Patient-specific blood pressure correction technique for arterial stiffness: evaluation in a cohort on anti-angiogenic medication

Abstract

Arterial pulse wave velocity (PWV) depends on blood pressure (BP). Correction of PWV for BP is commonly performed using a statistical approach, requiring a patient cohort. We recently developed a mechanistic, model-predictive approach to assess BP-independent changes in carotid PWV (cPWV) at the level of the individual. The goal of the present study is to compare our novel technique to conventional statistical correction, in the context of anti-cancer therapy using anti-angiogenic drugs (AADs). AADs frequently lead to a PWV increase, but also to hypertension, underlining the need for BP correction of PWV measurements. We obtained carotid artery systolic and diastolic cross-sectional areas (echotracking) and corresponding BPs (tonometry) in 48 patients before starting AAD treatment (sorafenib/sunitinib), and at four follow-up visits spaced 2 weeks apart. For each patient, we derived cPWV and a baseline single-exponential BP cross-sectional area curve. Based on these baseline curves and follow-up BPs, we predicted cPWV at follow-up due to BP. By comparing predicted and measured cPWVs at follow-up, we assessed the BP-independent cPWV increase. In the same way, we assessed whether diastolic cross-sectional area (A) changed beyond the BP-induced amount. The AAD-induced BP-independent increase in cPWV was 0.43(0.09,0.77) m s (mean (95%CI), P=0.014, mechanistic approach) and 0.48(0.14,0.82) m s (P=0.006, statistical approach). A increased with 1.92(0.93,2.92) mm (P<0.001) and 2.14(1.06,3.23) mm (P<0.001), respectively. In conclusion, the present study demonstrates the feasibility and potential of our mechanistic, model-predictive approach to quantify BP-independent effects on arterial stiffness at the level of the individual, in a clinically relevant setting of AAD therapy.

Constitutive interpretation of arterial stiffness in clinical studies: a methodological review

“…Transit time PWV and single-point measures (DC, CC, and single-point PWV) are all well known to show pressure dependence, requiring adjustment for blood pressure (123,126). Statistical adjustments are a valid and powerful approach when groups or populations are considered but lack applicability in the setting of individual patient management (121,124). Two of the selected studies (2 of 63 studies) used the cardio-ankle vascular index (CAVI) obtained by measuring transit time over the heart-to-ankle trajectory (116,136) to account for pressure dependence by approximating the pressure-area relationship by a single exponential (akin to stiffness index ␤; see Ref.…”

Aortic Dissection and Cardiac Dysfunction Emerged Coincidentally During the Long-Term Treatment with Angiogenesis Inhibitors for Metastatic Renal Cell Carcinoma

“…8) Furthermore, analyses of carotid PWV in patients with cancer treated with sunitinib or sorafenib revealed the BP-independent effects of these drugs on arterial stiffness. 25) This study adjusted the angiogenesis inhibitor-induced changes of BP and showed a BP-independent increase in carotid PWV, 25) thus suggesting the possibility that the long-term inhibition of angiogenesis due to sorafenib and axitinib could detrimentally and BP independently increase aortic stiffness and develop arteriosclerosis in our patient.…”

The Role of Vascular Smooth Muscle Cells in Arterial Remodeling: Focus on Calcification-Related Processes

“…PWV, as well as DC, are well known to be pressure dependent and require blood pressure adjustment [199]. Adjustment is valid when considering group analyses, but lacks applicability in the use of individual cases [32,200].…”