Relation of Proprotein Convertase Subtilisin/Kexin Type 9 to Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Choi, Ik Jun; Lim, Soo Min; Lee, Dongjae; Lee, Won Jik; Lee, Kwan Yong; Kim, Mi-Jeong; Jeon, Doo Soo

doi:10.1016/j.amjcard.2020.07.032

Cited by 6 publications

(9 citation statements)

References 29 publications

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“…Recently, a positive association of PCSK9 levels with adverse cardiovascular events has been observed in general population, in patients with familial hypercholesterolemia, in stable CAD, in atrial fibrillation, and in those undergoing PCI [ 6 , 14 – 17 ]. However, the prognostic value of PCSK9 for the risk of MACEs in ACS and/or DM patients remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

“…Our data showed that PCSK9 levels were not correlated with LDL-C and total cholesterol levels despite the lack of prior lipid-lowering therapy. Indeed, associations of PCSK9 levels with lipid metabolism-related parameters are inconsistent in different cardiovascular risk populations [ 6 , 9 , 11 , 17 , 18 , 25 ]. Further, previous studies suggested that plasma PCSK9 levels were elevated at the acute phase of MI and were uncoupled from LDL-C levels which fell transiently following MI [ 20 , 26 , 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…The involvement of PCSK9 in systemic or vascular inflammation has been demonstrated by experimental studies [ 32 – 34 ]. Furthermore, clinical studies have also found a positive association between PCSK9 and hs-CRP levels [ 6 , 7 , 9 , 17 ]. DM itself is associated with chronic low-level inflammation, so the association between PCSK9 and inflammation markers in DM may be different from non-DM populations.…”

Section: Discussionmentioning

confidence: 99%

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Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Song

Zhao

Chen

et al. 2022

Cardiovasc Diabetol

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Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers. Methods A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated. Results PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan–Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094–4.764, P = 0.028), but not in the whole cohort or non-diabetic patients. Conclusions The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Song

Zhao

Chen

et al. 2022

Cardiovasc Diabetol

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“…Of the 11 studies included, only 1 ( 22 ) was a retrospective cohort study and the others were prospective cohort studies, with a publication period from 2014 to 2020. Four trials ( 20 , 22 , 27 , 28 ) reported RRs according to continuous concentrations of PCSK9, three studies ( 19 , 24 , 26 ) reported RRs according to categorical levels, and four studies ( 8 , 21 , 23 , 28 ) reported RRs according to both continuous and categorical levels. We included 8,471 patients, and the sample size of each study ranged from 249 to 2,030.…”

Section: Resultsmentioning

confidence: 99%

“…Table 1 shows the characteristics of the included studies (8,9,(19)(20)(21)(22)(23)(24)(26)(27)(28). Of the 11 studies included, only 1 ( 22) was a retrospective cohort study and the others were prospective cohort studies, with a publication period from 2014 to 2020.…”

Section: Study Selection and Patient Populationmentioning

confidence: 99%

Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis

Liu

Fan

Luo

et al. 2021

Front. Cardiovasc. Med.

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Background: A large amount of evidence suggests that proprotein convertase subtilisin/Kexin type 9 (PCSK9) inhibitors have clinical benefits in patients with cardiovascular disease (CVD). However, whether PCSK9 concentrations predict future cardiovascular (CV) events remains unclear.Methods: We conducted a meta-analysis to investigate the ability of PCSK9 concentrations to predict future CV events in patients with established CVD. A comprehensive search of electronic databases was conducted in June 2021. We included relative risk (RR) estimates with 95% CI or events of interest.Results: Eleven cohort studies including 8,471 patients with CVD were enrolled. The pooled RR of CV events for the increase in the circulating baseline PCSK9 concentrations by 1 SD showed a positive association in a random-effect model (RR 1.226, 95% CI: 1.055–1.423, P = 0.008). Similarly, the risk of the total CV events increased by 52% in the patients in the highest tertile compared with those in the lowest tertile of circulating PCSK9 concentrations (RR 1.523, 95% CI: 1.098–2.112, P = 0.012). The association between PCSK9 and CV events was stronger in stable patients with CVD, patients treated with statins, and Asian patients.Conclusions: High PCSK9 concentrations are significantly related to the increased risk of future CV events. These results enrich the knowledge of PCSK9 function and suggest the further possible clinical role of PCSK9 inhibitors.

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Circulating PCSK9 as a prognostic biomarker of cardiovascular events in individuals with type 2 diabetes: evidence from a 16.8-year follow-up study

Ruscica,

Macchi,

Giuliani

et al. 2023

Cardiovasc Diabetol

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Background Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of morbidity and mortality, being twofold to fourfold more common in patients with type 2 diabetes mellitus (T2DM) than in individuals without diabetes. However, despite this decade-old knowledge, the identification of a specific prognostic risk biomarker remains particularly challenging. Methods Taking advantage of a large sample of Caucasian patients (n = 529) with a diagnosis of T2DM followed for a median of 16.8 years, the present study was aimed at testing the hypothesis that fasting serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels could be prognostic for major adverse cardiovascular events (MACE) and all-cause mortality. Results Median levels of PCSK9 were 259.8 ng/mL, being higher in women compared to men and increasing even more in the presence of a complication (e.g., diabetic kidney disease). PCSK9 positively correlated with markers of blood glucose homeostasis (e.g., HbA1c, fasting insulin and HOMA-IR) and the atherogenic lipid profile (e.g., non-HDL-C, apoB and remnant cholesterol). Serum PCSK9 predicted new-onset of MACE, either fatal or non-fatal, only in women (Odds Ratio: 2.26, 95% CI 1.12–4.58) and all-cause mortality only in men (Hazard Ratio: 1.79, 95% CI 1.13–2.82). Conclusions Considering that up to two-thirds of individuals with T2DM develop ASCVD in their lifetime, the assessment of circulating PCSK9 levels can be envisioned within the context of a biomarker-based strategy of risk stratification. However, the sex difference found highlights an urgent need to develop sex-specific risk assessment strategies. Trial registration: It is a retrospective study.

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Relation of Proprotein Convertase Subtilisin/Kexin Type 9 to Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Cited by 6 publications

References 29 publications

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Association Between Circulating Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations and Cardiovascular Events in Cardiovascular Disease: A Systemic Review and Meta-Analysis

Circulating PCSK9 as a prognostic biomarker of cardiovascular events in individuals with type 2 diabetes: evidence from a 16.8-year follow-up study

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