AHA Scientific Sessions 2026 Abstract · Nov 2, 2026
Leukogram-Derived Biomarkers and Cardiovascular Risk in Genetically Confirmed Heterozygous Familial Hypercholesterolemia
By TAKEMATSU H, Santos RD, Henares BB et al.
Background: Leukogram-derived biomarkers have been associated with cardiovascular risk in the general population. However, no longitudinal study has yet evaluated their prognostic value in heterozygous familial hypercholesterolemia (HeFH). We investigated whether leukocyte counts and derived indices predict cardiovascular events in genetically confirmed HeFH. Methods: We retrospectively analyzed the Hipercol Brasil cohort (2010-2025), including adults with genetically confirmed HeFH and baseline leukograms. We evaluated differential leukocyte counts, as well as the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII = platelets х neutrophils / lymphocytes), and systemic inflammation response index (SIRI = monocytes х neutrophils / lymphocytes). The primary outcome was MACE, defined as cardiovascular death, nonfatal myocardial infarction or stroke, unstable angina, or coronary revascularization. Secondary outcomes were all-cause mortality (ACM) and ASCVD, including MACE, carotid and peripheral arterial disease, significant aortic stenosis, and chronic coronary disease. Kaplan-Meier and Cox models estimated hazard ratios (HRs) per 1-SD increase, adjusted for age, sex, smoking, hypertension, diabetes, BMI, prevention status, LDL-C, HDL-C, triglycerides, and lipid-lowering therapy. Results: The study included 549 participants (40% male; median age 49 [35-60] years; 76% White), of whom 74% were in primary prevention, 40% had hypertension, 16% diabetes, 37% were current/former smokers, and 82% had prior lipid-lowering therapy. Over a median follow-up of 8.1 [3.6-12.1] years, 82 participants experienced MACE (incidence 1.93/100 PY) and 106 developed ASCVD (incidence 2.59/100 PY). Those with MACE were older and more likely to be male, smokers, hypertensive, and diabetic, and had higher monocyte counts and SIRI values (all p<0.01). Kaplan-Meier curves stratified by monocyte count and SIRI tertiles showed different event-free survival for both MACE and ASCVD (log-rank p<0.05). In unadjusted analyses, monocyte count (HR 1.47, 95%CI 1.23-1.74), platelet count (HR 0.78, 95%CI 0.62-0.98) and SIRI (HR 1.38, 95%CI 1.11-1.72) were associated with MACE; after full adjustment, only monocyte count independently predicted MACE (HR 1.29, 95%CI 1.06-1.56). For ASCVD, total leukocyte (HR 1.28, 95%CI 1.04-1.57), neutrophil (HR 1.23, 95%CI 1.01-1.50), and monocyte counts (HR 1.31, 95%CI 1.10-1.55), as well as SIRI (HR 1.29, 95%CI 1.05-1.59), independently predicted risk after adjustment. No leukogram-derived marker independently predicted ACM after adjustment. Conclusions: Only monocyte count independently predicted incident MACE, whereas multiple leukocyte-derived measures were associated with ASCVD in HeFH. These findings support the prognostic value of leukocyte-derived measures in HeFH.