The current study has demonstrated that arterial stiffness, as measured by CAVI (OR 5.5, 95% CI: 2.8–10.7, p < 0.001), and resting pulse pressure (OR 1.05, 95% CI: 1.02–1.08, p < 0.001), constitutes statistically significant predictors of HRE. Furthermore, the results of this study have provided new insights into the impact of arterial stiffness on excessive exercise systolic blood pressure. In the non-HRE group, the CAVI result was 6.9 ± 0.7, whereas in the HRE group, it was 8.3 ± 1.1 (p < 0.001). Thus, our results substantiate the hypothesis that HRE is mechanistically associated with arterial stiffness, independent of other established cardiovascular disease risk factors.

We have also demonstrated that CAVI, serving as a surrogate marker of arterial stiffness, can discriminate against arterial compliance. This study has identified a CAVI value greater than 8 as the optimal cutoff for predicting HRE. ROC curve analysis has shown that CAVI is a statistically significant predictor of HRE, with an AUC of 0.827 (95% CI: 0.76–0.89, p < 0.001), and sensitivity and specificity values of 53% and 92%, respectively.

These findings suggest that CAVI could have clinical utility in identifying arterial stiffness in individuals at an elevated risk of cardiovascular disease. However, it's important to note that our findings may not be generalizable to patients with established cardiovascular disease, as our study population consisted of individuals at low and intermediate ASCVD risk.

CAVI and resting pulse pressure as independent predictors of hypertensive response to exercise

When considering hypertensive response to exercise (HRE) as the dependent variable, the significant univariate predictors for HRE included age, DM, HT, dyslipidemia, beta-blocker history, exercise time, resting pulse pressure, and CAVI. Interestingly, conventional ASCVD risk factors were not significant in the multivariate analysis.

Cutoff CAVI

To the best of our knowledge, this study marks the first attempt to propose a CAVI cutoff value of 8.0 for the early detection of hypertensive responses to exercise. This value is recommended as the optimal threshold for screening arterial stiffness in asymptomatic populations, based on previously published research [25]. In 2007–2008, the largest longitudinal cohort study in Thailand was conducted on 3,807 Electricity Generating Authority of Thailand (EGAT) employees. The ideal CAVI threshold for coronary artery disease (CAD) is 8. Incorporating CAVI into the conventional risk score (RAMA-EGAT) enhances the C-statistics from 0.72 to 0.85 and leads to a 27% net reclassification improvement (NRI) (p< 0.0001) [15]. Additionally, arterial stiffness, as measured by CAVI in this population, may enhance the predictive capacity for future major adverse cardiovascular events (MACEs). Individuals with CAVI > 9 had a 1.34-fold increased risk of MACEs (95 percent CI: 1.01, 1.79) compared to those with CAVI < 9 [26].

SBP and DBP Cut-off for HRE

This study utilized a cut-off value of SBP ≥ 210 mmHg for men and ≥ 190 mmHg for women, or DBP ≥ 110 mmHg for both genders. These thresholds were established based on the exceeding of the 90th centile blood pressure responses to maximal or peak intensity exercise. This cut-off has been demonstrated to correlate with future hypertension [5, 6], increased left ventricular hypertrophy [8], and significant predictors of major adverse cardiac events [2, 7]. Sharman et al. [27] have similarly shown that hypertensive response to exercise (HRE), using the same cut-point as our study, can aid in the detection of masked hypertension, as identified through 24-h ambulatory blood pressure monitoring (ABPM). Furthermore, CAVI has also been identified as an independent risk factor for masked uncontrolled hypertension [28], with the CAVI results in the masked hypertension group in one study ranging from approximately 8.2 to 9.9, a range that closely aligns with the CAVI values observed in the HRE group in our study. Endothelial dysfunction and increased arterial stiffness have been proposed as the mechanisms underlying HRE [29]. Chung et al. [30] have demonstrated that arterial stiffness, assessed using brachial-ankle pulse wave velocity (baPWV), serves as an independent predictor of HRE, consistent with the same cut-off point as in our study. Moreover, this study also found a higher prevalence of HRE in women (56%), which is consistent with our study's findings, where 67% of women exhibited HRE. Hence, this cut-off value represents an appropriate threshold for HRE that can be associated with the CAVI results observed in our study.

Validated CAVI by pulse wave velocity

In a cohort nationwide registry in Japan, the CAVI reference value was investigated by measuring CAVI in 4,542 patients with at least one cardiovascular risk factor and baPWV in 1,737 of these 4,542 patients on the same day. A significant and positive correlation was observed between CAVI and baPWV (r = 0.50, p0.001). CAVI was 8.303 for baPWV at 14 m/s and 9.059 for baPWV at 18 m/s as calculated by the regression line [31].

Clinical implications

This study is the first to demonstrate a significant correlation between arterial stiffness using CAVI and hypertensive response during exercise (HRE). Previous study has shown the linkage between arterial stiffness using pulse wave velocity (PWV) and HRE [32]. Although both methods of measurement are practicable, the marker of arterial stiffness using CAVI has an advantage beyond the PWV (carotid-femoral) since it is less affected by blood pressure at the time of measurement. The blood pressure (BP) response to exercise is a significant predictor of cardiovascular disease and prognosis. The results of this study have the following consequence for clinical practice: As is well known, several factors, such as technical measurements, the patient clenching his arm during exercise, and sleep deprivation, can affect how the blood pressure responds to exercise. CAVI can assist in separating an HRE from a false positive when we discover a patient who has a hypertensive response during exercise [33]. The blood pressure response to exercise is a significant predictor of cardiovascular disease and prognosis. Thus, regular monitoring of blood pressure is crucial for patients with HRE and CAVI > 8 to ensure early detection of any potential cardiovascular complications. This comprehensive approach helps in accurately diagnosing and managing patients with exercise-induced hypertension. Additionally, healthcare professionals should provide comprehensive education and guidance to these patients on lifestyle modifications and medication adherence to effectively manage their condition.

Study limitations

Our study has certain limitations. Firstly, it was a retrospective, single-center study that relied on patient medical records from a health promotion center, primarily involving participants with low to moderate risk. There was an inadequate representation of individuals with heart disease or those at high risk for it. Secondly, CAVI is a relatively new measurement with notable interobserver and interobservers variability. Given that multiple technicians conducted our CAVI studies, there may have been variations in measurement techniques and variations in the emotional stress conditions experienced by the patients.

Future direction

Hypertensive response to exercise is linked to endothelial dysfunction, decreased proximal aortic compliance, and increased neurohormonal activation, which may explain why cardiovascular disease will happen in the future [10, 34]. Future research needs to find out if a hypertensive response to exercise is linked to heart disease in the future. Moreover, a delayed blood pressure recovery ratio may indicate increased arterial stiffness in hypertensive patients with reduced aerobic exercise capacity [35]. Furthermore, research on this correlation and future cardiovascular disease is required Link to future HT or ASCVD.

An exaggerated blood pressure response to exercise emerged as a significant and independent risk marker for the development of hypertension from a high-normal state. Therefore, exercise testing can offer valuable insights in identifying individuals at a higher likelihood of developing future hypertension, warranting focused preventive interventions. This finding underscores its potential utility in early risk assessment for both hypertension and ASCVD (atherosclerotic cardiovascular disease) [8].