Comment on “Kario et al. Impact of vascular biomarkers and supine hypertension on cardiovascular outcomes in hypertensive patients: first results from the Cardiovascular Prognostic COUPLING Study in Japan”

Increased arterial stiffness is commonly observed in hypertensive patients, and behaves an important predictor of future cardiovascular events [1, 2]. Among all the indexes for arterial stiffness measurement, carotid-femoral pulse wave velocity (PWV) remains the gold standard for noninvasive measurement [3]. However, it has several limitations, such as a complex measurement procedure. Most importantly, it is a measure of the speed of the pulse wave and therefore is affected by blood pressure.

The cardio-ankle vascular index (CAVI) was developed as a clinical test for arterial stiffness based on the principle of stiffness parameter β [4]. In the CAVI-J (Prospective Multicenter Study to Evaluate Usefulness of Cardio-Ankle Vascular Index in Japan) study, patients with a higher (≥9.50) CAVI had elevated risks of all-cause and cardiovascular death, nonfatal stroke, and heart failure with hospitalization [5]. Ankle brachial index (ABI) serves as a simple procedure for the detection of peripheral artery disease. There seems to be a J-shaped association between ABI and cardiovascular outcomes, since both high and low ABI have been reported to increase cardiovascular risks [6, 7]. Supine hypertension is seen in up to 70% patients with neurologic orthostatic hypotension, which are two hemodynamically opposite forms of blood pressure dysregulation. In the middle-aged, community-based population of the ARIC (Atherosclerosis Risk in Communities) study, supine hypertension was more strongly associated with adverse clinical outcomes than standing hypotension even among adults with orthostatic hypotension [8].

In this issue of the Journal, Kario and colleagues reported that the combination of a CAVI of ≥8.0 and an ABI of ≤1.10 in outpatients with hypertension was associated with a significantly greater risk of cardiovascular events [9]. This advocates for simultaneous assessment of CAVI and ABI in the management of hypertension. The study also showed that uncontrolled supine hypertension was associated with a 1.36-fold higher rate of cardiovascular event, compared with controlled supine hypertension.

Combining ABI and PWV has been shown to facilitate predictive power for all-cause and cardiovascular mortality. Chang et al. found that the combination of abnormal ABI and high brachial ankle PWV had a stronger association with mortality than normal ABI plus low brachial ankle PWV in patients with diabetes [10]. Matsushima et al. found that among patients with a first-ever non-cardioembolic stroke, the combination of an ABI < 0.9 and high brachial ankle PWV was associated with clinical outcomes 3 months after stroke onset [11]. Potential mechanisms that maybe involved in the association between ABI/PWV and mortality include oxidative stress, insulin resistance, inflammation, endothelial damage and dysfunction and other functional and/or morphological changes in the blood vessel wall, and hemodynamic alterations with arterial stiffness [12]. The antagonistic interaction between ABI and PWV may be attributable to their competing risks, that is, any abnormality on ABI or PWV leads to unfavorable conditions for the other factor and induces its effect. This also applies for CAVI and ABI. Future research should further clarify the role and interplay of these underlying biological mechanisms of ABI and CAVI.

CAVI, ABI, and supine blood pressure measurement are all useful in the prediction of cardiovascular risk and may be incorporated into daily clinical practice to individualize risk assessment and guide clinical decisions. Since supine blood pressure measurement is already included in the CAVI measurement, the prognostic value of measurement including CAVI, ABI, and supine blood pressure can and should be investigated in future studies.