Na-Qiong Wu

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.

PCSK9 gene mutations and low-density lipoprotein cholesterol.

Proprotein convertase subtilisin-like/kexin type 9 (PCSK9) is a newly-identified circulating protein in cholesterol metabolism in mammals, including humans, which has emerged as a new pharmacological target for hypocholesterolemia. It has been demonstrated that PCSK9 gene mutations are associated with hyper- or hypocholesterolemia. In the latter case, the incidence of coronary heart disease (CHD) is markedly reduced, suggesting that low level of low-density lipoprotein cholesterol (LDL-C) at birth is highly beneficial. Loss-of-function PCSK9 mutations will result in lower LDL-C levels and protect against CHD. Conversely, patients harboring gain-of-function PCSK9 mutations will suffer from familial autosomal dominant hypercholesterolemia (ADH), a disease characterized by elevated LDL-C plasma concentration. Although compelling evidence has suggested that PCSK9 can impair the LDL receptor (LDLR) pathway, its biological role in cholesterol metabolism remains to be defined. According to data from previous studies, PCSK9 appears to be a promising therapeutic target due to its role as a major LDLR regulator. Specific pharmacological inhibitors of PCSK9 have demonstrated a significant impact on plasma LDL-C concentrations. Therefore, understanding the relationship between PCSK9 and its genetic variants, on one hand, and the level of plasma LDL-C, on the other hand, may be clinically useful due to the fact that this protein has become a key target of lipid-lowering therapy. In this manuscript we mainly review recent data with regard to the association between PCSK9 genetic variants and plasma LDL-C concentrations, and outline the clinical implications.

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.

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.

Increased red cell distribution width in patients with slow coronary flow syndrome

OBJECTIVE: An elevated red cell distribution width has been recognized as a predictor of various cardiovascular diseases. Slow coronary flow syndrome is an important angiographic clinical entity with an unknown etiology. This study aimed to examine the relationship between red cell distribution width and the presence of slow coronary flow syndrome. METHODS: In total, 185 patients with slow coronary flow syndrome and 183 age- and gender-matched subjects with normal coronary flow (controls) were prospectively enrolled in this study. Red cell distribution width and C-reactive protein were measured upon admission, and the results were compared between the patients with slow coronary flow syndrome and normal controls. RESULTS: Red cell distribution width levels were significantly higher in the patients with slow coronary flow syndrome than the normal controls. Moreover, the data showed that the plasma C-reactive protein levels were also higher in the patients with slow coronary flow syndrome than in the normal controls. In addition, a multivariate analysis indicated that C-reactive protein and red cell distribution width were the independent variables most strongly associated with slow coronary flow syndrome. Finally, the red cell distribution width was positively correlated with C-reactive protein and mean thrombosis in the myocardial infarction frame counts of the patients with slow coronary flow syndrome. CONCLUSION: The data demonstrated that red cell distribution width levels are significantly higher and strongly positively correlated with both C-reactive protein and thrombosis in the myocardial infarction frame counts of patients with slow coronary flow syndrome. These findings suggest that red cell distribution width may be a useful marker for patients with slow coronary flow syndrome.

Non-HDL-C is a Better Predictor for the Severity of Coronary Atherosclerosis Compared with LDL-C

BACKGROUND Recent guidelines recommended both low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) are the primary target of lipid modulating therapy. However, which lipid measure is most closely related to the severity of coronary atherosclerosis has not yet been assessed. METHODS We studied 1757 consecutive subjects undergoing coronary angiography who were not receiving any lipid-lowering therapy. Low-density lipoprotein cholesterol was measured directly, and non-HDL-C was calculated. The severity of coronary stenosis was determined using the Gensini Score (GS) system. RESULTS In the overall population, LDL-C and non-HDL-C were all dramatically increased according to the quartiles of GS (p<0.001, both). In patients with coronary atherosclerosis (n=1097), non-HDL-C (r=0.138, p<0.001) was more closely related to GS than LDL-C (r=0.113, p<0.001) tested by Spearman correlation analysis. Multivariate logistic regression analysis suggested that non-HDL-C (OR=1.326, 95% CI 1.165-1.508, p<0.001) was slightly superior to LDL-C (OR=1.286, 95% CI 1.130-1.463, p<0.001) in predicting high GS after adjusting for potential confounders. Among patients with LDL-C less than the median, discordant non-HDL-C could not provide extra value in predicting high GS (OR=0.759, 95% CI 0.480-1.201). However, among patients with LDL-C greater than or equal to the median, the cardiovascular risk was overestimated for patients with discordant non-HDL-C (OR=0.458, 95% CI 0.285-0.736). CONCLUSIONS Our data support the use of non-HDL-C ahead of LDL-C in predicting the severity of coronary atherosclerosis, especially among patients with LDL-C greater than or equal to the median.

Relation of Leukocytes and Its Subsets Counts with the Severity of Stable Coronary Artery Disease in Patients with Diabetic Mellitus

Background Both coronary artery disease (CAD) and diabetes mellitus (DM) are associated with inflammation. However, whether and which leukocytes can predict the presence and extent of CAD in patients with DM has not been investigated. The aim of the present study was to examine the association of leukocyte and its subsets counts with the severity of CAD in patients with DM. Methods and Findings Three hundred and seventy-three diabetic patients who were scheduled for coronary angiography due to typical stable angina pectoris were enrolled in this study. They were classified into the three groups according to tertiles of Gensini score (GS, low group <8, n = 143; intermediate group 8∼28, n = 109; high group >28, n = 121). The relationship between the leukocyte and its subsets counts with the severity of CAD were evaluated. The data indicated that there were significant correlations between leukocyte and neutrophil counts with GS (r = 0.154 and 0.156, respectively, all P<0.003 for Pearsons correlation). Similarly, area under the receivers operating characteristic curve of leukocyte and neutrophil counts were 0.61 and 0.60 respectively (95%CI: 0.55–0.67, all P = 0.001) for predicting high GS. Multivariate logistic regression analysis demonstrated that leukocyte count was an independent predictor for high GS patients with DM (OR = 1.20, 95%CI 1.03–1.39, P = 0.023) after adjusting for conventional risk factors of CAD. Conclusions Compared with its subsets, leukocyte count appeared to be an independent predictor for the severity of CAD and the optimal cut-off value for predicting high GS (>28 points) was 5.0×109 cells/L in diabetic patients.