Establishing Apolipoprotein-B and non-high-density-lipoprotein-C goals in Indian population: A Cross-sectional study.

BACKGROUND: Defining lipid goals solely on low-density lipoprotein-cholesterol (LDL-C) levels in Indian population may cause misclassification due to high prevalence of hypertriglyceridemia and small dense LDL-C particles. International guidelines now recommend Apoliporotein-B (Apo-B) and non-high-density lipoprotein-cholesterol (non-HDL-C) levels as alternative targets. In this study, we used a cross-sectional representative population database to determine Apo-B and non-HDL-C cut-offs corresponding to identified LDL-C targets and compared them to international guidelines. METHODS: A community-based survey carried out in urban Delhi and adjacent rural Ballabhgarh provided lipid values for 3047 individuals. The Spearman correlation coefficient was used to evaluate the degree of relationship between Apo-B and LDL-C and non-HDL-C. Cut-off values for Apo-B and non-HDL-C were established using receiver operator curve analysis correlating with guideline-recommended LDL-C targets. RESULTS: Spearman's rank correlations between Apo-B and LDL-C (0.82) and non-HDL-C and LDL-C (0.93) were significant (p < 0.05). Proposed corresponding cut-off values for LDL-C of 55, 70,100,130 and 160 mg/dl for Apo-B and non-HDL-C in our population were 75.3, 75.5, 91.3, 107.6, 119.4 mg/dL and 92.5,96.5, 123.5, 154.5, 179.5 mg/dL respectively. However, in those with triglycerides >150 mg/dl the corresponding Apo-B and non-HDL-C values were 85.1, 92.7, 103.5, 117.5 and 135 mg/dL and 124.5, 126.5, 147.5, 167.5 and 190.5 mg/L respectively. CONCLUSION: Based on this study we provide Apo-B and non-HDL cut-offs corresponding to target LDL-C values in Indian patients with and without high triglycerides. It is noted that in individuals with triglycerides ≥ 150 mg/dl, the Apo-B levels are much higher than the values recommended by guidelines.

Apolipoprotein B and Lipid Profile in Italian Children and Adolescents.

RATIONALE: The prevention of cardiovascular (CV) disease is mandatory from childhood onwards. Among biochemical markers related to the clinical cardiovascular outcome, LDL cholesterol (LDL-C), non-HDL-C and apolipoprotein B (ApoB) are recognized as main target parameters. Emphasis on ApoB concentrations is growing, as representative of any class of atherogenic lipoprotein. This consideration allows checking of subjects under 18 years of age when the CV risk occurs. The aim of this study is to evaluate ApoB levels in a sample of Italian hyperlipidemic children and adolescents, and their siblings, to test any relationship with their lipid profile. METHODS: A retrospective study, including 1877 children and adolescents (aged 0-18 years), was performed. Clinical and biochemical data were selected from a database, including the lipid profile, ApoB analysis and anthropometric parameters of any proband. Participants had been checked as potentially hyperlipidemia affected, the suspicion raised by familial CV risk or because the dyslipidemia was already known. Data from the first visit at the University Hospitals in Rome and Turin were collected. Patients affected by secondary hyperlipidemia or obesity were excluded. Blood test analysis was performed in fasting conditions by automated commercial kits. Participants were classified according to gender, age (stratified in subgroups: 0-5, 6-10, 11-14, and 15-18 years old) and anthropometric parameters, referred to as weight in Kg and height in cm, and BMI calculated. Lipid profile results were stratified in relation to acceptable, borderline, or increased levels, as indicated by NCEP, and any potential relation with ApoB established. Statistics were performed by Epi-Info 7 programs to evaluate the variance analysis. Either parent could sign the informed consent. RESULTS: Among the whole sample n.1010 and n.867 participants were females and males, respectively. TC values acceptable (≤170 mg/dL), borderline (171-200 mg/dL) and elevated (≥201 mg/dL) were found in 411 (22%), 585 (31%) and 881 (47%) participants, respectively. The LDL-C cut-off considered was 110 mg/dL (90° percentile). Mean ApoB progressively increased from 65 to 110 mg/dL according to TC levels and resulted in significant correlation when any age subgroup and gender was considered. The highest ApoB values, TC and LDL-C related, were found in the youngest subgroup, regardless of gender. CONCLUSION: ApoB results increase progressively and in parallel with TC and LDL-C and represent a further parameter to distinguish between normal and hyperlipidemic subjects. Serum levels are close to 70 mg/dL and to 100 mg/dL in the former and latter group, respectively.

Aneurysm wall enhancement, atherosclerotic proteins, and aneurysm size may be related in unruptured intracranial fusiform aneurysms.

OBJECTIVE: This cross-sectional study aimed to investigate the associations between aneurysm wall enhancement (AWE), atherosclerotic protein levels, and aneurysm size in unruptured intracranial fusiform aneurysms (IFAs). METHODS: Patients with IFAs underwent high-resolution magnetic resonance imaging (HR-MRI) and atherosclerotic protein examinations from May 2015 to December 2021 were collected. A CRstalk (signal intensity [SI] of IFA wall/SI of pituitary stalk) > 0.60 was considered to indicate AWE. Atherosclerotic protein data was obtained from the peripheral blood. Aneurysmal characteristics included the maximal diameter of the cross-section (Dmax), location, type of IFA, presence of mural thrombus, and mural clots. Statistical analyses were performed with univariate analysis, logistic regression analysis, and Spearman's correlation coefficient. RESULTS: Seventy-one IFAs from 71 patients were included in the study. Multivariate analysis revealed statin use (OR = 0.189, p = 0.026) and apolipoprotein B (Apo-B) level (OR = 6.019, p = 0.026) were the independent predictors of AWE in IFAs. In addition, statin use (OR = 0.813, p = 0.036) and Apo-B level (OR = 1.610, p = 0.003) were also the independent predictors of CRstalk. Additionally, we found that CRstalk and AWE were significantly positively associated with Dmax (rs = 0.409 and 0.349, respectively; p < 0.001 and p = 0.003, respectively). CONCLUSIONS: There may be correlations between AWE, atherosclerotic protein levels, and aneurysm size in patients with IFAs. Apo-B and statin use were independent predictors of AWE in IFAs, which have the potential to be new therapeutic targets for IFAs. KEY POINTS: • There may be correlations between aneurysm wall enhancement, atherosclerotic protein levels in the peripheral blood, and aneurysm size in patients with intracranial fusiform aneurysms. • Apolipoprotein B and statin use were independent predictors of aneurysm wall enhancement in intracranial fusiform aneurysms.

Ambient Air Pollution and Atherosclerosis: A Potential Mediating Role of Sphingolipids.

BACKGROUND: The pathophysiological mechanisms of air pollution-induced atherosclerosis are incompletely understood. Sphingolipids serve as biological intermediates during atherosclerosis development by facilitating production of proatherogenic apoB (apolipoprotein B)-containing lipoproteins. We explored whether sphingolipids mediate the proatherogenic effects of air pollution. METHODS: This was a prospective panel study of 110 participants (mean age 56.5 years) followed from 2013 to 2015 in Beijing, China. Targeted lipidomic analyses were used to quantify 24 sphingolipids in 579 plasma samples. The mass concentrations of ambient particulate matter ≤2.5 µm in diameter (PM2.5) were continuously monitored by a fixed station. We evaluated the associations between sphingolipid levels and average PM2.5 concentrations 1-30 days before clinic visits using linear mixed-effects models and explored whether sphingolipids mediate PM2.5-associated changes in the levels of proatherogenic apoB-containing lipoproteins (LDL-C [low-density lipoprotein cholesterol] and non-HDL-C [nonhigh-density lipoprotein cholesterol]) using mediation analyses. RESULTS: We observed significant increases in the levels of non-HDL-C and fourteen sphingolipids associated with PM2.5 exposure, from short- (14 days) to medium-term (30 days) exposure time windows. The associations exhibited near-monotonic increases and peaked in 30-day time window. Increased levels of the sphingolipids, namely, sphinganine, ceramide C24:0, sphingomyelins C16:0/C18:0/C18:1/C20:0/C22:0/C24:0, and hexosylceramides C16:0/C18:0/C20:0/C22:0/C24:0/C24:1 significantly mediated 32%, 58%, 35% to 93%, and 23% to 86%, respectively, of the positive association between 14-day PM2.5 average and the non-HDL-C level, but not the LDL-C level. Similar mediation effects (19%-91%) of the sphingolipids were also observed in 30-day time window. CONCLUSIONS: Our results suggest that sphingolipids may mediate the proatherogenic effects of short- and medium-term PM2.5 exposure.

Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab.

BACKGROUND: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models. RESULTS: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata <75, 75-<90, ≥90 mg/dL, respectively; Ptrend<0.0001) and after adjustment for low-density lipoprotein cholesterol (Ptrend=0.035). Higher baseline apoB stratum was associated with greater relative (Ptrend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78-4.79], 3.09 [95% CI, 2.69-3.54], and 2.41 [95% CI, 2.11-2.76] events per 100 patient-years in strata ≥50, >35-<50, and ≤35 mg/dL, respectively). Compared with propensity score-matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol but not vice versa. CONCLUSIONS: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as ≤35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT01663402.

Mean and Variability of Lipid Measurements and Risk for Development of Subclinical Left Ventricular Diastolic Dysfunction.

BACKGROUND: Subclinical left ventricular diastolic dysfunction (LVDD) is an emerging consequence of increased insulin resistance, and dyslipidemia is one of the few correctable risk factors of LVDD. This study evaluated the role of mean and visit-to-visit variability of lipid measurements in risk of LVDD in a healthy population. METHODS: This was a 3.7-year (interquartile range, 2.1 to 4.9) longitudinal cohort study including 2,817 adults (median age 55 years) with left ventricular ejection fraction >50% who underwent an annual or biannual health screening between January 2008 and July 2016. The mean, standard deviation (SD), coefficient of variation (CV), variability independent of the mean (VIM), and average real variability of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB), non-HDL-C, and triglycerides were obtained from three to six measurements during the 5 years preceding the first echocardiogram. RESULTS: Among the 2,817 patients, 560 (19.9%) developed LVDD. The mean of no component of lipid measurements was associated with risk of LVDD. CV (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.10 to 1.67), SD (HR, 1.27; 95% CI, 1.03 to 1.57), and VIM (HR, 1.26; 95% CI, 1.03 to 1.55) of LDL-C and all the variability parameters of apoB were significantly associated with development of LVDD. The association between CV-LDL and risk of LVDD did not have significant interaction with sex, increasing/decreasing trend at baseline, or use of stain and/or lipid-modifying agents. CONCLUSION: The variability of LDL-C and apoB, rather than their mean, was associated with risk for LVDD.

Apolipoprotein B and ischemic stroke / 国际脑血管病杂志

Studies have shown that plasma apolipoprotein B (ApoB) has a good predictive value for ischemic stroke and plays an important role in the prevention and treatment of ischemic stroke. More and more guidelines and consensus opinions began to recommend ApoB as a routine intervention target. This article reviews the biological characteristics, clinical detection advantages, and role and treatment prospect of ApoB in the prevention and treatment of ischemic stroke.

Analysis of small dense low-density lipoprotein cholesterol level and the relationship with corresponding lipid components in healthy adults / 中华检验医学杂志

Objective:To investigate the small and dense low density lipoprotein cholesterol (sdLDL-C) level, ratios of sdLDL-C/low density lipoprotein cholesterol (LDL-C), sdLDL-C/high density lipoprotein cholesterol (HDL-C) and sdLDL-C/apolipoprotein B (apoB), and their correlation with lipid components in healthy adults.Methods:A total of 1 151 healthy adults, who underwent physical examination in Beijing Anzhen Hospital Affiliated to Capital Medical University from September to December 2020 (557 men and 594 women), were included in this study. They were divided into five age groups: 18-29 years old ( n=247), 30-44 years old ( n=269), 45-59 years old ( n=225), 60-74 years old ( n=207) and 75-90 years old ( n=203) according to the age classification standard of the United Nations World Health Organization in 2018. The levels of total cholesterol (TC), triglyceride (TG), HDL-C, LDL-C, sdLDL-C, apoA1 and apoB were measured, and the distribution of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in different sex and age groups were analyzed. Pearson/Spearman correlation was used to analyze the correlation between the above four indexes and other blood lipid components. Results:SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in male group ([0.56±0.23] mmol/L, 0.24±0.07, 0.49±0.22, 0.27±0.07) than those in female group ([0.48±0.18] mmol/L, 0.20±0.06, 0.36±0.17, 0.23±0.07) (all P<0.01). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were different among different age groups of male and female participants (all P<0.001). SdLDL-C level was significantly higher in males than in females among 18-29 years old group, 30-44 years old group, 45-59 years old group (all P<0.05). SdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB were higher in males of 18-29 years old group, 30-44 years old group, 45-59 years old group and 60-74 years old group than in females of corresponding age groups (all P<0.05). The level of sdLDL-C of all participants was positively correlated with TC, TG, LDL-C, apoB, non-HDL-C and remnant cholesterol ( r＝0.50, 0.45, 0.67, 0.68, 0.61, 0.11, all P<0.01), and negatively correlated with HDL-C and apoA1 ( r＝-0.17 and -0.10, P<0.01). Conclusions:The levels of sdLDL-C, sdLDL-C/LDL-C, sdLDL-C/HDL-C and sdLDL-C/apoB in healthy adults are different in healthy adults of different ages and sex. There is a high correlation between sdLDL-C and apoB.

Diet intervention improves cardiovascular profile in patients with rheumatoid arthritis: results from the randomized controlled cross-over trial ADIRA.

BACKGROUND: The chronic inflammation in patients with rheumatoid arthritis (RA) increases the risk for cardiovascular diseases (CVD). The contribution of diet as a risk factor for CVD among these patients is however not fully understood. The aim of this study is to investigate if a proposed anti-inflammatory diet improves cardiovascular profile in weight stable patients with RA. METHODS: Patients (n = 50) with RA were included in a cross-over trial. They were randomized to either a diet rich in whole grain, fatty fish, nuts, vegetables and fruit and supplemented with probiotics, or a control diet resembling average nutritional intake in Sweden, for ten weeks. After a 4-month washout they switched diet. Participants received food bags and dietary guidelines. Primary outcome was triglyceride (TG) concentration. Secondary outcomes were total-, high density lipoprotein- (HDL) and low density lipoprotein- (LDL) cholesterol, Apolipoprotein-B100 and -A1, lipoprotein composition, plasma phospholipid fatty acids and blood pressure. RESULTS: Forty-seven patients completed at least one period and they remained weight stable. There was a significant between-dietary treatment effect in TG and HDL-cholesterol concentration in favor of intervention (p = 0.007 and p = 0.049, respectively). Likewise, Apolipoprotein-B100/A1 ratio shifted toward a less atherogenic profile in favor of the intervention (p = 0.007). Plasma fatty acids increased in polyunsaturated- and decreased in monounsaturated- and saturated fatty acids between diet periods in favor of the intervention period. CONCLUSION: Blood lipid profile improved indicating cardioprotective effects from an anti-inflammatory dietary intervention in patients with RA. TRIAL REGISTRATION: This trial is registered at ClinicalTrials.gov as NCT02941055 .

Associations between apolipoprotein B and selected perfluoroalkyl substances among diabetics and nondiabetics.

Previous population investigation of perfluoroalkyl substances (PFAS) features associations with lipids in a number of populations; these investigations have seldom included consideration of apolipoproteins. Apolipoprotein B (Apo B) fractions were considered in this descriptive analysis because they are essential to the assembly, transport, and cellular uptake of lipid classes associated with poorer health outcomes, and they are associated with incident and prevalent disease. Regression models stratified by diabetes and lipid lowering medication (LLM) status for data from National Health and Nutrition Examination Survey for 2007-2014 were fitted to interrogate associations between selected PFAS and Apo B for US adults aged ≥ 20 years. Adjusted concentrations of Apo B were positively associated with perfluorooctanoic acid (PFOA ß = 0.03878, p < 0.01), perfluorooctane sulfonic acid (PFOS ß = .02029, p = 0.02), and perfluorononanoic acid (PFNA ß = .01968, p = .03) for nondiabetics who were not taking lipid lowering medications. These associations were not seen among diabetic participants, except for perfluorodecanoic acid (PFDA) in those taking LLMs (ß = 0.03831, p = 0.02). We also note that LLMs have an inferred greater impact on Apo B in the diabetics compared to the nondiabetic populations. We have considered several sources of confounding and think the data are most consistent with a weak causal association that PFAS exposure increases Apo B. The rodent toxicology literature also contains evidence that PFAS disrupt fatty acid trafficking including Apo B, although how the specific findings may relate to circulating human Apo B concentrations is unclear. We therefore advocate for attempts to replicate the findings in other populations and to consider additional types of mechanistic studies.

Apolipoprotein B Levels Predict Future Development of Hypertension Independent of Visceral Adiposity and Insulin Sensitivity.

BACKGROUND: High plasma apolipoprotein B (apoB) levels have been shown to be associated with hypertension, central obesity, and insulin resistance in cross-sectional research. However, it is unclear whether apoB levels predict future hypertension independent of body composition and insulin sensitivity. Therefore, we prospectively investigated whether plasma apoB concentrations independently predicted the risk of hypertension in a cohort of Japanese Americans. METHODS: A total of 233 normotensive Japanese Americans (77 men, 156 women; mean age, 46.4±11.0 years) were followed over 10 years to monitor them for the development of hypertension. Fasting plasma concentrations of apoB, glucose, and insulin were measured at baseline. Insulin sensitivity was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR). The abdominal visceral and subcutaneous fat areas were measured at baseline using computed tomography. Logistic regression analysis was used to estimate the association between apoB concentrations and the odds of incident hypertension. RESULTS: The 10-year cumulative incidence of hypertension was 21.5%. The baseline apoB level was found to be positively associated with the odds of incident hypertension over 10 years after adjustment for age, sex, body mass index, systolic blood pressure, abdominal visceral fat area, abdominal subcutaneous fat area, total plasma cholesterol concentration, diabetes status, and HOMA-IR at baseline (odds ratio and 95% confidence interval for a 1-standard deviation increase, 1.89 [1.06 to 3.37]; P=0.030). CONCLUSION: Higher apoB concentrations predicted greater risks of future hypertension independent of abdominal visceral fat area and insulin sensitivity in Japanese Americans.

SR-BI (Scavenger Receptor BI), Not LDL (Low-Density Lipoprotein) Receptor, Mediates Adrenal Stress Response-Brief Report.

OBJECTIVE: Adrenal gland secretes stress-induced glucocorticoids (iGCs) to coping with stress. Previous study showed that SR-BI (scavenger receptor BI) null (SR-BI-/-) mice failed to generate iGC in stress conditions, suggesting that SR-BI-mediated cholesterol uptake from HDL (high-density lipoprotein) is a key regulator for iGC production. However, the LDL (low-density lipoprotein)/LDLr (LDL receptor) pathway can also provide cholesterol for iGC synthesis, but rodents have limited LDL levels in circulation. Here, we generated SR-BI-/-ApoBtg (apolipoprotein B transgenic) mice with normal LDL levels in circulation to determine the relative contribution of the HDL/SR-BI and LDL/LDLr pathways to iGC production in stress conditions. Approach and Results: To obtain mouse models with normal LDL levels, SR-BI-/- mice were bred to ApoBtg mice. Then, the F1 SR-BI±ApoBtg mice were backcrossed to SR-BI-/- to obtain SR-BI-/-ApoBtg, SR-BI-/-ApoBwt (apolipoprotein B wild type), and SR-BI+/+ApoBtg mice. We first examined the lipoprotein profile, which shows a 6.5-fold increase in LDL levels in SR-BI-/-ApoBtg mice compared with SR-BI-/-ApoBwt mice. Then, we induced stress with adrenocorticotropic hormone and cecal ligation and puncture. One hour after adrenocorticotropic hormone stimulation, SR-BI+/+ApoBtg control mice produced iGC (14.9-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg showed no iGC production (P<0.001). Three hours after cecal ligation and puncture treatment, SR-BI+/+ApoBtg control mice showed iGC production (6.4-fold), but both SR-BI-/-ApoBwt and SR-BI-/-ApoBtg mice showed no iGC production (P<0.001). CONCLUSIONS: SR-BI-/-ApoBtg mice fail to produce iGC in stress conditions even though with restored LDL levels in circulation. These findings clarify that the HDL/SR-BI, not LDL/LDLr, pathway is responsible for iGC production in stress conditions.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus.

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (-94.3±15.4 and -62.0±20.9 mg/dL in the rosuvastatin group, -89.9±22.7 and -66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (-0.44±0.16 in the rosuvastatin group and -0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (-10.5 mg/dL [interquartile range (IQR), -37.5 to 29.5] and 0.0 µEq/L [IQR, -136.8 to 146.0] in the rosuvastatin group, -49.5 mg/dL [IQR, -108.5 to -27.5] and -170.5 µEq/L [IQR, -353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Comparison of the Efficacy of Rosuvastatin Monotherapy 20 mg with Rosuvastatin 5 mg and Ezetimibe 10 mg Combination Therapy on Lipid Parameters in Patients with Type 2 Diabetes Mellitus

BACKGROUND: The apolipoprotein B/A1 (apoB/A1) ratio is a stronger predictor of future cardiovascular disease than is the level of conventional lipids. Statin and ezetimibe combination therapy have shown additional cardioprotective effects over statin monotherapy. METHODS: This was a single-center, randomized, open-label, active-controlled study in Korea. A total of 36 patients with type 2 diabetes mellitus were randomized to either rosuvastatin monotherapy (20 mg/day, n=20) or rosuvastatin/ezetimibe (5 mg/10 mg/day, n=16) combination therapy for 6 weeks. RESULTS: After the 6-week treatment, low density lipoprotein cholesterol (LDL-C) and apoB reduction were comparable between the two groups (−94.3±15.4 and −62.0±20.9 mg/dL in the rosuvastatin group, −89.9±22.7 and −66.8±21.6 mg/dL in the rosuvastatin/ezetimibe group, P=0.54 and P=0.86, respectively). In addition, change in apoB/A1 ratio (−0.44±0.16 in the rosuvastatin group and −0.47±0.25 in the rosuvastatin/ezetimibe group, P=0.58) did not differ between the two groups. On the other hand, triglyceride and free fatty acid (FFA) reductions were greater in the rosuvastatin/ezetimibe group than in the rosuvastatin group (−10.5 mg/dL [interquartile range (IQR), −37.5 to 29.5] and 0.0 µEq/L [IQR, −136.8 to 146.0] in the rosuvastatin group, −49.5 mg/dL [IQR, −108.5 to −27.5] and −170.5 µEq/L [IQR, −353.0 to 0.8] in the rosuvastatin/ezetimibe group, P=0.010 and P=0.049, respectively). Both treatments were generally well tolerated, and there were no differences in muscle or liver enzyme elevation. CONCLUSION: A 6-week combination therapy of low-dose rosuvastatin and ezetimibe showed LDL-C, apoB, and apoB/A1 ratio reduction comparable to that of high-dose rosuvastatin monotherapy in patients with type 2 diabetes mellitus. Triglyceride and FFA reductions were greater with the combination therapy than with rosuvastatin monotherapy.

Predictive value of apolipoprotein B in the risk of progression to renal replacement therapy in diabetic kidney diseases patients / 中华肾脏病杂志

Objective To analyze the predictive value of apolipoprotein B (ApoB) in the risk of progression to renal replacement therapy (RRT) in diabetic kidney disease (DKD) patients with chronic kidney disease (CKD) stage 3-5. Methods The data of DKD patients with CKD stage 3-5 who were hospitalized and followed up with detailed clinical data from January 2011 to November 2014 in the Third Affiliated Hospital of Sun Yat-sen University were retrospectively collected. Estimated glomerular filtration rate (eGFR) was calculated according to the CKD-EPI formula. After 2 years of follow-up, the patients were divided into RRT group and non-RRT group according to whether they had entered renal replacement therapy. Cox regression analysis was used to analyze the influencing factors of DKD progression to RRT. The predicted value of ApoB in the risk of progression to renal replacement therapy (RRT) of DKD patients within 2 years of follow-up was analyzed by plotting the receiver operating characteristic curve (ROC). By establishing multiple Cox models, the effect of ApoB elevation on the progression of DKD patients to RRT was analyzed after adjusting for the influencing factors gradually. Results A total of 258 cases were included in this study, including 156 males and 102 females. They were (66.13±11.88) years old (27-91 years old). CKD 3-5 patients were 181 cases, 50 cases and 27 cases respectively. There were 165 cases in the non-RRT group and 93 cases in the RRT group. There were statistically significant difference in hemoglobin, hematocrit, blood phosphorus, ApoB, serum creatinine, urea nitrogen, serum cystatin C, eGFR and in the proportion of using angiotensin converting enzyme inhibitor, diuretic, β blockers between the two groups (all P＜0.05). Multivariate Cox regression analysis showed that ApoB was an independent predictor of progression to RRT in patients with DKD within 2 years (HR=2.203, 95% CI 1.352-3.589, P=0.002). The area under the ROC curve of ApoB for DKD progression to RRT within 2 years of follow-up was 0.641 (C-index=0.749, P＜0.01). After adjusting for confounding factors, Cox regression analysis showed that for every 1 mmol/L increase in ApoB, the risk of RRT increased by 1.038 times in DKD patients with CKD stage 3-5 (HR=2.038, 95% CI 1.312-3.168, P=0.002). Conclusions ApoB is an independent predictor of progression to RRT with CKD stage 3-5 diabetic kidney disease (DKD). For every 1 mmol/L increase in ApoB, the risk of progression to RRT in patients with CKD 3-5 DKD increases by 1.038 times.

Peptides releasing study of serum apolipoprotein A-I and apolipoprotein B by ID-LC-MS / 中华检验医学杂志

Objective To investigate the digestion kinetics of Apolipoprotein A-I and B by ID-LC-MS method for accurate quantification of proteins .Methods Methodological research .The target peptides of ApoA-I and B were determined .The ApoA-I and B from 5 human serum samples on market with levels from 0.90-2.54 g/L and 0.54-1.39 g/L separately , were measured in terms of target peptides by isotope dilution liquid chromatography mass spectrometry method .The releasing amount and rate of peptides were analyzed and plotted according to different time points .The correlation coefficient R2 was calculated among peptide releasing amount between samples .Results Most peptides reached their peaks within 4 hours.The peptides VQ , DY and VS from Apo A-I, TR and FP from Apo B were released relatively slowly .After getting to their peak stage , the ratio between TEV and SIL-TEV, AK and SIL-AK, VQ and SIL-VQ presented stable state.As for Apo A-I the correlations among peptides are high , from 0.904 to 0.999.Some peptides from Apo B show lower correlations , such as TG-SV with R20.543 (3 h).Conclusions Peptides from Apo A-I and Apo B present different releasing properties after trypsin digestion .Proper selection of representative peptides and enzymatic conditions can benefit accurate quantification of target proteins .

Risk Factors and Clinical Manifestations of Juxtacortical Small Lesions: A Neuroimaging Study.

BACKGROUND AND OBJECTIVE: White matter hyperintensities can be easily identified by brain imaging. Juxtacortical small lesion (JCSL) is a special type of white matter lesion, defined as no greater than 5 mm in diameter and adjacent to the cerebral cortex in location. We notice lately that JCSLs alone may be associated to various neurological symptoms. Here, we design the present study to determine the risk factors for JCSLs and their clinical manifestations in patients in our neurology clinic. METHODS: 206 participants suffered from neurological disorders and completed magnetic resonance imaging (MRI) examinations were divided into two groups: patients with JCSLs and patients without lesions on MRI. Meanwhile, 129 age- and sex-matched healthy volunteers were also recruited. Laboratory examinations and the phenotypes and distributions of the symptoms of the three groups were compared. RESULTS: The serum levels of apoB and homocysteine (HCY) were independently related to the appearance of JCSLs and HCY level was also associated with the number of JCSLs. Patients with JCSLs might present with headache, insomnia, and/or anxiety/depression, which were related with the anatomical locations of the lesions. CONCLUSION: These data suggest that JCSLs are symptomatic and might in result fromarteriole atherosclerosis, which should raise our attention.

Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study.

OBJECTIVE: Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a). APPROACH AND RESULTS: A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease. OxPL carried by apoB (apolipoprotein B-100; OxPL-apoB) or apolipoprotein(a) (OxPL-apo(a)) containing lipoproteins, lipoprotein(a) levels, LPA kringle IV type 2 repeat, and rs10455872 genetic variants were measured. OxPL-apoB and OxPL-apo(a) levels correlated with lipoprotein(a) levels among cases (r=0.75 and r=0.95; both P<0.001) and controls (r=0.65 and r=0.93; both P<0.001). OxPL-apoB levels associated with risk of CAVD with odds ratios of 1.2 (95% confidence interval [CI]:1.0-1.6) for 34th to 66th percentile levels, 1.6 (95% CI, 1.2-2.1) for 67th to 90th percentile levels, 2.0 (95% CI, 1.3-3.0) for 91st to 95th percentile levels, and 3.4 (95% CI, 2.1-5.5) for levels >95th percentile, versus levels <34th percentile (trend, P<0.001). Corresponding odds ratios for OxPL-apo(a) were 1.2 (95% CI, 1.0-1.5), 1.2(95% CI, 0.9-1.6), 2.1(95% CI, 1.4-3.1), and 2.9(95% CI, 1.9-4.5; trend, P<0.001) and were similar for lipoprotein(a). LPA genotypes associated with OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels and explained 34%, 46%, and 39%, respectively, of the total variation in levels. LPA genotypes associated with risk of CAVD; a doubling in genetically determined OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels associated with odds ratio of CAVD of 1.18 (95% CI, 1.10-1.27), 1.09 (95% CI, 1.05-1.13), and 1.09 (95% CI, 1.05-1.14), respectively, comparable to the corresponding observational estimates of 1.27 (95% CI, 1.16-1.39), 1.13 (95% CI, 1.08-1.18), and 1.11 (95% CI, 1.06-1.17). CONCLUSIONS: OxPL-apoB and OxPL-apo(a) are novel genetic and potentially causal risk factors for CAVD and may explain the association of lipoprotein(a) with CAVD.