Ambulatory arterial stiffness index is increased in hypertensive childhood disease

Arterial hypertension in adults is often associated with an increased arterial stiffness, which correlates with the ambulatory arterial stiffness index (AASI) as derived from ambulatory blood pressure (BP) measurements. The purpose of this study was to demonstrate whether children with diagnosed hypertension have an increased AASI as in hypertensive adults. AASI was calculated from 185 ambulatory BP measurements of 114 hypertensive and 71 normotensive, healthy children. Hypertensive children had higher AASI values compared with their normotensive healthy counterparts (0.370 +/- 0.120 versus 0.204 +/- 0.199, p < 0.0001). Children with longer duration of hypertension or a history of primary or secondary aortic coarctation displayed even more elevated AASI values. A receiver operator curve derived cut-off of AASI set at 0.301 distinguished (p < 0.0001) hypertensive from normotensive children with an odds ratio of 8.2, a sensitivity of 81%, and a specificity of 65%. Moreover, AASI correlated with pulse and systolic BP. In conclusion, AASI is elevated in hypertensive children and correlates with the duration and the origin of hypertension in childhood.

Increased ambulatory arterial stiffness index in obese children.

OBJECTIVE Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Ambulatory arterial stiffness index (AASI, defined as one minus the regression slope of diastolic on systolic blood pressure values derived from a 24 h arterial blood pressure monitoring, ABPM) is an upcoming and readily available marker of arterial stiffness. Our hypothesis was that AASI is increased in obese children compared to age- and gender matched healthy subjects. METHODS AASI was calculated from ABPM in 101 obese children (BMI ≥ 1.88 SDS according to age- and sex-specific BMI charts), 45% girls, median BMI SDS 2.8 (interquartile range (IQR) 2.5-3.4), median age 11.5 years (9.1-13.4) and compared with an age and gender matched healthy control group of 71 subjects with median BMI SDS 0.0 (-0.8-0.5). Multivariate regression analysis was applied to identify significant independent factors explaining AASI variability in this population. RESULTS AASI was significantly higher in obese children compared to controls (0.388 (0.254-0.499) versus 0.190 (0.070-0.320), p < 0.0001), but blood pressure values were similar. In a multivariate analysis including obese children only, AASI was independently predicted by 24-h systolic blood pressure SDS (p = 0.012); in a multivariate analysis including obese children and controls BMI SDS and pulse pressure independently influenced AASI (p < 0.001). CONCLUSIONS This study shows that AASI, a surrogate marker of arterial stiffness, is increased in obese children. AASI seems to be influenced by BMI and pulse pressure independently of systolic and diastolic blood pressure values, suggesting that other factors are involved in increased arterial stiffness in obese children.

Arterial stiffness is increased in asthmatic children.

UNLABELLED Altered arterial stiffness is a recognized risk factor of poor cardiovascular health. Chronic inflammation may increase arterial stiffness. We tested whether arterial stiffness is increased children with asthma, a chronic disease characterized by fluctuating airway and systemic inflammation. Arterial stiffness, expressed as carotid-femoral pulse wave velocity (PWVcf), was measured in 37 mild-to-moderate asthmatic children: 11 girls, median (range) age 11.1 years (6-15). PWVcf in asthma was compared to PWVcf in 65 healthy controls matched for age, height, and gender previously studied in Germany and was correlated with airway inflammation and obstruction. PWVcf was higher in asthmatic children compared to controls: PWVcf median (interquartile range) was 4.7 m/s (4.5-4.9) vs. 4.3 m/s (4.1-4.7), p < 0.0001. In asthmatic children, PWVcf was inversely associated (r (2) = 0.20, p = 0.004) with forced expiratory volume in 1 s (FEV1). This association remained significant after adjusting for possible confounders including body mass index, blood pressure, steroid use, and FeNO. CONCLUSION Arterial stiffness is increased in children with mild-to-moderate asthma. The association between impaired lung function and increased arterial stiffness suggests that severity of disease translates into detrimental effects on the cardiovascular system.

ARTERIAL STIFFNESS IN CHILDREN WITH AND WITHOUT DEVELOPMENTAL COORDINATION DISORDER

The purpose of this study was to determine whether children with potential developmental coordination disorder (p-DCD) demonstrate increased arterial stiffness and thickness compared to age and school matched controls (mean age 14.7 yrs). We also assessed whether these measures differed by sex. Compliance, distensibility, and intima-media thickness (IMT) were measured at the common carotid artery for 28 children with p-DCD and 47 controls. ECG-R-wave-toe pulse wave velocity (PWV) was also measured for 29 children with p-DCD and 45 controls. We found that compared to controls males with p-DCD had significantly higher PWV (3.8±0.2 vs. 4.1±0.3, p=0.001) and lower distensibility (0.82± 0.19 vs. 0.70± 0.17, p=0.034) while females showed no significant differences (p=0.523 and p=0.123 respectively). As a result, it is apparent that sex differences exist with respect to arterial health within this population and that children with p-DCD may be more likely to develop cardiovascular disease later in life.

Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population

de Oliveira Alvim R, Lima Santos PCJ, Goncalves Dias R, Rodrigues MV, de Sa Cunha R, Mill JG, Junior WN, Krieger JE, Pereira AC. Association between the C242T polymorphism in the p22phox gene with arterial stiffness in the Brazilian population. Physiol Genomics 44: 587-592, 2012. First published April 10, 2012; doi:10.1152/physiolgenomics.00122.2011.-NADPH oxidase p22phox subunit is responsible for the production of reactive oxygen species in the vascular tissue. The C242T polymorphism in the p22phox gene has been associated with diverse coronary artery disease phenotypes, but the findings about the protective or harmful effects of the T allele are still controversial. Our main aim was to assess the effect of p22phox C242T genotypes on arterial stiffness, a predictor of late morbidity and mortality, in individuals from the general population. We randomly selected 1,178 individuals from the general population of Vitoria City, Brazil. Genotypes for the C242T polymorphism were detected by PCR-RFLP, and pulse wave velocity (PWV) values were measured with a noninvasive automatic device Complior. p22phox and TNF-alpha gene expression were quantified by real-time PCR in human arterial mammary smooth muscle cells. In both the entire and nonhypertensive groups: individuals carrying the TT genotype had higher PWV values and higher risk for increased arterial stiffness [odds ratio (OR) 1.93, 95% confidence interval (CI) 1.27-2.92 and OR 1.78, 95% CI 1.07-2.95, respectively] compared with individuals carrying CC + CT genotypes, even after adjustment for covariates. No difference in the p22phox gene expression according C242T genotypes was observed. However, TNF-alpha gene expression was higher in cells from individual carrying the T allele, suggesting that this genetic marker is associated with functional phenotypes at the gene expression level. In conclusion, we suggest that p22phox C242T polymorphism is associated with arterial stiffness evaluated by PWV in the general population. This genetic association shed light on the understanding of the genetic modulation on vascular dysfunction mediated by NADPH oxidase.

Thioredoxin interacting protein (TXNIP) rs7212 polymorphism is associated with arterial stiffness in the Brazilian general population

Thioredoxin interacting protein plays a pivotal role in several important processes of cardiovascular homeostasis by functioning as a biological sensor for biomechanical and oxidative stress. However, the effects of genetic variants in the modulation of arterial stiffness are unknown. In this scenario, the present study evaluated the relationship between the TXNIP rs7212 polymorphism and arterial stiffness. In the overall sample and in the diabetic group, individuals carrying CG + GG genotypes had higher PWV values compared with CC genotype group ( 10.0 vs 9.8 ms(-1), P = 0.03; 12.3 vs 11.2 ms(-1), P = 0.01; respectively). Our findings indicated that the G allele may contribute to increased arterial stiffness in the Brazilian general population and suggest a possible interaction with diabetes.

Impact of diabetes mellitus on arterial stiffness in a representative sample of an urban Brazilian population

Background Independent of other cardiovascular (CV) risk factors, increased arterial stiffness has been established as a predictor of morbidity and mortality. The main aim of this study was to investigate the impact of diabetes on arterial stiffness in a representative sample of an urban Brazilian population plus Amerindians. Methods A total of 1,415 individuals from the general population were randomly selected plus 588 Amerindians from a native community in Brazil. In addition, a sub-sample of 380 individuals from the general population had 5-year follow-up data. Pulse wave velocity (PWV) was measured with a non-invasive automatic device (Complior, Colson; Garges les Gonesses, France) and increased arterial stiffness was defined as PWV ≥ 12 m/s. Results In the overall group, diabetic individuals had higher frequencies of increased arterial stiffness and hypertension. They also had higher values of PWV, body mass index, total cholesterol, triglycerides, systolic and diastolic blood pressures compared to non-diabetic individuals (p < 0.01). In an analysis stratified by hypertension, PWV values and increased arterial stiffness frequency were higher in diabetic individuals in both groups (hypertensive and non-hypertensive) (p < 0.05). Furthermore, higher risk for increased arterial stiffness was observed in the diabetic individuals from the overall group (OR = 2.27; CI = 1.47-3.52, p < 0.001) and from the hypertensive group (OR = 2.70; CI = 1.58-4.75, p < 0.001), adjusted for covariates. Regarding the ethnic stratification, diabetic individuals from Amerindian, White, and Mulatto (mixed-race) groups had higher PWV values and a greater frequency of increased arterial stiffness compared to non-diabetic individuals. Both diabetic and non-diabetic individuals had higher PWV values after 5 years. There was no significant difference in the 5-year PWV progression in diabetic compared to non-diabetic individuals. Conclusions These results confirm, in a sample of Brazilian population, that the presence of diabetes is associated with increased arterial stiffness and it may contribute in part to increased cardiovascular risk in diabetic patients.

Arterial stiffness and arteriovenous fistula failure of maturation

PURPOSE: Increased arterial stiffness is a common finding in patients with end-stage renal disease. Following creation of an arteriovenous fistula (AVF), appropriate dilation of the feeding artery must occur to facilitate AVF maturation. Arterial stiffness may impair the arterial dilation required to facilitate AVF development and contribute to subsequent failure to mature (FTM). The aim of this pilot study was to investigate the association between measurements of central and peripheral arterial stiffness, and AVF FTM.

METHODS: Patients undergoing AVF creation in a single centre (Belfast City Hospital, UK) between January and December 2015 were invited to have their carotid-femoral pulse wave velocity (PWV), brachial-radial PWV and augmentation index (AI) measured prior to AVF creation. Subsequent AVF outcomes were identified.

RESULTS: Fifty-nine patients who had an AVF procedure were included in the final analysis (mean age 62 years); 50.8% had diabetes mellitus. The mean pre-operative arterial diameter for all AVFs was 3.9 mm. Average values for carotid-femoral PWV were 9.5 m/s, brachial-radial PWV 7.7 m/s and AI 25.6%. Using logistic regression, these arterial stiffness parameters did not predict AVF FTM: carotid-femoral PWV (P = 0.20), brachial-radial PWV (P = 0.13), AI (P = 0.50).

CONCLUSIONS: This is the largest study to date exploring the association between arterial stiffness and AVF FTM. The measured central and peripheral arterial stiffness parameters were not associated with AVF FTM. Further research is needed to define if non-invasive arterial physiological measurements would be clinically useful in the prediction of AVF FTM.

Arterial stiffness and cardiovascular risk factors

Background: As the human body ages, the arteries gradually lose their elasticity and become stiffer. Although inevitable, this process is influenced by hereditary and environmental factors. Interestingly, many classic cardiovascular risk factors affect the arterial stiffness. During the last decade, accelerated arterial stiffening has been recognized as an important cardiovascular risk factor associated with increased mortality as well as with several chronic disorders. Objectives: This thesis examines the role of arterial stiffness in relation to variations in a physiological feature in healthy individuals. In addition, the effect on arterial stiffness of an acute transitory disease and the effect of a chronic disease are studied. Furthermore, the thesis analyzes the prognostic value of a marker of arterial stiffness in individuals with chronic disease. Finally, a potential method of reducing arterial stiffness is evaluated. Material and study design: The first study examines pulse wave reflection and pulse wave velocity in relation to muscle fibre distribution in healthy middle-aged men. In the second study, pulse wave reflection in women with current or previous preeclampsia is compared to a healthy control group. The effect of aging on the different blood pressure indices in patients with type 1 diabetes is examined in the third study, whereas the fourth paper studies the relation between these blood pressure indices and mortality in type 2 diabetes. The fifth study evaluates how intake of a fermented milk product containing bioactive peptides affects pulse wave reflection in individuals with mild hypertension. Results and conclusions: Muscle fibre type distribution is not an independent determinant of arterial stiffness in middle-aged males. Pulse wave reflection is increased in pregnant women with preeclampsia, but not in previously preeclamptic non-pregnant women. Patients with type 1 diabetes have a higher and more rapidly increasing pulse pressure, which suggests accelerated arterial stiffening. In elderly type 2 diabetic patients, very high and very low levels of pulse pressure are associated with higher mortality. Intake of milk-derived bioactive peptides reduces pulse wave reflection in hypertensive males but not in hypertensive females.

Fenofibrate and pioglitazone improve endothelial function and reduce arterial stiffness in obese glucose tolerant men

Obesity is a low grade inflammatory state associated with premature cardiovascular morbidity and mortality. Along with traditional risk factors the measurement of endothelial function, insulin resistance, inflammation and arterial stiffness may contribute to the assessment of cardiovascular risk. We conducted a randomised placebo controlled trial to assess the effects of 12 weeks treatment with a PPAR-alpha agonist (fenofibrate) and a PPAR-gamma agonist (pioglitazone) on these parameters in obese glucose tolerant men. Arterial stiffness was measured using augmentation index and pulse wave velocity (PWV). E-selectin, VCAM-1 and ICAM-1 were used as markers of endothelial function. Insulin sensitivity improved with pioglitazone treatment (p=0.001) and, in keeping with this, adiponectin increased by 85.2% (p

Does altering brachial artery tone with lower-body negative pressure and flow-mediated dilation affect arterial stiffness?

Although medium sized, muscular vessels normally respond to sympathetic stimulation by reducing compliance, it is unclear whether the large brachial artery is similarly affected by sympathetic stimulation induced via lower-body negative pressure (LBNP). Similarly, the impact of flow-mediated dilation (FMD) on brachial artery compliance and distensibility remains unresolved, hi addition, before such measures can be used as prognostic tools, it is important to investigate the reliability and repeatability of both techniques. Using a randomized order design, the effects of LBNP and FMD on the mechanical properties of the brachial artery were examined in nine healthy male subjects (mean age 24y). Non-invasive Doppler ultrasound and a Finometer were used to measure simultaneously the variation in systolic and diastolic diameter, and brachial blood pressure, respectively. These values were used to calculate compliance and distensibility values at baseline, and during both LBNP and FMD. The within-day and between-day repeatability of arterial diameter, compliance, distensibility, and FMD measures were assessed using the error coefficient and intra-class correlation coefficient (ICC). While heart rate (P<0.01) and peripheral resistance increased during LBNP (P<0.05), forearm blood flow and pulse pressure decreased (P<0.01). hi terms of mechanical properties, vessel diameters decreased (P<0.05), but both compliance and distensibility were not changed. On the other hand, FMD resulted in a significant increase in diameter (P<0.001), with no change in compliance or distensibility. hi summary, LBNP and FMD do not appear to alter brachial artery compliance or distensibility in young, healthy males. Whereas measures ofFMD were not found to be repeatable between days, the ICC indicated that compliance and distensibility were repeatable only within-day.

Arterial stiffness assessed by digital volume pulse correlates with comorbidity in patients with ESRD

BACKGROUND: Digital volume pulse (DVP), a noninvasive method for indirect assessment of arterial stiffness, was not tested previously in patients with end-stage renal disease (ESRD). Therefore, we compared the DVP-derived stiffness index (SI(DVP)) with aortic pulse wave velocity (PWV) determined by means of Doppler ultrasonography in 2 groups of patients with ESRD and analyzed the correlation between SI(DVP) and comorbidity. METHODS: Photoplethysmography was performed on the index finger of the dominant hand or the hand from the nonfistula arm in 49 renal transplant (TX) recipients and 48 hemodialysis (HD) patients. Pulse curves were analyzed with computer assistance. Comorbidity was assessed by using an established index. RESULTS: The intrasubject variability of SI(DVP) was 5.7%. SI(DVP) and aortic PWV values correlated significantly (r = 0.66; P = 0.001) in patients with ESRD. SI(DVP) could not be assessed reliably in 25% and 6% of HD patients and TX recipients, respectively. Multivariate regression analyses showed that SI(DVP) increased with age in both HD patients and TX recipients (r = 0.61; P < 0.001) and with systolic blood pressure (r = 0.53; P < 0.025), mean arterial pressure (r = 0.47; P < 0.05), and pulse pressure (r = 0.52; P = 0.02) in TX recipients. Severity of comorbid status was associated highly with individual residuals of age-adjusted SI(DVP) in HD patients and TX recipients (P < 0.001). CONCLUSION: DVP allows the measurement of arterial stiffness in most, but not all, patients with ESRD. SI(DVP) values correlate with comorbidity in HD patients and TX recipients.

Pulse contour analysis: a valid assessment of central arterial stiffness in children?

In adults the contour analysis of peripheral pressure waves in the upper limb reflects central aortic stiffness. Here, we wanted to demonstrate the appropriateness of pulse contour analysis to assess large artery stiffness in children. Digital volume pulse analysis, with the computation of the stiffness index and pulse wave velocity between carotid and femoral artery, were simultaneously determined in 79 healthy children between 8 years and 15 years (mean age 11.4 years, 32 girls). The stiffness index of 42 healthy adults (mean age 45.6 years, 26 women) served as control. Pulse wave velocity between carotid and femoral artery was directly correlated with systolic pressure and mean blood pressure, as well as with pulse pressure. The results from the stiffness index of children revealed the expected values extrapolated from the linear regression of adulthood stiffness index vs. age. Childhood stiffness index positively correlated with pulse wave velocity (r(2) = 0.07, P = 0.02) but not with blood pressure parameters. The exclusion of individuals with an increased vascular tone, as indicated by a reflexion index > 90%, improved the correlation between stiffness index and pulse wave velocity (r(2) = 0.13, P = 0.001). Our data indicate that digital volume pulse-based analysis has limitations if compared with pulse wave velocity to measure arterial stiffness, mostly in patients with a high vascular tone.

Inactive Matrix Gla-Protein Is Associated With Arterial Stiffness in an Adult Population-Based Study

Increased pulse wave velocity (PWV) is a marker of aortic stiffness and an independent predictor of mortality. Matrix Gla-protein (MGP) is a vascular calcification inhibitor that needs vitamin K to be activated. Inactive MGP, known as desphospho-uncarboxylated MGP (dp-ucMGP), can be measured in plasma and has been associated with various cardiovascular markers, cardiovascular outcomes, and mortality. In this study, we hypothesized that high levels of dp-ucMGP are associated with increased PWV. We recruited participants via a multicenter family-based cross-sectional study in Switzerland. Dp-ucMGP was quantified in plasma by sandwich ELISA. Aortic PWV was determined by applanation tonometry using carotid and femoral pulse waveforms. Multiple regression analysis was performed to estimate associations between PWV and dp-ucMGP adjusting for age, renal function, and other cardiovascular risk factors. We included 1001 participants in our analyses (475 men and 526 women). Mean values were 7.87±2.10 m/s for PWV and 0.43±0.20 nmol/L for dp-ucMGP. PWV was positively associated with dp-ucMGP both before and after adjustment for sex, age, body mass index, height, systolic and diastolic blood pressure (BP), heart rate, renal function, low- and high-density lipoprotein, glucose, smoking status, diabetes mellitus, BP and cholesterol lowering drugs, and history of cardiovascular disease (P≤0.01). In conclusion, high levels of dp-ucMGP are independently and positively associated with arterial stiffness after adjustment for common cardiovascular risk factors, renal function, and age. Experimental studies are needed to determine whether vitamin K supplementation slows arterial stiffening by increasing MGP carboxylation.