Pediatric reference values for arterial stiffness parameters cardio-ankle vascular index and CAVI0

The process of arteriosclerosis begins early in life, and cardiovascular risk factors identified in childhood tend to persist into adulthood. Cardio-ankle vascular index (CAVI), a recent parameter of arterial stiffness, is considered an independent predictor of cardiovascular risk. However, there are no studies reporting sex- and age-specific physiological values of CAVI in childhood. We aimed to establish reference values for CAVI and its blood pressure-corrected variant (CAVI0) in 500 healthy children and adolescents aged 7 to 19 years and to study potential relationships with anthropometric indices. Sex- and age-specific distributions of CAVI and CAVI0 values in healthy children and adolescents are presented. Boys aged 15-19 years had lower CAVI than girls, which could result from CAVI's slight blood pressure dependence. CAVI0 did not show such sex difference. Body roundness index-a novel parameter to quantify abdominal fat-was a strong anthropometric predictor of both CAVI and CAVI0. This is the first study providing pediatric age- and sex-specific reference values for arterial stiffness parameters CAVI and CAVI0. The presented data can contribute to the understanding of the evolution of these indices during childhood and adolescence. Under specific conditions, CAVI0 may offer more robust information about arterial stiffness than standard CAVI

Early Signs of Microvascular Endothelial Dysfunction in Adolescents with Newly Diagnosed Essential Hypertension

Endothelial dysfunction represents one of the key pathomechanisms in many diseases, including hypertension. Peripheral arterial tonometry (PAT) evaluates the functional status of microvascular endothelium and offers a biomarker of early, potentially reversible, vascular damage. This study aimed to assess endothelial function using conventional and novel indices of PAT in pediatric hypertensives. As such, 100 adolescents with normal blood pressure, and essential and white-coat hypertension were examined using EndoPAT 2000. Conventional reactive hyperemia index (RHI) and novel indices of hyperemic response, including the area under the curve of hyperemic response (AUC), were evaluated. AUC was the only parameter sensitive to the effect of hypertension, with significantly lower values in essential hypertensives compared to normotensives and white-coat hypertensives (p = 0.024, p = 0.032, respectively). AUC was the only parameter significantly correlating with mean ambulatory monitored blood pressure (r = −0.231, p = 0.021). AUC showed a significant negative association with age (p = 0.039), but a significant positive association with pubertal status indexed by plasma levels of dehydroepiandrosterone (p = 0.027). This is the first study reporting early signs of microvascular endothelial dysfunction evaluated using PAT in adolescents with newly diagnosed essential hypertension. Detailed analysis of hyperemic response using overall magnitude indexed by AUC provided a more robust method compared to the conventional evaluation of RHI

The Effect of Age, Hypertension, and Overweight on Arterial Stiffness Assessed Using Carotid Wall Echo-Tracking in Childhood and Adolescence

Arterial stiffness represents an independent predictor of the risk of subsequent cardiovascular events. Early identification of high-risk individuals is necessary for effective prevention and targeted interventions. Carotid wall echo-tracking is a modern method for an accurate evaluation of the structural and functional properties of carotid arteries. This study aimed to assess age and sex-specific reference values of the echo-tracking parameters of carotid stiffness in 400 healthy children and adolescents and to evaluate the potential early effect of elevated blood pressure and overweight in 69 overweight normotensives, 45 white coat hypertensives, and 44 essential hypertensives. Stiffness index β, pressure–strain elastic modulus (Ep), arterial compliance (AC), and pulse wave velocity β (PWV β) were evaluated using Aloka ProSound F75. Both white coat and essential hypertension were associated with impaired carotid wall properties with the greatest effect on Ep, followed by PWV β, index β, and AC. The excess weight showed a weaker effect on Ep and PWV β. This is the first study to compare the effects of white coat and essential hypertension on carotid arterial stiffness assessed using the echo-tracking technique in childhood and adolescence with direct application of pediatric reference values specific to age and sex

Reply to Comments:Using the Cardio-Ankle Vascular Index (CAVI) or the Mathematical Correction Form (CAVI(0)) in Clinical Practice

We read with great interest Alizargar et al [...

Direct means of obtaining CAVI0-a corrected cardio-ankle vascular stiffness index (CAVI)-from conventional CAVI measurements or their underlying variables

OBJECTIVE: Cardio-ankle vascular index (CAVI) as measured using the VaSera device (CAVIVS, Fukuda Denshi), has been proposed as a stiffness index that does not depend on blood pressure. We have recently shown theoretically that CAVIVS still exhibits blood pressure dependence, and proposed the corrected index CAVI0. The present study aims to establish a method of calculating [Formula: see text] either (i) from VaSera-reported values of cardiac-brachial and brachial-ankle pulse transit times (tb and tba, respectively) and blood pressure, or (ii) directly from CAVIVS. To derive this method, the relationship among CAVIVS and its scale constants a and b, tb, tba, and blood pressure has to be established. APPROACH: From data of 497 subjects, eight candidate CAVI parameters were defined and calculated, containing all combinations of left or right tb/tba/blood pressure. Candidates were evaluated through correlation with measured left and right CAVIVS. Correlations were compared statistically. Once the correct candidates were determined, two constants (a and b) required for converting CAVIVS to CAVI0 were estimated through linear regression. MAIN RESULTS: Left and right CAVIVS are calculated using left and right tba; however, both left and right CAVIVS are calculated using right brachial blood pressures and right tb. Constants a and b for conversion of CAVIVS to CAVI0 were estimated to be 0.842 [0.836 0.848] and 0.753 [0.721 0.786] (mean [95%CI]), respectively. Equations to estimate CAVI0 from CAVIVS, and to directly calculate CAVI0 from the VaSera output are provided in this paper, as well as in a directly usable spreadsheet supplement. SIGNIFICANCE: Our results permit straightforward calculation of [Formula: see text] during a study, as well as retrospective estimation of [Formula: see text] from CAVIVS in already published studies or where the original transit time values are not available, paving the way for thorough comparison of CAVI0 to CAVIVS in clinical and research settings. Novelty and significance Cardio-ankle vascular index (CAVI) as measured using the VaSera device (CAVIVS, Fukuda Denshi), has been proposed as a blood pressure-independent arterial stiffness index. We have recently shown theoretically that CAVIVS still exhibits pressure dependence, and proposed a corrected index, CAVI0. In the present study, we derived equations to directly obtain CAVI0 using data from the VaSera device. Our results permit straightforward calculation of [Formula: see text] during a study, as well as retrospective estimation of [Formula: see text] from CAVIVS in already published studies, paving the way for thorough comparison of CAVI0 to CAVIVS in clinical and research settings

Improved assessment of arterial stiffness using corrected cardio-ankle vascular index (CAVI0) in overweight adolescents with white-coat and essential hypertension

Arterial stiffness is a marker of vascular damage. Although adiposity increases cardiovascular risk, the relationship between paediatric overweight and arterial stiffness is unclear. The study aimed to evaluate the simultaneous effect of hypertension and overweight on arterial stiffness using cardio-ankle vascular index (CAVI) and related novel, theoretically blood pressure (BP)-independent, index CAVI0. CAVI and CAVI0 were measured in 140 adolescent boys (16.0 ± 1.9 years) divided into age-matched groups: normal-weight normotensives, overweight normotensives, overweight white-coat hypertensives, and overweight essential hypertensives. Overweight normotensives had significantly lower CAVI and CAVI0 compared to normal-weight normotensives (4.81 ± 0.64 vs. 5.33 ± 0.66, p < .01; 7.10 ± 0.99 vs. 7.81 ± 1.00, p < .01, respectively). CAVI and CAVI0 in overweight essential hypertensives showed no significant difference compared to normal-weight normotensives and were significantly higher compared to overweight normotensives (5.32 ± 0.77 vs. 4.81 ± 0.64, p < .01; 7.77 ± 1.19 vs. 7.10 ± 0.99, p < .01, respectively). CAVI, but not CAVI0, was associated positively with diastolic pressure (0.022 mmHg-1, p = .002) and negatively with pulse pressure (-0.022 mmHg-1, p = .001), and it was significantly higher in overweight white-coat hypertensives compared to overweight normotensives (5.20 ± 0.63 vs. 4.81 ± 0.64, p < .05). The lowering effect of overweight on arterial stiffness indexed by CAVI and CAVI0 in hypertensive adolescents seems to counterbalance the early arteriosclerotic effect of essential hypertension. The increase in CAVI, but not CAVI0, in overweight white-coat hypertensives could be attributable to residual BP dependence of CAVI, which is not present in CAVI0. Under certain conditions, CAVI0 may offer a clinically relevant improved assessment of arterial stiffness superior to CAVI

Novel Biomarkers of Early Atherosclerotic Changes for Personalised Prevention of Cardiovascular Disease in Cervical Cancer and Human Papillomavirus Infection

Cervical cancer is associated with a causative role of human papillomavirus (HPV), which is a highly prevalent infection. Recently, women with a genital HPV infection were found to have increased incidence of cardiovascular diseases (CVD), including severe cardiovascular events such as myocardial infarction and stroke. The pathomechanisms of this relation are not yet fully understood, and may significantly affect the health of a large part of the population. Accelerated atherosclerosis is assumed to play a key role in the pathophysiology of this relationship. To identify high-risk groups of the population, it is necessary to stratify the CVD risk. Current algorithms, as widely used for the estimation of CVD risk, seem to be limited by the individual misclassification of high-risk subjects. However, personalised prediction of cardiovascular events is missing. Regarding HPV-related CVD, identification of novel sensitive biomarkers reflecting early atherosclerotic changes could be of major importance for such personalised cardiovascular risk prediction. Therefore, this review focuses on the pathomechanisms leading to HPV-related cardiovascular diseases with respect to atherosclerosis, and the description of potential novel biomarkers to detect the earliest atherosclerotic changes important for the prevention of CVD in HPV infection and cervical cancer