3.5: Changes in Blood Pressure and Arterial Mechanical Properties after Antiangiogenic Drugs: Association with Cancer Progression and Mortality

Abstract

Objective

Hypertension is a frequent side effect of antiangiogenic drugs (AAD). Targeting VEGF pathway may also affect large and small artery properties, along with or independently of blood pressure changes. We hypothesized that large and small artery property changes in response to AAD reflect their effect on the microcirculation at the site of the tumor, and thus may be related to cancer progression and mortality.

Design and Method

We included 60 patients [age 58 (15) years, mean SBP 127(21) mmHg] in whom treatment with AAD was indicated for various metastatic solid tumors. Noninvasive arterial investigation was performed before AAD (V0), 1 week later (V1) and then every two weeks for two months (V1 to V4): carotid-femoral pulse wave velocity (cfPWV), central SBP and augmentation index (cAIx) by applanation tonometry (SphygmoCor®), and carotid stiffness (CStiff) and internal diameter (CiD) by high resolution echotracking (Artlab®). Cancer progression and mortality were assessed at 6 months.

Results and Conclusion

28(47%) patients developed hypertension during follow-up. bSBP significantly increased during follow-up (V0−V1: +9.3 ± 15.2mmHg, P < 0.001; V0−V4: +6.0 ± 17.8mmHg, P = 0.03), as well as PWV, CStiff, and CiD. Baseline cAIx predicted cancer progression (RR = 0.73 per 10%) and mortality (RR=0.73 per 10%, P < 0.001) while SBP did not. The V0−V1 increase in CStiff predicted cancer progression (RR = 1.37 per 1 m/s, P = 0.02), independently of age and MBP. In conclusion, increased AIx and arterial stiffness, but not brachial or central SBP, were related with the effects of AAD on cancer progression and mortality.