Assessment of N/L ratio and subclinical atherosclerosis in FH subjects with or without LDLR mutation
Francesco Barbagallo, Giosiana Bosco, Maurizio Di Marco, Sabrina Scilletta, Nicoletta Miano, Marina Martedì, Ivan Privitera, M. Papa, Chiara Piazza, Francesca Valenza, Giovanni Pennisi, Ernestina Marianna De Francesco, Roberta Malaguarnera, Antonino Di Pino, Salvatore Piro, Roberto Scicali
Abstract
Abstract Background Familial hypercholesterolemia (FH) is a genetic disorder characterized by elevated low-density lipoprotein-cholesterol (LDL-C) and increased cardiovascular risk. While the role of LDL-C in atherogenesis is well established, the contribution of inflammatory activation in FH, particularly in relation to genotype, remains poorly defined. We aimed to evaluate the impact of genotype on neutrophil-to-lymphocyte ratio (NLR) and on subclinical atherosclerosis in a cohort of FH subjects. Methods We conducted a cross-sectional study on 423 FH subjects not on lipid-lowering therapy and free from atherosclerotic cardiovascular disease. Biochemical, genetic, and vascular assessments were performed in all participants. The population was divided into 2 groups based on genotype: low-density lipoprotein receptor (LDLR; n = 273) and non-LDLR (NLDLR, n = 150). Vascular profile was assessed by coronary artery calcium score and carotid/femoral plaque presence. NLR was calculated from peripheral blood counts. Results The LDLR group exhibited an higher NLR (2.27 ± 0.86 vs 2.05 ± 0.68, P < .05) than the NLDLR group. LDL-C levels and LDLR genotype were significantly associated with NLR (both P < .05). Multiterritorial plaque involvement was more frequent in the LDLR group than the NLDLR group (P for trend <.05). Age (P < .001), LDL-C (P < .001), smoking status (P < .05), and NLR (P < .05) were independently associated with subclinical atherosclerosis. Conclusion FH subjects with LDLR mutations had a higher NLR and a more severe atherosclerosis distribution. Our findings support the role of NLR as a noninvasive biomarker of early immune activation and highlights the importance of lipoinflammatory status evaluation in FH subjects.