Development Of Arterial Stiffness Research Articles

Markers of Vascular Dysfunction in Hypertension.

Hypertension is a modifiable cardiovascular risk factor and displays a rapidly growing incidence due to aging and the acquisition of an unhealthy lifestyle. Hypertension is linked to the development of target organ damage in several vascular beds such as coronary arteries, peripheral, cerebral, and renal arteries. Besides, along with the presence of other cardiovascular risk factors, it aggravates vascular dysfunction due to the aging process. The mechanisms of vascular dysfunction in hypertension are complex and involve excessive salt intake and water retention, activation of neurohormonal systems, induction of endothelial dysfunction of large arteries and microcirculation, development of arterial stiffness, and complex interactions with cellular pathways of inflammation, oxidative stress, and thrombosis. The extent of vascular dysfunction in patients with hypertension can be assessed by evaluating endothelial function, measuring arterial stiffness, and testing the levels of circulating biomarkers of oxidative stress, pro-inflammatory cytokines, and thrombosis. Assessing these markers in subjects with and without hypertension could aid in identifying those at risk of vascular damage and improving risk prediction for future cardiovascular events. While several lifestyle and pharmacological therapies have shown promise in addressing vascular dysfunction in hypertension, none of these biomarkers have been established as an independent risk factor or treatment target. Therefore, in this article, we review the literature on the evidence that exists regarding the role of vascular dysfunction in the pathophysiology, diagnosis, progression, and treatment of hypertension, highlighting the lack of conclusive evidence in this field.

Role of Chemerin and Perivascular Adipose Tissue Characteristics on Cardiovascular Risk Assessment by Arterial Stiffness Markers in Patients with Morbid Obesity.

The development of arterial stiffness (AS) in obesity is a multifactorial and complex process. The pleomorphic actions of adipokines and their local activity in perivascular adipose tissue (PVAT) are potential modulators of AS appearance and progression. We aimed to assess the correlations between two adipokines (chemerin, adiponectin), PVAT morphological changes (adipocyte size, blood vessel wall thickness) and AS parameters in the special subgroup of patients with morbid obesity. We enrolled 25 patients with morbid obesity and 25 non-obese patients, who were age- and gender-matched, untreated for cardiovascular risk factors, and admitted to hospital for laparoscopic surgical procedures (bariatric surgery for morbid obesity and non-inflammatory benign pathology surgery for non-obese patients). Before the surgical procedures, we evaluated demographic and anthropometric data and biochemical parameters including the studied adipokines. Arterial stiffness was evaluated using a Medexpert ArteriographTM TL2 device. In both groups, adipocyte size and vascular wall thickness as well as local adiponectin activity were analyzed in PVAT from intraoperative biopsies. In our study, adiponectin (p = 0.0003), chemerin (p = 0.0001) and their ratio (p = 0.005) had statistically significant higher mean values in patients with morbid obesity compared to normal-weight patients. In patients with morbid obesity there were significant correlations between chemerin and AS parameters such as aortic pulse wave velocity (p = 0.006) and subendocardial viability index (p = 0.009). In the same group adipocyte size was significantly correlated with another AS parameter, namely, aortic systolic blood pressure (p = 0.030). In normal-weight patients, blood vessel wall thickness positively correlated with AS parameters such as brachial (p = 0.023) and aortic augmentation index (p = 0.023). An important finding was the negative adipoR1 and adipoR2 immunoexpression in PVAT adipocytes of patients with morbid obesity. Additionally, we found significant correlations between blood vessel wall thickness and blood fasting glucose (p < 0.05) in both groups. Chemerin and adipocyte size could be predictive biomarkers for AS in patients with morbid obesity. Given the small number of patients included, our results need further validation.

Evaluating the Arterial Stiffness as a Useful Tool in the Management of Obese Children

Childhood obesity speeds up the development of arterial stiffness and progressively increases the values of arterial pressure. The purpose of this study is to investigate the value of using pulse wave analysis (PWA) to measure arterial stiffness as a sign of vascular wall impairment in obese children. The research was focused on 60 subjects: 33 obese and 27 normal-weight. Ages ranged from 6 to 18 years old. PWA includes parameters such as pulse wave velocity (PWV), augmentation index (AIx), peripheral and central blood pressure (SBP, DBP, cSBP, cDBP), heart rate, and central pulse pressure (cPP). The device used was a Mobil-O-Graph. Blood parameters were taken from the subject's medical history, not older than 6 months. A high BMI and a large waist circumference are linked to a high PWV. The levels of LDL-c, triglycerides (TG), non-HDL-c, TG/HDL-c ratio, and total cholesterol-HDL-c ratio significantly correlate to PWV, SBP, and cSBP. Alanine aminotransferase is a reliable predictor of PWV, AIx, SBP, DBP, and cDBP, while aspartate aminotransferase is a significant predictor of AIx, mean arterial pressure (MAP), cSBP, and cPP. 25-OH-Vitamin D negatively correlates with PWV, SBP, and MAP and significantly predicts the MAP. Cortisol and TSH levels are not significant to arterial stiffness in obese children without specific comorbidities and neither is fasting glucose in obese children without impaired glucose tolerance. We conclude that PWA contributes valuable data regarding patients' vascular health and should be considered a reliable tool in the management of obese children.

PS-P01-2: ARTERIAL STIFFNESS IN PATIENTS WITH ARTERIAL HYPERTENSION INFLUENCED BY AGTR2 GENE G1675A POLYMORPHISM IN UZBEK POPULATION

Material and Methods: 109 Uzbek male and female with I / III AH (ESH / ESC, 2018), mean age 54.1 ± 11.3 years, average duration of AH was 9.1 ± 5.9 years. Applanation tonometry was performed using SphygmoCor device (AtCor Medical, Australia) to measure the carotidfemoral pulse wave velocity (PWV). The genotyping of G1675A polymorphism of AGTR2 gene in 109 patients was carried out. Results are presented as M ± SD. For all types of analysis, P values less 0.05 were considered statistically significant. Results: 109 patients were examined and divided into two groups: 1st group with increased arterial stiffness: patients with pulse wave velocity (PWV) more 10 m/s (cases, n = 62) and 2nd group: patients with PWV less 10 m/s (controls, n = 47). 1st group, following distribution of G1675A polymorphism of AGTR2 gene was revealed: GG genotype determined in 54.8% of patients, GA genotype in 12.9%, AA genotype 32.3%, x2 = 18.21, P = 2.0. The allelic distribution showed the predominance of G allele carriers: G allele 61.3%, A allele 38.7%, x2 = 11.758, P = 0.000. 2nd group, the allelic distribution was uniform: A allele in 56.4% and G allele in 43.6%, respectively, x2 = 2.574, P = 0.109. The ratio of GG:GA:AA genotypes was as follows: 27.7%: 31.9%: 40.4%, x2 = 2.88, P = 0.09. An association of G allele with the development of arterial stiffness in patients with AH was found: among 62 patients of 1st group, G allele was common than in patients of 2nd group (61.3%; x2 = 6.72; p = 0.01; OR = 2.05, 95% CI 1.19–3.53) and only 38.7% of patients had A allele. That demonstrated an accumulation of GG genotype among patients of 1st group (54.8%; x2 = 9.66; P = 0.008; OR = 3.18, 95% CI 1.41), while GA genotype occurred in 12.9% of cases and AA genotype in 32.3% of cases. Whereas in the 2nd group, the GG genotype was less common in 27.7% of cases than the GA genotype (31.9%) and AA genotype (40.4%) cases. Conclusion: The study indicates greater accumulation of the G allele of the AGTR2 gene G1675A polymorphism among patients, where G allele and GG genotype are associated with the development of arterial stiffness in patients with AH of the Uzbek population.

Features of vascular rigidity in patients with arterial hypertension in combination with chronic heart failure and senile asthenia syndrome

Objective. The aim of the study was to evaluate the features of vascular rigidity in patients with arterial hypertension (AH) depending on the presence of chronic heart failure (CHF) and senile asthenia syndrome (SAS).Design and methods. 320 patients with AH were divided into two main groups: group 1 — patients with AH and CHF (n = 161), group 2 — patients with AH without CHF (n = 159). Depending on the presence of SAS, patients of each group were divided as follows: subgroup 1A — patients with AH, CHF and SAS (n = 84), subgroup 1B — patients with AH, CHF without SAS (n = 77), subgroup 2A — patients with AH, SAS without CHF (n = 84), subgroup 2B — patients with AH without CHF and without SAS (n = 75). To identify SAS, we used the “Age is not a barrier” questionnaire and a short battery of physical functioning tests. The parameters of vascular stiffness were determined using a device for daily monitoring of blood pressure BPLab using Vasotens technology (Peter Telegin, Nizhny Novgorod). The obtained data were processed using STATISTICA 12.0 (StatSoft Inc., USA), SPSS 21.0, MedCalc (version 9.3.5.0).Results. Analysis of the effect of SAS on vascular stiffness showed that in patients with AH, CHF and SAS, compared with patients with AH, CHF without SAS, there were statistically significantly lower values of the reflected wave propagation time (RWTT) (p = 0,001) against the background of higher values pulse wave velocity in the aorta (РWVао) (p &lt; 0,001), arterial stiffness index (ASI) (p = 0,0001) and ambulatory arterial stiffness index (AASI) (p = 0,002), which indicates more pronounced vascular stiffness in patients with AH, CHF in the presence of SAS. In the group of patients with AH and SAS without CHF, compared with patients with AH without CHF and without SAS, higher values of РWVао (p &lt; 0,001) and “adjusted” index of augmentation index (AIх@75) (p &lt; 0,001) were revealed, which allows to judge the effect of SAS on the development of arterial stiffness in patients with AH without CHF. Analysis of the effect of CHF on vascular stiffness showed that in patients with AH, SAS and CHF, compared with patients with AH, SAS without CHF, statistically significantly lower values of RWTT (p &lt; 0,001) and higher values of РWVао (p = 0,024) were noted, ASI (p &lt; 0,001), AASI (p &lt; 0,001), maximum rate of blood pressure rise (dP/dtmax) (p &lt; 0,001) and AIх@75 (p &lt; 0,001). In the group of patients with AH, CHF without SAS, compared with patients with AH without CHF and without SAS, lower values of RWTT (p &lt; 0,001) and higher values of РWVаo (p = 0,004), ASI (p &lt; 0,001), AASI (p &lt; 0,001) and dP/dtmax (p &lt; 0,001), which in turn demonstrates the contribution of CHF to the development of vascular stiffness in AH patients without SAS. CS.Conclusions. In hypertensive patients over 80 years of age, the development of both SAS and CHF was accompanied by limited compliance of the aortic walls and increased vascular stiffness in the peripheral arteries. Significantly more pronounced changes in vascular stiffness parameters were noted in patients with a combination of AH, CHF and SAS compared with those in patients with AH and CHF or AH and SAS, which indicates an increase in vascular stiffness, and, consequently, a higher risk of cardiovascular diseases in this combined pathology.

Prevalence of Isolated Nocturnal Hypertension and Development of Arterial Stiffness, Left Ventricular Hypertrophy, and Silent Cerebrovascular Lesions: The KoGES (Korean Genome and Epidemiology Study).

Background Apart from nondippers' impact on cardiovascular events, the prevalence of isolated nocturnal hypertension (INH) and its consequences on both the heart and brain were not clearly investigated in the general population. Methods and Results The participants underwent ambulatory blood pressure monitoring evaluations for arterial stiffness, echocardiography, and brain magnetic resonance imaging. They were grouped into normotension, INH, and overt diurnal hypertension, based on ambulatory blood pressure monitoring and history of antihypertensive treatment. White matter hyperintensity, arterial stiffness, and echocardiographic parameters were compared. Of the 1734 participants, there were 475 (27.4%) subjects with normotension, 314 with INH (18.1%), and 945 with overt diurnal hypertension (54.5%). Prevalence of INH was not different between sex or age. Of INH, 71.3% (n=224) was caused by elevated diastolic blood pressure. After multivariable adjustment, INH showed higher pulse wave velocity (P<0.001) and central systolic blood pressure (P<0.001), left ventricular mass index (P=0.026), and worse left ventricular diastolic function (early diastolic mitral annular velocity) (P<0.001) than normotension. Mean white matter hyperintensity scores of INH were not different from normotension (P=0.321), but the odds for white matter hyperintensity presence were higher in INH than normotension (odds ratio, 1.504 [95% CI, 1.097-2.062]; P=0.011). Conclusions INH was common in the general population and associated with increased arterial stiffness, left ventricular hypertrophy, and diastolic dysfunction. White matter hyperintensity was more likely to be present in the INH group than in the normotension group. The use of ambulatory blood pressure monitoring should be encouraged to identify masked INH and prevent the occurrence of cardiovascular events.

Pathophysiological and clinical aspects of the circadian rhythm of arterial stiffness in diabetes mellitus: A minireview.

Several cross-sectional trials have revealed increased arterial stiffness connected with the cardiac autonomic neuropathy in types 2 and 1 diabetic patients. The pathophysiological relationship between arterial stiffness and autonomic dysfunction in diabetes mellitus is still underinvestigated and the question whether the presence of cardiac autonomic neuropathy leads to arterial stiffening or increased arterial stiffness induced autonomic nervous system impairment is still open. Both arterial stiffness and dysfunction of the autonomic nervous system have common pathogenetic pathways, counting state of the chronic hyperinsulinemia and hyperglycemia, increased formation of advanced glycation end products, activation of protein kinase C, development of endothelial dysfunction, and chronic low-grade inflammation. Baroreceptor dysfunction is thought to be one of the possible reasons for the arterial wall stiffening development and progression. On the contrary, violated autonomic nervous system function can affect the vascular tone and by this way alter the large arteries walls elastic properties. Another possible mechanism of attachment and/or development of arterial stiffness is the increased heart rate and autonomic dysfunction corresponding progression. This minireview analyzes the current state of the relationship between the diabetes mellitus and the arterial stiffness. Particular attention is paid to the analysis, interpretation, and application of the results obtained in patients with type 2 diabetes mellitus and diabetic cardiac autonomic neuropathy.

The independent association between salivary alpha-amylase activity and arterial stiffness in Japanese men and women: the Toon Health Study.

Psychological stress is considered to be a potential contributor in the development of arterial stiffness. However, an independent association between arterial stiffness and biological markers of stress has not yet been established. We examined the independent association between salivary alpha-amylase (sAA) activity and arterial stiffness, not mediated by cardiometabolic disease associated with arterial stiffness, in a sample of healthy Japanese men and women. Participants (992 in total, 296 men and 696 women aged 30-79 years) had neither previous cardiovascular events or stroke, nor coexisting hypertension, diabetes, or dyslipidemia. Arterial stiffness was measured by the cardio-ankle vascular index (CAVI), and increased CAVI was defined as a CAVI value of 9 or higher. A saliva sample was collected in the morning and sAA was measured with a commercial assay kit. Higher sAA activity was positively associated with greater arterial stiffness particularly among women (β = 0.070; 95% CI = 0.014-0.126; p = 0.01), and not across all participants (β = 0.042; 95% CI = -0.005-0.089; p = 0.08) and in men (β = -0.005; 95% CI = -0.097-0.087; p = 0.91). The association was strongest in the group of women aged 60 years and older (β = 0.121; 95% CI = 0.018-0.224; p = 0.02). Although the association between sAA and increased CAVI (CAVI ≥ 9) was not significant in all and sex subgroups, odds ratios (OR) for CAVI ≥ 7 were significantly high in all participants (OR = 1.25; 95% CI = 1.03-1.53) and women (OR = 1.43; 95% CI = 1.12-1.82). Elevation of sAA was associated with an increase in arterial stiffness, particularly for women aged 60 years or older.

Low serum 25-Hydroxy (OH) vitamin D levels are associated with increased arterial stiffness in healthy children: An echocardiographic study from Turkey.

Arterial stiffness refers to arterial wall rigidity, particularly in central vessels, and is an independent predictor of cardiovascular disease in many chronic diseases. 25-Hydroxy (OH) vitamin D has beneficial effects on blood pressure, vascular endothelial function, and arterial stiffness; most importantly, its deficiency is common worldwide. Therefore, we aimed to elucidate the role of 25-OH vitamin D deficiency in arterial stiffness development and its relationship with arterial stiffness in healthy children. This study included 80 patients with low levels of 25-OH vitamin D and 40 healthy control subjects. The study participants were then divided into three groups: group 1 consisted of patients with a deficient 25-OH D level of<19.9ng/ml, group 2 with an insufficient 25-OH D level between 20 and 29.9ng/ml; group 3 were considered control group with a sufficient serum 25-OH vitamin D level of ≥30ng/ml. Aortic strain, distensibility, stiffness index, and standard left ventricular measurements were calculated using M-mode echocardiographic data. Left ventricular mass index (LVMI) and inter-ventricular septal diastolic thickness (IVST) appeared to increase in group 1 compared to groups 2 and 3. Aortic strain and distensibility were significantly decreased in group 1, whereas aortic stiffness index and elastic modulus were significantly increased. The aortic stiffness index was negatively correlated with serum 25-OH vitamin D levels; however, aortic strain, aortic distensibility, and LVMI were positively correlated. Our study results revealed a significant relationship between 25-OH vitamin D levels indicative of a deficiency and aortic stiffness. Hence, we suggest that arterial stiffness may also occur in healthy children with a 25-OH vitamin D deficiency. Future in-depth studies are needed to understand the exact mechanisms underlying the aortic stiffness development associated with 25-OH vitamin D deficiency.

Association of Parental Socioeconomic Status and Physical Activity with Development of Arterial Stiffness in Prepubertal Children.

The present study examined the prospective association of parental household income, education level, migration background, and physical activity (PA) behavior with the development of pulse wave velocity (PWV) in prepubertal children. A total of 223 children (initial age 6–8 years) were included in this prospective school-based cohort study from 2014 to 2018. Parental socioeconomic status, migration background, and PA behavior were assessed by the use of questionnaires at both times points. PWV was measured by an oscillometric device at follow-up (2018). No significant association of household income, education level, and parental migration background with PWV in children after four years was found. However, a high level of maternal PA was related to a lower childhood PWV at follow-up (mean (95% CI) 4.6 (4.54–4.66) m/s) compared to children of mothers with a low PA behavior (mean (95% CI) 4.7 (4.64–4.77) m/s) (p = 0.049). Children of mothers with a high PA level revealed a beneficial arterial stiffness after four years. Little evidence for an association of socioeconomic status and migration background with childhood arterial stiffness was found. Increased parental PA seems to support the development of childhood vascular health and should be considered in the generation of future primary prevention strategies of childhood cardiovascular health.

Adipokines and Arterial Stiffness in Obesity

Adipokines are active molecules with pleiotropic effects produced by adipose tissue and involved in obesity-related metabolic and cardiovascular diseases. Arterial stiffness, which is a consequence of arteriosclerosis, has been shown to be an independent predictor of cardiovascular morbidity and mortality. The pathogenesis of arterial stiffness is complex but incompletely understood. Adipokines dysregulation may induce, by various mechanisms, vascular inflammation, endothelial dysfunction, and vascular remodeling, leading to increased arterial stiffness. This article summarizes literature data regarding adipokine-related pathogenetic mechanisms involved in the development of arterial stiffness, particularly in obesity, as well as the results of clinical and epidemiological studies which investigated the relationship between adipokines and arterial stiffness.

Assessing the Impact of Helicobacter pylori Infection and Inflammatory Bowel Disease on Pulse Wave Velocity and Arterial Stiffness.

There is some evidence that pulse wave velocity (PWV) is increased in gastrointestinal conditions such as Helicobacter pylori (H. pylori) infections and inflammatory bowel disease (IBD). However, the limited number of well-designed studies and sometimes inconsistent results have yielded more questions than answers highlighting a need for further investigation. The purpose of this review is to clarify the effects of H. pylori infections and IBD on PWV and arterial wall stiffness. The goal is to highlight the extent of the linkage between these gastrointestinal conditions and PWV and to help evaluate the practicality of PWV as a potential clinical diagnostic aid when examining arterial stiffness. PubMed, CINAHL, EMBASE, Cochrane Central Register of Controlled Trials, and Biomedical Reference Collection: Comprehensive were used to search for the full-text English language articles using keywords “pulse wave velocity” combined with either “H. pylori” or “IBD” present anywhere in the abstracts. A total of 59 papers matched the search criteria and were retrieved for evaluation. These were screened based on their relevance and availability of published papers. Full papers were analyzed based on inclusion criteria with a total of 10 articles selected and included in this review. In younger populations, H. pylori seropositivity might play a role in the development of arterial stiffness, as assessed by PWV; while in older populations, the effect of H. pylori on arterial stiffness seems to be minimal, with aging playing a major role in these older patients. PWV does not appear to be an accurate parameter to assess arterial stiffness in older patients with H. pylori. On the other hand, PWV might be useful to assess the efficacy of anti-tumor necrosis factor-alpha (anti-TNF-alpha) immunotherapy in reducing the degree of arterial stiffness caused by inflammation in patients with IBD.

The 2017 ACC/AHA stage 1 hypertension is associated with arterial stiffness: a prospective analysis.

Objective: To examine the association between stage 1 hypertension defined by the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and risk of developing arterial stiffness.Methods: During 2010-2015, 4595 adults aged ≥40 years without cardiovascular disease were followed up for a median of 4.3 years. BP levels at baseline were categorized into normal, elevated, stage 1 hypertension, and stage 2 hypertension. The development of arterial stiffness was defined as a normal brachial-ankle pulse wave velocity (ba-PWV) at baseline and an increased ba-PWV at follow-up.Results: Compared with participants with normal BP, participants with stage 1 hypertension had a 1.48-fold increased risk of developing arterial stiffness [odds ratio (OR) =2.48; 95% confidence interval (CI) =1.59-3.85] after adjustment for cardiovascular risk factors. The association was more evident in adults aged 40-59 years (OR =4.08; 95% CI =2.06-8.08) than that in those aged ≥60 years (OR =1.47; 95% CI =0.81-2.67). A systolic BP 130~139 mmHg was significantly associated with arterial stiffness independent of diastolic BP (OR =2.90; 95% CI =1.86-4.52). Stage 1 hypertension either at baseline or at follow-up was associated with increased risks compared with normal BP at both baseline and follow-up.Conclusions: The 2017 ACC/AHA stage 1 hypertension was significantly associated with higher risks of arterial stiffness.

Modern methods for determining and risk factors for the development of arterial stiffness in the practice of family medicine

Vascular stiffness is an independent prognostic parameter for the development of cardiac pathology and cardiovascular mortality. The predictive value is high at the preclinical stages of the development of the disease, since blood vessels are an integral marker of cardiovascular pathology, through which classic risk factors for cardiovascular diseases (CVD) are realized. Vascular stiffness increases due to cholesterol deposits and calcification of the vessel wall. On the other hand, an increase in blood pressure (BP) causes changes in the vascular wall, including with the development of arteriolosclerosis, which can also lead to an increase in vascular stiffness.

Sex differences in impact of long-term burden and trends of body mass index and blood pressure from childhood to adulthood on arterial stiffness in adults: A 30-year cohort study

Background and aimsObesity and hypertension play important roles in the development of arterial stiffness. We aimed to examine the sex differences in the impact of the cumulative long-term burden and trends of body mass index (BMI) and blood pressure (BP) since childhood on adult arterial stiffness (AS). MethodsThis longitudinal study consisted of 1553 individuals aged 6–15 years, who were examined 4 or more times for BMI and BP since childhood, with a follow-up period of 30 years. The area under the curve (AUC) was calculated as a measure of the long-term burden (total AUC) and trends (incremental AUC) of BMI and BP from childhood to adulthood. Brachial–ankle pulse wave velocity (baPWV) was recorded by a non-invasive automatic waveform analyser in adulthood. ResultsThe total AUC and incremental AUC of systolic BP and diastolic BP were significantly associated with higher baPWV in adults, both male and female, after adjustment for other covariates. There was no association between the total AUC of BMI and arterial stiffness regardless of sex. However, there were sex differences in the association between the incremental AUC of BMI and arterial stiffness (p = 0.019 for interaction). The incremental AUC of BMI indicated an increased risk of arterial stiffening during adulthood in males, but this association was not found in females. ConclusionsThese results emphasize the importance of developing prevention and intervention strategies for hypertension and obese men (especially those who are gradually gaining weight) to reduce the risk of arterial stiffening and cardiovascular disease in adulthood.

Pathophysiology and consequences of arterial stiffness in children with chronic kidney disease

Changes in arterial structure and function are seen early in the course of chronic kidney disease (CKD) and have been causally associated with cardiovascular (CV) morbidity. Numerous potential injuries encompassing both traditional and uremia-specific CV risk factors can induce structural arterial changes and accelerate arterial stiffening. When the buffering capacity of the normally elastic arteries is reduced, damage to vulnerable microcirculatory beds can occur. Moreover, the resultant increase to cardiac afterload contributes to the development of left ventricular hypertrophy and cardiac dysfunction. Adult studies have linked arterial stiffness with increased risk of mortality, CV events, cognitive decline, and CKD progression. Pulse wave velocity (PWV) is currently the gold standard of arterial stiffness assessment but its measurement in children is challenging due to technical difficulties and physiologic aspects related to growth and poor standardization between algorithms for calculating PWV. Nevertheless, studies in pediatric CKD have reported increased arterial stiffness in children with advanced CKD, on dialysis, and after kidney transplantation. Development of arterial stiffness in children with CKD is closely related to mineral-bone disease and hypertension, but other factors may also play a significant role. The clinical relevance of accelerated arterial stiffness in childhood on cardiovascular outcomes in adult life remains unclear, and prospective studies are needed. In this review we discuss mechanisms leading to arterial stiffness in CKD and its clinical implications, along with issues surrounding the technical aspects of arterial stiffness assessment in children.

Abstract MP22: GRP78 Protects Against Angiotensin II-induced Protein Aggregation, Profibrotic VSMC Phenotype, And Vascular Remodeling

Arterial stiffening is a critical risk factor contributing to the development of cardiovascular disease and end organ damage. Vascular smooth muscle cell (VSMC) hypercontractility, vessel fibrosis, and proinflammatory responses are involved. The renin angiotensin system plays critical roles in the development of VSMC stiffness phenotype, as well as CVD pathophysiology. Angiotensin II (Ang II) stimulation induces these stiffness-promoting mechanisms, however, the involvement of dysfunctional proteostasis governing Ang II contribution to vascular stiffness remains underdefined. While endoplasmic reticulum (ER) stress has been implicated in the development of arterial stiffness and hypertension, it is unknown whether the protein aggregation potentially due to maladapted unfolded protein response (UPR) in VSMCs is involved. We hypothesize AngII induced ER stress initiates protein misfolding and effects VSMC stiffness phenotype. We identify a significant increase in protein aggregate size (P&lt;0.001: from 1,000 to 4,500 pixel/aggregate) and number per cell (P&lt;0.01: from 20 to 100 aggregate #/cell) in rat VSMCs stimulated with AngII, which is attenuated with adenoviral overexpression of resident ER chaperone, GRP78 (P&lt;0.01: 2000 pixels/aggregate and P&lt;0.05: 25 aggregate #/cell). Furthermore, UPRosome associated IRE1α phosphorylation induced at 3 and 6 h following AngII stimulation is reduced in GRP78 overexpressing VSMCs (P&lt;0.05), which may contribute to reduced monocyte adhesion (P&lt;0.001), assessed utilizing THP-1 cells. In mice, pharmacological chaperone 3-HNA reduced AngII induced vascular hypertrophy (P=0.056), cardiac perivascular fibrosis (P=0.065), and pulse propagation velocity from 0.35 m/s to 0.23 m/s (P&lt;0.05). A trend in pre-amyloid oligomer accumulation was seen in the medial layer of thoracic aortas following 2 weeks of AngII infusion, which was reduced with 3-HNA treatment. Similar findings were investigated in a SM22α cre-GRP78 mouse model, where a trend in reduction of these parameters are also seen. Overall, GRP78 regulation over VSMC proteostasis influences vascular stiffness phenotype and therefore, these findings may elude new pharmacological intervention for arterial stiffness and aging associated CVD.

Effect of metabolically healthy obesity on the development of arterial stiffness: a prospective cohort study

BackgroundMetabolically healthy obesity (MHO) has been reported to be associated with the development of vascular damage by the carotid intima-media thickness, but the relationship between metabolic health and obesity phenotypes and arterial stiffness is still unknown. Our hypothesized that different metabolic health and obesity phenotypes might be associated with the development of arterial stiffness, and that subjects in MHO phenotype might not have increased risks of arterial stiffness compared with those in metabolically healthy nonobesity phenotype (MHNO), while metabolic unhealthy individuals might have increased risks of arterial stiffness.MethodsA prospective cohort of 2076 participants (aged 36–48 years) who were enrolled in the Hanzhong Adolescent Hypertension Cohort Study in 2017 was analyzed in a cross-sectional analysis. A subgroup of 202 participants from 2005 to 2017 was selected by an isometric sampling method and was included in the final longitudinal analysis.ResultsWe identified four metabolic health and obesity phenotypes for both the cross-sectional and longitudinal analyses as follows: MHNO, metabolically unhealthy nonobesity (MUNO), MHO, and metabolically unhealthy obesity (MUO). In the cross-sectional analysis, individuals with the MHO phenotype had the lowest brachial-ankle pulse wave velocity (baPWV) levels of the four phenotypes (P < 0.001), and participants with the MHO phenotype had a similar risk of arterial stiffness after fully adjustment [odds ratio (OR) = 0.99 (0.61–1.60)] as the MUNO subjects. Subjects with metabolically unhealthy status had a significantly higher risk of arterial stiffness than the MHNO individuals, particularly females (P < 0.005). In the longitudinal analysis, subjects with the MUNO and MUO phenotypes had a significantly higher risk of arterial stiffness than the MHNO individuals after adjustment for age and sex [OR = 5.21 (2.26–12.02), OR = 3.32 (1.18–9.32), respectively].ConclusionsThe MHO phenotype did not significantly increase the progression of arterial stiffness. Metabolically unhealthy individuals (MUNO, MUO), regardless of obesity status, showed a worse effect for the development of arterial stiffness, particularly females.Trial registrationNCT02734472. Registered 12 April 2016 - Retrospectively registered, http:www.clinicaltrials.gov.

Ventilation disorders and arterial stiffness indicators in patients with chronic obstructive pulmonary disease

The aim of the study was to identify the correlation between ventilation disorders of the lungs and the development of arterial stiffness in patients with chronic obstructive pulmonary disease (COPD).Methods. The following parameters were evaluated in the patients (n = 61) enrolled in the study: spirometry, bodyplethysmography, cardiac-ankle vascular index (CAVI) and an ancho-brachial vascular index. Additionally, the pulse wave propagation velocity was calculated in the area from the ostium of the aorta to the infragenicular arteries.Results. According to the study results, a direct correlation, characterized by moderate to noticeable strength, was found between the parameters of pulmonary ventilation (bronchial resistance, intrathoracic gas volume, residual lung volume (RLV), total lung capacity (TLC), RLV/TLC) and the CAVI parameter, characterizing vascular stiffness on the section from the aorta ostium to the infragenicular arteries. It was shown that the best method for assessing changes in blood vessels is CAVI, which is independent of the level of blood pressure at the moment of the study.Conclusion. It has been established that if there is a correlation between impaired ventilation and arterial stiffness, the systemic nature of the lesion in COPD is confirmed, which explains the high incidence of cardiovascular diseases in patients with COPD.

The Role of Adipokines in the Development of Arterial Stiffness and Hypertension.

The study aimed to assess the role and the relationship of adipokines as well as parameters of arterial stiffness in newly diagnosed hypertension. Forty-nine newly diagnosed hypertensive cases (median age 47 ± 6 years) and 48 normotensive patients (median age 47 ± 6 years) were enrolled to this study. Patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using SphygmoCor tonometer (Atcor Med). The levels of the adipokines-leptin, adiponectin, and resistin-were investigated. The augmentation pressure, augmentation index, and pulse wave velocity (PWV) were higher in patients with hypertension compared with controls (Ps < .05). Patients with hypertension had higher E/E' ratio, higher diameter of left atrium, and lower tricuspid annular plane systolic excursion compared with the control group (Ps < .05). Patients with hypertension had significant higher levels of leptin (ng/mL) and lower levels of adiponectin (μg/mL) compared with normotensive patients. The multivariate analysis showed that PWV (odds ratio [OR] 1.95, 95% CI, 1.2-2.9; P = .002) and leptin level (OR 1.01, 95% CI, 1.004-1.031; P = .01) were significantly associated with hypertension. Arterial stiffness as determined by PWV and leptin are associated with newly diagnosed hypertension. Elevated serum leptin level may influence the potential mechanism leading to sympathetic activation.