ASSOCIATION OF LEUKOCYTE PARAMETERS WITH CARDIOVASCULAR EVENTS IN PATIENTS WITH FAMILIAL HYPERCHOLESTEROLEMIA

• Grant number: 25/21165-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: December 01, 2025
• End date: November 30, 2026
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Marcio Hiroshi Miname
• Grantee: Henrique Takematsu
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Introduction: Familial hypercholesterolemia (FH) is a genetic condition characterized by persistently elevated LDL-c levels and an increased risk of atherosclerotic cardiovascular disease (ASCVD). In addition to dyslipidemia, inflammation plays a relevant role in this context. Although macrophages are recognized as key players in the inflammatory response, recent studies have also highlighted the role of neutrophils-previously considered secondary-in the development and progression of atherosclerosis. Simple hematological parameters, such as absolute neutrophil count and the neutrophil-to-lymphocyte ratio (NLR), have been associated with higher rates of cardiovascular outcomes in the general population, but evidence of their prognostic value in FH patients remains scarce. Objectives: To investigate the association between hematological parameters-including total leukocyte count, absolute neutrophil count, and NLR-and the occurrence of ASCVD and all-cause mortality in individuals with FH. Methods: This will be a retrospective observational study including adult patients with a genetically confirmed diagnosis of FH, defined by pathogenic or likely pathogenic variants in the LDLR, APOB, or PCSK9 genes. Clinical, laboratory, and imaging data collected at the time of enrollment in the Hipercol Brasil program will be obtained through medical record review. The parameters to be assessed include: total leukocyte count, absolute neutrophil count and other leukocyte subpopulations, NLR, platelet count, mean platelet volume (MPV), and platelet-to-lymphocyte ratio (PLR). Outcomes will include the occurrence of ASCVD and all-cause mortality. Exploratorily, the association between leukocyte parameters and coronary artery calcium (CAC) score will also be evaluated in individuals with this exam available in their records. Statistical analyses will include Student's t-test or Mann-Whitney test for continuous variables, chi-square test for categorical variables, and multivariate logistic regression and Cox proportional hazards models for associations with outcomes.