In this study, we found significant associations between API or AVI and known risk factors for CVD, which might support the clinical validity of these new arterial stiffness indices. In addition, the test-retest reliabilities of API and AVI were acceptably high. This is the first study to assess associations between known risk factors for CVD and API or AVI in a large healthy population. Typical risk factors such as sex, age, BMI, and sBP were independently associated with API as determinants. Similarly, AVI was independently associated with sex, age, BMI, sBP, FPG, and smoking condition. This suggests that the indices could be useful total vascular risk markers.

Regarding test-retest reliability of the measurements, the ICCs of API (0.74) and AVI (0.80) were acceptably high, because the indices were affected by enduring hemodynamic changes, even after a 5-minute interval.

API and AVI were associated with typical risk factors for arterial stiffness such as age, sex, blood pressure, diseases (hypertension, dyslipidemia, diabetes), and family history of hypertension. Other arterial stiffness indices such as PWV or CAVI evaluate vascular condition, especially reduction in arterial compliance along the long axis of arteries, by attaching two or more cuffs. IMT assesses structural changes in arteries. API and AVI evaluate arterial compliance similarly; however, these indices focus the pulse wave component, extracted with a cuff attached, at only one place. This study showed that API significantly correlated with IMT and CAVI. In addition, AVI significantly correlated with IMT, ABI, and CAVI. Despite differences in technical theory of the measurements, the findings above support the validity of API and AVI as vascular risk markers.

Although, in univariate analysis, mean API and AVI in current smokers were lower compared with non-smokers, this relationship disappeared in multiple regression analysis. Confounders such as sex or age might affect this association. Furthermore, items related to API or AVI were different between the indices. This might indicate differences in vascular sites evaluated based on the background technical theory. Specifically, API mainly reflects stiffness of the peripheral arteries, whereas AVI reflects stiffness of the central arteries [9, 10]. Compared with API, AVI includes pulse wave reflected central blood pressure as a component. Indeed, some studies showed that AVI was an independent predictor of central blood pressure in patients with cardiovascular disease [11, 12]. We found that moderate or strong correlations between API and BMI, sBP, dBP, and between AVI and age, sBP, dBP existed while that modest but statistically significant correlations existed between these arterial stiffness indices and other factors. We can say that both of API and AVI are obviously BP-dependent indices as this study showed. However, BPs were not directly included as part of calculation as mentioned above, and therefore, the association was due to factors related arterial stiffness but not mathematical reasons. The same applied for BMI and age. These observations deserve further investigation.

Some limitations of the present study must be acknowledged. First, self-report measurements are generally less accurate; therefore, past history or family history of diseases might be biased. However, the prevalences of family history of each disease were consistent with available Japanese data (13). Second, participants in the current study were not necessarily representative of the general Japanese population. Participants in this study were individuals who had a medical checkup of their own volition at a large-scale medical facility. While a large number of community residents visit the facility, study participants were not chosen at random. However, this population comprised people mainly in their 40s, with the prevalence of cardiovascular risk factors similar to available Japanese data [13]. Third, other unmeasured factors such as socioeconomic factors may have affected our findings. Social structure and educational background in the catchment area of the current study is somewhat different from typical urban areas, because the number of residents engaged in primary industry is about 1.6 times the average in Japan [14]. Fourth, we could not compare new arterial stiffness indices with traditional and standard ones such as carotid-femoral PWV because of the study design. Finally, the cross-sectional nature of this study limited our ability to discuss causality.

In the future, a longitudinal study to determine the extent of the effect that measuring API and AVI has on the development of cardiovascular diseases, and all-cause mortality, should be conducted. Because API and AVI are measured non-invasively in a short time (about 1 minute), similar to conventional measurement of blood pressure, the indices could allow people easy access to vascular condition information, not only in medical checkups, but also in daily life settings, without any need for medical technicians. This study suggests that API and AVI might have clinical significance as arterial stiffness measures. Thus, further research into API and AVI in terms of arterial stiffness prevention is warranted.