Using the Cardio-Ankle Vascular Index (CAVI) or the Mathematical Correction Form (CAVI ₀) in Clinical Practice

Abstract

Tonhajzerova et al. [1] published a review paper in the International Journal of Molecular Sciences in which they evaluated atherosclerosis and other pathophysiological mechanisms involved in cardiovascular disease (CVD) in patients with human papillomavirus (HPV). The paper explored new biomarkers that could be used for affected individuals. They mentioned the cardio-ankle vascular index (CAVI), proposed by Shirai et al. [2] in 2006, as a method that can be used to assess the overall stiffness of arteries and provide information about the status of atherosclerosis in patients (Equation (1)). Although CAVI can be a proper stiffness index from the origin of the aorta to the ankle, there are some points that should be considered before using this index (and the indices associated with CAVI) in clinical practice. CAVI0 (Equation (2)) is the mathematically corrected formula that has been derived from the CAVI formula. Spronck et al. [3] claimed that this marker is less dependent on blood pressure changes in the patient. In another article that was recently published, they also provided another tool to easily convert CAVI into CAVI0 values [4]. It is worth noting that CAVI0 has been doubted by the developer of CAVI because it has some flaws and cannot provide accurate measurements of arterial stiffness. CAVI = a {(2ρ/∆P) × ln (Ps/Pd) PWV2} + b(1) CAVI0=2ρ × (PWV2/Pd) − ln (Pd/P0)(2) where PWV: pulse wave velocity of the arterial tree from the origin of the aorta to the ankle; Ps: systolic blood pressure; Pd: diastolic blood pressure; ρ: blood density; Δ P: Ps – Pd; a, b: coefficients; P0: reference pressure (100 mmHg). The use of CAVI0 was proposed by Spronck et al. [3] in 2017. They used data from 497 subjects to modify the original CAVI formula (by Shirai et al. [2]). There are some fundamental differences between CAVI and CAVI0. Unlike CAVI, which uses Pd and Ps in its formula, in calculating CAVI0, only Pd, not Ps, is used. Another difference between CAVI and CAVI0 is the use of P0 in the formula of CAVI0. Although Spronck et al. [3] claimed that the new formula of CAVI0 is independent of blood pressure, in a large study on 5293 individuals, Shirai et al. [5] recently showed that CAVI0 is not accurate because of its strong dependency on Pd. Another reason that CAVI0 provides equivocal results is that Spronck et al. [3] did not take into account the physiological properties of individuals, such as their body mass index (BMI). BMI has been shown to be inversely associated with CAVI [6,7]. It is also interesting to know that the information about CAVI has been recently updated. Takahashi et al. [8] showed that the CAVI without the coefficients (coefficients a and b in Equation (1)) is also a valid index of arterial stiffness (Equation (3)). CAVI without coefficients a and b is parameter β, which is referred to as haβ (heart to ankle beta). Takahashi et al. [8] also revealed the coefficient “a” and “b” values that are being used in the CAVI calculation (Table 1). A review of this information raised some interesting discussion about the validity and use of the CAVI index. A study that aimed to simulate the influence of adjusting the coefficients in the equation of CAVI by Ato D. [9] suggested that the developers of CAVI fix these coefficients or terminate the use of CAVI. The reason is that those coefficients are dependent on the level of haβ (Table 1), and CAVI underestimates the original value of parameter β (haβ) that is used in the CAVI formula. Because the CAVI concept is driven by haβ (Equation (4)), it might cause inaccuracy in the calculation of the CAVI values. haβ = (2ρ/∆P) × ln (Ps/Pd) haPWV2 (3) CAVI= a haβ + b(4) where haPWV: heart-ankle PWV. As there are many concerns about using CAVI and CAVI0, we can say that PWV and parameter β can be considered as more reliable indices. As Tonhajzerova et al. [1] mentioned, PWV can still be considered an important risk marker, but given the fact that PWV and parameter β only include the more elastic aortic arterial wall and do not include the more muscular arm and leg arterial beds, researchers consider the use of more wholistic indices such as haPWV or haβ instead of PWV and parameter β, especially in older and high-risk patients, as muscular arteries are more likely to be affected by atherosclerosis after the proximal elastic arteries are affected [10]. The use of PWV and parameter β might yield similar results to haPWV and haβ in younger individuals. Blood pressure is dependent on arterial stiffness (as a result of both structural and functional mechanisms) and arterial stiffness can be accelerated in the presence of hypertension [11]. Considering these facts, it is important to know which factors influence CAVI as an index of arterial stiffness. A recent study by Kamon et al. [11] showed that the blood pressure (BP) category was only associated with high CAVI in males, not females. This further emphasizes the role of sex along with age, diabetes and obesity in the management of hypertension.