IJCA-18125; No of Pages 3 International Journal of Cardiology xxx (2014) xxx–xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis Sha Li 1, Yuan-Lin Guo 1, Rui-Xia Xu, Yan Zhang, Cheng-Gang Zhu, Jing Sun, Ping Qing, Na-Qiong Wu, Jian-Jun Li ⁎ Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China
a r t i c l e
i n f o
Article history: Received 15 April 2014 Accepted 18 April 2014 Available online xxxx Keywords: Proprotein convertase subtilisin/kexin type 9 Lipid Atherosclerosis Gensini score
Proprotein convertase subtilisin/kexin type 9 (PCSK9), originally discovered as a third gene involved in autosomal dominant hypercholesterolemia, has gained intensive research over the past decade into its central role on low density lipoprotein (LDL) metabolism via LDL-receptors (LDLR) dependent or independent pathway [1–3]. Experimental and clinical studies have also established that over-expression of PCSK9 induced an excess of atherosclerosis while its poor-expression linked to a reduction of cardiovascular risk, strongly suggesting that the functional changes of PCSK9 is significantly involved in the development of atherosclerotic process [4,5]. In addition, recent studies indicated that the predictive value of PCSK9 level on cardiovascular events (CVE) was not weaker than the strength of LDL-cholesterol (LDL-C) even in patients with well-controlled LDL level [6]. However, the possible correlation of PCSK9 and severity of coronary atherosclerosis is little known. Our group hypothesized that PCSK9 might play an interesting and prospective role in the development of cardiovascular disease (CVD). The relation between plasma PCSK9 level and the severity of coronary atherosclerotic disease might be an issue, which is worthy of investigating. In this cross-sectional study, a total of 243 consecutive,
⁎ Corresponding author at: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China. Tel.: +86 10 88396077; fax: +86 10 88396584. E-mail address: [email protected] (J.-J. Li). 1 The first two authors contribute equally to this study.
atherosclerotic patients were enrolled from a cohort where patients prospectively entered to assess the prognostic significance of biomarkers in suspected known CVD in our center to test this interesting conjecture. Inclusion criteria included definite clinical evidence of atherosclerotic lesions from coronary angiography using the standard Judkin's technique with filming of multiple views of each vessel, which was defined as the stable lesion in at least one vessel segment that had the reduction ≥25% in lumen diameter, the starting point of calculating Gensini score [7]; no treatment history of statins and/or other lipid-lowering drugs at least 3 months prior to entering the study; and assessment of clinical history, anthropometric characteristics and standard cardiovascular risk factors. Exclusion criteria included lack of informed consent, acute coronary syndrome (ACS), history of artery revascularization, heart failure (the left ventricular ejection fraction b45%), significant hematologic disorders (white blood cell count ≤3.0 × 109/L or ≥20 × 109/L), infectious or systematic inflammatory disease, thyroid dysfunction, severe liver and/or renal insufficiency and malignant disease. The peripheral blood samples were drawn after a 12-hour overnight fasting for determinants of clinical variables consisting with our previous study [8]. The extent of coronary stenosis was expressed using Gensini scoring system [9]. According to Gensini score, we divided the study population into three subgroups with 0–24, 25–53 and ≥54 score [7]. Moreover, we also studied the population from the perspective of the number of diseased vessels. Data are described as median (interquartile range) or mean ± standard deviation. The analysis of variance and Jonckheere–Terpstra test were used for comparison of clinical parameters between different subgroups. Categorical variables were compared by the chi-square test. Spearman correlation was used to examine correlations of PCSK9 and other parameters with Gensini score. Multivariable regression analysis was used for determining independent factors of Gensini score. A p-value b0.05 was considered statistically significant. Statistical analysis was performed with SPSS version 19.0 software (SPSS Inc., Chicago, IL, USA). In this study population, the Gensini score ranged from 2 to 148 and its distribution was right-skewed (median: 20). The PCSK9 level varied from 121.53 to 477.70 ng/ml and also right-skewed (median: 218.77 ng/ml). The clinical and biological features of the whole study population and of subgroups with the Gensini score are summarized in Table 1. Compared to each lipid parameter, lipid ratios such as LDL/ high density lipoprotein (HDL) and total cholesterol (TC)/HDL, which indicated the balance between atherogenic and anti-atherogenic lipoproteins,
http://dx.doi.org/10.1016/j.ijcard.2014.04.224 0167-5273/© 2014 Published by Elsevier Ireland Ltd.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
2
S. Li et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Table 1 Baseline characteristics. Variables
Age (years) Male gender, n (%) BMI, kg/m2 Smoking, n (%) Family history of CVD, n (%) SBP, mm Hg DBP, mm Hg Glucose, mmol/L Triglycerides, mmol/L TC, mmol/L HDL-C, mmol/L LDL-C, mmol/L LDL-C/HDL-C ratio TC/HDL-C ratio PCSK9, ng/ml
Total patients (n = 243)
57.58 ± 9.78 173 (71.2) 25.79 ± 3.30 116 (47.7) 32 (13.2) 128 ± 16 77 ± 10 5.60 ± 1.35 1.57 (1.18–2.19) 4.86 ± 1.01 1.12 ± 0.36 3.08 ± 0.84 2.91 ± 0.97 4.61 ± 1.30 218.77 (179.84–271.64)
Gensini score groups Scores 1–24 (n = 135)
Scores 25–53 (n = 54)
Score ≥ 54 (n = 54)
P-value
57.33 ± 9.74 94 (69.6) 25.31 ± 3.21 68 (50.4) 15 (11.1) 128 ± 16 77 ± 10 5.54 ± 1.21 1.47 (1.12–2.00) 4.75 ± 0.95 1.16 ± 0.39 2.99 ± 0.78 2.74 ± 0.87 4.36 ± 1.19 208.61 (170.05–255.19)
57.02 ± 10.12 35 (64.8) 26.63 ± 3.62 19 (35.2) 6 (11.1) 128 ± 16 77 ± 12 5.74 ± 1.53 1.93 (1.36–2.45) 4.97 ± 0.95 1.05 ± 0.27 3.13 ± 0.86 3.12 ± 1.01 4.97 ± 1.31 217.43 (194.66–256.52)
58.76 ± 9.63 44 (81.5) 26.18 ± 3.00 29 (53.7) 11 (20.4) 126 ± 14 76 ± 8 5.59 ± 1.48 1.52 (1.18–2.17) 5.02 ± 1.19 1.09 ± 0.35 3.24 ± 0.96 3.13 ± 1.08 4.87 ± 1.43 246.81 (193.38–314.73)
0.592 0.134 0.027 0.102 0.207 0.650 0.835 0.631 0.093 0.167 0.150 0.151 0.009 0.004 0.001
Data shown are n (%), median (IQR) or mean (SD). Bold values indicate statistical significance to improve the readability. BMI, body mass index; CVD, cardiovascular disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
and PCSK9, have been shown stronger associations with the degree of coronary stenosis according to the Gensini score (Table 1). On the other way, the associations of PCSK9 and lipid ratios with the severity of coronary atherosclerosis were also observed according to the number of diseased vessels (p b 0.05). In spearman correlation analysis, moreover, concentrations of PCSK9, LDL/HDL, and TC/HDL are positively related to the Gensini score (r = 0.191, p = 0.003; r = 0.197, p = 0.002; r = 0.218, p = 0.001; respectively). Further, multivariable analysis revealed that PCSK9 levels were significantly and independently associated with the Gensini score (β = 0.139, p = 0.034) after controlling age, gender, BMI, systolic blood pressure, smoking, family history of CVD, glucose, LDL-C, HDL-C, and lipid ratios (Table 2). To our knowledge, this study is the first report to an association between the plasma PCSK9 level and the severity of coronary atherosclerosis. The present study shows that PCSK9 level is positively and independently associated with the degree of coronary stenosis in patients with atherosclerosis. This association could not be explained by the condition of lipids disorder, since it persisted after adjustment for lipid parameters. Previous studies on the association between each lipid parameter and severity of CVD are controversial, while the quantitative variables most relevant to severity of CVD are the lipid ratios such as LDL/HDL
and TC/HDL ratio [10]. However, it is interesting to note that both in Jonckheere–Terpstra test model and multiple regression model showed significant association between PCSK9 level and severity of coronary stenosis even after controlling for the lipids. Thus the novel finding from this study indicates a possibility that PCSK9 influences the degree of coronary atherosclerosis independently from lipids. Understanding the linkage between PCSK9 and the severity of coronary atherosclerosis may help greatly in taking care of patients with CVD. Further studies that observe the biological role of plasma PCSK9 in atherosclerosis and, by extension, CVD on a long-term basis may be built. Acknowledgments This work was partially supported by the National Natural Science Foundation of China (81070171, 81241121), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20111106110013), the Capital Special Foundation of Clinical Application Research (Z121107001012015), the Capital Health Development Fund (2011400302), and the Beijing Natural Science Foundation (7131014) awarded to Dr. Jian-Jun Li, MD, PhD. Authorship
Table 2 Multiple regression analysis.
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Variables
Standardized coefficients
P-value
BMI SBP Glucose Triglyceride TC LDL-C HDL-C LDL-C/HDL-C ratio TC/HDL-C ratio PCSK9
0.153 0.112 0.003 −0.092 0.064 −0.158 0.108 0.178 0.120 0.139
0.036 0.102 0.968 0.466 0.894 0.791 0.492 0.795 0.852 0.034
Multiple linear regression analysis was performed. The dependent variable was Gensini score. The regression equation included gender, age, body mass index, systolic blood pressure, smoking, family history of CVD, glucose, triglycerides, TC, LDL-C, HDL-C, LDL-C/ HDL-C ratio, TC/HDL-C ratio, and PCSK9. Bold values indicate statistical significance to improve the readability. BMI, body mass index; SBP, systolic blood pressure; TC: total cholesterol; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
References [1] Norata GD, Tibolla G, Catapano AL. Targeting PCSK9 for hypercholesterolemia. Annu Rev Pharmacol Toxicol 2014;54:273–93. [2] Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013;127:2403–13. [3] Urban D, Pöss J, Böhm M, Laufs U. Targeting the proprotein convertase subtilisin/ kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 2013;62:1401–8. [4] Wu NQ, Guo YL, Xu RX, et al. Acute myocardial infarction in an 8-year old male child with homozygous familiar hypercholesterolemia: laboratory findings and response to lipid-lowering drugs. Clin Lab 2013;59:901–7. [5] Wu NQ, Li JJ. PCSK9 gene mutations and low-density lipoprotein cholesterol. Clin Clim Acta 2014;431:148–53. [6] Werner C, Hoffmann MM, Winkler K, et al. Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascul Pharmacol 2014;14:S1537–891.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
S. Li et al. / International Journal of Cardiology xxx (2014) xxx–xxx [7] Sinning C, Lillpopp L, Appelbaum S, et al. Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application. Clin Res Cardiol 2013;102:495–503. [8] Li S, Guo YL, Xu RX, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis 2014. http://dx.doi.org/10.1016/j.atherosclerosis.2014.04.001.
3
[9] Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606. [10] Momiyama Y, Ohmori R, Fayad ZA, et al. The LDL-cholesterol to HDL-cholesterol ratio and the severity of coronary and aortic atherosclerosis. Atherosclerosis 2012;222:577–80.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Letter to the Editor
Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis Sha Li 1, Yuan-Lin Guo 1, Rui-Xia Xu, Yan Zhang, Cheng-Gang Zhu, Jing Sun, Ping Qing, Na-Qiong Wu, Jian-Jun Li ⁎ Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, BeiLiShi Road 167, Beijing 100037, China
a r t i c l e
i n f o
Article history: Received 15 April 2014 Accepted 18 April 2014 Available online xxxx Keywords: Proprotein convertase subtilisin/kexin type 9 Lipid Atherosclerosis Gensini score
Proprotein convertase subtilisin/kexin type 9 (PCSK9), originally discovered as a third gene involved in autosomal dominant hypercholesterolemia, has gained intensive research over the past decade into its central role on low density lipoprotein (LDL) metabolism via LDL-receptors (LDLR) dependent or independent pathway [1–3]. Experimental and clinical studies have also established that over-expression of PCSK9 induced an excess of atherosclerosis while its poor-expression linked to a reduction of cardiovascular risk, strongly suggesting that the functional changes of PCSK9 is significantly involved in the development of atherosclerotic process [4,5]. In addition, recent studies indicated that the predictive value of PCSK9 level on cardiovascular events (CVE) was not weaker than the strength of LDL-cholesterol (LDL-C) even in patients with well-controlled LDL level [6]. However, the possible correlation of PCSK9 and severity of coronary atherosclerosis is little known. Our group hypothesized that PCSK9 might play an interesting and prospective role in the development of cardiovascular disease (CVD). The relation between plasma PCSK9 level and the severity of coronary atherosclerotic disease might be an issue, which is worthy of investigating. In this cross-sectional study, a total of 243 consecutive,
⁎ Corresponding author at: Division of Dyslipidemia, State Key Laboratory of Cardiovascular Disease, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100037, China. Tel.: +86 10 88396077; fax: +86 10 88396584. E-mail address: [email protected] (J.-J. Li). 1 The first two authors contribute equally to this study.
atherosclerotic patients were enrolled from a cohort where patients prospectively entered to assess the prognostic significance of biomarkers in suspected known CVD in our center to test this interesting conjecture. Inclusion criteria included definite clinical evidence of atherosclerotic lesions from coronary angiography using the standard Judkin's technique with filming of multiple views of each vessel, which was defined as the stable lesion in at least one vessel segment that had the reduction ≥25% in lumen diameter, the starting point of calculating Gensini score [7]; no treatment history of statins and/or other lipid-lowering drugs at least 3 months prior to entering the study; and assessment of clinical history, anthropometric characteristics and standard cardiovascular risk factors. Exclusion criteria included lack of informed consent, acute coronary syndrome (ACS), history of artery revascularization, heart failure (the left ventricular ejection fraction b45%), significant hematologic disorders (white blood cell count ≤3.0 × 109/L or ≥20 × 109/L), infectious or systematic inflammatory disease, thyroid dysfunction, severe liver and/or renal insufficiency and malignant disease. The peripheral blood samples were drawn after a 12-hour overnight fasting for determinants of clinical variables consisting with our previous study [8]. The extent of coronary stenosis was expressed using Gensini scoring system [9]. According to Gensini score, we divided the study population into three subgroups with 0–24, 25–53 and ≥54 score [7]. Moreover, we also studied the population from the perspective of the number of diseased vessels. Data are described as median (interquartile range) or mean ± standard deviation. The analysis of variance and Jonckheere–Terpstra test were used for comparison of clinical parameters between different subgroups. Categorical variables were compared by the chi-square test. Spearman correlation was used to examine correlations of PCSK9 and other parameters with Gensini score. Multivariable regression analysis was used for determining independent factors of Gensini score. A p-value b0.05 was considered statistically significant. Statistical analysis was performed with SPSS version 19.0 software (SPSS Inc., Chicago, IL, USA). In this study population, the Gensini score ranged from 2 to 148 and its distribution was right-skewed (median: 20). The PCSK9 level varied from 121.53 to 477.70 ng/ml and also right-skewed (median: 218.77 ng/ml). The clinical and biological features of the whole study population and of subgroups with the Gensini score are summarized in Table 1. Compared to each lipid parameter, lipid ratios such as LDL/ high density lipoprotein (HDL) and total cholesterol (TC)/HDL, which indicated the balance between atherogenic and anti-atherogenic lipoproteins,
http://dx.doi.org/10.1016/j.ijcard.2014.04.224 0167-5273/© 2014 Published by Elsevier Ireland Ltd.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
2
S. Li et al. / International Journal of Cardiology xxx (2014) xxx–xxx
Table 1 Baseline characteristics. Variables
Age (years) Male gender, n (%) BMI, kg/m2 Smoking, n (%) Family history of CVD, n (%) SBP, mm Hg DBP, mm Hg Glucose, mmol/L Triglycerides, mmol/L TC, mmol/L HDL-C, mmol/L LDL-C, mmol/L LDL-C/HDL-C ratio TC/HDL-C ratio PCSK9, ng/ml
Total patients (n = 243)
57.58 ± 9.78 173 (71.2) 25.79 ± 3.30 116 (47.7) 32 (13.2) 128 ± 16 77 ± 10 5.60 ± 1.35 1.57 (1.18–2.19) 4.86 ± 1.01 1.12 ± 0.36 3.08 ± 0.84 2.91 ± 0.97 4.61 ± 1.30 218.77 (179.84–271.64)
Gensini score groups Scores 1–24 (n = 135)
Scores 25–53 (n = 54)
Score ≥ 54 (n = 54)
P-value
57.33 ± 9.74 94 (69.6) 25.31 ± 3.21 68 (50.4) 15 (11.1) 128 ± 16 77 ± 10 5.54 ± 1.21 1.47 (1.12–2.00) 4.75 ± 0.95 1.16 ± 0.39 2.99 ± 0.78 2.74 ± 0.87 4.36 ± 1.19 208.61 (170.05–255.19)
57.02 ± 10.12 35 (64.8) 26.63 ± 3.62 19 (35.2) 6 (11.1) 128 ± 16 77 ± 12 5.74 ± 1.53 1.93 (1.36–2.45) 4.97 ± 0.95 1.05 ± 0.27 3.13 ± 0.86 3.12 ± 1.01 4.97 ± 1.31 217.43 (194.66–256.52)
58.76 ± 9.63 44 (81.5) 26.18 ± 3.00 29 (53.7) 11 (20.4) 126 ± 14 76 ± 8 5.59 ± 1.48 1.52 (1.18–2.17) 5.02 ± 1.19 1.09 ± 0.35 3.24 ± 0.96 3.13 ± 1.08 4.87 ± 1.43 246.81 (193.38–314.73)
0.592 0.134 0.027 0.102 0.207 0.650 0.835 0.631 0.093 0.167 0.150 0.151 0.009 0.004 0.001
Data shown are n (%), median (IQR) or mean (SD). Bold values indicate statistical significance to improve the readability. BMI, body mass index; CVD, cardiovascular disease; SBP, systolic blood pressure; DBP, diastolic blood pressure; TC, total cholesterol; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
and PCSK9, have been shown stronger associations with the degree of coronary stenosis according to the Gensini score (Table 1). On the other way, the associations of PCSK9 and lipid ratios with the severity of coronary atherosclerosis were also observed according to the number of diseased vessels (p b 0.05). In spearman correlation analysis, moreover, concentrations of PCSK9, LDL/HDL, and TC/HDL are positively related to the Gensini score (r = 0.191, p = 0.003; r = 0.197, p = 0.002; r = 0.218, p = 0.001; respectively). Further, multivariable analysis revealed that PCSK9 levels were significantly and independently associated with the Gensini score (β = 0.139, p = 0.034) after controlling age, gender, BMI, systolic blood pressure, smoking, family history of CVD, glucose, LDL-C, HDL-C, and lipid ratios (Table 2). To our knowledge, this study is the first report to an association between the plasma PCSK9 level and the severity of coronary atherosclerosis. The present study shows that PCSK9 level is positively and independently associated with the degree of coronary stenosis in patients with atherosclerosis. This association could not be explained by the condition of lipids disorder, since it persisted after adjustment for lipid parameters. Previous studies on the association between each lipid parameter and severity of CVD are controversial, while the quantitative variables most relevant to severity of CVD are the lipid ratios such as LDL/HDL
and TC/HDL ratio [10]. However, it is interesting to note that both in Jonckheere–Terpstra test model and multiple regression model showed significant association between PCSK9 level and severity of coronary stenosis even after controlling for the lipids. Thus the novel finding from this study indicates a possibility that PCSK9 influences the degree of coronary atherosclerosis independently from lipids. Understanding the linkage between PCSK9 and the severity of coronary atherosclerosis may help greatly in taking care of patients with CVD. Further studies that observe the biological role of plasma PCSK9 in atherosclerosis and, by extension, CVD on a long-term basis may be built. Acknowledgments This work was partially supported by the National Natural Science Foundation of China (81070171, 81241121), the Specialized Research Fund for the Doctoral Program of Higher Education of China (20111106110013), the Capital Special Foundation of Clinical Application Research (Z121107001012015), the Capital Health Development Fund (2011400302), and the Beijing Natural Science Foundation (7131014) awarded to Dr. Jian-Jun Li, MD, PhD. Authorship
Table 2 Multiple regression analysis.
All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.
Variables
Standardized coefficients
P-value
BMI SBP Glucose Triglyceride TC LDL-C HDL-C LDL-C/HDL-C ratio TC/HDL-C ratio PCSK9
0.153 0.112 0.003 −0.092 0.064 −0.158 0.108 0.178 0.120 0.139
0.036 0.102 0.968 0.466 0.894 0.791 0.492 0.795 0.852 0.034
Multiple linear regression analysis was performed. The dependent variable was Gensini score. The regression equation included gender, age, body mass index, systolic blood pressure, smoking, family history of CVD, glucose, triglycerides, TC, LDL-C, HDL-C, LDL-C/ HDL-C ratio, TC/HDL-C ratio, and PCSK9. Bold values indicate statistical significance to improve the readability. BMI, body mass index; SBP, systolic blood pressure; TC: total cholesterol; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; PCSK9, proprotein convertase subtilisin/kexin type 9.
References [1] Norata GD, Tibolla G, Catapano AL. Targeting PCSK9 for hypercholesterolemia. Annu Rev Pharmacol Toxicol 2014;54:273–93. [2] Tavori H, Fan D, Blakemore JL, et al. Serum proprotein convertase subtilisin/kexin type 9 and cell surface low-density lipoprotein receptor: evidence for a reciprocal regulation. Circulation 2013;127:2403–13. [3] Urban D, Pöss J, Böhm M, Laufs U. Targeting the proprotein convertase subtilisin/ kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol 2013;62:1401–8. [4] Wu NQ, Guo YL, Xu RX, et al. Acute myocardial infarction in an 8-year old male child with homozygous familiar hypercholesterolemia: laboratory findings and response to lipid-lowering drugs. Clin Lab 2013;59:901–7. [5] Wu NQ, Li JJ. PCSK9 gene mutations and low-density lipoprotein cholesterol. Clin Clim Acta 2014;431:148–53. [6] Werner C, Hoffmann MM, Winkler K, et al. Risk prediction with proprotein convertase subtilisin/kexin type 9 (PCSK9) in patients with stable coronary disease on statin treatment. Vascul Pharmacol 2014;14:S1537–891.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
S. Li et al. / International Journal of Cardiology xxx (2014) xxx–xxx [7] Sinning C, Lillpopp L, Appelbaum S, et al. Angiographic score assessment improves cardiovascular risk prediction: the clinical value of SYNTAX and Gensini application. Clin Res Cardiol 2013;102:495–503. [8] Li S, Guo YL, Xu RX, et al. Association of plasma PCSK9 levels with white blood cell count and its subsets in patients with stable coronary artery disease. Atherosclerosis 2014. http://dx.doi.org/10.1016/j.atherosclerosis.2014.04.001.
3
[9] Gensini GG. A more meaningful scoring system for determining the severity of coronary heart disease. Am J Cardiol 1983;51:606. [10] Momiyama Y, Ohmori R, Fayad ZA, et al. The LDL-cholesterol to HDL-cholesterol ratio and the severity of coronary and aortic atherosclerosis. Atherosclerosis 2012;222:577–80.
Please cite this article as: Li S, et al, Plasma PCSK9 levels are associated with the severity of coronary stenosis in patients with atherosclerosis, Int J Cardiol (2014), http://dx.doi.org/10.1016/j.ijcard.2014.04.224
