Systemic Arterial Stiffness Research Articles

Acute increase in arterial stiffness after swimming in cooler water.

Cold stimuli increase arterial stiffness, but it has not been explored whether arterial stiffness increases after swimming in cooler water. To investigate the effects of water temperature on changes in arterial stiffness after swimming, 13men participated in three trials of 20-min swimming in 25 and 30°C water (S25 and S30, respectively) and sitting at poolside (CON) in random order. There were no significant differences between the S25 and S30 trials in mean swimming distance (719 vs. 722m) and heart rate reserve during swimming (63% vs. 63%). Sublingual temperature was lower after swimming in 25°C water versus before swimming. Aortic pulse wave velocity (aortic PWV, an index of central arterial stiffness based on applanation tonometry) and brachial-ankle pulse wave velocity (baPWV, an index of systemic arterial stiffness based on air plethysmography) were higher 30min after versus before swimming in 25°C water. Aortic PWV recovered to pre-swimming levels by 60min after swimming in 25°C water, but baPWV was higher even at 60min after swimming. PWVs did not change in the CON and S30 trials. Systemic vascular resistance based on Doppler ultrasonography did not change, but forearm vascular resistance based on strain-gauge plethysmography was higher 30 and 60min after swimming in 25°C water. Heart rate was higher, but stroke volume was lower 30min after swimming in 25°C water, resulting in no detectable change in cardiac output. In conclusion, arterial stiffness increases acutely after moderate-intensity swimming in cooler water.

Machine Learning-Based Pulse Wave Analysis for Early Detection of Abdominal Aortic Aneurysms Using In Silico Pulse Waves

An abdominal aortic aneurysm (AAA) is usually asymptomatic until rupture, which is associated with extremely high mortality. Consequently, the early detection of AAAs is of paramount importance in reducing mortality; however, most AAAs are detected by medical imaging only incidentally. The aim of this study was to investigate the feasibility of machine learning-based pulse wave (PW) analysis for the early detection of AAAs using a database of in silico PWs. PWs in the large systemic arteries were simulated using one-dimensional blood flow modelling. A database of in silico PWs representative of subjects (aged 55, 65 and 75 years) with different AAA sizes was created by varying the AAA-related parameters with major impacts on PWs—identified by parameter sensitivity analysis—in an existing database of in silico PWs representative of subjects without AAAs. Then, a machine learning architecture for AAA detection was trained and tested using the new in silico PW database. The parameter sensitivity analysis revealed that the AAA maximum diameter and stiffness of the large systemic arteries were the dominant AAA-related biophysical properties considerably influencing the PWs. However, AAA detection by PW indexes was compromised by other non-AAA related cardiovascular parameters. The proposed machine learning model produced a sensitivity of 86.8 % and a specificity of 86.3 % in early detection of AAA from the photoplethysmogram PW signal measured in the digital artery with added random noise. The number of false positive and negative results increased with increasing age and decreasing AAA size, respectively. These findings suggest that machine learning-based PW analysis is a promising approach for AAA screening using PW signals acquired by wearable devices.

COMPARISON OF SYSTEMIC ARTERIAL STIFFNESS IN PATIENTS WITH NEW DIAGNOSED IDIOPATHIC PULMONARY AND SYSTEMIC ARTERIAL HYPERTENSION

Objective: This study is the first attempt to use cardio-ankle vascular index (CAVI) for evaluation of systemic arterial stiffness in patients with idiopathic pulmonary arterial hypertension (IPAH). Design and method: 45 patients with IPAH, 32 patients with arterial hypertension (AH), 35 healthy persons adjusted by age were included in study. RHC, ECG, 6 minute walk test (6 MWT), echocardiography, blood pressure (BP) measurement and ambulatory BP monitoring, pulse wave elastic artery stiffness (PWVe) and muscular artery stiffness (PWVm), CAVI, NT-proBNP level were provided. The Spearman correlation, a linear regression and multivariable binary logistic analysis were performed to indicate the predictors associated with PWV and CAVI. Results: IPAH patients had significant (P < 0.001) shorter 6MWT distance and higher Borg dyspnea score than patients with AH (systolic/diastolic BP- 146.1 ± 3.7/94.2 ± 3.8mmHg) and control group - 330.2 ± 14.6 vs 523.8 ± 35.3 and 560.9 ± 30.2m respectively and 6.2 ± 1.8 vs 1.2 ± 2.1 and 0.9 ± 2.8 points. The PWVm and PWVe were highest in hypertensive patients - 10.3 ± 1.5 and 11.42 ± 1.70m/s. The control group and IPAH did not have significant differences in aorta BP, but PWVm/PWVe values were significant (P < 0.003/0.008) higher in IPAH patients, than in control group - 8.1 ± 1.9/8.49 ± 1.92vs6.63 ± 1.34/7.29 ± 0.87m/s. The CAVIs on both sides were significant lower in healthy subjects (5.91 ± 0.99/5.98 ± 0.87 right/left side). Patients with IPAH did not differ from AH patients by CAVIs in comparison with control group - 7.40 ± 1.32/7.22 ± 1.32vs7.19 ± 0.78/7.2 ± 1.1. PWVe did not correlate with any parameters except uric acid. PWVm correlated with uric acid (r = 0.58, P < 0.001), NT-proBNP (r = 0.33, P = 0.03) and male gender (r = 0.37, P = 0.013) at Spearman analysis, but not at multifactorial linear regression analysis. Unlike the CAVI correlated with age and parameters characterized functional capacity (6 MWT distance) and right ventricle function (NT-proBNP, TAPSE) at Spearman analysis and with age and TAPSE at multifactorial linear regression analysis. At binary logistic regression analysis CAVI > 8.0 at right or/and left side had correlation with age, 6MWT distance, TAPSE, but independent correlation was only with age (beta = 1.104,P = 0.008) and TAPSE (beta = 0.66,P = 0.016). Conclusions: Patients with IPAH had significant stiffer arteries than healthy persons and they were comparable with AH patients. Arterial stiffness evaluated by CAVI correlated with age and TAPSE in IPAH patients.

Abstract P358: Association of Kidney Function and Cerebral Arterial Stiffness

Background and Purpose: Chronic kidney disease (CKD) is known to have affected the systemic vasculature and its remodeling, which eventually led to the systemic arterial stiffness. However, the relationship between cerebral circulation and impaired renal function is poorly understood. To evaluate the effect of renal dysfunction to increase systemic and intracranial arterial stiffness, we assessed the relation between renal resistive index (RRI) and pulsatility index (PI) of the middle cerebral artery (MCA). Methods: We included patients with acute lacunar infarction. Demographic and clinical data were collected by retrospective chart review. Bilateral transcranial Doppler ultrasound (TCD) examination of the MCAs was performed using the ST3 Ultrasound system (Spencer Technologies) and PI were calculated. RRI was obtained through kidney Doppler sonography. Subjects with occlusion or significant stenosis of MCA, atrial fibrillation, bilaterally absent transtemporal sonographic windows were excluded. Results: Of the 283 included subjects (mean age 67.8 ± 10.2), 74 patients had renal dysfunction (glomerular filtration rate < 60ml/min/1.73m2 at admission) and 49 patients underwent kidney Doppler ultrasound within 1 year since their acute stroke. Renal dysfunction was significantly associated with higher arterial stiffness (median PI 1.12, IQR 0.85 to 1.57 vs. controls PI 0.84, IQR 0.54 to 1.22 [p<0.0001]). There was a proportional relationship between the degree of renal dysfunction and the distal vascular resistance. In multivariate adjusted regression analysis, renal function was related to high PI (p<0.001). Furthermore, there is strong correlation between RRI and PI ( r =0.65, p <0.001). Conclusions: In patients with lacunar infarction, renal impairment is an independent determinant of increased arterial stiffness in cerebral circulations. In addition, PI is significantly associated with RRI.

Carotid Beta Stiffness Association with Thyroid Function

Background: Thyroid hormone modulation of cardiovascular function has been associated with cardiovascular disease. Recent evidence suggests that free thyroxine (FT4) levels are associated with an increase in systemic arterial stiffness, but little is known about the effects of FT4 at the local level of the common carotid artery. β-stiffness index is a local elastic parameter usually determined by carotid ultrasound imaging. Methods: We conducted a cross-sectional analysis in the ProgeNIA cohort, including 4846 subjects across a broad age range. For the purpose of this study, we excluded subjects with increased thyrotropin (TSH) levels and those treated with levothyroxine or thyrostatic. We assessed β stiffness, strain, wall–lumen ratio, carotid cross-sectional area (CSA), and stress and flow in the right common carotid artery. We tested whether FT4, heart rate, and their interactions were associated with carotid parameters. Results: FT4 was positively and independently associated with β stiffness index (β = 0.026, p = 0.041), and had a negative association with strain (β = −0.025, p = 0.009). After adding heart rate and the interaction between FT4 and heart rate to the model, FT4 was still associated with the β stiffness index (β = 0.186, p = 0.06), heart rate was positively associated with the stiffness index (β = 0.389, p < 0.001) as well as their interaction (β = 0.271, p = 0.007). Conclusion: This study suggests that higher FT4 levels increase arterial stiffness at the common carotid level, consistent with a detrimental effect on elastic arteries. The effect of FT4 is likely to be primarily attributable to its effect on heart rate.

Increased systemic arterial stiffness in patients with chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a complication of venous thromboembolism (VTE) resulting from non-dissolving thromboemboli in the pulmonary arteries. Previous observations indicate a higher prevalence of atherosclerosis and cardiovascular risk factors in patients with VTE and CTEPH. The purpose of the present study was to evaluate the arterial stiffening assessed by pulse wave velocity (PWV), a marker of arterial stiffness, in CTEPH patients in comparison with a matched control group (CG). The study group consisted of 26 CTEPH patients (9 male and 17 female, age 69 ± 10 years) and 22 CG (10 male, 12 female, age 67 ± 8 years). In all subjects a physical examination, carotid-femoral PWV and transthoracic echocardiography were performed. Right heart catheterization was done in all CTEPH. Chronic tromboembolic pulmonary hypertension patients had significantly higher PWV than CG (10.3 ± 2.5 m/s vs. 9 ± 1.3 m/s, p < 0.05), even though systolic blood pressure was higher in CG (120 ± 11 vs. 132 ± 14 mmHg, p = 0.002). PWV correlated only with age and pulmonary vascular resistance (PVR) in CTEPH (r = 0.45, p = 0.03 and r = 0.43, p = 0.03, respectively). Arterial stiffening defined as PWV > 10 m/s was found in 11 (42%) CTEPH patients and in 5 (23%) cases from CG (p = 0.13). CTEPH patients with PWV > 10 m/s were older (74 ± 8 vs. 66 ± 10 years, p < 0.05), had decreased oxygen saturation (SaO2 89 [73-96]% vs. 96 [85-98]%, p < 0.01) and tended to have higher PVR (8.1 [3.1-14.0] vs. 5.2 [3.1-12.7] HRU, p = 0.10). Arterial stiffness, assessed with PWV, is increased in CTEPH. The elevated PWV is associated with older age, lower SaO2 and higher PVR in CTEPH.

Cognitive impairment related to arterial stiffness in cardiovascular disease patients with severe periodontitis

Severe periodontal disease (SPD) associated with systemic peripheral inflammation, cognitive impairment (CI) and arterial stiffness (AS) has been recognized. The aim of this study was to investigate whether CI and arterial stiffness (AS) occur in cardiovascular disease (CVD) patients with SPD. A crosssectional case-control study included hospitalized patients with CVD. Demographic characteristics, CVD and atherogenic risk factors were recorded. SPD was diagnosed by clinical and radiographic dental examinations. Dental clinical attachment level (CAL) and CAL % were recorded. A Mini-Mental State Examination test (MMSE) assessed cognition, a MMSE score of &lt; 27 was set as the cut-off point of CI; a score ≥ 27 was considered as no CI. Patients were categorized into: MMSE&lt; 27 in the three models. The risk of having MMSE &lt; 27 increased an average of 2.404-fold for each 1-unit increase in PWV. SPD and AS had significant and independent associations on the risk for development CI. MMSE negatively correlated with CAL% (r=0.69) and PWV (r=0.70). PWV positively correlated with CAL% (r=0.67). Serum VCAM-1 levels were higher in SPD with lower MMSE scores. In conclusion, SPD increases the risk of development of cognitive decline in CVD patients. PWV was directly associated with the risk of cognitive decline. These findings denote a significant opportunity to improve periodontal health in order to avert CI in CVD patients.

Evaluation of arterial stiffness in new diagnosed idiopathic pulmonary arterial hypertension patients

Abstract Objective This study is the first attempt to use cardio-ankle vascular index (CAVI) for the evaluation of systemic arterial stiffness in patients with IPAH. Methods 112 patients were included in the study: group 1 – 45 patients with new diagnosed IPAH, group 2 – 32 patients with arterial hypertension, control group – 35 healthy persons adjusted by age. Right heart catheterization, ECG, a 6-minute walk test (6 MWT), echocardiography, blood pressure (BP) measurement and ambulatory BP monitoring, pulse wave elastic artery stiffness (PWVe) [segment carotid-femoral arteries] and muscular artery stiffness (PWVm) [segment carotid-radial arteries], CAVI, N-terminal pro-B-type natriuretic peptide (NT-proBNP) level were provided. The Spearman correlation, a linear regression and multivariable binary logistic analysis were performed to indicate the predictors associated with PWV and CAVI. Results The PWVm and PWVe were the highest in hypertensive patients – 10.3±1.5 and 11.42±1.70 m/s. The control group and IPAH did not have significant differences in aorta BP, but PWVm/PWVe values were significantly (P&amp;lt;0.003/0.008) higher in IPAH patients than in the control group - 8.1±1.9/8.49±1.92 vs 6.63±1.34/7.29±0.87 m/s. The CAVIs on both sides were significantly lower in the healthy subjects (5.91±0.99/5.98±0.87 right/left side). Patients with IPAH did not differ from the arterial hypertension patients by CAVIs in comparison with the control group - 7.40±1.32/7.22±1.32 vs 7.19±0.78/7.2±1.1. PWVe did not correlate with any parameters except uric acid. PWVm correlated with uric acid (r=0.58, P&amp;lt;0.001), NT-proBNP (r=0.33, P=0.03) and male gender (r=0.37, P=0.013) at Spearman analysis, but not at multifactorial linear regression analysis. The CAVI correlated with age and parameters characterized functional capacity (6 MWT distance) and right ventricle function (NT-proBNP, TAPSE) at Spearman analysis and with age and TAPSE at multifactorial linear regression analysis. At binary logistic regression analysis CAVI &amp;gt;8.0 at right or/and left side had a correlation with age, 6MWT distance, TAPSE, but an independent correlation was only with age (β=1.104, P=0.008, CI 1.026–1.189) and TAPSE (β=0.66, P=0.016, CI 0.47–0.93). Conclusion In spite of equal and at normal range BP level the age adjusted patients with IPAH had significantly stiffer arteries than the healthy persons and they were comparable with the arterial hypertensive patients. Arterial stiffness evaluated by CAVI correlated with age and TAPSE in IPAH patients. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): National Academy of Medical science of Ukraine

High hemoglobin glycation index is associated with increased systemic arterial stiffness independent of hyperglycemia in real-world Japanese population: A cross-sectional study.

Aims:To investigate the association of metabolic parameters including hemoglobin glycation index (HGI, observed HbA1c – predicted HbA1c) with systemic arterial stiffness assessed by cardio-ankle vascular index (CAVI).Subjects:We analyzed the cross-sectional data from 22,696 subjects (mean age 48.0 years, mean FPG 88 mg/dL, mean HbA1c 5.5%) with or without past history of metabolic disorders including diabetes.Results:Men had higher body mass index (BMI), CAVI, blood pressure (BP), FPG, HbA1c, total cholesterol and triglyceride; and lower age, HGI and HDL-cholesterol. After stratifying subjects into HGI quartiles, the highest quartile (Q4) group showed higher age, female ratio, and frequencies of obesity, hypertension, diabetes, and dyslipidemia. Furthermore, bivariate logistic regression model revealed that the Q4 of HGI was a significant predictor of high CAVI (⩾9.0) independent of the presence of diabetes.Conclusion:High HGI is associated with systemic arterial stiffening independent of hyperglycemia. This index is therefore expected to be not only a predictor of hypoglycemia, but also a therapeutic guide for atherosclerosis.

New index of abdominal obesity, a body shape index, is BMI-independently associated with systemic arterial stiffness in real-world Japanese population.

To clarify that the new index of abdominal obesity, a body shape index (ABSI), is associated with obesity-related metabolic disorders and arterial stiffness. We analyzed the cross-sectional data from 62,514 Japanese subjects (mean age 44.4years, mean body mass index (BMI) 22.2kg/m2) without a past history of cardiovascular disease, stroke, or treatment for obesity-related metabolic disorders. Various body adiposity indices including BMI, waist circumference (WC), and ABSI were evaluated for abilities to indicate metabolic disorders and arterial stiffness assessed by cardio-ankle vascular index (CAVI). WC, WC/height ratio, and WC/BMI ratio correlated with BMI regardless of gender or obesity, whereas ABSI hardly correlated with BMI. ROC analyses demonstrated that ABSI had the highest discriminatory power in predicting high CAVI (≥90th percentile) compared to other body adiposity indices, and the cut-off value was 0.080. Increases in ABSI as well as BMI reflected severity of metabolic disorders. After adjusting for confounders identified by multiple regression analysis, adjusted CAVI correlated positively with ABSI, whereas an inverted relationship was observed between adjusted CAVI and BMI. Additionally, the contribution of high ABSI (≥0.080) for high CAVI was independent of gender, age, obesity, and obesity-related metabolic disorders in the multivariate logistic regression model. ABSI is an easily calculated index of abdominal obesity which reflects metabolic disorders and systemic arterial stiffening, and may be useful in primary health screening even without any medical equipment for visceral fat quantification.

Association Between Systemic and Pulmonary Vascular Dysfunction in COPD.

IntroductionIn chronic obstructive pulmonary disease (COPD), endothelial dysfunction and stiffness of systemic arteries may contribute to increased cardiovascular risk. Pulmonary vascular disease (PVD) is frequent in COPD. The association between PVD and systemic vascular dysfunction has not been thoroughly evaluated in COPD.MethodsA total of 108 subjects were allocated into four groups (non-smoking controls, smoking controls, COPD without PVD and COPD with PVD). In systemic arteries, endothelial dysfunction was assessed by flow-mediated dilation (FMD) and arterial stiffness by pulse wave analysis (PWA) and pulse wave velocity (PWV). PVD was defined by a mean pulmonary artery pressure (PAP) ≥25 mmHg at right heart catheterization or by a tricuspid regurgitation velocity >2.8 m/s at doppler echocardiography. Biomarkers of inflammation and endothelial damage were assessed in peripheral blood.ResultsFMD was lower in COPD patients, with or without PVD, compared to non-smoking controls; and in patients with COPD and PVD compared to smoking controls. PWV was higher in COPD with PVD patients compared to both non-smoking and smoking controls in a model adjusted by age and the Framingham score; PWV was also higher in patients with COPD and PVD compared to COPD without PVD patients in the non-adjusted analysis. FMD and PWV correlated significantly with forced expiratory volume in the first second (FEV1), diffusing capacity for carbon monoxide (DLCO) and systolic PAP. FMD and PWV were correlated in all subjects.DiscussionWe conclude that endothelial dysfunction of systemic arteries is common in COPD, irrespective if they have PVD or not. COPD patients with PVD show increased stiffness and greater impairment of endothelial function in systemic arteries. These findings suggest the association of vascular impairment in both pulmonary and systemic territories in a subset of COPD patients.

Relationship between arterial stiffness and variability of home blood pressure monitoring.

Variability of blood pressure (BP) is known as a prognostic value for the subsequent target organ damage in hypertensive patients. Arterial stiffness is a risk factor for cardiovascular morbidity and mortality. The relationship between the arterial stiffness and the BP variability has been controversial. The objective of the present study was to investigate the relationship between arterial stiffness and home BP variability in patients with high normal BP and new onset hypertension (HTN).Four hundred sixty three patients (252 males, 49 ± 12 year-old) with high normal BP or HTN were enrolled. Using radial applanation tonometry, pulse wave analysis (PWA) was performed for evaluation of systemic arterial stiffness. All patients underwent both home BP monitoring (HBPM) and PWA. Home BP variability was calculated as the standard deviation (SD) of 7 measurements of HBPM. Multiple linear regression analysis was performed to estimate and test the independent effects of home BP variability on the arterial stiffness.Mutivariate analysis showed that both systolic and diastolic morning BP variabilities were correlated with arterial stiffness expressed as augmentation pressure (AP, β-coefficient = 1.622, P = .01 and β-coefficient = 1.07, P = .035). The SDs of systolic and diastolic BP of evening were also associated with AP (β-coefficient = 1.843, P = .001 and β-coefficient = 1.088, P = .036). The SDs of morning and evening systolic BP were associated with augmentation index (AI, β-coefficient = 1.583, P = .02 and β-coefficient = 1.792, P = .001) and heart rate (75 bpm) adjusted AI (β-coefficient = 1.592, P = .001 and β-coefficient = 1.792, P = .001).In present study, the variability of systolic BP was closely related with arterial stiffness. The home BP variability might be important indicator of arterial stiffness.

Association of renal resistance index and arterial stiffness on clinical outcomes in patients with mild-to-moderate renal dysfunction and presence or absence of heart failure with preserved ejection fraction.

The renal arterial resistance index (RI) and the brachial-ankle pulse wave velocity (baPWV) are known as indicators of renal vascular resistance/systemic vascular damage and systemic arterial stiffness. The clinical significance of those parameters on clinical outcomes is poorly known in patients with and without heart failure with preserved ejection fraction (HFpEF). Baseline clinical data and the RI assessed by renal Doppler data, baPWV were obtained in patients with (HFpEF group, n = 60) and without HFpEF (non-HFpEF group, n = 51) who had a reduced estimated glomerular filtration rate (eGFR) of > 30 and < 60mL/min/1.73m2). We investigated the association between the RI and baPWV and major clinical outcomes including hospitalization for heart failure, cardiovascular death, myocardial infarction or unstable angina or other cardiovascular events and death from another cause. The RI and baPWV were greater in the HFpEF group than in the non-HF group (0.75 ± 0.07 vs. 0.69 ± 0.08, p <0.001; 2002 ± 430 vs. 1762 ± 300cm/s, p =0.001). The RI correlated significantly with baPWV in the HFpEF (r = 0.382, p = 0.003) and non-HFpEF groups (r = 0.414, p = 0.002). During the median follow-up period of 54months, major clinical outcomes occurred in 41 (36.9%) patients. The RI value, statin use and the presence of HFpEF were major factors for predicting clinical outcomes by multivariate analysis. Among the patients who had mild-to-moderate renal dysfunction, an increased RI and baPWV were observed in HFpEF patients as compared to non-HFpEF patients, but the baPWV similarly correlated with the RI value regardless of HFpFE patients or not. The strong association between the high RI value and presence of HFpEF and major clinical outcomes, suggests that not only the presence of HFpEF but also the high RI value may help to identify the high-risk patients leading to poor clinical outcomes.

Effects of dipeptidyl peptidase-4 inhibitor linagliptin versus sulphonylurea glimepiride on systemic haemodynamics in overweight patients with type 2 diabetes: A secondary analysis of an 8-week, randomized, controlled, double-blind trial.

AimTo determine the glucose‐independent effect of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D).Materials and MethodsIn this prespecified secondary analysis of a phase IV, double‐blind trial, 46 metformin‐treated, overweight patients with T2D were included and randomly assigned (1:1) to once‐daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub‐study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style). Systemic haemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry) and cardiac sympathovagal balance (heart rate variability [HRV]) were measured in the fasting state and repetitively following the meal. Ewing tests were performed in the fasting state.ResultsFrom baseline to week 8, linagliptin compared with glimepiride did not affect systemic haemodynamics, arterial stiffness or HRV in the fasting state. Linagliptin increased parasympathetic nervous activity, as measured by the Valsalva manoeuvre (P = .021) and deep breathing test (P = .027) compared with glimepiride. Postprandially, systolic blood pressure (SBP) dropped an average of 7.6 ± 1.6 mmHg. Linagliptin reduced this decrease to 0.7 ± 2.3 mmHg, which was significant to glimepiride (P = .010).ConclusionsWhen compared with glimepiride, linagliptin does not affect fasting blood pressure. However, linagliptin blunted the postprandial drop in SBP, which could benefit patients with postprandial hypotension.

Hemodynamic Characterization of Primary Hypertension in Children and Adolescents.

BackgroundPrimary hypertension in children is often characterized by high pulse pressure that could be attributable to increased ventricular ejection velocities and volumes and/or increased arterial stiffness. The objective of this study was to examine the contributions of cardiac (ventricular ejection) and vascular (systemic vascular resistance, arterial stiffness, and pressure wave reflection) properties to primary hypertension in children and adolescents.Methods and ResultsChildren aged 8 to 18 years referred to a tertiary center for evaluation of hypertension and found to have primary hypertension (n=31) were compared with normotensive controls of similar age (n=50). Peripheral (brachial) and central (carotid) blood pressure waveforms and carotid‐femoral pulse wave velocity were measured by tonometry. Left ventricular outflow tract velocities and ejection volumes were measured by echocardiography. Wave separation and wave intensity analysis were used to assess pressure wave propagation. Increased mean arterial pressure in hypertensive children (90±15 versus 76±10 mmHg in hypertensive versus normotensive children; means±SD; P<0.001) was explained by increased heart rate and cardiac output (5.3±2.0 versus 4.5±1.2 L/min adjusted for age and sex; P<0.05) rather than increased systemic vascular resistance (18.0±4.6 versus 19.3±7.3 mmHg/min/mL; P=0.374). A more‐marked increase in pulsatility (peripheral pulse pressure 66±21 versus 46±12 mmHg; P<0.001) was explained by increased proximal aortic stiffness (pulse wave velocity, 3.3±1.4 versus 2.5±0.8 m/s; P<0.005) and increased left ventricular ejection velocity (1.33±0.24 versus 1.21±0.18 m/s; P<0.05).ConclusionsCardiac overactivity characterized by increased heart rate and left ventricular ejection velocities and increased proximal pulse wave velocity may be the main cause of primary hypertension in children.

Two Distinct Classes of Heart Failure with Preserved Ejection Fraction Emerge from Analysis of Standard Clinical Measures using Mechanistic Models of the Cardiovascular System

Diagnosis and treatment of heart failure are determined through the analysis of echocardiography (EC) and right heart catheterization (RHC) measures made in the clinic. To uncover the underlying causes of heart failure with reduced ejection fraction (HFrEF, ejection fraction &lt; 50%) and heart failure with preserved ejection fraction (HFpEF, ejection fraction &gt; 50%), thirty‐one patient records (ten HFrEF, twenty‐one HFpEF) have been obtained from the Cardiovascular Health Improvement Project (CHIP) database at the University of Michigan. Using these patient specific EC and RHC measures, we identify key parameters representing mechanical and hemodynamic function including systemic arterial stiffness, contractility of the right and left ventricle, diastolic relaxation as well as ventricular filling in a closed loop model of the cardiovascular system. Model simulations were tuned to match RHC and EC measures of systolic and diastolic pressures in the right ventricle, pulmonary artery, and aorta, along with cardiac output, pulmonary capillary wedge pressure, and left ventricular volumes in each patient with average error between data and model of 6.0 ± 2.3%. The underlying physiological parameters of these thirty‐one tuned models were then plotted against model‐based norms (blue dotted line in Figure 1 below) and compared between the HFrEF and HFpEF groups. Our results confirm that the main parameter driving HFrEF is reduced left ventricular contractility, while for HFpEF there is an evident increase in systemic arterial stiffness and left ventricle elastance, and a reduced relaxation during diastolic filling. Conducting a Principal Component Analysis (PCA) of both clinical measures and optimized model parameters shows a distinct group of HFpEF patients sharing strong patterns with our HFrEF cohort. However, only the analysis of our optimized parameters give us an understanding of the mechanistic differences between the two HFpEF groups. The optimized parameter PCA indicates significant differences (p‐value&lt;. 05) in left ventricular active contractility, left ventricular relaxation, right ventricular relaxation and systemic arterial stiffness when comparing our classical HFpEF patients to those grouped as similar to HFrEF. These results as well as the wide range of parameter values in HFpEF supports the observed clinical heterogeneity and suggests that cardiovascular system modeling of standard clinical data is able to phenotype and group HFpEF as different sub diagnoses, elucidating patient specific treatment strategies for these patients.Support or Funding InformationThis work is supported by grants from the National Institute of Health HL139813, R01 HL139813, U01 HL122199, T32GM008322, F31HL149214Normalized model parameters from analysis of clinical measures. A: Ejection fraction from patient data records. Panels B, C and D: Left ventricular active contractility, systemic arterial stiffness and left ventricular passive stiffness, respectively. Model parameters are normalized to a value representing normal cardiovascular function. Gray dashed line is average, light dotted is standard deviation and the grey box contains the middle 50% of the parameter values.Figure 1

The Effects of Mat Pilates Training on Vascular Function and Body Fatness in Obese Young Women With Elevated Blood Pressure.

Effective nonpharmacological interventions targeting the enhancement of vascular function and decline of body fatness (BF) in obese individuals are indispensable for the prevention of hypertension and cardiovascular events in young adults. Mat Pilates training (MPT) has gained significant popularity worldwide, yet its effects on vascular function and body composition are understudied. We examined the effects of MPT on vascular function and BF in young obese women with elevated blood pressure (BP). Twenty-eight young obese women with elevated BP were randomized to an MPT (n = 14) or a nonexercising control (CON, n = 14) group for 12 weeks. Systemic arterial stiffness (brachial-ankle pulse wave velocity (baPWV)), brachial and aortic BP, wave reflection (augmentation index (AIx)), plasma nitric oxide (NO) levels, and BF percentage (BF%) were assessed before and after 12 weeks. MPT significantly reduced (P ˂ 0.05) baPWV (-0.7 ± 0.2 m/s), AIx (-4 ± 1%), brachial systolic BP (-5 ± 1 mm Hg), aortic systolic BP (-6 ± 1 mm Hg), and BF% (-2 ± 1%), while significantly increasing plasma NO (6 ± 2 µM) (P ˂ 0.05) compared with CON. MPT improved systemic arterial stiffness, aortic BP, wave reflection, circulating plasma NO, and BF% in young obese women with elevated BP. MPT may be an effective intervention for the improvement of vascular function and BF in young obese women with elevated BP, a population at risk for hypertension and early vascular complications. Trial Number NCT03907384.

Association of systemic cardio-vasculature status with retinal vascular endothelium in diabetes

The relationship between diabetic retinopathy and macro-vascular complications in diabetes suggests a pathogenic association between these conditions. Vascular endothelium has been identified as a main site of blood vessel injury in diabetes. Diabetic retinopathy is associated with systemic arterial stiffness and altered vascular endothelium function and structure. Retinal vasculature endothelium at the macula, arterio-venous crossings, and in the optic nerve at the lamina cribrosa region is reported to differ from the endothelium in the rest of the retinal blood vessels. The central retinal artery and vein are in close proximity in the optic nerve where they share a common adventitia; thus, increased arterial wall stiffness and thickness may affect blood flow in the neighboring central retinal vein in this region. Moreover, increased arterial stiffness in small arterial beds is associated with retinal venular widening; it suggests the possibility of central retinal artery compressing the central retinal vein at the lamina cribrosa, thereby compromising venular outflow in the retina of diabetic patients. Altered blood flow in the central retinal vein in the postlaminar region has been detected in patients who experience progression of diabetic retinopathy. Increased hydrostatic pressure in the central retinal vein may play a major role in the pathogenesis of diabetic retinopathy. The aim of this review article is to emphasize this pathogenetic mechanism that has often been overlooked.

Bedside Renal Doppler Ultrasonography and Acute Kidney Injury after TAVR.

Acute kidney injury (AKI) following transcatheter aortic valve replacement (TAVR) is associated with a dismal prognosis. Elevated renal resistive index (RRI), through renal Doppler ultrasound (RDU) evaluation, has been associated with AKI development and increased systemic arterial stiffness. Our pilot study aimed to investigate the performance of Doppler based RRI to predict AKI and outcomes in TAVR patients. From May 2018 to May 2019, 100 patients with severe aortic stenosis were prospectively enrolled for TAVR and concomitant RDU evaluation at our institution (Nouvel Hôpital Civil, Strasbourg University, France). AKI by serum Creatinine (sCr-AKI) was defined according to the VARC-2 definition and AKI by serum Cystatin C (sCyC-AKI) was defined as an sCyC increase of greater than 15% with baseline value. Concomitant RRI measurements as well as renal and systemic hemodynamic parameters were recorded before, one day, and three days after TAVR. It was found that 10% of patients presented with AKIsCr and AKIsCyC. The whole cohort showed higher baseline RRI values (0.76 ± 0.7) compared to normal known and accepted values. AKIsCyC had significant higher post-procedural RRI one day (Day 1) after TAVR (0.83 ± 0.1 vs. 0.77 ± 0.6, CI 95%, p = 0.005). AUC for AKIsCyC was 0.766 and a RRI cut-off value of ≥ 0.795 had the most optimal sensitivity/specificity (80/62%) combination. By univariate Cox analysis, Mehran Risk Score, higher baseline right atrial pressure at baseline >0.8 RRI values one day after TAVR (HR 6.5 (95% CI 1.3–32.9; p = 0.021) but not RRI at baseline were significant predictors of AKIsCyC. Importantly, no significant impact of baseline biological parameters, renal or systemic parameters could be demonstrated. Doppler-based RRI can be helpful for the non-invasive assessment of AKI development after TAVR.

Abstract WP212: Arterial Stiffness is Associated With Apolipoprotein B 100, Not LDL-Cholesterol in Patients With Acute Ischemic Stroke

Background: Arterial stiffness has been reported to be associated with hypertension, vascular disease including cerebral small vessel disease and increased mortality. Also, dyslipidemia is one of the potent risk factors for atherosclerosis. We aim to investigate the association of arterial stiffness and various lipid fractions including low density lipoprotein cholesterol (LDL-cholesterol), lipoprotein(a), and apolipoprotein B 100 in patients with acute ischemic stroke. Methods: We identified 2187 consecutive patients with acute ischemic stroke confirmed on MR imaging or CT. Brachial-ankle pulse wave velocity (baPWV) was measured using a volume-plethysmography device (VP-1000; Collin, Komaki, Japan). Lipid fractions were measured with blood sample taken after at least 8-hour fast. Vascular risk factors and demographics of patients were assessed by our prospectively collected stroke database. The association between baPWV and lipid fractions was tested using linear regression analysis. Results: Mean age of patients was 68.5 +/- 12.3 years and male was 1214 (55.5%). Mean baPWV was 20.85 +/- 5.55 m/sec. On simple regression analysis, baPWV was associated with lipoprotein(a) and LDL-cholesterol (p &lt; 0.05). However, on multivariable linear regression adjusting for age, sex, lipid fractions and other vascular risk factors, apolipoprotein B 100 was the only significant lipid fraction for baPWV (beta 1.42; 95% confidence interval 0.45 - 2.40; p &lt; 0.001). We included LDL-cholesterol instead of apolipoprotein B 100 in another model due to multicollinearity, which showed that neither LDL-cholesterol nor lipoprotein(a) was significant. Conclusion: Among lipid fractions, apolipoprotein B 100 is associated with systemic arterial stiffness in patients with acute ischemic stroke. Our finding suggests that apolipoprotein B 100 might be a better predictor for arterial stiffness than LDL-cholesterol and lipoprotein(a).