Plasma proprotein‐convertase‐subtilisin/kexin type 9 (PCSK9) and cardiovascular events in type 2 diabetes

Khoury, Petra El; Roussel, Ronan; Fumeron, Frédéric; Abou-Khalil, Yara; Mohammedi, Kamel; Jacob, Marie‐Paule; Steg, Philippe Gabríel; Potier, Louis; Ghaleb, Youmna; Elbitar, Sandy; Ragot, Stéphanie; Andreata, Francesco; Caligiuri, Giuseppina; Hadjadj, Samy; Boileau, Cathérine; Marre, Michel; Abifadel, Marianne; Varret, Mathilde; Hansel, Boris

doi:10.1111/dom.13181

Cited by 17 publications

(27 citation statements)

References 59 publications

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“…In contrast, a prospective cohort study of primary prevention included 716 initially healthy American women and displayed that the baseline plasma levels of PCSK9 cannot predict future cardiovascular events [32]. Moreover, the SURDI-AGENE study found a similar result in DM population [33]. Hence, whether PCSK9 can be a novel predictor of prognosis and its correlation with metabolic factors need more investigations, especially in CAD patients with or without DM.…”

Section: Discussionmentioning

confidence: 99%

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Jia

Liu

Jin

et al. 2020

Cardiovasc Diabetol

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Background Whether plasma proprotein convertase subtilisin/kexin type 9 (PCSK9) levels is a predictor for cardiovascular outcomes has currently been controversial. No data is currently available regarding the relation of PCSK9 to cardiovascular metabolic markers (CVMMs) and major adverse cardiovascular events (MACEs) in stable coronary artery disease (CAD) patients with diabetes or without diabetes. Methods A total 1225 untreated patients with stable CAD were consecutively enrolled and their baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients followed up for the occurrence of MACEs and received standard therapy after admission. The associations of PCSK9 with CVMMs and MACEs were evaluated. Results PCSK9 levels were positively correlated with multiple CVMMs including total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol and hemoglobin A1c at baseline (all p < 0.05). During a median follow-up of 3.3 years, 103 (8.4%) events occurred. PCSK9 levels were higher in patients with events compared to those without (p < 0.05). The Kaplan–Meier analysis displayed that patients in high PCSK9 group had lower event-free survival than that in low group (p < 0.05). Multivariable Cox regression analysis revealed that PCSK9 levels were independently associated with MACEs in diabetic patients (adjusted hazard ratio [HR]: 1.361, 95% confidence interval [CI]: 1.037–1.785, p < 0.05). When added the combination of PCSK9 levels and diabetic status to stratifying factors, patients in high PCSK9 group appeared to have extremely high risk of subsequent MACEs with diabetes (adjusted HR: 5.233, 95% CI: 2.546–10.757, p < 0.01). Conclusions The present study firstly showed that elevated PCSK9 levels were related to multiple CVMMs and MACEs in stable CAD with diabetes, suggesting that plasma PCSK9 measurement could help to identify diabetic patients with CAD at higher cardiovascular risk. More studies may be needed to confirm our findings.

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Section: Discussionmentioning

confidence: 99%

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Jia

Liu

Jin

et al. 2020

Cardiovasc Diabetol

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show abstract

“…However, there were significantly more cases of diabetes mellitus, myocardial infarction, stroke and percutaneous coronary intervention among the patients of group I, compared to group II, which in some cases could be accompanied by a higher level of PCSK9. The correlation between an increase in the level of circulating PCSK9 and the risk of a MACE had been shown in a number of recent studies [21, 22]. In particular, PCSK9 level was associated with insulin levels and HOMA-IR index in patients with stable CAD on statin treatment [7].…”

Section: Discussionmentioning

confidence: 99%

Can metformin stabilize PCSK9 level in stable coronary artery disease patients treated with statins?

Shek

Alieva

Kurbanov

et al. 2019

Arch Med Sci Atheroscler Dis

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Introduction Proprotein convertase subtilisin/kexin type 9 (PCSK9) has emerged as an important marker of cardiovascular risk and a new target for therapeutic interventions. We aimed to study the influence of metformin on the level of circulating PCSK9 in patients with stable coronary artery disease (SCAD) and type 2 diabetes (T2DM) or metabolic syndrome (MetS), receiving moderate doses of statins used in routine clinical practice. Material and methods The study included 80 patients with T2DM or MetS receiving rosuvastatin for at least three months prior the study. MetS was diagnosed based on the Global Consensus Definition of the International Diabetes Federation (IDF). Serum level of PCSK9 was measured with an ELISA kit. Results Patients with T2DM or MetS, who took part in the research, were divided into 2 groups – those who received metformin prior the main study (21 patients – 1 st group) and patients who did not (59 patients – 2 nd group). Addition of metformin to the 3-month statin therapy of the 2nd group patients, divided into subgroup A ( n = 27) with the addition of metformin and subgroup B ( n = 29) without one, did not significantly affect the level of lipids. However, the level of circulating PCSK9 in subgroup A patients decreased, compared to subgroup B ( p < 0.01). At the same time, ongoing metformin and rosuvastatin therapy in the 1 st group patients was not accompanied by a further decrease of the PCSK9 level. Conclusions The addition of metformin to ongoing rosuvastatin therapy did not significantly affect serum lipid levels, but stabilized the level of circulating PCSK9, compared with the group without metformin treatment.

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“…76 Additionally, in diabetic patients with pathological albuminuria enrolled in the large DIABHYCAR study, plasma PCSK9 tertiles were associated with the incidence of cardiovascular events. 77 Although this was not replicated in the smaller SURDIAGENE cohort that enrolled patients with milder albuminuria, 77 Since the publication of our work where we presented a previously described variant in the PRKG1 gene as a cause of nonsyndromic familial aortic disease (NSAD), 81 no new work describing causal variants in this gene has been published. However, the application of the subsequent published guidelines of the American College of Medical Genetics and Genomics-Association for Molecular Pathology (ACMG-AMP) for the interpretation of genetic variants 82 reinforces the variant classification as pathogenic and therefore the consideration of the PRKG1 gene as a strong candidate gene for gen-based diagnosis of NSAD.…”

Section: Pcsk9 In Diabetic Kidney Disease 7 5 (Beatriz Fernandez-fementioning

confidence: 93%

“…76 Additionally, in diabetic patients with pathological albuminuria enrolled in the large DIABHYCAR study, plasma PCSK9 tertiles were associated with the incidence of cardiovascular events. 77 Although this was not replicated in the smaller SURDIAGENE cohort that enrolled patients with milder albuminuria, 77 the potential for serum PCSK9 to stratify patients who may benefit from PCSK9 inhibitors should be further explored. In this regard, in post hoc analyses of RCTs, PCSK9 inhibitors reduced cardiovascular events and LDL-cholesterol in diabetic patients 78,79 and phase 3 trials have been designed to specifically evaluate the lipid-lowering efficacy and safety of PCSK9 inhibitors in patients with type 2 diabetes mellitus and dyslipidemia.…”

Section: Pcsk9 In Diabetic Kidney Disease 7 5 (Beatriz Fernandez-fementioning

confidence: 99%

Research update for articles published in EJCI in 2016

Adlbrecht

Blanco-Verea

Bouzas-Mosquera

et al. 2018

Eur J Clin Investigation

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Plasma proprotein‐convertase‐subtilisin/kexin type 9 (PCSK9) and cardiovascular events in type 2 diabetes

Abstract: We found that PCSK9 was inconsistently associated with CV events in populations with type 2 diabetes. The association may depend on the level of CV risk and the background treatment.

Cited by 17 publications

References 59 publications

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Association of circulating PCSK9 concentration with cardiovascular metabolic markers and outcomes in stable coronary artery disease patients with or without diabetes: a prospective, observational cohort study

Can metformin stabilize PCSK9 level in stable coronary artery disease patients treated with statins?

Research update for articles published in EJCI in 2016

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