Carotid Artery Stiffness Mechanisms Associated With Cardiovascular Disease Events and Incident Hypertension: the MESA

Background: Elastic arteries stiffen via 2 main mechanisms: (1) load-dependent stiffening from higher blood pressure and (2) structural stiffening due to changes in the vessel wall. It is unknown how these different mechanisms contribute to incident cardiovascular disease (CVD) events. Methods: The MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6814 men and women without CVD at enrollment, from 6 communities in the United States. MESA participants with B-mode carotid ultrasound and brachial blood pressure at baseline Exam in (2000–2002) and CVD surveillance (mean follow-up 14.3 years through 2018) were included (n=5873). Peterson’s elastic modulus was calculated to represent total arterial stiffness. Structural stiffness was calculated by adjusting Peterson’s elastic modulus to a standard blood pressure of 120/80 mm Hg with participant-specific models. Load-dependent stiffness was the difference between total and structural stiffness. Results: In Cox models adjusted for traditional risk factors, load-dependent stiffness was significantly associated with higher incidence of CVD events (hazard ratio/100 mm Hg, 1.21 [95% CI, 1.09–1.34] P <0.001) events while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.10). Analysis of participants who were normotensive (blood pressure <130/80, no antihypertensives) at baseline exam (n=2122) found higher load-dependent stiffness was also associated with significantly higher incidence of hypertension (hazard ratio, 1.53 [95% CI, 1.35–1.75] P <0.001) while higher structural stiffness was not (hazard ratio, 1.03 [95% CI, 0.99–1.07] P =0.16). Conclusions: These results provide valuable new insights into mechanisms underlying the association between arterial stiffness and CVD. Load-dependent stiffness was significantly associated with CVD events but structural stiffness was not.

Cross-Talk Between Large Artery Stiffness and Retinal Microvasculature in Children: The ExAMIN Youth SA Study

Background: Cross-talk between the macro-and microvasculature is considered an important contributor to target organ damage. Previous findings were predominantly in adult populations and investigation into this mechanism in children may provide insight into the development of early adverse vascular changes. Whether any ethnic differences in cross-talk is evident, also remains to be determined.Objective: To determine whether retinal microvascular diameters are associated with large artery stiffness in young children and whether ethnic differences are evident.Materials and Methods: In this cross-sectional study, 730 black (n = 437) and white (n = 293) school children aged 5-9 years were included. Pulse wave velocity (PWV) was measured and the central retinal arteriolar equivalent (CRAE) and central retinal venular equivalent (CRVE) diameters were calculated from fundus images. The arterio-venous ratio (AVR) was subsequently calculated.Results: Pulse wave velocity was lower (p ≤ 0.001) in the black group when compared to the white group. The black group had a narrower CRAE, wider CRVE and lower AVR (all p &lt; 0.001). Pulse wave velocity associated negatively with CRAE (r = –0.141, p = 0.003) and AVR (r = –0.185, p ≤ 0.001) in the black group only. A positive association between PWV and CRVE was seen in the black (r = 0.174, p ≤ 0.001) and white (r = 0.119, p = 0.043) group.Conclusion: Large artery stiffness is associated with retinal arterial narrowing and venular widening in children, suggesting cross-talk between the macro-and microvasculature. Ethnic differences in these associations are also evident. Our findings warrant further investigation into environmental and sociocultural risk factors contributing to premature cardiovascular disease development.

Sex Differences in Large Artery Stiffness: Implications for Cerebrovascular Dysfunction and Alzheimer’s Disease

Two in every three Alzheimer’s disease diagnoses are females, calling attention to the need to understand sexual dimorphisms with aging and neurodegenerative disease progression. Dysfunction and damage to the vasculature with aging are strongly linked to Alzheimer’s disease. With aging there is an increase in stiffness of the large elastic arteries, and this stiffening is associated with cerebrovascular dysfunction and cognitive impairment. However, it is unclear how the deleterious effects of arterial stiffness may differ between females and males. While environmental, chromosomal, and sex hormone factors influence aging, there is evidence that the deficiency of estrogen post-menopause in females is a contributor to vascular aging and Alzheimer’s disease progression. The purpose of this mini review is to describe the recent developments in our understanding of sex differences in large artery stiffness, cerebrovascular dysfunction, and cognitive impairment, and their intricate relations. Furthermore, we will focus on the impact of the loss of estrogen post-menopause as a potential driving factor for these outcomes. Overall, a better understanding of how sex differences influence aging physiology is crucial to the prevention and treatment of neurodegenerative diseases.

EVALUATION OF THE RELATIONSHIP BETWEEN PULMONARY ARTERY STIFFNESS AND RIGHT VENTRICULAR FUNCTION IN PATIENTS WITH BEHÇET’S DISEASE USING TRANSTHORACIC ECHOCARDIOGRAPHY

Background: Behçet’s disease is a systemic vasculitis that can affect all sizes of arteries and veins. Arterial stiffness is a term used to describe the visco-elastic properties of vessel wall. In this study, we aimed to evaluate the relationship between pulmonary artery stiffness (PAS) and the right ventricular (RV) functions in asymptomatic Behçet’s patients with no cardiovascular risk factors. Methods: We studied 40 patients who were diagnosed by the international diagnostic criteria of Behçet’s disease and 40 healthy individuals who were matching demographic properties with the patients. Two groups were matched by age, gender, clinical history and other clinical features. Substantial medical history concerning the factors that can affect right ventricle diastolic function (such as medications, smoking status, other comorbities, etc.) was taken and general physical examination was carried out. The right and left ventricular functions as well as valvular functions were evaluated by using echocardiography. Also Two-dimensional, M-mode, pulsed wave (PW) Doppler echocardiographic parameters were measured for right ventricular functions. PW Doppler flow trace was obtained from the pulmonary valve with regards to pulmonary artery stiffness. Results: There was no significant difference in terms of clinical and demographic properties. No statistically significant difference was found upon comparison of the left ventricular end of systole and diastole diameters, the diastolic and systolic thicknesses of the interventricular septum (IVS) and left ventricular posterior wall (LVPW), left atrium (LA) diameter and left ventricular ejection fraction (LVEF) values (p>0.05) of the two groups. Right ventricular myocardial performance index (MPI) value was found higher in Behçet’s patients and a statistically significant difference was detected between the groups (p<0.01). Tricuspid annular plane systolic excursion (TAPSE) values were found to be statistically significantly lower in the patient group as compared to the control group (p<0.01). In PW Doppler measurements, early passive filling (E) wave flow velocity and E/A ratio were found to be statistically significantly lower, deceleration time (DT) was higher in the patient group (p<0.01). In Behçet’s patients without clinical pulmonary involvement, the pulmonary artery systolic pressure (PASP) was found to be statistically significantly higher in the patient group (p<0.01). The values of pulmonary artery stiffness (PAS) were found to be significantly higher in the patient group (p<0.01). The relationship between the right ventricular function markers and PAS were evaluated in the patient group. There was no statistically significant relationship between PAS and MPI and TAPSE. But there was a significant correlation between PAS and PASP and duration of illness (p<0.001 and r=0.682 ; p=0.047 and r=0,316). Conclusion: Behçet’s patients without cardiac symptoms and signs, reduction in right ventricular functions and increase in PAS was detected. Although there is no correlation between right ventricular functions and PAS, increased PAS may be an early marker of reduction of the right ventricular functions. Consequently, routine cardiological examination and detailed evaluation of biventricular functions by using echocardiography should be greatly beneficial in Behcet’s patients, even though there are no signs or symptoms.

Loss of Angiotensin II Type 2 Receptor Improves Blood Pressure in Elastin Insufficiency

There is ample evidence supporting a role for angiotensin II type 2 receptor (AT2R) in counterbalancing the effects of angiotensin II (ang II) through the angiotensin II type 1 receptor by promoting vasodilation and having anti-inflammatory effects. Elastin insufficiency in both humans and mice results in large artery stiffness and systolic hypertension. Unexpectedly, mesenteric arteries from elastin insufficient (Eln+/−) mice were shown to have significant vasoconstriction to AT2R agonism in vitro suggesting that AT2R may have vasoconstrictor effects in elastin insufficiency. Given the potential promise for the use of AT2R agonists clinically, the goal of this study was to determine whether AT2R has vasoconstrictive effects in elastin insufficiency in vivo. To avoid off-target effects of agonists and antagonists, mice lacking AT2R (Agtr2−/Y) were bred to Eln+/− mice and cardiovascular parameters were assessed in wild-type (WT), Agtr2−/Y, Eln+/−, and Agtr2−/Y;Eln+/− littermates. As previously published, Agtr2−/Y mice were normotensive at baseline and had no large artery stiffness, while Eln+/− mice exhibited systolic hypertension and large artery stiffness. Loss of AT2R in Eln+/− mice did not affect large artery stiffness or arterial structure but resulted in significant reduction of both systolic and diastolic blood pressure. These data support a potential vasocontractile role for AT2R in elastin insufficiency. Careful consideration and investigation are necessary to determine the patient population that might benefit from the use of AT2R agonists.

Deciphering the Role of microRNAs in Large-Artery Stiffness Associated With Aging: Focus on miR-181b

Large artery stiffness (LAS) is a major, independent risk factor underlying cardiovascular disease that increases with aging. The emergence of microRNA signaling as a key regulator of vascular structure and function has stimulated interest in assessing its role in the pathophysiology of LAS. Identification of several microRNAs that display age-associated changes in expression in aorta has focused attention on defining their molecular targets and deciphering their role in age-associated arterial stiffening. Inactivation of the microRNA-degrading enzyme, translin/trax, which reverses the age-dependent decline in miR-181b, confers protection from aging-associated arterial stiffening, suggesting that inhibitors targeting this enzyme may have translational potential. As LAS poses a major public health challenge, we anticipate that future studies based on these advances will yield innovative strategies to combat aging-associated arterial stiffening.

Large Artery Stiffness: A Companion to the 2015 AHA Science Statement on Arterial Stiffness

Large artery stiffness (LAS) has proven to be an independent risk factor for cardiovascular disease and mortality. Nevertheless, the position of current hypertension guidelines regarding the usefulness of assessing LAS differs across different continents. In general, European Guidelines recognize pulse wave velocity (PWV) as a marker of target organ damage but do not recommend its systematic use in general population. Asian guidelines consider PWV as a recommended test at diagnosis of hypertension, in contrast to North American guidelines that do not state any position about its usefulness. However, PWV predicts cardiovascular events, and several studies have shown that it improves risk classification adjusting for established risk factors especially for intermediate-risk patients. Finally, some advances have been made related to treatments affecting LAS. Dietary interventions such as sodium restriction and exercise-based interventions have a modest effect in reducing LAS. Pharmacological interventions, such as statins, or more recent advances with mineralocorticoid blocker seem to have a beneficial effect. Last, controversial effects of renal denervation on LAS have been found. Our goal here is to update the reader on LAS on these areas since the 2015 American Heart Association Scientific Statement.

Is fetuin-A a biomarker of dialysis access dysfunction?

Background: The arteriovenous (AV) access function of hemodialysis (HD) patients can be impaired by afferent artery stiffness due to preexisting microcalcification and by venous stenosis secondary to neointimal hyperplasia in whose development participates an upregulated local inflammatory process. Fetuin-A is a circulating potent inhibitor of vascular calcification and plays an important anti-inflammatory role. The aims of this prospective study were to investigate the relationship between baseline serum fetuin-A levels and: blood flow (QA) values at baseline, AV access failure (thrombosis or intervention for stenosis) during follow-up and primary unassisted AV access patency. Methods: We measured baseline serum fetuin-A levels and QA values of the AV access in 64 HD patients under routine QA surveillance for stenosis. Patients were classified into tertiles according to their baseline fetuin-A levels (g/L): <0.5 (tertile-1), 0.5–1.20 (tertile-2), and >1.20 (tertile-3). Results: Fetuin-A was positively correlated with QA (Spearman coefficient = 0.311, p = 0.012). Fourteen patients (21.9%) underwent AV access failure and they had lower fetuin-A (0.59 ± 0.32 g/L) and lower QA (739.4 ± 438.8 mL/min) values at baseline compared with the remaining patients (1.05 ± 0.65 g/L and 1273.0 ± 596.3 mL/min, respectively) ( p = 0.027 and p < 0.001, respectively). The AV access failure rate was highest (34.8%) in tertile-1 (lowest fetuin-A level). Unadjusted Cox regression analysis showed a decrease in the risk of AV access patency loss by increasing fetuin-A concentration (hazard ratio 0.395 (95% confidence interval: 1.42–1.69), p = 0.044) but it was not confirmed in the adjusted model, although the hazard ratio was low (0.523). Kaplan–Meier analysis showed that patients in tertile-3 (highest fetuin-A concentration) had the highest primary unassisted AV access patency (λ2 = 4.68, p = 0.030, log-rank test). Conclusion: If our results are confirmed in further studies, fetuin-A could be used as a circulating biomarker to identify HD patients at greater risk for AV access dysfunction, who would benefit from much closer dialysis access surveillance.