Dataset Information

Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy.

ABSTRACT:

Background

Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy.

Methods

A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score???6) was enrolled and followed up for the occurrence of MACEs. Multidetector CT and coronary angiography were performed to determine coronary artery calcification score (CACS) and Gensini score (GS). Multivariable Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs). Plasma PCSK9 concentrations were determined by enzyme immunoassay.

Results

PCSK9 was independently and positively associated CACS and GS at baseline. During a mean follow-up of 3 years, 33 (9.8%) events occurred. Patients with MACEs had higher median PCSK9 compared with those without (332.47 vs. 311.89 ng/mL, p?=?0.038). Kaplan-Meier analysis revealed that patients with higher PCSK9 presented lower event-free survival (p?=?0.0017). PCSK9 was statistically correlated with MACEs after adjusting for confounding factors, with the HR per SD being 1.86 (1.31-2.65) and 3.70 (1.16-11.82) for the highest tertile compared with the lowest tertile. Adding PCSK9 to Cox prediction model led to a statistical improvement in net reclassification and integrated discrimination.

Conclusion

Elevated levels of PCSK9 were positively associated with the development of CAD and future cardiovascular events, suggesting that measurement of PCSK9 concentration might be useful for cardiovascular risk stratification. Further studies are needed to confirm our results.

SUBMITTER: Cao YX

PROVIDER: S-EPMC6849213 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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Publications

Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy.

Cao Ye-Xuan YX Jin Jing-Lu JL Sun Di D Liu Hui-Hui HH Guo Yuan-Lin YL Wu Na-Qiong NQ Xu Rui-Xia RX Zhu Cheng-Gang CG Dong Qian Q Sun Jing J Li Jian-Jun JJ

Journal of translational medicine 20191111 1

<h4>Background</h4>Proprotein convertase subtilisin/kexin 9 (PCSK9) has been proposed as a novel target for coronary artery disease (CAD). Familial hypercholesterolemia (FH) is characterized by high prevalence of CAD and major cardiovascular events (MACEs). However, no data is available on the association between PCSK9 levels and MACEs in FH patients with standard lipid lowering therapy.<h4>Methods</h4>A total of 338 consecutive heterozygous FH (Dutch Lipid Clinic Network score ≥ 6) was enrolled ...[more]

PMID: 31711505

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Project description:IntroductionConventional lipid-lowering agents, including statins, ezetimibe, fibrates, bile acid sequestrants, nicotinic acid, bempedoic acid and Omega-3, are essential to the management of dyslipidaemia. However, these agents have been shown to increase the level of plasma proprotein convertase subtilisin/kexin 9 (PCSK9), a serine protease associated with increased cardiovascular risk. This review aims to investigate the impact of commonly available conventional lipid-lowering agents on circulating PCSK9 levels and lipid profiles.Methods and analysisThis protocol is conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines. A systematic search will be conducted in the following databases: MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, Web of Science, SCOPUS and ScienceDirect. Additional information will be retrieved from clinical trial registries or from reference list searches. Published and peer-reviewed randomised controlled trials with adults receiving statin, ezetimibe, fibrate, bile acid sequestrant, nicotinic acid, bempedoic acid or Omega-3 monotherapy or in combination for at least 2 weeks, with availability of plasma PCSK9 at the beginning and end of treatment or the net changes in values, will be included. Study selection, data extraction and assessment of the risk of bias will be independently conducted by two investigators. Continuous data will be presented as a standardised mean difference with 95% confidence interval (CI) and dichotomous data as risk ratios with 95% CI. Subgroup analysis and sensitivity analysis will be performed when sufficient studies are included. Publication bias will be assessed with a funnel plot and Egger's test.Ethics and disseminationEthics approval is not required as this review will only include data from published sources. The results will be published in a peer-reviewed journal.Patient and public involvementNo patient or members of the general public are involved.Prospero registration numberCRD42022297942.

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Dataset Information

Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy.

Background

Methods

Results

Conclusion

Publications

Circulating PCSK9 and cardiovascular events in FH patients with standard lipid-lowering therapy.

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