Prognostic value of PCSK9 levels in patients with acute coronary syndromes

Gencer, Baran; Montecucco, Fabrizio; Nanchen, David; Carbone, Federico; Klingenberg, Roland; Vuilleumier, Nicolas; Aghlmandi, Soheila; Heg, Dik; Räber, Lorenz; Auer, Reto; Jüni, Peter; Windecker, Stephan; Lüscher, Thomas F.; Matter, Christian M.; Rodondi, Nicolas; Mach, François

doi:10.1093/eurheartj/ehv637

Cited by 133 publications

(125 citation statements)

References 31 publications

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“…Differences in PCSK9 levels during acute and stable periods have been reported [16], but few studies have focused on patients with AMI and the predictive value of the acute-phase plasma PCSK9 level for risk of recurrent CV events. One study assessed the association between PCSK9 and recurrent CV events in patients with ACS who presented within 5 days of pain onset [9]. Our study, however, was restricted to patients with AMI who provided samples within 24 h of symptom onset, which allowed us to assess associations between PCSK9 level during the acute phase and clinical outcomes.…”

Section: Discussionmentioning

confidence: 99%

“…To date, few prospective studies [9-11] have considered the predictive value of plasma PCSK9 level for future CV events in patients with CVD, and these studies have produced inconsistent results. Two studies reported that circulating PCSK9 concentration predicted recurrent CV events in patients with stable coronary artery disease [10, 11].…”

Section: Discussionmentioning

confidence: 99%

“…However, in one of these studies, the effect was nonsignificant after adjusting for triglycerides [10]. In addition, the only study of the predictive role of PCSK9 in patients with ACS indicated that high initial plasma PCSK9 did not predict mortality at 1 year [9]. A meta-analysis of 8 cohort studies found that higher PCSK9 was modestly but significantly associated with increased risk of total CV events.…”

Section: Discussionmentioning

confidence: 99%

“…One study assessed the predictive value of PCSK9 in patients with acute coronary syndrome (ACS) [9], and other studies have examined the predictive value of PCSK9 in patients with stable coronary artery disease [10, 11]. The upregulation of PCSK9 at the initiation of lipid-lowering therapy has been suggested as a potential mechanism leading to statin resistance [12].…”

Section: Introductionmentioning

confidence: 99%

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Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Gao

Qiu²,

Wu³

et al. 2018

Cardiology

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Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising target for lowering plasma low-density lipoprotein cholesterol and preventing cardiovascular (CV) disease. Whether plasma PCSK9 measured during the acute phase predicts recurrent CV events in patients with acute myocardial infarction (AMI) remains unresolved. Methods and Results: Plasma PCSK9 levels were measured in 1,646 patients with AMI from the China PEACE-Prospective AMI Study at the acute phase. Additionally, 248 patients were resampled and measured at 1 month post-AMI. Associations of acute-phase PCSK9 tertiles with clinical characteristics and recurrent CV events within 1 year were assessed. Female gender (OR 1.94, 95% CI 1.24–3.03), premature coronary heart disease (CHD; OR 2.12, 95% CI 1.37–3.26), higher high-sensitivity C-reactive protein (OR 1.67, 95% CI 1.44–1.95), and higher triglycerides (OR 1.46, 95% CI 1.03–2.09) were associated with higher baseline PCSK9. Plasma PCSK9 levels in the highest tertile (versus lowest) did not have an increased risk of 1-year recurrent CV events in the AMI cohort (HR 0.78, 95% CI 0.52–1.16) or any subgroup. There was also no association between percentage changes in PCSK9 over the first month and 1-year recurrent events, although there was a trend of differences between patients in the upper versus lower tertiles. Conclusion: Plasma PCSK9 levels measured during the acute phase were associated with high-sensitivity C-reactive protein, triglycerides, premature CHD, and gender in patients with AMI but did not predict recurrent CV events within 1 year. Dynamic changes in PCSK9 suggested a trend yet no significance value in predicting recurrent CV events.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Gao

Qiu²,

Wu³

et al. 2018

Cardiology

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“…22 Mean PCSK9 in these 6 studies was 303 ng/mL and ranged from 94.3 to 546.5 ng/mL. Of the 7 studies included, only 1 reported all-cause mortality, 23 and the other studies reported CVD events including similar CVD outcomes. None of the 7 studies, however, reported associations between PCSK9 and the risk of discrete CVD events (e.g., cardiovascular mortality, myocardial infarction, stroke, or heart failure).…”

Section: Data Extraction and Quality Assessmentmentioning

confidence: 99%

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration and Risk of Cardiovascular Events　― Systematic Review and Meta-Analysis of Prospective Studies ―

Xiao

Peng

Huang

et al. 2017

Circ J

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Background: Previous studies have not found a consistent association between circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) and the risk of cardiovascular events. The aim of this meta-analysis was to evaluate this association in prospective studies. Methods and Results:A systematic search of prospective studies published through October 2016 was carried out in order to identify studies that met pre-specified inclusion criteria. After independent data extraction, summary relative risks were calculated using random-effects models. On meta-analysis of 6 cohort and 1 nested case-control study, circulating PCSK9 concentration as a continuous variable was not significantly associated with the risk of cardiovascular events (overall RR, 1.12; 95% CI: 0.98-1.29; P=0.09), with significant heterogeneity (I 2 =55.1%, Pheterogeneity=0.038). The highest but not middle categories of circulating PCSK9 was significantly associated with the risk of cardiovascular events. On subgroup analysis of study design, mean age at baseline, sample size, follow-up time, and pre-existing disease, there was no significant association between PCSK9 and cardiovascular events. Sensitivity analysis with various exclusion and inclusion criteria did not materially change the results. Conclusions:Circulating PCSK9 concentration as a continuous variable was not significantly associated with the risk of cardiovascular events. More well-designed studies are needed to clarify the role of PCSK9 in cardiovascular risk.

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Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography

Stähli

Wischnewsky

Jakob

et al. 2018

Cathet Cardio Intervent

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Objectives The number of elderly patients undergoing coronary revascularization is steadily increasing, and data on the impact of gender on outcomes are scarce. This study sought to assess gender‐related differences in outcomes in elderly patients with acute coronary syndromes (ACS). Methods We investigated outcomes in elderly ACS patients referred for coronary angiography and prospectively enrolled in the Swiss ACS Cohort between December 2009 and October 2012. Adjudicated major adverse cardiovascular and cerebrovascular events (MACCE) included all‐cause death, non‐fatal myocardial infarction, clinically indicated repeat coronary revascularization, definite stent thrombosis, and transient ischemic attack/stroke. Results Among 2,168 patients recruited, 481 (22%) patients were >75 years of age (37% women). In patients >75 years, 1‐year MACCE rates were 15% and 23% in women and men (OR 0.59, 95% CI 0.36–0.97, P = 0.04), respectively, and differences remained significant after adjustments for baseline variables (adjusted OR 0.48, 95% CI 0.26–0.90, P = 0.02). Women >75 years had a lower cardiovascular mortality (6% versus 12%, adjusted OR 0.31, 95% CI 0.12–0.81, P = 0.02). In patients ≤75 years, 1‐year MACCE rates did not differ between gender (10% and 8% for women and men, adjusted OR 1.28, 95% CI 0.77–2.14, P = 0.34). Rates of TIMI major bleeding for women and men were 4% and 4% in patients >75 years (P = 0.96), and 5% and 3% in those ≤75 years (P = 0.11). Conclusions The low rates of MACCE observed in elderly women in this patient cohort suggest that with current interventional strategies the gender gap in ACS management has been attenuated.

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Prognostic value of PCSK9 levels in patients with acute coronary syndromes

Abstract: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Cited by 133 publications

References 31 publications

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration and Risk of Cardiovascular Events　― Systematic Review and Meta-Analysis of Prospective Studies ―

Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography

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Prognostic value of PCSK9 levels in patients with acute coronary syndromes

Abstract: In ACS patients, high initial PCSK9 plasma levels were associated with inflammation in the acute phase and hypercholesterolaemia, but did not predict mortality at 1 year.

Cited by 133 publications

References 31 publications

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Acute-Phase Plasma PCSK9 Levels and Recurrent Cardiovascular Events in a Chinese Acute Myocardial Infarction Cohort

Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration and Risk of Cardiovascular Events ― Systematic Review and Meta-Analysis of Prospective Studies ―

Gender and age differences in outcomes of patients with acute coronary syndromes referred for coronary angiography

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Circulating Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) Concentration and Risk of Cardiovascular Events　― Systematic Review and Meta-Analysis of Prospective Studies ―