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

Sha, Lei; Zhang, Yan; Xu, Rui‐Xia; Guo, Yuan‐Lin; Zhu, Cheng‐Gang; Wu, Na‐Qiong; Peng, Qing; Li, Geng; Dong, Qian; Li, Jianjun

doi:10.3109/07853890.2015.1042908

Cited by 69 publications

(57 citation statements)

References 29 publications

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“…Reductions in the luminal diameter of 1–25%, 26–50%, 51–75%, 76–90%, 91–99% and total occlusion were respectively evaluated as 1, 2, 4, 8, 16 and 32. Each principal vascular segment was multiplied by a factor in accordance with the functional importance of the myocardial area supplied by that segment, that is, the left main (LM) was assigned a multiplier × 5; the proximal segment of the left anterior descending (LAD) and the proximal segment of the left circumflex (LCX) × 2.5; the middle of the LAD × 1.5; the distal segment of the LAD, the right coronary artery (RCA), the posterolateral artery, and the obtuse marginal artery × 1; and other small vascular branches × 0.5 [17]. …”

Section: Methodsmentioning

confidence: 99%

Elevated levels of preβ1-high-density lipoprotein are associated with cholesterol ester transfer protein, the presence and severity of coronary artery disease

Niu

et al. 2017

Lipids Health Dis

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BackgroundPreβ1-high-density lipoprotein (preβ1-HDL), plays an important role in reverse cholesterol transport and exhibits potent risk for coronary artery disease (CAD). However, the association of plasma preβ1-HDL and cholesterol ester transfer protein (CETP) levels in CAD patients and the relationship of preβ1-HDL with extent of CAD are debatable.MethodsPreβ1-HDL and CETP levels were measured by enzymed-linked immunosorbent assay (ELISAs) in 88 acute coronary syndromes (ACS), 79 stable coronary artery disease (SCAD) patients and 85 control subjects. The correlation analyses, multiple linear regression analyses and logistic regression analyses were performed, respectively.ResultsThe preβ1-HDL and CETP levels in ACS patients were significantly higher than those in SCAD patients and both of them were higher than controls’. Preβ1-HDL levels were positively associated with CETP (R = 0.348, P = 0.000), the diameter of stenosis (R = 0.253, P = 0.005), the number of vessel disease (R = 0.274, P = 0.002) and Gensini score (R = 0.227, P = 0.009) in CAD patients. Stepwise multiple linear regression analyses showed that CETP was one of the determinants of preβ1-HDL levels. Logistic regression analysis revealed that elevated preβ1-HDL and CETP were potential risk factors for both ACS and SCAD.ConclusionThe elevated preβ1-HDL levels may change with CETP concentrations in CAD patients and were related to the presence and severity of CAD.

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Section: Methodsmentioning

confidence: 99%

Elevated levels of preβ1-high-density lipoprotein are associated with cholesterol ester transfer protein, the presence and severity of coronary artery disease

Niu

et al. 2017

Lipids Health Dis

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“…To study the associations of PCSK9, apoC3, and sdLDL-C with current dyslipiemias, we enrolled the patients with no lipid-lowering treatment at least 3 months prior to entering the study from the patients scheduled for diagnostic/interventional CAG because of their first angina-like chest pain and/or positive treadmill exercise test or clinically suspected CVD in our division as our previous studies [16, 19]. Therefore, we recruited the study patients with angiography and lipid-lowering-therapy being parts of the screening process.…”

Section: Methodsmentioning

confidence: 99%

“…All patients underwent clinical examination and blood testing as our previous studies [16, 19]. Blood samples were obtained for all patients from the cubital vein after a 12-hour overnight fast.…”

Section: Methodsmentioning

confidence: 99%

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

Zhao

Zhang

et al. 2016

Oncotarget

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Plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9), apolipoprotein C-III (apoC3) and small dense low density lipoprotein cholesterol (sdLDL-C), have been recently recognized as circulating atherosclerosis-related lipid measurements. We aimed to elucidate their associations with current dyslipidemias, and identify their levels at increased risk to dyslipidemia. A total of 1,605 consecutive, non-treated patients undergoing diagnostic/interventional coronary angiography were examined. Plasma PCSK9 and apoC3 levels were determined using a validated ELISA assay, and sdLDL-C was measured by the Lipoprint LDL System. Plasma levels of PCSK9, apoC3, and sdLDL-C were associated with the current dyslipidemias classification (all p<0.001). PCSK9 significantly conferred prediction of both hypercholesterolemia and combined hyperlipidemia at a level of 235 ng/ml; apoC3 levels for hypertriglyceridemia, hypercholesterolemia and combined hyperlipidemia were 80.0, 71.5, and 86.4 g/ml, respectively; and sdLDL-C for hypertriglyceridemia, hypercholesterolemia, combined hyperlipidemia and hypo high density lipoprotein (HDL) cholesterolemia 3.5, 2.5, 4.5, and 2.5 mg/dl, respectively (all p<0.001 for area under the receiver-operating characteristic curve). In a polytomous logistic model comparing increasing LDL-C categories, the interactions with high PCSK9, apoC3, and sdLDL-C elevated gradually. Similarly, apoC3 and sdLDL-C showed elevated interaction with increased triglyceride categories, and only sdLDL-C showed interaction with decreased HDL cholesterol (HDL-C) categories. Furthermore, discordances of PCSK9, apoC3, and sdLDL-C with current dyslipidemias were observed. PCSK9, apoC3, and sdLDL-C showed significant interactions with current dyslipidemias, and were predictive in the screening. The substantial discordances with current dyslipidemias might provide novel view in lipid management and further cardiovascular benefit.

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“…Therefore, the progression of kidney dysfunction may influence the expression or clearance of circulating PCSK9 levels, or in other words contribute to the change in plasma concentrations of PCSK9. Previous studies have reported that elevated PCSK9 concentrations are strongly associated with increased LDL-C levels and the development of atherosclerosis [8,16,18,19]. Consequently, PCSK9 inhibitors have become a novel therapeutic target for the therapy of hypercholesterolemia, which has been demonstrated to reduce the risk of cardiovascular disease [21,22].…”

Section: Discussionmentioning

confidence: 99%

“…All samples were subsequently stored at -80 ° C and analyzed after thawing. Plasma PCSK9 levels were measured by a high-sensitivity, quantitative sandwich enzyme immunoassay (Quantikine ELISA, R&D Systems Europe Ltd.) as described in our previous studies [16,18,19]. The lowest limit of detection was 0.096 mg/L.…”

Section: Laboratory Analysismentioning

confidence: 99%

Relationship between Plasma Proprotein Convertase Subtilisin/Kexin Type 9 and Estimated Glomerular Filtration Rate in the General Chinese Population

Zhang

Zhao

et al. 2018

Cardiorenal Med

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Background: Elevated levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) have been reported to be related to dyslipidemia, including patients with kidney dysfunction. However, its association with estimated glomerular filtration rate (eGFR) in individuals with normal serum creatinine (SCr) has not been determined. Methods: A total of 2,089 subjects with normal SCr and without lipid-lowering treatment were consecutively enrolled in this study. Plasma PCSK9 levels were measured by ELISA kit and eGFR was evaluated by the Chronic Kidney Disease Epidemiology Collaboration equation. Subjects were divided into a normal eGFR group (n = 1,205, ≥90 mL/min/1.73 m²) and a decreased eGFR group (n = 884, < 90 mL/min/1.73 m²). Baseline characteristics and laboratory findings were compared between the two groups. Spearman’s correlation and linear regression were performed to determine the association between PCSK9 and eGFR. Results: No significant difference in PCSK9 levels was found between the normal eGFR group and the decreased eGFR group (236.84 ± 67.87 vs. 239.98 ± 68.72 ng/mL, p = 0.303). In Spearman’s correlation and multivariable linear regression analysis, no association of PCSK9 levels with eGFR was detected in the total cohort (r = –0.039, p = 0.079; adjusted β = –0.013, p = 0.630). This result remained the same in the subgroups of normal eGFR (r = –0.038, p = 0.190; adjusted β = –0.031, p = 0.367) and decreased eGFR (r = –0.054, p = 0.109; adjusted β = –0.034, p = 0.319). Conclusion: In this single-center study with moderate sample size, the data showed no relationship of PCSK9 levels with normal or decreased eGFR in untreated patients with normal SCr, suggesting that further studies may be needed to understand the relationship between PCSK9 and lipid disorder in different stage of kidney dysfunction.

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

Abstract: 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.

Cited by 69 publications

References 29 publications

Elevated levels of preβ1-high-density lipoprotein are associated with cholesterol ester transfer protein, the presence and severity of coronary artery disease

Elevated levels of preβ1-high-density lipoprotein are associated with cholesterol ester transfer protein, the presence and severity of coronary artery disease

Novel circulating lipid measurements for current dyslipidemias in non-treated patients undergoing coronary angiography: PCSK9, apoC3 and sdLDL-C

Relationship between Plasma Proprotein Convertase Subtilisin/Kexin Type 9 and Estimated Glomerular Filtration Rate in the General Chinese Population

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