No impact of statin treatment on integrin expression on leucocytes in patients with stable coronary artery disease

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): FWF Background and aims Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis and can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14 + CD16++; NCM). Results Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n = 55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p = 0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R = 0.29; p = 0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p = 0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p = 0.05). Conversely, PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p = 0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

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High HbA1c levels correlate with reduced plaque regression during statin treatment in patients with stable coronary artery disease: Results of the coronary atherosclerosis study measuring effects of rosuvastatin using intravascular ultrasound in Japanese subjects (COSMOS)

Cardiovascular Diabetology ◽

10.1186/1475-2840-11-87 ◽

2012 ◽

Vol 11 (1) ◽

pp. 87 ◽

Cited By ~ 17

Author(s):

Hiroyuki Daida ◽

Tadateru Takayama ◽

Takafumi Hiro ◽

Masakazu Yamagishi ◽

Atsushi Hirayama ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Coronary Atherosclerosis ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

High Hba1c ◽

Plaque Regression ◽

Artery Disease ◽

Japanese Subjects ◽

Hba1c Levels

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The influence of statin treatment on the inflammatory biomarkers YKL-40 and HsCRP in patients with stable coronary artery disease

Inflammation Research ◽

10.1007/s00011-010-0266-5 ◽

2010 ◽

Vol 60 (3) ◽

pp. 281-287 ◽

Cited By ~ 35

Author(s):

Naja Dam Mygind ◽

◽

Marina J. Harutyunyan ◽

Anders Bruun Mathiasen ◽

Rasmus S. Ripa ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Inflammatory Biomarkers ◽

Artery Disease

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Abstract 15930: Circulating Levels of Proprotein Convertase Subtilisin/kexin Type 9 (pcsk9) are Associated With Monocyte Subsets in Patients With Stable Coronary Artery Disease

Circulation ◽

10.1161/circ.142.suppl_3.15930 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Konstantin Krychtiuk ◽

Max Lenz ◽

Philipp Hohensinner ◽

Klaus Distelmaier ◽

Lore Schrutka ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Lipid Lowering ◽

Monocyte Subsets ◽

Proprotein Convertase ◽

Artery Disease ◽

Circulating Levels ◽

Classical Monocytes

Introduction: Proprotein convertase subtilisin/kexin type-9 (PCSK9) is an enzyme promoting the degradation of low-density lipoprotein receptors (LDL-R) in hepatocytes. Inhibition of PCSK9 has emerged as a novel target for lipid-lowering therapy. Monocytes are crucially involved in the pathogenesis of atherosclerosis. Circulating monocytes can be divided into three subsets. The aim of this study was to examine whether circulating levels of PCSK9 are associated with monocyte subsets. Methods: We included 69 patients with stable coronary artery disease. PCSK9 levels were measured and monocyte subsets were assessed by flow cytometry and divided into classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). Results: Mean age was 64 years and 80% of patients were male. Patients on statin treatment (n=55) showed higher PCSK9-levels (245.4 (206.0-305.5) ng/mL) as opposed to those without statin treatment (186.1 (162.3-275.4) ng/mL; p=0.05). In patients on statin treatment, CM correlated with circulating PCSK9 levels (R=0.29; p=0.04), while NCM showed an inverse correlation with PCSK9 levels (R=-0.33; p=0.02). Patients with PCSK9 levels above the median showed a significantly higher proportion of CM as compared to patients with PCSK-9 below the median (83.5 IQR 79.2-86.7 vs. 80.4, IQR 76.5-85.2%; p=0.05). Conversely, patients with PCSK9 levels >median were associated with a significantly lower proportion of NCM as compared to those with PCSK9 <median (10.2, IQR 7.3-14.6 vs. 14.3, IQR 10.9-18.7%; p=0.02). In contrast, IM showed no association with PCSK-9 levels. Conclusions: We hereby provide a novel link between PCSK9 regulation, innate immunity and atherosclerotic disease in statin-treated patients.

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Serum osteoprotegerin as a long-term predictor for patients with stable coronary artery disease and its association with diabetes and statin treatment: A CLARICOR trial 10-year follow-up substudy

Atherosclerosis ◽

10.1016/j.atherosclerosis.2020.03.030 ◽

2020 ◽

Vol 301 ◽

pp. 8-14

Author(s):

Mette Bjerre ◽

Jørgen Hilden ◽

Per Winkel ◽

Gorm Boje Jensen ◽

Erik Kjøller ◽

...

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Artery Disease

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Patients with Stable Coronary Artery Disease Receiving Chronic Statin Treatment Who Are Undergoing Noncardiac Emergency Surgery Benefit from Acute Atorvastatin Reload

Cardiology ◽

10.1159/000362593 ◽

2014 ◽

Vol 128 (3) ◽

pp. 285-292 ◽

Cited By ~ 8

Author(s):

Jinggang Xia ◽

Yang Qu ◽

Hong Shen ◽

Xiuhua Liu

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

Emergency Surgery ◽

Stable Coronary Artery Disease ◽

Statin Treatment ◽

Artery Disease

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P1227Remnant lipoprotein is a residual risk of future cardiovascular events in patients with stable coronary artery disease and on statin LDL-cholesterol levels less than 70 mg/dl

European Heart Journal ◽

10.1093/eurheartj/ehz748.0185 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

Y Fujihara ◽

T Nakamura ◽

T Horikoshi ◽

J E Obata ◽

D Fujioka ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Cardiovascular Events ◽

Stable Coronary Artery Disease ◽

Density Lipoprotein ◽

Statin Treatment ◽

Residual Risk ◽

Traditional Risk Factors ◽

Artery Disease

Abstract Background Recent guidelines recommend a target of low density lipoprotein cholesterol (LDL-C) <70 mg/dL in patients at very high risk of cardiovascular disease (CVD). However, a considerable residual risk of CVD persists despite achievement of the LDL-C goal on statin treatment. Purpose This study examined the predictive value of remnant lipoprotein levels for cardiovascular events (CVE) in patients with stable coronary artery disease (CAD) and LDL-C levels <70 mg/dL on statin treatment. Methods Serum levels of remnant lipoproteins (remnant-like lipoprotein particles cholesterol; RLP-C) were measured by an immunoseparation method in 247 consecutive patients with CAD who had on-statin LDL-C levels <70 mg/dL. All the patients were followed prospectively for a period of ≤60 months or until the occurrence of the primary composite endpoint of cardiac death, nonfatal myocardial infarction, unstable angina requiring coronary revascularization, worsening heart failure, peripheral artery diseases requiring endovascular or surgical intervention, aortic events, and ischemic stroke. Results During a mean follow-up period of 38 months, 33 CVEs occurred. Kaplan-Meier estimates in time-to-first-event analysis demonstrated that higher RLP-C levels (>3.9 mg/dL, determined by ROC-curve) resulted in a significantly higher probability for the primary endpoint than did lower RLP-C levels (<3.9 mg/dL) (p<0.01 by log-rank test). Stepwise multivariate Cox proportional hazard analysis showed that RLP-C was a significant predictor of the primary endpoint after adjustment for known risk factors and lipid variables including triglycerides (TG), and total apolipoprotein B (ApoB) (HR 1.62, 95% CI 1.26–2.07, p<0.01). The c-statistics showed that addition of RLP-C had a significant incremental effect on the predictive value of traditional risk factors (area under curve; traditional risk factors: 0.68 vs. traditional risk factors + RLP-C: 0.77, p=0.02). Category-free NRI and IDI demonstrated the additive value of RLP-C to the traditional risk factors plus non-high-density lipoprotein (HDL)-C and ApoB levels (NRI 0.52, p<0.01; IDI 0.06, p<0.01). Conclusions RLP-C levels are a residual risk factor for future CVEs in patients with CAD and on-statin LDL-C <70 mg/dL.

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