Yuan-Lin Guo

Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease

OBJECTIVE Recent studies have suggested that proprotein convertase subtilisin/kexin type 9 (PCSK9) is associated with atherosclerosis and plays a potential role in inflammation. However, the correlation between PCSK9 and white blood cell count (WBCC) has not yet been assessed. The objective of the present study was to examine the association of the WBCC and its subset counts with plasma PCSK9 levels in patients with stable coronary artery disease (CAD). METHODS In this cross-sectional study, a total of 251 consecutive, stable CAD patients who were not treated with lipid-lowering drugs were enrolled at our center between October 2012 and October 2013. The baseline clinical characteristics were collected, and the plasma PCSK9 levels were determined using ELISA. The associations of plasma PCSK9 levels with the WBCC and its subsets were investigated. RESULTS In the overall population, plasma PCSK9 levels were positively associated with the WBCC (r = 0.167, p = 0.008). Multivariable regression analysis revealed that the plasma PCSK9 levels were significantly and independently associated with the WBCC (β = 0.217, p < 0.001) and its subsets (neutrophil β = 0.152, p < 0.05; lymphocyte β = 0.241, p < 0.001). However, the relationships between PCSK9 and WBCC and its subsets remained significant in men (WBCC r = 0.234, p = 0.001; neutrophil r = 0.181, p = 0.014; lymphocyte r = 0.226, p = 0.002) but were not significant in women when the analysis was performed based on gender. CONCLUSIONS These data demonstrate that the plasma PCSK9 levels are independently associated with the WBCC and its subsets, suggesting a potential interaction between PCSK9 and chronic inflammation in patients with CAD.

Proprotein convertase subtilisin-kexin type 9 as a biomarker for the severity of coronary artery disease

Abstract Aim. To evaluate the relation of proprotein convertase subtilisin-kexin type 9 (PCSK9) levels to coronary artery disease (CAD). Methods. A total of 1031 consecutive individuals (552 CAD and 479 controls) were prospectively enrolled. The associations of plasma PCSK9 levels with the incidence and severity of CAD were investigated. Further, mediator analysis was performed to detect the potential mechanisms of the associations. Results. No difference in PCSK9 levels between CAD patients and controls was detected (median 224.75 versus 224.64 ng/mL, P > 0.05). However, the CAD group had higher PCSK9 levels than the control group when adjusting for the confounding factors (228.03 ± 1.01 versus 219.28 ± 1.02 ng/mL, P = 0.019). PCSK9 levels were also associated with the severity of CAD assessed by the Gensini score (GS) system (P for trend < 0.05). Logistic regression analysis showed that PCSK9 levels were associated with an increased CAD risk (OR 3.296 and 5.130 for the incidence and severity, respectively). Importantly, mediator analysis indicated that the effects of PCSK9 levels on CAD were mediated by lipid (around 20%) and inflammation (around 15%). Conclusions. PCSK9 levels were positively associated with the severity of CAD; the relatively important mechanisms including lipid and inflammation pathways were partly involved in this association.

Proprotein Convertase Subtilisin/kexin type 9, C-reactive Protein, Coronary Severity, and Outcomes in Patients With Stable Coronary Artery Disease: A Prospective Observational Cohort Study

AbstractProprotein convertase subtilisin/kexin type 9 (PCSK9) is suggested as a novel factor associated with coronary artery disease (CAD). However, few studies have comprehensively evaluated plasma PCSK9 with cardiovascular risk till now. Hence, we aimed to prospectively investigate the association between baseline PCSK9 and cardiovascular risk graded with number of risk factors (RFs), coronary severity, and outcomes in patients with stable CAD.Baseline characteristics and biomarkers were measured in 616 consecutive, nontreated patients with stable CAD. Coronary severity was measured using SYNTAX, Gensini, and Jeopardy scoring systems. Patients were then received treatment and followed for a median of 17 months. The primary endpoints were cardiac death, stroke, myocardial infarction (MI), post-discharge revascularization, or unstable angina (UA).Overall, follow-up data were obtained from 603 patients. A total of 72 (11.9%) patients presented with at least 1 major adverse cardiovascular event (MACE) (4 cardiac deaths, 4 strokes, 6 MIs, 28 revascularizations, and 30 UAs). At baseline, PCSK9 was increased with an increasing number of RFs and positively associated with coronary severity scores (P < 0.05, all). After follow-up, those with MACE had a higher baseline PCSK9, hs-CRP, and coronary scores than those without (P < 0.05, all). Multivariate analysis showed that PCSK9, hs-CRP, and coronary scores were independently predictive for MACEs (P < 0.05, all). Interestingly, more significant predictive values of PCSK9 in medical-alone-treated population but no such associations in revascularization-treated patients were found.Together, plasma PCSK9, as well as hs-CRP and coronary scores, could independently predict MACEs in patients with stable CAD.

High-density lipoprotein subfractions in relation with the severity of coronary artery disease: A Gensini score assessment.

BACKGROUND The exact role of different high-density lipoprotein (HDL) subfractions in the pathogenesis of coronary artery disease (CAD) has not yet been fully explored. The aim of the present study was to examine the relationship between HDL subfractions and the severity of CAD in patients without statin therapy. METHODS A total of 382 consecutive patients (mean: 55.36 ± 11.30 years of age) who underwent coronary angiography from angina-like chest pain were investigated. Patients were classified into 2 groups according to the angiographic results: a CAD group (n = 283) and a control group (n = 99). The distribution of HDL subfractions was analyzed using a Quantimetrix Lipoprint HDL system. CAD severity was measured by Gensini score (GS). RESULTS Compared with the control group, HDL-cholesterol (HDL-C), large HDL-C level, and the large HDL subfraction percentages in the CAD group were significantly lower (P = .002, P < .001, P < .001, respectively). Meanwhile, a small HDL-C level and the percentage of small HDL subfraction were significantly higher (P = .003, P < .001, respectively). Correlation analysis showed that the percentage of a large HDL subfraction was negatively correlated with GS (β = -0.191, P = .005), whereas the percentage of a small HDL subfraction positively correlated with GS (β = 0.145, P = .023) in patients with CAD. CONCLUSIONS Small HDL subfraction was associated with the presence of CAD, whereas the percentage of large HDL and small HDL subfraction was negatively and positively associated with the severity of CAD, respectively.

Relation of plasma PCSK9 levels to lipoprotein subfractions in patients with stable coronary artery disease

BackgroundPlasma 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).MethodsA 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.ResultsIn 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).ConclusionsPCSK9 levels were independently associated with the changes of lipoprotein subfractions, suggesting a potential interaction between PCSK9 and lipoprotein subfractions in CAD.

Relation of ABO blood groups to the severity of coronary atherosclerosis: an Gensini score assessment.

OBJECTIVE Although the study on the relationship between ABO blood groups and coronary atherosclerosis has a long history, few data is available regarding ABO to severity of coronary atherosclerosis in a large cohort study. Therefore, the present study aimed to investigate the relation of the ABO blood groups to the severity of coronary atherosclerosis assessed by Gensini score (GS) in a large Chinese cohort undergoing coronary angiography. METHODS A total of 2919 consecutive patients undergoing coronary angiography were enrolled, and their baseline characteristics and ABO blood groups were collected. The GS was calculated as 1st tertile (0-10), 2nd tertile (11-36), 3rd tertile (>36) according to angiographic results. The relation of the ABO blood groups to GS was investigated. RESULTS The frequency of blood group A was significantly higher in the upper GS tertiles (24.4% vs. 28.2% vs. 29.5%, p = 0.032). Multivariable linear regression analysis revealed that blood group A was independently associated with GS (β = 0.043, p = 0.017). Likewise, multivariable logistic regression analysis showed that group A remained significantly associated with mid-high GS (OR = 1.44, 95% CI 1.16-1.80, p = 0.001), and the group O was showed as a protective factor (OR = 0.77, 95% CI = 0.65-0.92, p = 0.004). CONCLUSION In this large Chinese cohort study, the data indicated that there was an association between ABO blood groups and the severity of coronary atherosclerosis. Moreover, the blood group A was an independent risk factor for serious coronary atherosclerosis.

PCSK9 and lipid lowering drugs

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a novel circulating protein, which plays an important role in the regulation of cholesterol metabolism. Over the past decade, experimental and clinical studies have established that over- or poor expression of PCSK9 had a key impact not only on circulating PCSK9 and low density lipoprotein cholesterol (LDL-C) levels but also on cardiovascular risk and atherosclerotic process. Since the first discovery of PCSK9-related gene in 2003, factors that can influence circulating PCSK9 concentration are of great interest in a variety of medical fields, especially in pharmacology. In this review we focus on the impact of lipid-lowering drugs on circulating PCSK9 concentration and its clinical implications in order to optimal consideration for the current strategies with regard to cholesterol control.

Positive correlation of plasma PCSK9 levels with HbA1c in patients with type 2 diabetes

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been demonstrated to be involved in not only lipid metabolism but also glucose homeostasis. Glycated haemoglobin (HbA1c) is a ‘gold standard’ for monitoring long‐term glycaemic control. However, the correlation of plasma PCSK9 levels with HbA1c remains undetermined.

Impact of 10 mg rosuvastatin daily or alternate-day on lipid profile and inflammatory markers

BACKGROUND Statins are commonly administrated daily, while rosuvastatin can be given every other day due to its longer half-lives. We evaluated the potential efficacy of alternate-day dosing of 10mg rosuvastatin compared with daily dosing of 10mg rosuvastatin with regarding to lipid and inflammatory markers in patients with dyslipidemia. METHODS Thirty-seven patients were randomly divided into the 2 groups: alternate-day group (rosuvastatin 10mg every other day, n=19) and once-daily group (rosuvastatin 10mg every day, n=18) for 6 weeks. The primary endpoints of the study were changes of the serum concentrations of low-density lipoprotein cholesterol (LDL-C), C-reactive protein (CRP) and interleukin-6 (IL-6) following 6-week rosuvastatin therapy. RESULTS Baseline characteristics of the 2 groups were well balanced. LDL-C decreased by 37.5% after the once-daily dosing period and by 36.9% after alternate-day dosing period (p>0.05). Both dosing regimens provided similar improvement in high-density lipoprotein cholesterol and triglyceride. And also, both dosing regimens significantly decreased serum concentrations of CRP, which had an 18.3% reduction in once-daily dosing and a 16.7% reduction in alternate-day dosing of rosuvastatin (p>0.05). Moreover, the pattern of plasma IL-6 concentrations was also similar between the two groups (p>0.05). CONCLUSIONS Alternate-day dosing of rosuvastatin could be effective comparable with once-daily dosing of rosuvastatin in Chinese patients in improving not only lipid profile but also inflammatory markers, which may provide some cost savings and increase the compliance of patients.

The relationship between the plasma PCSK9 levels and platelet indices in patients with stable coronary artery disease.

AIM Recent studies have shown that platelet indices are linked to metabolic and cardiovascular diseases, in addition to being markers of hemostasis. These studies suggested that they could be modified by various biomolecules, including lipids. Proprotein convertase subtilisin/kexin type 9 (PCSK9), a newly-identified member, plays a key role in lipid metabolism and atherosclerosis. Therefore, we evaluated the relationship between the plasma PCSK9 level and platelet indices. METHODS In this cross-sectional study, a total of 330 consecutive, stable coronary artery disease (CAD) patients were enrolled at our center between October 2012 and April 2014. The baseline clinical characteristics were collected, and the plasma PCSK9 levels were determined using an ELISA. The associations between PCSK9 and the platelet indices were investigated. RESULTS The plasma PCSK9 levels were positively correlated with the platelet (PLT) count and plateletcrit (PCT) (r = 0.218, p ＜ 0.001; r = 0.250, p ＜ 0.001; respectively), while no correlation of PCSK9 with either the mean platelet volume (MPV) or platelet distribution width (PDW) was found. The association of PCSK9 with the PLT and PCT remained after adjusting for cardiometabolic risk factors (β=0.300, p ＜ 0.001; β = 0.269, p ＜ 0.01; respectively), but the latter disappeared when further adjusted for inflammatory markers (β = 0.212, p ＜ 0.05; β = 0.151, p = NS). Additionally, a correlation analysis performed according to the number of diseased vessels showed that PCSK9 was related to the PLT and PCT in patients with single-, two- or multi-vessel disease, with a particularly strong correlation with two-vessel disease. CONCLUSIONS The plasma PCSK9 levels are positively associated with the PLT count in CAD patients, suggesting a potential link between PCSK9 and platelets that may be involved in atherosclerosis and metabolic disorders.