P5320Reduction in high-sensitivity C-reactive protein by pitavastatin was associated with improved outcomes in Japanese patients with stable coronary artery disease: results from REAL-CAD study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Iwata ◽  
S Iimuro ◽  
A Inoue ◽  
K Miyauchi ◽  
I Taguchi ◽  
...  
Keyword(s):  
Primary Endpoint ◽  
Cardiovascular Events ◽  
Stable Coronary Artery Disease ◽  
High Sensitivity ◽  
Japanese Patients ◽  
The Real ◽  
Reactive Protein ◽  
Hs Crp ◽  
Artery Disease ◽  
Stable Cad

Abstract Background The effect of statins on lowering high sensitivity C-reactive protein (hs-CRP) as well as low density lipoprotein cholesterol (LDL-C) has been associated with reduced risk for cardiovascular events in patients with elevated hs-CRP. However, it remains unclear whether this statin effect applies to low-risk patients with stable coronary artery disease (CAD). In this pre-specified sub-study within the REAL-CAD trial, we explored the association between achieved LDL-C/hs-CRP levels and cardiovascular events in Japanese patients with stable CAD who were treated with pitavastatin 1 mg or 4 mg/day. Methods The REAL-CAD trial randomly allocated 13,054 patients with stable CAD to pitavastatin 1 mg or 4 mg/day. LDL-C and hs-CRP were measured at baseline and at 6 months after randomization. We excluded those patients without 6-month data and those with endpoint events before 6 months (N=1915). The primary endpoint of the study was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. Outcomes were assessed by landmark analysis beyond 6 months among 4 groups that were configured based on LDL-C (median) and hs-CRP (median) targets: achieving neither target, achieving LDL-C target only, achieving hs-CRP target only, and achieving both targets. Data were adjusted for baseline characteristics including age, gender, diabetes and baseline values of LDL-C and hs-CRP. Results Median LDL-C and hs-CRP levels were 88 mg/dL and 0.52 mg/L at baseline and 80 mg/dL and 0.48 mg/L after 6 months, respectively. There was no correlation between the change in LDL-C and hs-CRP levels from baseline to 6 months (correlation coefficient: 0.009, P=0.331). Of the 11,677 patients included in the study, 25.1% (N=2799) achieved both LDL-C and hs-CRP targets, 25.3% (N=2282) met neither target, 24.8% (N=2765) met only the hs-CRP target, and 24.7% (N=2753) met only the LDL-C target. Risk of primary endpoint occurrence was significantly lower in those achieving either or both targets than in those meeting neither target (Figure A). In the subgroup analysis stratified by the randomized dose of pitavastatin, the risk for the primary endpoint was significantly lower in patients achieving both targets in both the 1mg and 4 mg arms, and in patients achieving only hs-CRP target in the 1 mg arm (Figure B, C). Figure 1 Conclusions In this subanalysis of the REAL-CAD trial, the hs-CRP lowering effect of pitavastatin was independent from LDL-C lowering. Lower achieved hs-CRP was associated with lower risk for cardiovascular events in Japanese patients with stable CAD. Acknowledgement/Funding Public Health Research Foundation, The company manufacturing the study drug (Kowa Pharmaceutical Co Ltd) was one of the entities providing financial s

scholarly journals Galectin-1 is associated with the severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ruey-Hsing Chou ◽  
Shao-Sung Huang ◽  
Chin-Sung Kuo ◽  
Shen-Chih Wang ◽  
Yi-Lin Tsai ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Cardiovascular Events ◽  
Ventricular Remodeling ◽  
Stable Coronary Artery Disease ◽  
High Sensitivity ◽  
Major Adverse Cardiovascular Events ◽  
Hs Crp ◽  
Artery Disease

AbstractGalectin-1, a β-galactoside-binding lectin mediating inflammation and neovascularization, is reported to attenuate ventricular remodeling after myocardial infarction. But its role in stable coronary artery disease (CAD) has not been fully elucidated. This study aimed to identify the relationship between the circulating galectin-1 level and the severity of CAD in patients with suspected CAD. Pre-procedure galectin-1 and high-sensitivity C-reactive protein (hs-CRP) concentrations were measured in 834 subjects who underwent scheduled coronary angiography. Subjects were grouped into tertiles of the galectin-1 levels. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019 or the occurrence of major adverse cardiovascular events (MACE). Patients with higher galectin-1 concentrations were older; had greater prevalence of hypertension, diabetes, chronic kidney disease, and heart failure; and were more likely to present with higher hs-CRP levels and SYNTAX scores. During the follow-up period of 1.3 ± 1.1 years, patients in the highest tertile of galectin-1 were associated with a greater risk of MACE after adjustment for age, sex, comorbidities, co-medications, serum levels of hemoglobin, creatinine, hs-CRP, ejection fraction, SYNTAX scores, and revascularization modalities (adjusted hazard ratio 10.95, 95% confidence interval 2.29–52.47, p = 0.003). Galectin-1 showed better discriminatory performance than hs-CRP, and non-inferior performance to SYNTAX scores, in predicting the incidence of MACE.

High-dose statin therapy and the risk of haemorrhagic stroke in Asian patients with stable coronary artery disease: insights from the REAL-CAD study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Takahashi ◽  
K Tsuchida ◽  
Y Sato ◽  
S Iimuro ◽  
K Kario ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Dose Group ◽  
Low Dose ◽  
Japanese Patients ◽  
Haemorrhagic Stroke ◽  
High Dose ◽  
The Real ◽  
Artery Disease ◽  
Stable Cad ◽  
Bleeding Score

Abstract Background/Introduction The REAL-CAD study identified that aggressive lipid lowering with high-dose statin reduced cardiovascular events also in Japanese patients with coronary artery disease (CAD). However, data from the SPARCL trial found that the benefits of high-dose atorvastatin treatment were partially offset by an increase in haemorrhagic stroke (HS). Although meta-analysis showed statin does not increase HS in Western countries, the evidence about the relation between statin and HS in Asian countries is still conflicting. In addition, the CREDO-Kyoto score is one of the prediction scorings for bleeding after coronary revascularization and might be a useful tool for the prediction of HS in this cohort. Recognizing the risk of HS and predicting of HS in the Asian cohort is clinically important. Purpose This study examined the factors associated with HS using the REAL-CAD cohort. Furthermore, we evaluated the performance of the CREDO-Kyoto bleeding risk score to predict HS in this cohort. We also performed the corresponding analysis of ischaemic stroke for reference purposes. Methods We sub-analysed the REAL-CAD study, prospective, multicentre, randomized, open-label, blinded endpoint study, in which 13,054 Japanese patients with stable CAD were randomized to high-dose (4 mg/day) or low-dose (1 mg/day) pitavastatin. Associations for stroke were determined using competing risk models: the Fine and Gray subdistribution hazards model accounting for the competing risk of death in models of haemorrhagic and ischaemic stroke in REAL-CAD trial. Patients were categorized to low (score 0), moderate (score 1–2), and high (score>3) according to CREDO-Kyoto bleeding score for predicting of HS. Results The HS events in high-dose group tended to be higher than low-dose group (4mg vs. 1mg: 43 (0.7%) vs. 30 (0.5%)). The associated factors of HS on univariate analysis were non-prior myocardial (hazard ratio (HR): 0.62, 95% CI: 0.39–0.99) and non-prior cerebral (HR: 0.25, 95% CI: 0.09–0.70) infarction, atrial fibrillation (HR: 2.4, 95% CI: 1.2–4.7), prior HS (HR: 4.2, 95% CI: 1.5–11.8), anaemia (HR: 2.4, 95% CI: 1.4–4.1), and non-statins use before run-in period (HR: 0.52, 95% CI: 0.28–0.99). High-dose pitavastatin was not a correlate with HS. The multivariate analysis revealed anaemia might have a relation with HS (HR: 4.3, 95% CI: 0.90–20.6). The number of HS was the highest in the high CREDO-Kyoto bleeding score group (Figure 1, HR: 2.4, 95% CI: 1.3–4.6), whereas there was no significant difference in the number of HS between the moderate- and low-risk groups (HR: 1.4, 95% CI: 0.84–2.3). Conclusions High-dose pitavastatin was not associated with the incidence of HS in this large Japanese cohort with stable CAD. High CREDO-Kyoto bleeding score was associated with HS as compared with low or moderate scores, even each of the variables consisting of CREDO-Kyoto score was not associated with HS. Figure 1 Funding Acknowledgement Type of funding source: None

Abstract 2872: Interleukin-18/interleukin-10 Ratio is an Independent Predictor of Cardiovascular Events in Patients with Stable Coronary Artery Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paulo V Camargo ◽  
Raquel M Roman ◽  
Ana Paula W Rossini ◽  
Anderson Dedonelli ◽  
Steffan F Stella ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Inflammatory Cytokine ◽  
Stable Coronary Artery Disease ◽  
Vascular Event ◽  
Coronary Syndrome ◽  
Anti Inflammatory ◽  
Hs Crp ◽  
Artery Disease ◽  
Stable Cad

Background: The balance between pro-inflammatory cytokine IL-18 and anti-inflammatory cytokine IL-10 has been suggested to play a role in atherogenesis and in the prognosis of acute coronary syndrome (ACS). We hypothesized that stable coronary artery disease (CAD) patients have a pro-inflammatory profile prior to an acute event. Methods : A case-control study nested in a cohort of stable CAD patients was performed. Patients were consecutively included and blood samples collected at 3-months intervals. Cases were patients who presented any vascular event (death, ACS, ischemic stroke, peripheral arterial occlusion and revascularization) and controls were retrieved from a sequential list, in a 1:2 ratio, after 22 ± 9 months of follow-up. Serum hs-CRP, interleukin (IL)-10, IL-18 were measured in two serial samples, collected before the events. Results : Among 176 CAD patients, 42 developed a vascular event (cases) and 76 were selected to the control group. Serum levels of IL-18 were significantly higher among cases (411 ± 185 vs. 340 ± 133pg/ml; p = 0.037). Hs-CRP levels (5.4 vs. 5.1mg/l), IL-10 (7.4 vs. 7.2pg/ml), and IL-18/IL-10 ratio (66 vs. 61) were not different between cases and controls in both samples. Cox regression analysis showed that IL-18 levels (HR 1.75 (0.89 –3.5;p = 0.11) and IL-18/IL-10 ratio (HR 1.97; 1.0 –3.8) were predictors of worse prognosis (Figure ). Conclusion: In this study, IL-18 and IL-18/IL-10 ratio were associated with clinical outcomes and support the hypothesis that the balance between pro-inflammatory and anti-inflammatory cytokines may be an important determinant of vascular events in stable CAD patients.

P3645Prognosis in relation to high-sensitivity C-reactive protein levels in patients with non-obstructive coronary artery disease

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H W Zhang ◽  
Y X Cao ◽  
J L Jin ◽  
Y L Guo ◽  
Y Gao ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Obstructive Coronary Artery Disease ◽  
High Sensitivity ◽  
C Reactive Protein ◽  
Development Fund ◽  
Reactive Protein ◽  
Increased Risk ◽  
Hs Crp ◽  
Artery Disease

Abstract Background It has been reported that coronary artery disease (CAD) is characterized by inflammation and non-obstructive CAD (NOCAD) increases the risk of cardiovascular events (CVEs) compared with ones with normal or near-normal coronary arteries (NNCA), even is similar to obstructive CAD (OCAD). We hypothesized that elevated high-sensitivity C-reactive protein (hs-CRP) may be linked to CVEs in those patients with NOCAD. Purpose To investigate the predictive role of hs-CRP in patients with NOCAD. Methods Of 7,746 consecutive patients with angina-like chest pain admissions, 4,662 eligible patients were enrolled who received coronary artery angiography (CAG) and followed up for the CVEs comprising all-cause mortality, myocardial infarction, stroke and late revascularization. According to the results of CAG, the patients were classified as NNCA group (<20% stenosis, n=698, 15.0%), NOCAD group (20–49% stenosis, n=639, 14.3%), and OCAD group (≥50% stenosis, n=3325, 70.7%). They were further subdivided into 3 groups according to baseline hs-CRP levels (<1, 1–3 and >3 mg/L). Proportional hazards models were used to assess the risk of CVEs in all patients enrolled. Results A total of 338 patients (7.3%) experienced CVEs during an average of 13403 person-years follow-up. Patients with NOCAD and OCAD had higher rates of CVEs compared to those with NNCA (p<0.05, respectively). In Cox's models after adjustment of confounders, the risk of CVEs elevated with the increasing degrees of CAD with hazard ratio of 2.01 [95% confidence interval (95% CI): 1.07–3.79, p=0.03] for patients with NOCAD and 2.81 (95% CI: 1.60–4.93, p<0.001) for patients with OCAD compared with the NNCA group. Moreover, elevated hs-CRP levels were associated with the severity of coronary lesions and an elevated increased risk of CVEs in patients with NOCAD and OCAD compared those with NNCA (p<0.05, respectively). Conclusions Patients with NOCAD had indeed worse outcomes and hs-CRP levels were positively in relation to the CVEs in those with NOCAD, which may help to the risk assessment in ones with NOCAD. Acknowledgement/Funding This study was partly supported by Capital Health Development Fund (201614035) and CAMS Innovation Fund for Medical Sciences (2016-I2M-1-011) awarded

P5515Circulating galectin 1 is associated with severity of coronary artery disease and adverse cardiovascular events in patients undergoing coronary angiography

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
R.-H Chou ◽  
Y.-W Lu ◽  
P.-H Huang
Keyword(s):  
Heart Failure ◽  
Stable Angina ◽  
Cardiovascular Events ◽  
Ventricular Remodeling ◽  
Major Adverse Cardiovascular Events ◽  
Syntax Score ◽  
Cardiac Inflammation ◽  
Hs Crp ◽  
Artery Disease ◽  
Stable Cad

Abstract Background Galectin-1, a β-galactoside-binding lectin, was reported to attenuate the cardiac inflammation and ventricular remodeling after AMI. Its role in stable CAD was not fully elaborated. This study aimed to identify the relationship between galectin-1 and severity of CAD in patients with stable angina. Methods Totally 834 subjects underwent elective CAG were enrolled. Pre-procedure galectin-1 and hsCRP concentrations were determined. Subjects were grouped into tertiles according to their galectin-1 concentrations. SYNTAX scores were calculated to evaluate the severity of CAD. All patients were followed until January 2019, or the occurrence of major adverse cardiovascular events (MACE). Results Patients with higher galectin-1 concentrations were older and had higher prevalence of hypertension, diabetes, heart failure, and with higher levels of hsCRP and STNYAX scores. Patients with the highest tertile of galectin-1 were associated with higher risk of MACE (Fig 1A), even after adjusting age, gender, hypertension, diabetes, hemoglobin, creatinine, and LVEF (aHR: 2.13, 95% CI: 1.04–4.33, p=0.038). Gelection-1 (AUC: 0.802) showed better discriminatory performance than hsCRP (AUC: 0.696) in prediction the incidence of MACE (Fig 1B). Table 1 Tertile 1 (n=278) Tertile 2 (n=278) Tertile 3 (n=278) P Age (years) 61.0 (54.8–71.0) 67.0 (60.0–75.0) 72.0 (61.0–80.3) <0.001 Male, n (%) 188 (67.6) 184 (66.2) 197 (70.9) 0.479 Hypertension, n (%) 153 (55.0) 185 (66.5) 219 (78.8) <0.001 Diabetes, n (%) 67 (24.1) 90 (32.4) 123 (44.2) <0.001 Heart failure, n (%) 10 (3.6) 8 (2.9) 44 (15.8) <0.001 Hemoglobin (g/dL) 13.5 (12.5–14.3) 13.4 (12.4–14.3) 12.3 (10.8–13.7) <0.001 Creatinine (mg/dL) 0.9 (0.8–1.1) 1.0 (0.9–1.2) 1.3 (1.1–1.9) <0.001 Hs-CRP (mg/dL) 0.1 (0.0–0.2) 0.1 (0.0–0.3) 0.2 (0.1–0.7) <0.001 Galectin 1 (ng/mL) 13.3 (10.2–14.7) 18.7 (17.4–20.5) 29.3 (25.5–38.5) <0.001 SYNTAX score 0.0 (0.0–5.0) 0.0 (0.0–7.0) 7.0 (0.0–16.1) <0.001 LVEF (%) 59.0 (54.6–62.2) 58.0 (52.0–63.0) 55.9 (49.0–60.9) 0.009 MACE: revascularization, n (%) 17 (6.1) 13 (4.7) 43 (15.5) <0.001 MACE: nonfatal MI, n (%) 1 (0.4) 1 (0.4) 7 (2.5) 0.018 MACE: nonfatal stroke, n (%) 0 (0.0) 1 (0.4) 2 (0.7) 0.367 MACE: death, n (%) 4 (1.4) 1 (0.4) 13 (4.7) 0.001 Conclusion Serum galectin-1 levels were associated with the severity of CAD and subsequent MACE in patients with stable angina. Acknowledgement/Funding This study was supported in part by research grants from the Taipei Veterans General Hospital and Taiwan Ministry of Science and Technology Academic E

scholarly journals Free Thiol β2-GPI (β-2-Glycoprotein-I) Provides a Link Between Inflammation and Oxidative Stress in Atherosclerotic Coronary Artery Disease

2020 ◽  
Vol 40 (11) ◽  
pp. 2794-2804
Author(s):  
James C. Weaver ◽  
Inaam Ullah ◽  
Miao Qi ◽  
Bill Giannakopoulos ◽  
Kerry Anne Rye ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Stable Coronary Artery Disease ◽  
High Sensitivity ◽  
St Segment Elevation ◽  
Reactive Protein ◽  
Coronary Syndrome ◽  
Free Thiol ◽  
St Segment ◽  
Artery Disease

Objective: Atherosclerotic coronary artery disease is well recognised as an inflammatory disorder that is also influenced by oxidative stress. β2-GPI (β-2-glycoprotein-I) is a circulating plasma protein that undergoes post-translational modification and exists in free thiol as well as oxidized forms. The aim of this study was to assess the association between these 2 post-translational redox forms of β2-GPI and atherosclerotic coronary artery disease. Approach and Results: Stable patients presenting for elective coronary angiography or CT coronary angiography were prospectively recruited. A separate group of patients after reperfused ST-segment–elevation myocardial infarction formed an acute coronary syndrome subgroup. All patients had collection of fasting serum and plasma for quantification of total and free thiol β2-GPI. Coronary artery disease extent was quantified by the Syntax and Gensini scores. A total of 552 patients with stable disease and 44 with acute coronary syndrome were recruited. While total β2-GPI was not associated with stable coronary artery disease, a higher free thiol β2-GPI was associated with its presence and extent. This finding remained significant after correcting for confounding variables, and free thiol β2-GPI was a better predictor of stable coronary artery disease than hs-CRP (high-sensitivity C-reactive protein). Paradoxically, there were lower levels of free thiol β2-GPI after ST-segment–elevation myocardial infarction. Conclusions: Free thiol β2-GPI is a predictor of coronary artery disease presence and extent in stable patients. Free thiol β2-GPI was a better predictor than high-sensitivity C-reactive protein.

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