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.

Arterial stiffness and haemodynamic regulation in adolescent anorexia nervosa versus obesity.

Cardiovascular complications contribute to higher morbidity and mortality in patients with anorexia nervosa. We aimed to study biomarkers of cardiovascular risk in anorexic, normal-weight, and obese adolescents with focus on complex cardiovascular autonomic regulation and early arteriosclerotic damage. We examined 20 adolescent girls with anorexia nervosa, 20 obese girls, and 20 healthy normal-weight controls. Collected data: body composition analysis, 5 min recordings of R-R intervals and beat-to-beat blood pressure (BP), and arterial stiffness evaluated using cardio-ankle vascular index (CAVI). Evaluated parameters: beat-to-beat heart rate and BP variability, haemodynamic parameters (total peripheral resistance (TPR) cardiac output), CAVI, and anthropometric indices, including novel body roundness index (BRI). Adolescents with anorexia nervosa had increased CAVI associated with lower arterial constriction indexed by low-frequency band of BP variability compared with normal-weight peers (p = 0.03, p = 0.04, respectively) and obese adolescents (p < 0.01, p = 0.01, respectively). After normalization of CAVI and TPR by BRI, the relationship between CAVI and TPR was significant for all groups with the highest slope in the anorexia nervosa group (R2 = 0.724, p < 0.01). This is the first study revealing early arteriosclerotic damage in anorexic girls with increased CAVI. Complex analysis of cardiovascular autonomic regulation, and early arteriosclerotic, hemodynamic, and anthropometric changes in spectrum anorexia nervosa, normal weight, and obesity could help to understand the mechanisms of increased cardiovascular risk in malnutrition. Novelty Girls with anorexia nervosa showed signs of early arteriosclerotic damage indexed by CAVI. Insufficient sympathetic cardiovascular control was found already in adolescents with anorexia nervosa. The effect of body composition on CAVI was best predicted by novel body roundness index.

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.

Complex cardiac vagal regulation to mental and physiological stress in adolescent major depression.

BACKGROUND: Cardiovagal control is known to be reduced in major depressive disorder (MDD), however, the neurocardiac reflex control to distinct types of stressors is still unclear. We aimed to study parasympathetically mediated cardiac reflex functioning in response to mental and physiological stressors using heart rate variability (HRV) linear and nonlinear analysis in adolescent MDD. METHODS: We examined 60 adolescents (40 girls) with MDD (age 14.9 ±â€¯0.3 years) and 60 age and gender-matched controls. ECG was continuously recorded during stress protocol: baseline, Go/NoGo test, recovery, supine position, and orthostasis. Evaluated HRV linear and nonlinear indices: RR interval, pNN50, rMSSD, HF-HRV, Poincaré plot (SD1), symbolic dynamics 2UV%. Cardiovagal reactivity expressed as percentual change (%) was calculated in response to both stressors. RESULTS: In each phase of stress protocol, the MDD group had significantly reduced HRV parameters compared to controls, except for symbolic dynamics index 2UV% in supine position. The reactivity of HRV indices was significantly greater in response to orthostasis in MDD compared to controls. No significant differences were found in response to Go/NoGo test. LIMITATIONS: The smoking status and the menstrual cycle phase potentially affecting the HRV parameters were not monitored. Future research is needed to expand a sample size with respect to sex and to study neurocardiac response to other different stressors in MDD. CONCLUSIONS: This study revealed reduced resting cardiovagal regulation and greater vagal withdrawal indicating abnormal neurocardiac reflex functioning to physiological stressor (orthostasis) in adolescent MDD patients. Nonlinear HRV analysis was sensitive to detect cardiac-linked regulatory differences in adolescent depression.

Respiratory sinus arrhythmia - testing the method of choice for evaluation of cardiovagal regulation.

Respiratory sinus arrhythmia (RSA) is an index of cardiovagal regulation, emotional and cognitive processing. RSA is quantified using heart rate variability (HRV) spectral analysis at respiratory-linked high-frequency band (HF-HRV) using Fast Fourier transformation (FFT) or autoregressive (AR) method, both requiring resampling of recordings - a potential source of error. We hypothesized that rarely used HRV time-frequency analysis with Lomb-Scargle periodogram (LSP) without resampling could be more sensitive to detect neurocardiac response to posture change than FFT and AR. Orthostasis (posture change from supine to standing) evoked significant decrease of HF-HRV well detectable by FFT, AR, and LSP. In contrast, during posture change from sitting to lying, significant increase of HF-HRV and peak HF was best detected using LSP. In regression analysis, the associations between RR-interval, HF-HRV, and peak HF were best detected when evaluated using LSP. Time-frequency HRV analysis with LSP could represent an important alternative to conventional FFT and AR methods for assessment of cardiovagal regulation indexed by RSA.

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.

Endothelial function in children with white-coat hypertension.

Several studies have demonstrated endothelial dysfunction in patients with essential hypertension. However, the presence of endothelial dysfunction in children with white-coat hypertension has not been studied. We evaluated the endothelial function in children with white-coat hypertension and essential hypertension using a novel method based on the assessment of flow-mediated dilation (FMD). Study involved 106 children: 30 white-coat hypertensives (age 16.3 ± 1.3 years, mean ± SD), 30 essential hypertensives (age 16.4 ± 1.3 years), and 46 healthy controls (age 16.2 ± 1.4 years). Ultrasound scans of the right brachial artery were performed using Prosound F75 Aloka system during protocol: baseline (1 min), forearm ischemia (5 min), and post-occlusion phase (3 min). FMD (%) was expressed as a change of the arterial diameter from baseline to maximum post-occlusion value and the values < 5% were considered as deficient FMD. We found significantly lower FMD in both essential and white-coat hypertension compared to control group (p < 0.05 for both) with no significant difference between the hypertensive groups. Deficient FMD was found in both hypertensive groups, but not in the control group. The occurence of deficient FMD was significantly higher in both essential and white-coat hypertensives compared to controls (p < 0.01 for both) with no significant difference between the hypertensive groups. Our findings of endothelial dysfunction indicated by impaired FMD in pediatric patients with white-coat hypertension could help to elucidate the mechanisms of the increased cardiovascular risk that could be similar as found in essential hypertension; therefore, white-coat hypertension should not be considered a benign phenomenon.

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.

The complexity of electrodermal activity is altered in mental cognitive stressors.

The aim of this study was to evaluate potential changes in the electrodermal activity (EDA) to enable the detection of variations in the sympathetic nervous system during mental load and recovery period. Several EDA parameters were used: SCA (skin conductance amplitude), frequency of NS-EDR (nonspecific electrodermal responses), SIE (symbolic information entropy), and ApEn (approximate entropy). The cohort consisted of 50 healthy students (average age: 23.33±0.24yr., 25 women). The stress profile consisted of five phases: baseline (P1), Stroop test (P2), recovery (P3), mental arithmetic test (P4), and recovery (P5). All phases of the stress profile lasted six minutes. The results indicate that the three EDA indices have sufficient sensitivity to detect changes in the sympathetic nervous system. The SCA, SIE and ApEn were significantly increased during mental loads and decreased during recovery periods. However, SCA remained significantly elevated during recovery periods versus baseline, and SIE and ApEn decreased significantly during recovery versus baseline. The frequency of NS-EDR had no significant changes during stress. The EDA is a sensitive marker for evaluation of changes during the activation of sympathetic nervous system under the influence of a load. Detailed knowledge of EDA regulatory mechanisms associated with stress could provide important information associated with autonomic dysregulation.

Symbolic dynamics of heart rate variability - a promising tool to investigate cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD)?

We aimed to evaluate complex cardiac sympathovagal control in attention deficit/hyperactivity disorder (ADHD) by using heart rate variability (HRV) nonlinear analysis - symbolic dynamics. We examined 29 boys with untreated ADHD and 25 healthy boys (age 8-13 years). ADHD symptoms were evaluated by ADHD-RS-IV scale. ECG was recorded in 3 positions: baseline supine position, orthostasis, and clinostasis. Symbolic dynamics indices were used for the assessment of complex cardiac sympathovagal regulation: normalised complexity index (NCI), normalised unpredictability index (NUPI), and pattern classification measures (0V%, 1V%, 2LV%, 2UV%). The results showed that HRV complexity was significantly reduced at rest (NUPI) and during standing position (NCI, NUPI) in ADHD group compared to controls. Cardiac-linked sympathetic index 0V% was significantly higher during all posture positions and cardiovagal index 2LV% was significantly lower to standing in boys suffering from ADHD. Importantly, ADHD symptom inattention positively correlated with 0V%, and negatively correlated with NCI, NUPI. Concluding, symbolic dynamics revealed impaired complex neurocardiac control characterised by potential cardiac beta-adrenergic overactivity and vagal deficiency at rest and to posture changes in boys suffering from ADHD that is correlated with inattention. We suggest that symbolic dynamics indices could represent promising cardiac biomarkers in ADHD.

Arterial stiffness evaluated by cardio-ankle vascular index (CAVI) in adolescent hypertension.

Elevated blood pressure (BP) is a major risk factor for atherosclerosis. As the studies concerning vascular alterations in pediatric patients are rare, we aimed to study the relationship between hypertension and arterial stiffness in adolescence by novel method independent from BP during examination. Twenty nonobese adolescent boys (16.5 ± 0.4 years) with newly diagnosed essential hypertension, 20 adolescent boys (16.7 ± 0.4 years) with newly diagnosed white-coat hypertension, and 20 healthy controls matched to age and body mass index were examined. Cardio-ankle vascular index (CAVI), brachial-ankle pulse wave velocity (baPWV), pre-ejection period (PEP), and ejection time (ET) were evaluated. CAVI was significantly increased in essential hypertension patients compared with controls (p < 0.05) with no significant difference in white-coat hypertension patients. Significantly higher baPWV was found in essential and white-coat hypertension patients compared with controls (both p < 0.001). White-coat hypertension patients showed significantly shortened PEP and ET compared with controls (p < 0.01 and p < 0.001, respectively) and essential hypertension patients (both p < 0.05). For the first time, the arterial stiffness in adolescents with newly diagnosed essential and white-coat hypertension was studied using BP-independent index CAVI combined with conventional baPWV. Our study revealed significantly increased CAVI in adolescents with newly diagnosed essential hypertension compared with controls. Our findings could help to understand hypertension-atherosclerosis interaction.

Respiratory sinus arrhythmia as a non-invasive index of 'brain-heart' interaction in stress.

Respiratory sinus arrhythmia (RSA) is accepted as a peripheral marker of cardiac-linked parasympathetic regulation. According to polyvagal theory, the RSA is also considered as the index of emotion regulation. The neurovisceral integration model posits that parasympathetic modulation of the heart marked by RSA is related to complex nervous regulation associated with emotional and cognitive processing. From this perspective, high resting RSA amplitude associated with a greater withdrawal during stressors and subsequent recovery could represent a flexible and adaptive physiological response system to a challenge. Conversely, low resting RSA accompanied by an inadequate reactivity to stress might reflect maladaptive regulatory mechanisms. The RSA reactivity is different with various types of stressors: while the RSA decreases to cognitive tasks indicating a vagal withdrawal, the RSA magnitude increases to emotional challenge indicating an effective cognitive processing of emotional stimuli. The RSA reactivity to stress could have important implications for several mental disorders, e.g. depressive or anxiety disorder. It seems that the study of the RSA, as a non-invasive index of 'brain-heart' communication, could provide important information on the pathway linked to mental and physical health.