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Background: Previous studies including our group have indicated the effects of ezetimibe on increased plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) concentration, while the rapid expression in different organs and the potential molecular mechanisms for this impact have not been carefully evaluated. Methods: Thirty rats were randomly divided into two groups (n = 15 for each), which were orally administrated with ezetimibe (10 mg/kg/day) or normal saline. Blood samples were obtained at day 3 after orally administration, and the PCSK9 levels were determined by ELISA. We further analyzed the mRNA expression of PCSK9, low-density lipoprotein receptor (LDLR), sterol regulator element-binding protein 2 (SREBP2), and hepatocyte nuclear factor 1 alpha (HNF-1α) by real-time PCR, as well as the protein expression by western blot, in liver, intestine and kidney respectively. Results: Ezetimibe significantly increased plasma PCSK9 levels compared with control group, while there was no significant difference between the two groups with regard to lipid profile at day 3. Moreover, ezetimibe remarkably increased the expression of PCSK9, LDLR, SREBP2 and HNF-1α in liver. Enhanced expression of PCSK9, LDLR and SREBP2 protein were found in intestine and kidney, while no changes in the expression of HNF-1α were observed in intestine and kidney of rats with ezetimibe treatment. Conclusions: The data demonstrated that ezetimibe increased PCSK9 expression through the SREBP2 and HNF-1α pathways in different organs, subsequently resulting in elevated plasma PCSK9 levels prior to the alterations of lipid profile in rats. [ABSTRACT FROM AUTHOR]

Background Plasma PCSK9 levels was positively associated with low-density lipoprotein (LDL) cholesterol (LDL-C) and atherosclerosis, while PCSK9 may also be implicated in the metabolism of lipoprotein subfractions. The study was to examine the association of plasma PCSK9 with lipoprotein subfractions in patients with stable coronary artery disease (CAD). Methods A total of 281 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled. The baseline clinical characteristics were collected, the plasma PCSK9 levels were determined using ELISA, and the LDL and high-density lipoprotein (HDL) subfractions were analyzed by Lipoprint System. The association of plasma PCSK9 levels with the lipoprotein subfractions was investigated. Results In the overall population, plasma PCSK9 levels were positively associated with the concentration of LDL-C, intermediate LDL-C, small LDL-C, and LDL score, while negatively correlated with mean LDL particle size. PCSK9 levels were positively associated with the concentration of HDL-C, intermediate HDL-C and small HDL-C. Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the concentration of intermediate LDL-C (β = 0.152, p = 0.013), small LDL-C (β = 0.179, p = 0.004), LDL score (β = 0.121, p = 0.043), and mean LDL particle size (β = -0.130, p = 0.035), while not HDL subfractions. Interestingly, when investigated in male and female patients separately, these relationships were only found in male but not in female, and the small HDL-C exhibited an association with PCSK9 levels in male patients (β = 0.149, p = 0.045). Conclusions PCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD. [ABSTRACT FROM AUTHOR]

Objective. Statin treatment alone has been demonstrated to significantly increase plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels. The effect of policosanol combined with statin on PCSK9 is unknown. Methods. Protocol I: 26 patients with atherosclerosis were randomly assigned to receive either atorvastatin 20mg/d or policosanol 20mg/d + atorvastatin 20mg/d for 8 weeks. Protocol II: 15 healthy volunteers were randomly assigned to either policosanol 20 mg/d or a control group for 12 weeks. Serum levels of PCSK9 were determined at day 0 and the end of each protocol. Results. Protocol I: atorvastatin 20mg/d significantly increased serum PCSK9 level by 39.4% (256 ± 84 ng/mL versus 357 ± 101 ng/mL, P = 0.002). However, policosanol 20mg/d + atorvastatin 20mg/d increased serum PCSK9 level by only 17.4% without statistical significance (264 ± 60 ng/mL versus 310 ± 86 ng/mL, P = 0.184). Protocol II: there was a trend toward decreasing serum PCSK9 levels in the policosanol group (289 ± 71 ng/mL versus 235 ± 46 ng/mL, P = 0.069). Conclusion. Policosanol combined with statin attenuated the statin-induced increase in serum PCSK9 levels.This finding indicates that policosanol might have a modest effect of lowering serum PCSK9 levels. [ABSTRACT FROM AUTHOR]

Background: Triglyceride glucose (TyG) and TyG-body mass index (TyG-BMI) are reliable surrogate indices of insulin resistance and used for risk stratification and outcome prediction in patients with atherosclerotic cardiovascular disease (ASCVD). Here, we inserted estimated average glucose (eAG) into the TyG (TyAG) and TyG-BMI (TyAG-BMI) as derived parameters and explored their clinical significance in cardiovascular risk prediction. Methods: This was a population-based cohort study of 9,944 Chinese patients with ASCVD. The baseline admission fasting glucose and A1C-derived eAG values were recorded. Cardiovascular events (CVEs) that occurred during an average of 38.5 months of follow-up were recorded. We stratified the patients into four groups by quartiles of the parameters. Baseline data and outcomes were analyzed. Results: Distribution of the TyAG and TyAG-BMI indices shifted slightly toward higher values (the right side) compared with TyG and TyG-BMI, respectively. The baseline levels of cardiovascular risk factors and coronary severity increased with quartile of TyG, TyAG, TyG-BMI, and TyAG-BMI (all P<0.001). The multivariate-adjusted hazard ratios for CVEs when the highest and lowest quartiles were compared from low to high were 1.02 (95% confidence interval [CI], 0.77 to 1.36; TyG), 1.29 (95% CI, 0.97 to 1.73; TyAG), 1.59 (95% CI, 1.01 to 2.58; TyG-BMI), and 1.91 (95% CI, 1.16 to 3.15; TyAG-BMI). The latter two showed statistical significance. Conclusion: This study suggests that TyAG and TyAG-BMI exhibit more information than TyG and TyG-BMI in disease progression among patients with ASCVD. The TyAG-BMI index provided better predictive performance for CVEs than other parameters. [ABSTRACT FROM AUTHOR]

Background Glycosylated hemoglobin A1C (HbA1c) has been widely recognized as a marker for predicting the severity of diabetes mellitus (DM) and several cardiovascular diseases. However, whether HbA1c could predict the severity and clinical outcomes in patients with stable coronary artery disease (CAD) remains largely unknown. We determine relationship of HbA1c with severity and outcome in patients with stable CAD. Methods We enrolled 1433 patients with stable angina who underwent coronary angiography and were followed up for an average 12 months. The patients were classified into three groups by tertiles of baseline HbA1c level (low group <5.7%, n = 483; intermediate group 5.7 - 6.3%, n = 512; high group >6.3%, n = 438). The relationships between the plasma HbA1c and severity of CAD and early clinical outcomes were evaluated. Results High HbA1c was associated with three-vessel disease. Area under the receivers operating characteristic curve (AUC = 0.67, 95% CI: 0.63-0.71, P < 0.001) and multivariate logistic regression analysis suggested that HbA1C was an independent predictor of severity of CAD (OR = 1.60, 95% CI: 1.29-1.99, P < 0.001) even after adjusting for gender, age, risk factor of CAD, lipid profile and fasting blood glucose. During follow-up, 133 patients underwent prespecified outcomes. After adjusting for multiple variables in the Cox regression model, HbA1C remained to be an independent predictor of poor prognosis (HR = 1.28, 95%CI: 1.12- 1.45, P < 0.001). Conclusions We concluded that high level of baseline HbA1c appeared to be an independent predictor for the severity of CAD and poor outcome in patients with stable CAD. [ABSTRACT FROM AUTHOR]

Background The role of triglyceride (TG) in predicting the outcomes in diabetic patients with coronary artery disease (CAD) has not been well investigated. Methods A total of 329 cases with stable angina pectoris (SAP) were prospectively enrolled and followed up for an average of 12 months. They were classified into the two groups according to the cut-off values of predicting early outcome of fasting TG level (low group <1.2 mmol/L, n = 103; High group ⩾1.2 mmol/L, n = 226). The relationship between the TG levels and early outcomes were evaluated. Results High TG group showed severer lipid profile and elevated inflammatory markers. During an average of 12-month follow-up, 47 out of 329 patients suffered from pre-specified outcomes. Area under the receivers operating characteristic curve suggested that TG, similar to serum Hemoglobin A1C (HbA1C), was a significant predictor of early outcome for diabetic patients with SAP (P = 0.002). In Cox regression models, after adjusted age, gender, body mass index, other lipid parameters, fasting blood glucose, high sensitivity C-reactive protein, neutrophil count and HbA1C, TG remained as an independent predictor of adverse prognosis. Conclusions High level of fasting TG (⩾1.2 mmol/L) was an independent predictor for early outcome of diabetic patients with SAP as like as HBA1c and number of affected coronary arteries in the era of revascularization and statin therapeutics. [ABSTRACT FROM AUTHOR]

Background An emerging data suggested a significant impact of statins on PCSK9 concentration, while the rapid impacts of other lipid-lowering drugs such as ezetimibe and xuezhikang alone or in combination on PCSK9 and lipid profile have not been assessed. This study aims to investigate whether an enhanced PCSK9 concentration by single or combined therapy of lipid-lowering drugs currently used precedes the changes of lipid profile in rats. Methods Sixty-three rats were randomly divided into six groups and orally administrated with placebo (N = 13), ezetimibe 10 mg/kg daily, Xuezhikang 1200 mg/kg daily, ezetimibe 10 mg/kg plus Xuezhikang 1200 mg/kg daily, pitavastatin 10 mg/kg daily or pitavastatin 10 mg/kg plus ezetimibe 10 mg/kg daily for 3 days (N = 10 for each group respectively). Blood samples were obtained at day 3 after orally administration. Plasma PCSK9 levels were determined by ELISA and lipid profile were measured by enzymatic assay. Results Ezetimibe, Xuezhikang and pitavastatin alone and Xuezhikang plus ezetimibe as well as pitavastatin plus ezetimibe increased PCSK9 levels by 124%, 56%, 111%, 63% and 204% respectively (p < 0.05 compared with placebo). However, Xuezhikang plus ezetimibe did not enhance greater PCSK9 levels compared to monotherapy. Ezetimibe and pitavastatin in combination induced higher PCSK9 levels than pitavastatin monotherapy or co-therapy with ezetimibe plus Xuezhikang. There was no significant difference between any groups with regard to lipid profile levels at day 3 (P > 0.05). Conclusions Elevated PCSK9 concentration by ezetimibe, Xuezhikang and pitavastatin alone or in combination was found prior to the alterations of lipid profile in rats. Combination of Xuezhikang and ezetimibe significantly attenuated increase in PCSK9 compared to ezetimibe plus pitavastatin, suggesting that the former combination may be better than the latter in future clinical application. [ABSTRACT FROM AUTHOR]

Background Red cell distribution width (RDW) has been recognized as a novel marker for several cardiovascular diseases. The aim of this study was to evaluate the association between RDW levels and the presence of isolated coronary artery ectasia (CAE). Methods We studied 414 subjects including 113 patients with isolated CAE (Group A), 144 patients with coronary artery disease (CAD, group B) and 157 angiographically normal controls (group C). Baseline clinical characteristics and laboratory findings including RDW were compared among three groups. Results The levels of RDW were significantly higher in group A and B compared with that in group C (12.97 ± 1.4 and 12.88 ± 1.0 vs 12.34 ± 0.9, p = 0.020) while no difference was found between CAE and CAD (p = 0.17). Additionally, the levels of CRP were also higher in patients with CAE and CAD compared with normal controls (0.26 ± 0.14 mg/L, 0.31 ± 0.27 mg/L vs 0.20 ± 0.06 mg/L, p = 0.04). The multivariate analysis indicated that RDW and CRP were the independent variables most strongly associated with the presence of isolated CAE and CAD. There was a positive correlation between levels of RDW and CRP in patients with isolated CAE (γ=0.532, p = 0.001). Conclusions Our data suggested that RDW may be a useful marker and independent predictor for the presence of isolated CAE. [ABSTRACT FROM AUTHOR]