Arterial stiffness index beta and cardio-ankle vascular index inherently depend on blood pressure, but can be readily corrected

Objectives: Arterial stiffness index β and cardio-ankle vascular index (CAVI) are widely accepted to quantify the blood pressure (BP)-independent, intrinsic exponent (β0) of the BP-diameter relationship. CAVI and β assume an exponential relationship between pressure (P) and diameter (d). We aim (1) to demonstrate that, under this assumption, β and CAVI as currently implemented are inherently BP-dependent and (2) to provide corrected, BP-independent forms of CAVI and β. Methods and results: In P=Pref*exp[β0(d/dref−1)], usually reference pressure (Pref) and reference diameter (dref) are substituted with diastolic BP and diameter to accommodate measurements. Consequently, the resulting exponent is not equal to the pressure-independent β0. CAVI does not only suffer from this reference pressure effect, but also from the approximation of dP/dd. For example, assuming β0=7, an increase of systolic/diastolic BP from 110/70 to 170/120 mmHg increased β by 8.1% and CAVI by 14.3%. We derived corrected forms of β and of CAVI (CAVI0) that did not change with BP and represent the pressure-independent β0. To substantiate the BP effect on CAVI in a typical follow-up study, we realistically simulated patients (n=161) before and following BP-lowering treatment (assuming no follow-up change in intrinsic β0 and therefore in actual P-d relationship). Lowering BP from 160±14/111±11 to 120±15/79±11 mmHg (p<0.001) resulted in a significant CAVI decrease (8.1±2.0 to 7.7±2.1, p=0.008) CAVI0 did not change (9.8±2.4 and 9.9±2.6, p=0.499). Conclusions: β and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness research. BP-independent forms were derived to overcome this problem.