The current study 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) were statistically significant predictors of HRE. The results of this study also provided new information regarding the impact of arterial stiffness on excessive exercise systolic BP. In the non-HRE group, the CAVI result was 6.9±0.7, while in the HRE group, it was 8.3±1.1 (p<0.001). Thus, our results support the hypothesis that HRE is mechanistically associated with arterial stiffness, independent of other established CVD risk factors.
We demonstrated that CAVI, a surrogate marker of arterial stiffness, could discriminate against arterial compliance. This study identified CAVI > 8 as the optimal cutoff for predicting HRE. ROC curve analysis demonstrated the CAVI was a statistically significant predictor of HRE with AUC 0.827 (95%CI: 0.76-0.89, p< 0.001), sensitivity and specificity were 53% and 92%, respectively
These findings suggest that CAVI could be clinically helpful in identifying arterial stiffness in individuals at increased CVD risk. However, our findings may not be generalized to patients with established cardiovascular disease since our study population was low and intermediate ASCVD risk.
CAVI and resting pulse pressure as independent predictors of hypertensive response to exercise
With hypertensive response to exercise (HRE) as the dependent variable, the significant univariate predictors for HRE were age, DM, HT, dyslipidemia, beta-blocker history, exercise time, resting pulse pressure, and CAVI. Interestingly, the univariate predictors, such as the conventional ASCVD risk factor, was not significant in multivariate analysis.
Cutoff CAVI
To our knowledge, this is the first study to propose a CAVI cutoff value of 8.0 for the early detection of hypertensive response to exercise. This value is recommended as the optimal threshold for arterial stiffness screening in the asymptomatic population, 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 CAD is 8. Adding CAVI to the conventional risk score (RAMA-EGAT) increases the C-statistics from 0.72 to 0.85 and results in a 27% net reclassification improvement (NRI). (p 0.0001).15 In addition, the arterial stiffness measured by CAVI in this population may improve the ability to predict future MACEs. Individuals with CAVI > 9 had a 1.34-fold (95 percent CI: 1.01, 1.79) increased risk of MACEs compared to those with CAVI <9.26
Ischemic threshold
Increased PWV shifts pressure wave reflections from diastole to systole, increasing systolic pressure. In addition, a stiff aorta has a lower capacity to act as a blood reservoir during cardiac ejection, hence reducing the amount of blood supplied for coronary perfusion during diastole. systolic pressure elevation increases the energetic cost to the heart to maintain adequate cardiac output.Age and time to ischemia. Patients ‘ages spanned 24 years (from 44 to 77 years). Because age will relate to both disease severity and large artery stiffness, it would also be expected to correlate with ischemic threshold. In this cohort age was a strong univariate predictor of time to ST-segment depression (Table 2). This study provides the first clinical evidence that indices of arterial stiffness are more predictive of time to ischemia than angiographic assessment of coronary stenosis severity in patients with coronary artery disease.27
In CAD patients with myocardial infarction, arterial stiffness is related to decreased cardiorespiratory fitness. Regardless of the link between age and arterial stiffness, exercise capacity is reduced when its values are above the risk threshold.28
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, p 0.001). 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.29
Mechanistic considerations
Our research was a retrospective cross_sectional analysis of data. Consequently, it is limited in the terms of potential mechanisms and causal relationships. The β-stiffness index, a BP-independent arterial stiffness measurement, was used to calculate CAVI.12
The corresponding changes in arterial stiffness indices were associated with changes in blood pressure in response to various pressor stimuli, and the strength of these associations varied greatly depending on which arterial stiffness indices were examined.30.
Studies comparing arterial stiffness and hypertensive response to exercise (HRE)
A hypertensive response to the exercise stress test (HRE) was linked to a worsening of the elasticity of the arteries in both hypertensive and non-hypertensive subjects (N = 33 for each group). People with HRE had a significantly higher mean aortic stiffness index (p = 0.001) but a significantly lower aortic distensibility (p = 0.029).31 A recent study showed that higher systolic blood pressure after exercise in older women with different blood pressure levels was linked to stiffer arteries.32 The brachial-ankle pulse wave velocity (PWV) was used to measure the arterial stiffness index in 92 men (aged 42±9 years) without a history of cardiovascular disease or stroke. Regression analysis revealed a significant correlation between HRE and PWV.33
In response to exercise, participants with T2DM demonstrated greater increases in carotid-femoral PWV (1.6 [95% CI, 0.4–2.9 m/s] and systolic blood pressure (9 [95) CI, 1–17 mm Hg) than those without T2DM. These findings suggest that exercise-induced blood pressure increases with an increase in arterial stiffness.34
Young adults performing a maximal exercise test are more likely to experience HRE during all phases of exercise, including rest, peak, and recovery, if they have stiffer arteries. PWV could serve as an additional risk assessment tool for the HRE. A high PWV at the onset of the study was associated with HRE (SBP > 210 mmHg for men and > 190 mmHg for women), after accounting for traditional cardiovascular risk factors and other exercise parameters (p = 0.04).35 In adolescents, exercise BP may be useful for detecting high BP and cardiovascular risk. The HRE was associated with increased left ventricular mass index and arterial stiffness by aortic pulse wave velocity.36
Study limitations
Our study demonstrates some limitations. First, we conducted a retrospective, single-center study utilizing patient medical records from a health promotion center where most participants had low to moderate risk. Not enough of the people who took part had heart disease or were at a high risk for it. Second, CAVI is a relatively new measurement with high interobserver and intraobserver reliability. Since many technicians collected our CAVI studies, the measurement techniques and emotional stress conditions of the patients may have varied.
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.10,37 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.38 Furthermore, research on this correlation and future cardiovascular disease is required.
Link to future HT or ASCVD
EBPR was a significant and independent risk marker in determining the onset of hypertension from a high-normal state. Exercise testing may, thus, provide valid information that helps identify the subgroup of individuals more likely to develop subsequent hypertension and in whom preventive interventions should be particularly warranted.39