Distinct blood pressure variability phenotype in VEGF–TKI–induced hypertension: a comparative study across cardio-oncology populations

Background Hypertension induced by vascular endothelial growth factor (VEGF)–targeting tyrosine kinase inhibitors (TKIs) is a prevalent adverse effect in cancer therapy. While the mechanisms of mean blood pressure (BP) elevation are well studied, less is understood about how VEGF–TKI–associated hypertension impacts blood pressure variability (BPV) and circadian BP regulation. This study aims to explore the differences in BPV across three hypertensive populations: patients with VEGF–TKI–associated hypertension, patients with primary hypertension plus tumor, and patients with primary hypertension without tumor. Methods A matched cohort study was conducted to compare ambulatory BP profiles across three groups: (1) VEGF–TKI–associated hypertension, (2) tumor-related hypertension without VEGF–TKI, and (3) primary hypertension without tumor. BPV was assessed using continuous metrics including variability independent of the mean (VIM-SBP), 24-hour systolic BP standard deviation (24h sSD), and systolic BP coefficient of variation (24h sCV). Mixed-effects models, categorical BPV phenotyping, and exploratory principal component analysis (PCA) were used to assess group differences and identify underlying BPV phenotypes. Results VEGF–TKI–associated hypertension was independently associated with higher BPV, including elevated VIM-SBP and 24h sSD, compared with both tumor-related hypertension and primary hypertension without cancer. In contrast, tumor-related hypertension without VEGF–TKI exposure was predominantly characterized by low BP variability and non-dipping BP patterns. PCA and clustering identified three BPV phenotypes, with VEGF–TKI–associated hypertension disproportionately represented in the high BP, high-variability phenotype. Group differences in BPV and circadian BP regulation were statistically significant (χ² test, P<0.001). Conclusions VEGF–TKI–associated hypertension is characterized by exaggerated short-term BP instability, independent of mean BP and antihypertensive treatment burden. This study underscores the utility of BPV as a clinically relevant and mechanistically informative dimension of cardiovascular toxicity in cardio-oncology, suggesting the need for phenotype-oriented cardiovascular risk assessment in this population.