Pulse wave velocity (PWV) is an important tool for the early identification of vascular damage caused by elevated blood pressure (BP), or the presence of other associated factors with accelerated vascular aging (1, 2). The use of PWV as a biomarker that can gauge the overall risk of patients, identify organ damage, and facilitate clinical decision-making has been acknowledged by guidelines and consensus documents mainly, but nonexclusively for hypertensive patients (3–5).

Carotid-femoral PWV is considered the gold-standard method for arterial stiffness, and it´s been used mainly in western countries (6). However, other methods for PWV measurement have been validated, like brachial-ankle PWV (7). Over the last years, some devices claim to estimate PWV from a single brachial cuff pressure recording, like the Cardio Mapa AOP® (Cardios, São Paulo, Brazil). By this method, central systolic BP was calculated using the ARCSolver® (Austrian Institute of Technology, Vienna, Austria) algorithm, which determines the aortic systolic BP. The aortic systolic BP can be calculated by the algorithm by two different calibration methods: C1 (using brachial systolic and diastolic BP), and C2 (using oscillometrically measured mean/diastolic BP) (8).

Despite growing evidence for the clinical applicability of noninvasive measurement of PWV (4, 9–10), its implementation in clinical practice is suboptimal and restricted to tertiary and research centers. This can be attributed to lack of regulation and reimbursement from healthcare authorities and cost of dedicated devices, among other factors (11).

The SAGE score is based on four clinical parameters (peripheral systolic blood pressure, age, fasting glucose, and glomerular filtration rate calculated by CKD-EPI) (11). It has been validated in European and Japanese populations, as well as in a Brazilian population (11–13). It has been used to screen and identify hypertensive patients with an elevated likelihood of PWV and a resulting high risk of cardiovascular events. Despite these important validation studies in hypertensive individuals, continuous efforts to validate the SAGE score throughout different communities have been made, particularly those with poor access to PWV analysis methods (12).

As such, the present study aimed to identify a SAGE score that would indicate a high risk of PWV ≥ 10 m/s in Brazilian hypertensive patients who had their PWV measured by an oscillometric device.

This retrospective study included medical records of outpatients who consulted in a private cardiology center in Brazil. We conducted a retrospective analysis of patients who had undergone central blood pressure measurement (CBPM) using the oscillometric method from August 2020 to December 2021. The present study was approved by the Research Ethics Committee of the Federal University of Santa Maria (UFSM), RS, Brazil (CAAE 51438421.4.0000.5346) and conducted according to the Declaration of Helsinki. We included patients with 18-years-old or older with the diagnosis of systemic arterial hypertension (SAH) who consulted in the referred service. Hypertensive patients were defined as those who had high blood pressure at the doctor's office, a CBPM of ≥140/90 mmHg, or an overall mean ≥130/80 mmHg in ambulatory blood pressure monitoring (ABPM) or were using antihypertensive medications (11). The glomerular filtration rate (GFR) was estimated using the creatinine value using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.

A total of 352 patient who underwent CHPM were identified. Of these, 212 were selected. Forty-five patients were excluded due to absence of clinical data necessary to calculate the SAGE score, and 95 because they were non-hypertensive (Figure 1).

The mean age of the sample was 64.0 ± 12.4 years (range 30–89 years), most often female (57.5%), overweight (47.6%) or obesity (34.3%), non-diabetic (75%) (Table 1). Most had PWV values < 10 m/s (68.9%). The performance of the SAGE score in predicting elevated PWV was analyzed. The sensitivity and specificity of different cutoff points are shown in Table 2. For the 212 patients, in the ROC analysis, the area under the curve (AUC) was 93.8% (95% CI from 90.8% to 96.8%, P ≤ 0.001) (Figure 2).

According to Youden's J statistic, a cutoff point of 6 provided the optimal combination of sensitivity and specificity for identifying patients with a PWV ≥ 10 m/s in individuals with SAH. Table 2 shows the ability of this cutoff point in hypertensive subjects. The values were as follows: SE of 97.0%, SP of 82.9%, PPV of 71.9%, and NPV of 98.4%. For this cutoff point, a positive test is about 5.6630 times more likely to be obtained in the presence of the disease than in the absence of it. If the test with the SAGE score is negative, the likelihood ratio is 0.0366.

Despite the Youden's J statistic demonstrated the cutoff point of 6 as the optimal combination of sensitivity and specificity for identifying patients with a PWV ≥ 10 m/s, the choice of a cutoff point of 7 improved the specificity, at the expense of sensitivity. A cutoff point of 7 (where score values of at least 7 were considered to indicate high risk) had a positive likelihood ratio of 8.2 and a negative likelihood ration of 0.346. Thus, the use of this cutoff point would aid decision-making by accurately excluding patients who are less likely to have PWV ≥ 10 m/s.

In this cross-sectional study, we reported the SAGE cutoff point to identify increased PWV using a validated oscillometric device in a Brazilian population of 212 hypertensive patients. Using the quantitative approach (based on the Youden index), the cutoff point was 6. However, using a qualitative approach that prioritized achieving satisfactory PPV while maintaining a high NPV, a SAGE cutoff of 7 was chosen as the best option. With this cutoff point, its emphasized that patients not selected for PWV measurement would have a low probability of PWV ≥ 10 m/s. This strategy optimizes financial resources in places with health systems that have limited PWV analysis availability (11, 13).

Our findings are similar to those reported by Tomiyama et al., who defined a SAGE cutoff point of 7 for Japanese hypertensive patients undergoing brachial-ankle PWV measurement (13). However, we reported slightly different cutoff than the one reported by Xaplanteris et al. and Oliveira et al. (11, 12). In 2019, Xaplanteris et al. validated the SAGE score using tonometry in a Greek population of patients with SAH (11). They defined the SAGE score cutoff of 8 as the best predictor of high PWV. More recently, Oliveira et al. identified the same SAGE score of ≥8 for predicting high PWV in a population of Brazilian hypertensive patients (12). In the last study, the authors measured PWV with the same oscillometric technique described in our study (12, 14, 15). The distinct cutoff observed in these studies could be related to methodological differences used to calculate the SAGE score and to measure PWV, particularly in the study by Tomiyama et al. in the last study (12, 18, 19). In the present study, the estimation of PWV was based on the Dyna Mapa AOP® oscillometric device based on its advantages and accessibility in our community (12, 14, 15). Besides it, there is a series of longitudinal studies showing a good correlation with target organ lesions and cardiovascular events with oscillometric devices (20–22), when compared to the gold standard noninvasive method of carotid-femoral tonometry (15). The differences observed between our data and the study by Oliveira et al. (12) could be related, at least partially, by regional and ethnical variations in the Brazilian population (23, 24). Additionally, the central systolic BP differences observed between C1 and C2 calibrations must also been acknowledged. Like Oliveira et al., we used C2 calibration (12). Regarding clinical validation, studies have focused on central systolic BP whereby C2 calibration is superior to cuff brachial SBP and C1 calibration in terms of association with organ damage (25–27) and mortality outcomes (27).

The present study reinforces the importance of optimizing PWV measurement in clinical practice of patients with SAH, because this technique is still restricted to tertiary centers (2, 11). In this setting, the SAGE score becomes a simple clinical tool to identify those patients who should undergo PWV measurement. Like Oliveira et al. (12), our paper evaluated the SAGE score cutoffs against oscillometric measurements in Brazilian hypertensive patients. The present study has some limitations. First, the SAGE cutoff was obtained using data from a specific Brazilian population in south of Brazil, with mixed ethnicity (24). The sample size was small, with different ethnic background compared to the previous studies. Reference values for PWV have been defined in the Brazilian population for categories defined by age, sex, and cardiovascular risk factors (28). However, the present study defined abnormal PWV as values greater or equal than 10 m/s, according to the original validation of the SAGE score (11).

Regarding future clinical implications, we believe that further studies with larger sample size that involves most Brazilian regions and the application of SAGE score in non-hypertensive individuals will be useful for determining the use of this score.

The SAGE score presented a good performance as a predictor of PWV measured in Brazilian hypertensive outpatients, using oscillometric device. The cutoff point was the same as reported in the Japanese cohort and close to that reported in the European cohort and the first published Brazilian cohort. Our data reinforce that the SAGE score is a useful and robust tool for identification of hypertensive individuals with probable PWV ≥ 10 m/s.