruited in Framingham, MA, USA). Participants were aged 40-69 years and free of diabetes and cardiovascular disease at a baseline examination done between April, 1987, and November, 1991, and were followed up until March, 2014. Cox proportional hazards regression with hierarchical adjustment for age and sex, waist circumference, and fasting blood glucose were used to model the relationship between each lipid marker and incident diabetes, as well as the relationship between hypertriglyceridaemic hyperapoB (defined as values greater than sample medians of triglycerides and apoB, and less than medians of HDL cholesterol and LDL cholesterol to apoB ratio) and incident diabetes. Of 3446 individuals aged 40-69 years who completed baseline examination, 2515 participants were eligible and included in all analyses. During median 21·1 years (IQR 11·1-23·1) of follow-up, 402 (16·0%) individuals developed diabetes. Age (p=0·032), waist circumference (p<0·0001), fasting blood glucose (p<0·0001), and natural logarithm-transformed triglycerides (p<0·0001) were associated with new-onset diabetes, as were apoB (p=0·0016), LDL cholesterol to apoB ratio (p=0·0018), and HDL cholesterol (p=0·0016) when added to this model. The age and sex-adjusted incidence of diabetes in the hypertriglyceridaemic hyperapoB group was 32·4% (95% CI 27·8-37·7) versus 5·5% (3·5-8·6) in the optimal lipid phenotype group and 15·5% (13·5-17·7) in the mixed lipid phenotype group. The fully adjusted hazard ratio, including glucose and waist circumference, for individuals with hypertriglyceridaemic hyperapoB was 3·30 (95% CI 2·06-5·30; p=0·0008) and for mixed lipid phenotype was 2·17 (1·38-3·40; p<0·0001) compared with those with the optimal lipid phenotype. Our findings suggest that individuals with hypertriglyceridaemic hyperapoB are at high risk of new-onset diabetes and might benefit from intensive measures to prevent diabetes. The association between this phenotype and incident diabetes is consistent with a pro-diabetic effect due to increased clearance of apoB particles from plasma, which could injure pancreatic islet cells. This mechanism might explain the increased risk of diabetes with statin therapy. Doggone Foundation.

A More Atherogenic Lipoprotein Status Is Present in Adults With Type 2 Diabetes Mellitus Than in Those Without With Equivalent Degrees of Hypertriglyceridemia

ObjectivesThe impact of type 2 diabetes (T2DM) on biomarkers denoting lipoprotein compositional status was studied in mild and moderate hypertriglyceridemia (HTG). Diabetic dyslipidemia pathophysiology could contribute to differences in lipoprotein compositional status, which could be reflected in the preferred cardiovascular disease risk prediction markers in HTG: non–high-density lipoprotein cholesterol (non-HDLC) and apolipoprotein B (apoB). MethodsA total of 2,775 fasting lipid profiles from a tertiary care lipid clinic were analyzed as 2 subgroups (with and without T2DM), stratified by triglyceride (TG) levels: normotriglyceridemia (TG 0.01 to 1.7 mmol/L), mild HTG (TG 1.71 to 5 mmol/L) and moderate HTG (TG 5.01 to 10 mmol/L). The mean non-HDLC:apoB ratio in each TG stratum and subgroup was analyzed. We also used linear regression to assess the correlation between non-HDLC and apoB. ResultsThe mean non-HDLC:apoB ratio was increased in both subgroups in patients with mild and moderate HTG, compared to those with normotriglyceridemia. In moderate HTG, the mean non-HDLC:apoB ratio in the subgroup with T2DM was significantly lower than the subgroup without T2DM. In mild and moderate HTG, the subgroup with T2DM had a stronger correlation between non-HDLC and apoB than did the subgroup without T2DM. Discussion and conclusionsIn mild and moderate HTG, adults with T2DM exhibit lipid profiles that represent a different and more atherogenic lipoprotein compositional status, when compared with adults without T2DM. For the same severity of HTG, the lipoprotein compositional status in diabetic dyslipidemia suggests that there is increased abundance of smaller non-HDL particles and their remnants, which are highly atherogenic.

Low-glycemic-load, omega-3 PUFA-enriched semi-vegetarian diet decreases serum apolipoprotein B and reduces the apoB/apoA-I ratio in familial hypercholesterolemia

Rationale: Patients with familial hypercholesterolemia (FH) are at high risk of premature atherosclerotic cardiovascular disease (ASCVD) due to the cumulative LDL-cholesterol (LDL-C) exposure. Apolipoprotein (apo) B has been recently shown to be a more accurate marker of ASCVD risk in statin-treated patients than LDL-C [1]. We aimed to evaluate the efficacy of a low-glycemic, semi-vegetarian diet enriched in omega-3 polyunsaturated fatty acids (PUFA) in reducing blood levels of apoB and in lowering the ratio of apoB to apoA-I in FH patients.

Disorders of lipid metabolism and lipid transport system in women with unstable angina in the dependence on smoking: pathogenetic connections and development risks

The aim of the study. To study the effect of smoking on lipid metabolism, lipid transport system and systemic inflammation, to find out their correlations and the risks of unstable angina in women, depending on the habit of smoking.Material and methods. 225 women were examined: 150 women - patients with unstable angina and 75 healthy women. The level of total cholesterol, low and high-density lipoprotein cholesterol, triglycerides, apolipoproteins A1 (ApoA1) and B (ApoB), C-reactive protein, fibrinogen were determined in all subjects. Multifactor correlation-regression analysis was performed using Fisher's test. Statistical processing of the results was performed using the applications "Microsoft Office Excel 2016" and "Statistics ver. 10.Results. The relative risk of developing unstable angina in patients with a smoking habit is most often associated with atherogenic dyslipidemia (total cholesterol &gt; 4 mmol, OR = 12.02, SI = 8.12-16.32; low-density lipoprotein cholesterol &gt; 1.8 mmol / l, OR = 9,32, SI = 6,13-12,56, high-density lipoprotein cholesterol &lt;1,2 mmol / l, OR = 3,91, SI = 2,12-5,45, the ratio of apolipoproteins ApoV / ApoA1&gt; 0.85, OR = 2.69, SI = 1.15-4.21) and the highest activity of systemic inflammation (C-reactive protein &gt;3 mg / l, OR = 3.62, SI = 2.15- 4.56). The risk of developing unstable angina associated with these indicators is 1.5-2 times higher in women with a smoking habit than in women who have never smoked. Significant direct correlations of high and medium strength between the severity of systemic inflammation, disorders of the lipid transport system (increase in the ratio of ApoB / ApoA1 and decrease in the level of ApoA1), in patients with unstable angina in women smokers.Conclusions. Smoking is one of the most aggressive factors of unstable angina in women, which contributes to the emergence and progression of other important risk factors and leads to disorders of lipid metabolism, lipid transport system, systemic inflammation and increased chances of unstable angina.

Exploring Serum NMR-Based Metabolomic Fingerprint of Colorectal Cancer Patients: Effects of Surgery and Possible Associations with Cancer Relapse

Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed and third most deadly cancer worldwide. Surgery is the main treatment option for early disease; however, a relevant proportion of CRC patients relapse. Here, variations among preoperative and postoperative serum metabolomic fingerprint of CRC patients were studied, and possible associations between metabolic variations and cancer relapse were explored. Methods: A total of 41 patients with stage I-III CRC, planned for radical resection, were enrolled. Serum samples, collected preoperatively (t0) and 4–6 weeks after surgery before the start of any treatment (t1), were analyzed via NMR spectroscopy. NMR data were analyzed using multivariate and univariate statistical approaches. Results: Serum metabolomic fingerprints show differential clustering between t0 and t1 (82–85% accuracy). Pyruvate, HDL-related parameters, acetone, and 3-hydroxybutyrate appear to be the major players in this discrimination. Eight out of the 41 CRC patients enrolled developed cancer relapse. Postoperative, relapsed patients show an increase of pyruvate and HDL-related parameters, and a decrease of Apo-A1 Apo-B100 ratio and VLDL-related parameters. Conclusions: Surgery significantly alters the metabolomic fingerprint of CRC patients. Some metabolic changes seem to be associated with the development of cancer relapse. These data, if validated in a larger cohort, open new possibilities for risk stratification in patients with early-stage CRC.

Association of the ApoB/ApoA-I ratio with stroke risk: Findings from the China Health and Nutrition Survey (CHNS)

Background and aimsStudies on associations of apolipoprotein B (ApoB), apolipoprotein A-I (ApoA-I) and the ApoB/ApoA-I ratio with stroke risk are scarce. We aimed to prospectively examine the associations of the ApoB/ApoA-I ratio and other lipid profiles with the risk of stroke using data from the China Health and Nutrition Survey (CHNS). Methods and resultsA total of 7318 participants without stroke at baseline in 2009 were included in the final analysis and followed for a median of 6.1 years. The serum lipid profiles including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), ApoA-I, and ApoB were measured at baseline. Multivariable Cox proportional hazards models were used to evaluate the associations between these parameters and stroke risk. The ApoB/ApoA-I ratio was positively associated with incident stroke, yielding adjusted hazard ratio (HR) of 1.32 (95% CI: 1.09–1.59, P = 0.004). In comparison, ratio of ApoB and ApoA-I containing lipoproteins, the non-HDL-C/HDL-C ratio, possessed relatively weaker association with incident stroke (HR: 1.24, 95% CI: 1.01–1.52, P = 0.036). Furthermore, the risk associations for the ApoB/ApoA-I and non-HDL-C/HDL-C ratios were prominent among those participants aged >51, body mass index ≤23, or female. There were no significant associations of other lipids and their ratios with the stroke risk. ConclusionsHigher ApoB/ApoA-I ratio was associated with an increased risk of stroke. Our findings suggest that the ApoB/ApoA-I ratio may serve as a better risk indicator of stroke than other lipid profiles and their ratios.

Association of ApoA1 to ApoB ratio and other serum ratios with ischemia and reperfusion injury in patients with acute myocardial infarction

Association of ApoA1 to ApoB ratio and other serum ratios with ischemia and reperfusion injury in patients with acute myocardial infarction