Abstract P231: Circulatory Gene Regulation in Youth With Primary Hypertension and Target Organ Damage

Introduction: Primary hypertension (PH) is a multifactorial disease mainly influenced by genetic, epigenetic and environmental dynamics. Despite the occurrence of PH-associated cardiovascular (CV) events in youth, we have acquired only a limited understanding of epigenetic and gene regulation of blood pressure (BP)-related target organ damage (TOD) in adolescents. Aims and Objectives: To define circulatory gene and miRNA expression levels and allied signaling pathways in hypertensive adolescents (Hyp) with TOD. Methods and Results: Three hundred adolescents of both genders aged 11 to 18 years participated in the AHA-funded Study of Hypertension in Pediatrics - Adult Hypertension Onset in Youth (SHIP AHOY) Project. Mean clinic SBP was 104.3 ±8.1 and 133.0 ± 8.2 mmHg in normal vs Hyp ( p<0.005 ) and mean daytime ambulatory SBP was 115.7 ±11.4 and 128.9 ±6.4 mmHg in normal vs Hyp ( p<0.005 ), respectively. Youth with PH also had higher BMI (22.33 ±3.67 vs 31.56 ±9.42; p< 0.05 ), elevated serum creatinine (0.73 ± 0.18 vs 0.92 ±0.12; p< 0.05 ), and left ventricular hypertrophy (LVM/ht 2.7 ; 25.4 ±1.8 vs 41.7 ±1.8; p< 0.05 ), and trend for increased arterial stiffness (PWV; 4.8 ±0.6 vs 5.8 ±2.0; p =0.18). mRNA and microRNA seq were performed using peripheral blood cells of 10 normal (mean 15.2 ±1.4 years; 50% male), and 10 Hyp patients (mean 15.5 ±1.5 years; 70% male). Seq data analysis revealed master genes (Fig. 1) and pathways that were differentially regulated in Hyp patients with TOD. Conclusions: PH in youth is associated with TOD that relates to a distinct gene expression profile. Knowledge of allied pathways may lead to new treatments in hypertensive youth to prevent future CV diseases.