Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Observational Study
. 2019 Oct 31;18(1):144.
doi: 10.1186/s12933-019-0949-3.

Association of PCSK9 plasma levels with metabolic patterns and coronary atherosclerosis in patients with stable angina

Chiara Caselli  1 , Serena Del Turco  2 , Rosetta Ragusa  2 , Valentina Lorenzoni  3 , Michiel De Graaf  4 , Giuseppina Basta  2 , Arthur Scholte  4 , Raffaele De Caterina  5 , Danilo Neglia  6
Affiliations
Observational Study

Association of PCSK9 plasma levels with metabolic patterns and coronary atherosclerosis in patients with stable angina

Chiara Caselli et al. Cardiovasc Diabetol. .

Abstract

Objective: Aim of this study was to evaluate the relationship of plasma PCSK9 with metabolic and inflammatory profile and coronary atherosclerotic burden in patients with suspected CAD enrolled in the EVINCI study.

Methods: PCSK9 was measured in 539 patients (60.3 ± 8.6 years, 256 males) with symptoms of CAD characterized by risk factors, bio-humoral profiles, and treatment. N = 412 patients underwent coronary computed tomography angiography (CTA) to assess the presence and characteristics of coronary atherosclerosis. A CTA score, combining extent, severity, composition, and location of plaques was computed.

Results: Patients were divided according to PCSK9 quartiles: I (< 136 ng/mL), II-III (136-266 ng/mL), and IV quartile (> 266 ng/mL). Compared with patients in quartile IV, patients in quartile I had a higher prevalence of the metabolic syndrome and higher values of body mass index. LDL- and HDL-cholesterol were significantly lower in patients in the quartile I than in those in quartile IV. Coronary CTA documented normal vessels in 30% and obstructive CAD in 35% of cases without differences among PCSK9 quartiles. Compared with patients with the highest levels, patients with the lowest PCSK9 levels had a higher CTA score mainly due to higher number of mixed non-obstructive coronary plaques. At multivariable analysis including clinical, medications, and lipid variables, PCSK9 was an independent predictor of the CTA score (coefficient - 0.129, SE 0.03, P < 0.0001), together with age, male gender, statins, interleukin-6, and leptin.

Conclusion: In patients with stable CAD, low PCSK9 plasma levels are associated with a particular metabolic phenotype (low HDL cholesterol, the metabolic syndrome, obesity, insulin resistance and diabetes) and diffuse non-obstructive coronary atherosclerosis. Trial registration ClinicalTrials.gov NCT00979199. Registered September 17, 2009.

Keywords: Coronary atherosclerosis; Metabolic syndrome; PCSK9; Stable angina.

PubMed Disclaimer

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow diagram. After exclusions, 539 subjects had a completed clinical profile and available blood samples for PCSK9 testing. In this clinical sample, 412 patients had available CTA
Fig. 2
Fig. 2
PCSK9 plasma levels in patients subdivided according to the presence of metabolic syndrome or diabetes, and according to BMI and HDL cholesterol classes
Fig. 3
Fig. 3
Relationship between circulating levels of PCSK9 and LDL cholesterol in patients with/without the metabolic syndrome, diabetes, obesity, and low HDL cholesterol
Fig. 4
Fig. 4
Effects of statin use on the relationships between PCSK9 and LDL and HDL cholesterol
Fig. 5
Fig. 5
PCSK9 plasma levels according to CTA score categories
See this image and copyright information in PMC

References

    1. Roth GA, Johnson C, Abajobir A, et al. Global, regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70(1):1–25. doi: 10.1016/j.jacc.2017.04.052. - DOI - PMC - PubMed
    1. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, Kirby A, Sourjina T, Peto R, Collins R, Simes R, Cholesterol Treatment Trialists’ (CTT) Collaborators Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005;366(9493):1267–1278. doi: 10.1016/S0140-6736(05)67394-1. - DOI - PubMed
    1. Shimada YJ, Cannon CP. PCSK9 (Proprotein convertase subtilisin/kexin type 9) inhibitors: past, present, and the future. Eur Heart J. 2015;36(36):2415–2424. doi: 10.1093/eurheartj/ehv174. - DOI - PubMed
    1. Allard D, Amsellem S, Abifadel M, Trillard M, Devillers M, Luc G, Krempf M, Reznik Y, Girardet JP, Fredenrich A, Junien C, Varret M, Boileau C, Benlian P, Rabès JP. Novel mutations of the PCSK9 gene cause variable phenotype of autosomal dominant hypercholesterolemia. Hum Mutat. 2005;26(5):497. doi: 10.1002/humu.9383. - DOI - PubMed
    1. Cohen JC, Boerwinkle E, Mosley TH, Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006;354(12):1264–1272. doi: 10.1056/NEJMoa054013. - DOI - PubMed

Publication types

MeSH terms

Associated data