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

Background: Arterial stiffness index β and cardio-ankle vascular index (CAVI) are widely accepted for quantification of the intrinsic exponent (β0) of the blood pressure (BP)- diameter relationship. CAVI and β assume an exponential relationship between pressure (P) and diameter (d). Aims: (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: In the intrinsic arterial BP-diameter relationship, usually reference BP (Pref) and reference diameter (dref) are substituted with diastolic BP and diastolic diameter to accommodate measurements. Consequently, the resulting exponent (stiffness index β) is not equal to the intrinsic, pressure-independent β0 , but instead varies with BP. CAVI does not only suffer from this “reference pressure” effect, but also from a linear approximation of dP dd . We derived corrected forms of β and of CAVI (CAVI0 ) that do not change with BP and represent the pressure-independent β0 . To further 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). Results: As an example, in a person with 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%. In our simulated patient study, 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). Conclusion: Stiffness index β and CAVI as currently implemented are inherently BP-dependent, potentially leading to erroneous conclusions in arterial stiffness trials. BP-independent forms of β and CAVI are presented to readily overcome this problem.