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Vol. 76. Issue 12.
Pages 1013-1020 (December 2023)
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Vol. 76. Issue 12.
Pages 1013-1020 (December 2023)
Original article
Serum and genetic markers related to rapid clinical progression of coronary artery disease
Marcadores genéticos y séricos relacionados con una rápida progresión clínica de la arteriosclerosis coronaria
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Tamara García-Camareroa,
Corresponding author
tgcamarero@gmail.com

Corresponding author.
, Sara Remuzgo-Martínezb, Fernanda Genreb, Raquel López-Mejíasb, Verónica Pulito-Cuetob, Gabriela Veigaa, Dae-Hyun Lee Hwanga, Fermín Sáinz Lasoa, Aritz Gil Ongaya, Miguel Ángel González-Gayc,d, José M. de la Torre Hernándeza
a Departamento de Cardiología, Hospital Universitario Marqués de Valdecilla, Instituto de Investigación Valdecilla, Santander, Cantabria, Spain
b Instituto de Investigación Valdecilla, Santander, Cantabria, Spain
c Departamento de Medicina y Psiquiatría, Universidad de Cantabria, Santander, Cantabria, Spain
d Instituto de Investigación Sanitaria-Fundación Jiménez Díaz, Madrid, Spain
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Tables (3)
Table 1. Demographic characteristics, risk factor profile, clinical presentation and extent of coronary artery disease at first event in all patients
Table 2. Serum levels of markers of inflammation/atherosclerosis and laboratory analytes in patients during a stable disease phase
Table 3. Findings of the molecules analyzed at the molecular 3 levels when comparing RCP vs LSS patients
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Abstract
Introduction and objectives

Patients with clinically evident coronary artery disease differ in their rate of progression, which impacts prognosis. We aimed to characterize serum and genetic markers in patients with rapid clinical progression (RCP) of coronary artery disease vs those with long standing stable (LSS) disease.

Methods

Retrospective study of cases (RCP) and controls (LSS) (1:2). Patients requiring ≥ 2 revascularizations due to atherosclerotic progression in the 10 years after a first angioplasty were considered to be RCP and those without events during the same period after the first angioplasty were considered to have LSS disease. After patient selection, we analyzed serum values, mRNA expression and genetic polymorphisms of inflammatory markers, including interleukin-6, C-reactive protein, and tumor necrosis factor (TNF)-a, and atherogenic markers consisted of proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein receptor, sterol regulatory element binding transcription factor 2, and apolipoprotein-B.

Results

The study included 180 patients (58 RCP and 122 LSS). Demographic characteristics, classic risk factors and the extent of coronary disease were similar in the 2 groups. Patients with RCP showed higher serum levels of interleukin-6 and PCSK9 and higher TNF mRNA expression. Interleukin-6 rs180075C, TNF rs3093664 non-G and PCSK9 rs2483205 T alleles conferred a risk of RCP (P<.05 in all cases). Among patients with RCP, 51.7% had all 3 risk alleles vs 18% of those with LSS (P<.001).

Conclusions

We suggest the existence of specific phenotypic and genotypic markers associated with RCP of coronary artery disease that could help to individualize the type and intensity of treatment.

Keywords:
Coronary artery disease
Inflammation
Lipids
Secondary prevention
Genetics
Abbreviations:
LSS
PCI
PCSK9
RCP
SNP
TNF
Resumen
Introducción y objetivos

La progresión de la enfermedad coronaria una vez se hace evidente a la clínica tiene una gran variabilidad interindividual. El objetivo es determinar marcadores séricos y genéticos en pacientes con rápida progresión clínica (RPC) de la enfermedad coronaria frente a pacientes con estabilidad clínica mantenida (ECM).

Métodos

Estudio retrospectivo de casos (RPC) y controles (ECM) (1:2). Se consideró RPC a los pacientes que precisaron al menos 2 revascularizaciones por progresión de la ateroesclerosis en los 10 años posteriores a una primera angioplastia y ECM a aquellos sin eventos durante el mismo periodo tras la primera angioplastia. Una vez seleccionados, se determinaron los valores séricos, la expresión de ácido ribonucleico mensajero (ARNm) y polimorfismos genéticos de interleucina 6, proteína C reactiva y factor de necrosis tumoral alfa (TNFα) como marcadores de inflamación y proproteína convertasa subtilisina/kexina tipo 9 (PCSK9), receptor de lipoproteínas de baja densidad, proteína 2 de unión a elementos reguladores de esteroles y apolipoproteína B como marcadores aterogénicos.

Resultados

Se incluyó a 180 pacientes (58 en RPC y 122 en ECM). Las características basales demográficas, del perfil de riesgo clásico y de la extensión de la enfermedad coronaria fueron comparables. El grupo de RPC presentó valores séricos más altos de interleucina 6 y PCSK9 y mayor expresión de ARNm de TNF. Los alelos de Interleucina-6 rs180075C, de TNF rs3093664 non-G y de PCSK9 rs2483205 T confieren riesgo de RPC (p<0,05 en todos los casos). Un 51,7% de los pacientes del grupo RPC presentaron los tres alelos de riesgo frente al 18% de los pacientes del grupo en ECM (p<0,001).

Conclusiones

Se propone la existencia de marcadores genotípicos y fenotípicos asociados con la RPC de enfermedad coronaria y que podrían servir para individualizar la intensidad y el tipo de tratamiento.

Palabras clave:
Enfermedad coronaria
Inflamación
Lípidos
Prevención secundaria
Genética

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