Higher Aortic Stiffness Research Articles

Aortic-Femoral Stiffness Gradient and Cardiovascular Risk in Older Adults.

The aortic-femoral arterial stiffness gradient, calculated as the ratio of lower-limb pulse-wave velocity (PWV) to central (aortic) PWV, is a promising tool for assessing cardiovascular disease (CVD) risk, but whether it predicts incident CVD is unknown. We examined the association of the aortic-femoral arterial stiffness gradient measures carotid-femoral stiffness gradient (femoral-ankle PWV divided by carotid-femoral PWV) and the heart-femoral stiffness gradient (femoral-ankle PWV divided by heart-femoral PWV), as well as PWV, with incident CVD (coronary disease, stroke, and heart failure) and all-cause mortality among 3109 participants of the Atherosclerosis Risk in Communities Study cohort (age, 75±5 years; carotid-femoral PWV, 11.5±3.0 m/s), free of CVD. Cox regression was used to estimate hazard ratios (HR) and 95% CIs. Over a median 7.4-year follow-up, there were 322 cases of incident CVD and 410 deaths. In fully adjusted models, only top quartiles of carotid-femoral stiffness gradient (quartile 4: HR, 1.43 [95% CI, 1.03-1.97]; and quartile 3: HR, 1.49 [95% CI, 1.08-2.05]) and heart-femoral stiffness gradient (quartile 4: HR, 1.77 [95% CI, 1.27-2.48]; and quartile 3: HR, 1.41 [95% CI, 1.00-2.00]) were significantly associated with a greater risk of incident CVD. Only high aortic stiffness in combination with low lower-limb stiffness was significantly associated with incident CVD (HR, 1.46 [95% CI, 1.06-2.02]) compared with the referent low aortic stiffness and high lower-limb stiffness. No PWVs were significantly associated with incident CVD. No exposures were associated with all-cause mortality. The aortic-femoral arterial stiffness gradient may enhance CVD risk assessment in older adults in whom the predictive capacity of traditional risk factors and PWV are attenuated.

Aortic Stiffness Measured by Carotid Femoral-Pulse Wave Velocity at Different Stages of Normal Glucose, Prediabetes, and Diabetes Mellitus: A Systematic Review and Meta-Analysis.

To explore aortic stiffness measured by carotid femoral-pulse wave velocity (cf-PWV) at different stages of normal glucose, prediabetes, and diabetes mellitus (DM). The literature comparing aortic stiffness (AS) with cf-PWV between DM and non-DM samples was systematically retrieved from Pubmed, Ovid Medline, Web of Science, Embase, Scopus, CNKI, and Wanfang databases. The Newcastle-Ottawa Scale was used to assess the quality of the literature. The primary endpoint was the mean difference (MD) of cf-PWV between the normal glucose and DM samples and normal glucose and prediabetes samples. The secondary endpoints were the MD of carotid intima-media thickness (cIMT) and carotid-radial pulse wave velocity (cr-PWV). Aggregated MD and 95% confidence intervals were calculated. When the I2 value was >50% or p < 0.01, the heterogeneity was considered large, and the random-effect model was used; otherwise, the fixed-effect model was used. A sensitivity analysis was conducted to identify the source of heterogeneity, and a funnel plot and the regression Egger test was utilized to assess the publication bias. A total of 37 studies were finally enrolled. Samples with DM had a higher cf-PWV value and cIMT value than those without DM, and the differences were statistically significant. The cr-PWV measurements tended to be higher in the DM group than in the non-DM group, but the difference was not significant. Samples with prediabetes also had a significantly higher cf-PWV value than samples with normal glucose. Samples with DM and prediabetes were associated with a higher cf-PWV value, indicating that DM patients had a higher central AS. Central AS progresses at the prediabetes stage. These data provide insight into understanding the mechanism of adverse effects of DM and prediabetes on artery stiffness.

Association of Arterial Stiffness With Mid- to Long-Term Home Blood Pressure Variability in the Electronic Framingham Heart Study: Cohort Study.

Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies have examined associations between arterial stiffness and digital home BPV over a mid- to long-term time span, irrespective of underlying hypertension. This study aims to investigate if arterial stiffness traits were associated with subsequent mid- to long-term home BPV in the electronic Framingham Heart Study (eFHS). We hypothesized that higher arterial stiffness was associated with higher home BPV over up to 1-year follow-up. At a Framingham Heart Study research examination (2016-2019), participants underwent arterial tonometry to acquire measures of arterial stiffness (carotid-femoral pulse wave velocity [CFPWV]; forward pressure wave amplitude [FWA]) and wave reflection (reflection coefficient [RC]). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly over up to 1-year follow-up. Participants with less than 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with average real variability (ARV) of week-to-week home systolic (SBP) and diastolic (DBP) BP adjusting for important covariates. We obtained ARV as an average of the absolute differences of consecutive home BP measurements. ARV considers not only the dispersion of the BP readings around the mean but also the order of BP readings. In addition, ARV is more sensitive to measurement-to-measurement BPV compared with traditional BPV measures. Among 857 eFHS participants (mean age 54, SD 9 years; 508/857, 59% women; mean SBP/DBP 119/76 mm Hg; 405/857, 47% hypertension), 1 SD increment in FWA was associated with 0.16 (95% CI 0.09-0.23) SD increments in ARV of home SBP and 0.08 (95% CI 0.01-0.15) SD increments in ARV of home DBP; 1 SD increment in RC was associated with 0.14 (95% CI 0.07-0.22) SD increments in ARV of home SBP and 0.11 (95% CI 0.04-0.19) SD increments in ARV of home DBP. After adjusting for important covariates, there was no significant association between CFPWV and ARV of home SBP, and similarly, no significant association existed between CFPWV and ARV of home DBP (P>.05). In eFHS, higher FWA and RC were associated with higher mid- to long-term ARV of week-to-week home SBP and DBP over 1-year follow-up in individuals across the BP spectrum. Our findings suggest that higher aortic stiffness and wave reflection are associated with higher week-to-week variation of BP in a home-based setting over a mid- to long-term time span.

Arterial Health After Preeclampsia: Role of Chronic Hypertension in the Early Vascular Aging (EVA) Study.

Preeclampsia (PE) is associated with increased cardiovascular risk. Recent data have shown worse left ventricular remodeling and diastolic function in women with PE and persistent hypertension (HTN). We performed a comprehensive arterial hemodynamic assessment to evaluate the contribution of persistent HTN on arterial health after PE. We recruited 40 women with PE history and 40 age-matched controls (6 months to 6 years postpartum). We evaluated arterial hemodynamics with validated techniques combining applanation tonometry and transthoracic echocardiography, comparing three groups: previous PE with persistent HTN (PE-HTN), previous PE with normalized blood pressure (PE-noHTN) and controls, using multivariable linear regression adjusted for age, body surface area, heart rate, diabetes, smoking history, creatinine, and gravidity. Eight (20%) of the post-PE women had persistent HTN. Mean age was 35.8 ± 3.9 years, median number of pregnancies was 2 (range 1-7), and time since last pregnancy 2.1 (range 0.5-5.7) years (not different between groups, P > 0.05). Compared to controls and to PE-noHTN, PE-HTN had higher aortic stiffness, wave reflections, pulsatile, and steady arterial load (P < 0.05 for each). Among PE-noHTN, aortic stiffness, wave reflections and steady arterial load were worse than controls (P < 0.05 for each), with smaller effect sizes. This is the most comprehensive assessment of arterial hemodynamics and first to demonstrate the contribution of persistent HTN on worse arterial health following PE. Since measures of arterial health are associated with cardiovascular events in the population, the combination of previous PE and chronic HTN may represent a higher risk subgroup who could benefit from targeted prevention strategies.

Coronary microvascular disease is associated with arterial stiffness in patients with ischemia and no obstructive coronary arteries

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Existing data suggest that stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. There is a gap in the current literature regarding the possible association between higher aortic stiffness and myocardial ischemia in this special population. Arterial Stiffness (AS) is an independent risk factor for cardiovascular disease, directly related to increased coronary atherosclerosis, an entity frequently encountered in hypertensive patients. Purpose The aim of this study is to determine whether arterial stiffness is increased in patients with Coronary Microvascular Dysfunction (CMD) compared to hypertensives controls. Methods We examined 21 hypertensive patients [9 female, 39%, mean age: 61.2±9.9 years, mean office blood pressure (BP) : 139/86±18/10 mmHg] and 25 CMD patients (16 female, 64%, mean age : 57.9±4.8 years, average office BP: 127/77±18/10 mmHg). In the group of patients with chronic angina pectoris, CMD was defined by a standardized systematic protocol in which coronary flow reserve (CFR) and index of microvascular resistance (IMR) were measured in the left anterior descending coronary artery using a temperature/pressure sensor-tipped guidewire. CMD patients were classified into 2 groups, structural and functional endotype, based on commonly used cut-offs (impaired CFR &amp;lt; 2.5, increased IMR ≥ 25). Functional CMD was defined as abnormal CFR in combination with normal IMR and structural CMD as abnormal CFR with abnormal IMR. In addition, in all participants, arterial stiffness was assessed using aortic augmentation index (AIx), derived from the analysis of central pulse waveforms, recorded by applanation tonometry directly from the radial artery. Results In CMD group, mean CFR and IMR were 1.6 ± 0.9 and 43.9± 30 IU, respectively. Of the 25 patients with abnormal CFR, 8 (32%) had normal IMR consistent with functional CMD endotype, and 17 (68%) had abnormal IMR consistent with structural endotype. AIx was found increased in CMD patients compared to asymptomatic hypertensives (36.44±11.1 vs 25.4±11.6%, p=0.024). This difference in AIx between the CMD and asymptomatic hypertensive controls was found to be statistically significant after adjustment for gender and age (p&amp;lt;0.05). No statistically significant difference was found in body mass index, renal function, history of dyslipidemia, diabetes mellitus and smoking between the two groups (p=NS). Conclusion Arterial stiffness was found increased in patients with CMD compared to hypertensives. These results suggest that therapies targeting vascular stiffening could provide additional clinical benefit in this special category of patients with impaired coronary microvasculature.

Association between preoperative arterial stiffness and postoperative atrial fibrillation

Postoperative atrial fibrillation (POAF) is the most frequent cardiac surgery complication, associated with poor morbid-mortality. POAF pathophysiology remains unclear. Aortic stiffness has been demonstrated to increase after aortic valve replacement (AVR). Moreover, atrial fibrillation incidence has been demonstrated to be correlated with aortic stiffness in the context of AF ablation and in the general population. Our goal was to test the association between preoperative aortic stiffness indexes and postoperative atrial fibrillation onset after cardiac surgery. We explored consecutive patients referred for surgical aortic valve replacement for symptomatic, severe aortic stenosis with or without coronary bypass at the University Hospital CHU Lille. Aortic tree properties were characterized non-invasively thanks to the Sphygmocor® at the preoperative time. Postoperative atrial fibrillation was assessed by EKG monitoring from the end of surgery to hospital discharge. POAF occurred in 40 (31.2%) patients among the 128 included from January 2019 to June 2022. Preoperative aortic stiffness indexes were different between POAF and sinus rhythm (SR) patients regarding pulse wave velocity 12.3 ± 1.3 m/s vs. 10.8 ± 0.9 m/s P = 0.0002, and reflection magnitude (respectively 76 ± 7% vs. 75 ± 8%; P = 0.56). Preoperative aortic compliance was also different between SR and POAF patients (1.7 ± 0.6 mL/mmHg vs. 1.3 ± 0.7 mL/mmHg respectively; P = 0.017). Peripheral vascular resistances were 1570 ± 430 dyn.s.cm−5 in SR vs. 1640 ± 450 dyn.s.cm-5 in POAF (P = 0.0.04). There is a higher aortic stiffness in preoperative period for patient who underwent POAF after aortic valve replacement.

Relation between aortic elasticity parameters and SYNTAX score in postmenopausal diabetic women

BackgroundPostmenopausal women are at increased risk of coronary artery disease (CAD). Diabetes Mellitus is a major risk factor for CAD. The stiffening of the aorta is associated with increased cardiovascular morbidity and mortality. We aimed to investigate the relation of aortic elasticity parameters to CAD severity assessed by SYNTAX score (SS) in diabetic postmenopausal women. The study prospectively included 200 consecutive diabetic postmenopausal women with CAD who underwent elective coronary angiography. Patients were classified into 3 groups based on SS, low-SS ≤ 22, intermediate-SS ≥ 23– ≤ 32, and high-SS ≥ 33. Echocardiographic aortic elasticity parameters, including aortic stiffness index (ASI), aortic strain (AS) (%) and aortic distensibility (AD) were obtained in all patients.ResultsPatients in the high SS group were older age and had a higher aortic stiffness. After adjusting different co-variates AD, AS, and ASI could be used as independent predictors of high SS with the following P-values (0.019, 0.016 and 0.010) and cut-off values (2.5, 3.6 and 2.9), respectively.ConclusionsIn diabetic postmenopausal women, the simple echocardiography-derived aortic elasticity parameters might predict the severity and complexity of angiographic coronary lesions assessed by the SS.

CEBPB/POU2F2 modulates Endothelin1 expression in prehypertensive SHR vascular smooth muscle cells.

The pathogenesis of hypertension is not fully understood; ET1 is involved in developing essential hypertension. ET1 can promote VSMC proliferation or hypertrophy through autocrine and paracrine effects. Proliferating smooth muscle cells in the aorta are "dedifferentiated" cells that cause increased arterial stiffness and remodeling. Male SHRs had higher aortic stiffness than normal control male WKY rats. Male SHR VSMCs expressed high levels of the ET1 gene, but endothelial cells did not. Therefore, it is necessary to understand the molecular mechanism of enhanced ET1 expression in SHR VSMCs. We identified POU2f2 and CEBPB as the main molecules that enhance ET1 expression in male SHR VSMCs. A promoter activity analysis confirmed that the enhancer region of the ET1 promoter in male SHR VSMCs was from -1309 to -1279 bp. POU2f2 and CEBPB exhibited an additive role in the enhancer region of the ET1 promoter. POU2f2 or CEBPB overexpression sufficiently increased ET1 expression, and co-transfection with the CEBPB and POU2f2 expression plasmids had additive effects on the activity of the ET1 promoter and ET1 secretion level of male WKY VSMCs. In addition, knockdown of POU2f2 also revealed that POU2f2 is necessary to enhance ET1 expression in SHR VSMCs. The enhancer region of the ET1 promoter is highly conserved in rats, mice, and humans. POU2f2 and CEBPB mRNA levels were significantly increased in remodeled human VMSCs. In conclusion, the novel regulation of POU2f2 and CEBPB in VSMCs will help us understand the pathogenesis of hypertension and support the development of future treatments for hypertension.

Abstract P392: Association Between Blood Pressure Variability and Subclinical Measures of Cardiovascular Disease in Desk Workers

Introduction: Previous research has demonstrated that variability in resting blood pressure (BP) across arms, measurements, or days may be associated with an increased risk for cardiovascular disease (CVD) and mortality. Yet, the extent to which BP variability increases cardiovascular risk and the mechanisms explaining this association are unclear. This study evaluated associations between BP variability with subclinical pathways of CVD development (arterial stiffness (pulse wave velocity [PWV]) and cardiac autonomic function (heart rate variability [HRV]) in desk workers. Hypothesis: Higher BP variability will be associated with higher PWV and lower (worse) HRV Methods: This secondary analysis of baseline data from the Effect of Reducing Sedentary on Blood Pressure randomized controlled trial included 265 sedentary and inactive desk workers (mean age 44.9±11.6 years; 82.0% white; 57.9% female) with elevated-to-stage 2 hypertension and who were not using antihypertensive medication. Sequential BP measurements determined the arm with the higher systolic BP by using an oscillometric device (Omron HEM-907XL). BP was then measured at least twice from the arm with the higher systolic BP at the first (visit-1) and second (visit-2) visits, occurring ≤30 days apart. Systolic BP variability metrics included inter-arm (first measurements between arms at visit-1), intra-arm (first two measurements on the arm with higher systolic BP at visit-1), and inter-visit (average BP from repeated measurements on the same arm across visits-1 and -2). Subclinical measures of CVD included resting carotid- femoral(cfPWV) and carotid-radial(crPWV) PWV (Complier Analyse) and the log transformed standard deviation of normal R-R intervals (SDNN) and the root mean square of the successive differences (RMSSD) HRV measures (Polar Electro). Adjusted linear regression estimated the associations between subclinical measures of CVD and BP variability metrics; Metrics were operationalized into three categories: differences of 0-5 mmHg, 6-10 mmHg, and 11 or more mmHg. Results: The prevalence of having 6 mmHg or more difference for the inter-arm, intra-arm, and inter-visit systolic BP was 43%, 38%, and 53%, respectively. PWV and HRV were not different across categories of inter-arm systolic BP variability or inter-visit systolic BP variability (all p&gt;0.05). However, a same-day intra-arm difference in systolic BP of 6-10 mmHg within visit-1 was associated with higher cfPWV (β=0.42 m/s, (95% CI: 0.07, 0.77) as compared to those with an intra-arm difference of 0-5 mmHg. Conclusion: These data suggest that higher systolic BP variability in the same arm within visit, but not variability across arms or between visits, may be associated with higher aortic stiffness in desk workers with untreated elevated-to-stage 2 hypertension.

PS-BPC10-3: DETERMINATION OF AORTIC STIFFNESS USING TWO ESTABLISHED ALGORITHMS

Objectives: Arterial stiffness is a risk factor for cardiovascular disease. Aortic stiffness is assessed by determination of pulse wave velocity using pulse transit time and the distance between carotid and femoral arteries. Transit time is obtained by using the foot-to-foot method to define the transit time through intersecting tangents algorithm or the point of maximal upstroke during systole (2nd derivative). Millasseau et al have proposed a formula for converting transit time between methods using SphygmoCor (intersecting tangents) and the Complior Analyse (2nd derivative). Based on a mathematical modeling of the proposed formula, there is discrepancy between values of pulse wave velocities, especially in subjects with higher aortic stiffness. The objective is to directly compare the two methods using the same pressure waveforms obtained by the newer generation of Complior Analyse and using Millasseau formula. Design and Methods: In a cross-sectional study of heterogeneous subjects, aortic stiffness was assessed by the Complior device which uses 2nd derivative. The pulse waveforms were extracted and used for the analysis by custom MATLAB algorithm for intersecting tangents, and the results were compared to the formula proposed by Millasseau. Results: The preliminary results of the first 24 patients (men: 71%; mean age: 61 ± 18 years) show that Millasseau formula underestimates the transit times values by about 19% in comparison with the transit times obtained by the intersecting tangents method using MATLAB software (50 ± 19 ms vs 62 ± 19 ms; P &lt; 0.001). This results in an overestimation of the pulse wave velocities values by about 30% (13.8 ± 3.8 m/s vs 10.6 ± 2.7 m/s; P &lt; 0.001). Conclusions: Our preliminary results allow us to conclude that the values of pulse wave velocities obtained with Millasseau formula overestimate values as compared to the values obtained by intersecting tangents method. Increasing the number of subjects will allow us to examine the possibility of a more reliable formula for converting transit times between methods.

Abstract 14300: Arterial Stiffness is Associated With Intermediate-Term Home Blood Pressure Variability: The Electronic Framingham Heart Study

Introduction: Short-term blood pressure variability (BPV) is associated with arterial stiffness in patients with hypertension. Few studies examined associations between arterial stiffness and digital home BPV over an intermediate time span. Objective: We investigated if antecedent arterial stiffness was associated with home BPV among participants in the electronic Framingham Heart Study (eFHS). We hypothesize that higher arterial stiffness predicts higher intermediate-term home BPV over one-year follow-up. Methods: At an FHS research exam (2016-2019), participants underwent arterial tonometry to acquire mean arterial pressure (MAP) and measures of arterial stiffness (carotid femoral pulse wave velocity, CFPWV; forward pressure wave amplitude, FWA) and wave reflection (reflection coefficient, RC). Participants who agreed to enroll in eFHS were provided with a digital blood pressure (BP) cuff to measure home BP weekly. Participants with &lt; 3 weeks of BP readings were excluded. Linear regression models were used to examine associations of arterial measures with home average real variability (ARV) of systolic (SBP) and diastolic (DBP) BP adjusting for covariates. We obtained ARV as an average of the absolute differences of consecutive BP measurements. ARV considers not only the dispersion of the BP readings around the mean, but also the order of BP readings. We used p&lt;0.05 for significance. Results: Among 857 eFHS participants (mean age 54 years, 59% women, mean BP 119/76, 47% hypertension, mean ARV of DBP 5.50, mean ARV of SBP 8.61), higher FWA and RC were associated with higher ARV of SBP ( Table ). Higher CFPWV was associated with lower ARV of DBP ( Table ). Conclusion: In eFHS, higher FWA and RC were associated with higher intermediate-term home BPV of SBP while higher CFPWV was associated with blunted BPV of DBP. Our findings suggest that higher aortic stiffness and wave reflection may affect day-to-day modulation of blood pressure in a home-based setting.

Prediction of long-term outcomes by arterial stiffness and pressure wave reflections in patients with acute stroke: the Athens Stroke Registry.

Stroke patients' management might be improved by addressing the role of aortic stiffness (carotid-femoral pulse wave velocity: cfPWV) and pressure wave reflections (PWRs, augmentation index: AIx) in their pathogenesis and outcome. We tested the hypothesis that cfPWV and AIx, separately and combined, predict long-term outcomes [all-cause mortality, incidence of cardiovascular events, stroke recurrence and disability defined by modified Ranking Scale (mRS) ≥3] in patients with acute stroke, using data from the 'Athens Stroke Registry'. Data from 552 patients (70% men, age: 66.1 ± 10.4 years, 13.4% deaths from any cause, 21.2% cardiovascular events, 14.1% stroke recurrences and 20.1% poor mRS, mean follow-up 68.4 ± 41.4 months) were analyzed. The main findings were that: high aortic stiffness (cfPWV > 13 m/s) alone is an independent predictor of all-cause mortality and cardiovascular (CV) events, but not of stroke recurrence and poor functional outcome; evaluated separately from aortic stiffness, neither low nor high PWRs have any prognostic value; even after multiple adjustments, patients with both high aortic stiffness (cfPWV > 13 m/s) and low PWRs (Aix < 22%) have almost two-fold higher hazard ratio, not only for all-cause mortality and CV events but also for stroke recurrence and poor functional outcome. The present study provides evidence about the role of aortic stiffness, PWRs and their combined incremental value in the long-term survival, morbidity, and functional disability after acute stroke.

DIRECT COMPARISON OF INTERSECTING-TANGENTS VERSUS SECOND DERIVATIVE FOR DETERMINATION OF PULSE TRANSIT TIME AND PULSE WAVE VELOCITY

Objective: Arterial stiffness is a non-traditional risk factor for cardiovascular disease. Aortic stiffness is assessed by determination of pulse wave velocity using pulse transit time and the distance between carotid and femoral arteries. Transit time is obtained by using the foot-to-foot method to define the transit time through intersecting tangents algorithm or the point of maximal upstroke during systole (2nd derivative). Millasseau et al have proposed a formula for converting transit time between methods using SphygmoCor (intersecting tangents) and the Complior Analyse (2nd derivative). Based on a mathematical modeling of the proposed formula, there is discrepancy between values of pulse wave velocities, especially in subjects with higher aortic stiffness. The objective of this study is to directly compare the two methods using the same pressure waveforms obtained by the newer generation of Complior Analyse and using Millasseau’s formula. Design and method: In a cross-sectional study of heterogeneous subjects, aortic stiffness was assessed by the Complior Analyse device which uses 2nd derivative. The pulse waveforms were extracted and used for the analysis by custom MATLAB algorithm for intersecting tangents, and the results were compared to the formula proposed by Millasseau. Results: The preliminary results of the first 24 patients (men: 71%; mean age: 61 ± 18 years) show that Millasseau’s formula underestimates the transit times values by about 19% in comparison with the transit times obtained by the intersecting tangents method using MATLAB software (49,8 ± 18,8 ms vs 61,6 ± 18,6 ms; P &lt; 0,001). This results in an overestimation of the pulse wave velocities values by about 30% (13,8 ± 3,8 m/s vs 10,6 ± 2,7 m/s; P &lt; 0,001). Conclusions: Our preliminary results allow us to conclude that the values of pulse wave velocities obtained with Millasseau’s formula are overestimated values when comparing with values obtained by using the intersecting tangents method. Increasing the number of subjects will allow us to examine the possibility of a more reliable formula for converting transit times from one method to the other.

Aortic Stiffness is Negatively Associated with Microvascular Glycocalyx Thickness and Microvascular Perfusion among Older Adults: Role of Carotid Pressure Pulsatility

IntroductionThe glycocalyx layer is essential to the maintenance of a healthy microvascular endothelium and diminishes with advancing age. Similarly, the aorta stiffens with aging and increases the risk of cardiovascular disease and target organ damage, possibly through pressure pulsatility‐associated microvascular damage. However, whether aortic stiffness and/or pressure pulsatility are associated with microvascular endothelial glycocalyx structure/function among older adults is unknown. Therefore, the objective of this analysis was to investigate the potential relation between aortic stiffness and pressure pulsatility with glycocalyx thickness and microvascular perfusion in older adults. We hypothesized that increased aortic stiffness and pressure pulsatility would be associated with less glycocalyx thickness and microvascular perfusion in older adults.MethodsSublingual microvessels were assessed using intravital microscopy in older adults (n=24; age 61 ± 6y, 46% women). Perfused boundary region (PBR) and red blood cell (RBC) filling %, indirect indices of glycocalyx thickness (larger PBR=smaller thickness) and microvascular perfusion respectively, were determined in vessels between 5‐25 µm RBC column width. Aortic stiffness was quantified by carotid‐femoral pulse wave velocity (cfPWV) and carotid pressure pulsatility as carotid pulse pressure (PP)/mean arterial pressure (MAP).ResultsAdjusting for age, sex and MAP, cfPWV was associated with larger PBR 5‐25 (β: 0.08; p=0.001) and lower RBC filling % (β: ‐0.02, p=0.002). Higher carotid pressure pulsatility was associated with lower RBC filling % (β: ‐0.12; p=0.03), but this relation was attenuated after adjusting for sex (p=0.11). Upon stratification by sex, higher carotid pressure pulsatility was associated with larger PBR 5‐25 (r=0.66, P=0.03) and lower RBC filling % (r=‐0.73, P=0.01) in women, but not men (P=0.94 and P=0.77 respectively).ConclusionHigher aortic stiffness was negatively associated with microvascular glycocalyx thickness and microvascular perfusion among older adults. Additionally, carotid pressure pulsatility was negatively associated with glycocalyx thickness and microvascular perfusion in women only. The mechanisms that contribute to sex differences in the relation between pressure pulsatility and glycocalyx structure/function in older adults require further study.

Negative Correlation of Serum Adiponectin Level with Aortic Stiffness in Elderly Diabetic Persons.

Adiponectin has anti-inflammatory activity against atherosclerosis. Aortic stiffness is a common manifestation of atherosclerosis in diabetes mellitus and elderly persons. This study aimed to evaluate whether low serum adiponectin levels were associated with aortic stiffness in geriatric diabetic patients. Blood samples were obtained from 130 diabetic participants aged ≥ 65 years. We defined high aortic stiffness based on a carotid–femoral pulse wave velocity (cfPWV) of >10 m/s. Circulating adiponectin concentrations were examined using enzyme-linked immunosorbent assays. Sixty-six participants (50.8%) had aortic stiffness. Patients with aortic stiffness had lower serum adiponectin concentrations than those in the control group (p < 0.001). Multivariate logistic regression analysis showed that the adiponectin level (odds ratio: 0.939, 95% confidence interval: 0.898–0.981, p = 0.005) was an independent predictor of aortic stiffness in elderly diabetic persons. Multivariate forward stepwise linear regression analysis also demonstrated that the adiponectin level (β = −0.256, adjusted R2 change = 0.100, p = 0.003) was negatively associated with cfPWV values in older diabetic patients. In conclusion, serum adiponectin is negatively correlated with cfPWV and is an independent predictor of aortic stiffness in elderly diabetic persons.

Isolated systolic hypertension is associated with increased left ventricular mass index and aortic stiffness in adolescents: a cardiac magnetic resonance study.

Despite the high prevalence of isolated systolic hypertension (ISH) among hypertensive adolescents, its clinical significance is not determined. In addition, it is hypothesized that ISH with normal central blood pressure (BP) in young patients is a benign phenomenon and was hence labeled spurious hypertension (sHTN). Using cardiac magnetic resonance we evaluated a group of 73 patients with suspected primary hypertension, aged 13-17 years (median: 16.9, interquartile range 15.8-17.4; 13 girls), in whom, based on 24-h ambulatory BP monitoring either ISH (n = 30) or white-coat hypertension (WCH) (n = 43) was diagnosed. Based on noninvasive central BP measurement 13 participants in the ISH group were classified as having sHTN and 17 were diagnosed with true hypertension. Compared with WCH adolescents, ISH patients presented with higher indexed left ventricular mass index (LVMI) (P < 0.001), maximal left ventricular (LV) wall thickness (P < 0.001), LV concentricity (P = 0.001) and more often had LV hypertrophy (47 vs. 14%, P = 0.002). They had higher average pulse wave velocity (PWV) in the proximal aorta (P = 0.016) and the whole thoracic aorta (P = 0.008). In addition, we observed higher indexed LV stroke volume (P = 0.025) in patients with ISH. The sHTN subgroup had significantly higher LVMI and aortic PWV, and more often had LV hypertrophy compared with the WCH group. The sHTN and true hypertension subgroups did not differ in terms of aortic PWV, LVMI or LV geometry. Compared with adolescents with WCH patients with ISH, including the sHTN subtype, have more pronounced markers of cardiac end-organ damage, higher aortic stiffness and stroke volume.

Aortic stiffness and incident diabetes: the hard, bittersweet truth

Abstract Background/Introduction Aortic stiffness increases with advancing age and is a major risk factor for age-related morbidity and mortality. Aortic stiffness and glycaemic dysregulation are related; however, temporal relationships between aortic stiffness and incidence of diabetes have not been fully delineated. Purpose We sought to investigate the role of arterial stiffness in the prediction of incident diabetes. Methods 376 untreated hypertensive patients (mean age 52.6±12.5 years, 201 males) without known cardiovascular disease and without known history of diabetes, were included in the study. Markers of subclinical organ damage [carotid-femoral pulse wave velocity (PWV) and estimated glomerular filtration rate (eGFR)] were evaluated in all patients. eGFR was estimated using the Cockcroft-Gault formula. Hemoglobin A1c (HbA1c) and blood glucose were measured in venous blood samples. Patients were prospectively followed-up, for incidence of diabetes as defined by the American Diabetes Association criteria. Results During a median 13.5 years follow-up, forty-six patients (12.2%) patients were diagnosed with diabetes. In multivariable logistic regression analysis, only higher PWV (Odds Ratio [OR] = 1.271, 95% Confidence intervals [CI]: 1.002–1.612, P=0.048) was associated with higher risk of incident diabetes, which was independent of age, sex, pulse pressure, HbA1c, fasting blood glucose and eGFR. In further analysis, receiver operating characteristic (ROC) curves were generated to evaluate the ability of PWV to discriminate subjects with diabetes. The area under the curve (AUC) and 95% CIs of the ROC curve was AUC=0.66 (95% CI: 0.58–0.74, P=0.001) for PWV (Figure 1). Conclusions In our cohort, higher aortic stiffness was associated with higher risk of incident diabetes. Figure 1. ROC curve for the prediction of diabetes Funding Acknowledgement Type of funding source: None

Beat-to-Beat Blood Pressure Variability in the First Trimester Is Associated With the Development of Preeclampsia in a Prospective Cohort

Women with preeclampsia, a hypertensive disorder of pregnancy, exhibit greater beat-to-beat blood pressure variability (BPV) in the third trimester after clinical onset of the disorder. However, it remains unknown whether elevated BPV precedes the development of preeclampsia. A prospective study cohort of 139 women (age 30.2±4.0 years) were enrolled in early pregnancy (<14 weeks gestation). BPV was quantified by time domain analyses of 10-minute continuous beat-to-beat blood pressure recordings via finger photoplethysmography in the first, second, and third trimesters. Aortic stiffness (carotid-femoral pulse wave velocity) and spontaneous cardiovagal baroreflex sensitivity were also measured each trimester. Eighteen women (13%) developed preeclampsia. Systolic BPV was higher in all trimesters among women who developed versus did not develop preeclampsia (first: 4.8±1.3 versus 3.7±1.2, P=0.001; second: 5.1±1.8 versus 3.8±1.1, P=0.02; third: 5.2±0.8 versus 4.0±1.1 mm Hg, P=0.002). Elevated first trimester systolic BPV was associated with preeclampsia (odds ratio, 1.94 [95% CI, 1.27-2.99]), even after adjusting for risk factors (age, body mass index, systolic blood pressure, history of preeclampsia, and diabetes mellitus) and was a significant predictor of preeclampsia (area under the receiver operator characteristic curve=0.75±0.07; P=0.002). Carotid-femoral pulse wave velocity was elevated in the first trimester among women who developed preeclampsia (5.9±0.8 versus 5.2±0.8 m/s; P=0.002) and was associated with BPV after adjustment for mean blood pressure (r=0.26; P=0.005). First trimester baroreflex sensitivity did not differ between groups (P=0.23) and was not related to BPV (P=0.36). Elevated systolic BPV is independently associated with the development of preeclampsia as early as the first trimester, possibly mediated in part by higher aortic stiffness.

Possible misclassification of cardiovascular risk by SCORE in antisynthetase syndrome: results of the pilot multicenter study RI.CAR.D.A.

To test the ability of an established traditional cardiovascular (CV) risk prediction score [Systematic COronary Risk Evaluation (SCORE)] and its EULAR modified version (mSCORE) to identify antisynthetase syndrome (ASyS) patients at high CV risk and to examine for the first time associations of CV and cerebrovascular surrogate markers with clinical and immunological ASyS parameters. SCORE/mSCORE and the gold standard marker of aortic stiffness [carotid-femoral pulse wave velocity (cfPWV)] were examined in ASyS patients and healthy controls. Moreover, sonography of the common- (CCA) and internal- (ICA) carotid arteries was performed in subsets of both groups, evaluating carotid intima-media thickness (cIMT), plaques and Doppler sonographic cerebrovascular surrogates [resistance (RI) and pulsatility (PI) indices]. We recruited 66 ASyS patients and 88 controls. According to mSCORE, 10% of the patients had high CV risk. However, cfPWV and carotid sonography revealed an increased CV risk in 21.2% and subclinical carotid atherosclerosis (SCA) in 85.7% of the patients, respectively. cfPWV and cIMT were higher in patients compared with controls (Padj=0.021 and Padj=0.003, respectively). In the ASyS group, cfPWV and cIMT correlated significantly with age (r = 0.679; P<0.001 and r = 0.664; P<0.001, respectively). Moreover, cfPWV correlated with BMI (Padj=0.001) and diabetes (Padj=0.043). CCA-RI and CCA-PI showed significant associations with creatine phosphokinase (r = 0.629; P=0.012 and r = 0.574; P=0.032, respectively) and ICA-RI and ICA-PI were higher in patients with lung involvement (both; P=0.039). ASyS patients had higher aortic stiffness and SCA compared with controls, even after adjustment for confounders. SCORE/mSCORE performed poorly in identifying high-risk patients compared with cfPWV and carotid sonography. Thus, cfPWV and carotid sonography may improve CV and cerebrovascular screening in ASyS.

Unexpected increase of aortic stiffness in juvenile Spondyloarthropathies.

Juvenile spondyloarthropathy is an umbrella term for a group of childhood rheumatic diseases that can cause chronic arthritis extending to the axial skeleton before the age of 16. Although ankylosing spondylitis has aortic involvement as one of its most important effects, this relationship has not been extensively studied in children with juvenile spondyloarthropathy. Here, a cross-sectional study of the elastic properties of the aorta of 43 patients with juvenile spondyloarthropathy and 19 healthy controls is reported. Aortic stiffness assessed by echocardiography was used to predict the presence of aortitis, supplemented by pulsed-wave tissue Doppler indices. The right ventricular fractional area change was found to be significantly lower in the patients with juvenile spondyloarthropathy than in the healthy controls; aortic strain and distensibility were also significantly lower, and aortic stiffness index β was significantly higher; and the aortic root diameter change was significantly lower. According to HLA-B27 positivity, there was no difference in the stiffness parameters between the two groups. There was a significant correlation between juvenile Ankylosing Spondylitis Disease Activity Index and aortic diameter change, between juvenile Ankylosing Spondylitis Disease Activity Index and aortic stiffness. Thus, juvenile spondyloarthropathy is linked to high aortic stiffness parameters.