Serum and genetic markers related to rapid clinical progression of coronary artery disease

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; Enfermedad coronaria; Genetics; Genética; Inflamación; Inflammation; Lipids; Lípidos; Prevención secundaria; Secondary prevention.