Arterial Stiffness in Hypertension and Function of Large Arteries.

BACKGROUND: Arterial stiffness-typically assessed from non-invasive measurement of pulse wave velocity along a straight portion of the vascular tree between the right common carotid and femoral arteries-is a reliable predictor of cardiovascular risk in patients with essential hypertension. METHODS: We reviewed how carotid-femoral pulse wave velocity increases with age and is significantly higher in hypertension (than in age- and gender-matched individuals without hypertension), particularly when hypertension is associated with diabetes mellitus. RESULTS: From the elastic aorta to the muscular peripheral arteries of young healthy individuals, there is a gradual but significant increase in stiffness, with a specific gradient. This moderates the transmission of pulsatile pressure towards the periphery, thus protecting the microcirculatory network. The heterogeneity of stiffness between the elastic and muscular arteries causes the gradient to disappear or be inversed with aging, particularly in long-standing hypertension. CONCLUSIONS: In hypertension therefore, pulsatile pressure transmission to the microcirculation is augmented, increasing the potential risk of damage to the brain, the heart, and the kidney. Furthermore, elevated pulse pressure exacerbates end-stage renal disease, particularly in older hypertensive individuals. With increasing age, the elastin content of vessel walls declines throughout the arterial network, and arterial stiffening increases further due to the presence of rigid wall material such as collagen, but also fibronectin, proteoglycans, and vascular calcification. Certain genes, mainly related to angiotensin and/or aldosterone, affect this aging process and contribute to the extent of arterial stiffness, which can independently affect both forward and reflected pressure waves.

Arterial Stiffness and Coronary Ischemia: New Aspects and Paradigms.

PURPOSE OF REVIEW: Aortic stiffness (AS) is widely associated with hypertension and considered as a major predictor of coronary heart disease (CHD). AS is measured using carotid-femoral pulse wave velocity (PWV), particularly when this parameter is associated with an index involving age, gender, heart rate, and mean blood pressure. The present review focuses on the interest of measurement of PWV and the calculation of individual PWV index for the prediction of CHD, in addition with the use of new statistical nonlinear models enabling results with very high levels of accuracy. RECENT FINDINGS: PWV index may so constitute a substantial marker of large arteries prediction and damage in CHD and may be also used in cerebrovascular and renal circulations models. PWV index determinations are particularly relevant to consider in angiographic CHD decisions and in the presence of vulnerable plaques with high cardiovascular risk. Due to the variability in symptoms and clinical characteristics of patients, together with some imperfections in results, there is no very simple adequate diagnosis approach enabling to improve the so defined CHD prediction in usual clinical practice. In recent works in relation to "artificial intelligence" and involving "decision tree" models and "artificial neural networks," it has been possible to determine consistent pathways introducing predictive medicine and enabling to obtain efficient algorithm classification models of coronary prediction.

Relationship between BMI and aortic stiffness: influence of anthropometric indices in hypertensive men and women.

BACKGROUND: Increased aortic stiffness could be one of the mechanisms by which obesity increases cardiovascular risk independently of traditional risk factors. Studies have suggested that anthropometric indices may be predictors of cardiovascular risk but few studies have investigated their relations with aortic stiffness in high cardiovascular risk population. We investigated the strength of correlation between different anthropometric indices with aortic stiffness in hypertensive and diabetic patients. METHODS: A cross-sectional study was performed in 474 hypertensive patients. Anthropometric indices were calculated: BMI, waist circumference, waist-hip ratio, and waist-height ratio (WHtR). Aortic stiffness was assessed by measurement of carotid-femoral pulse wave velocity (PWV). Correlations between indices and PWV were investigated by linear regression analyses and hierarchical analyses after adjusting for cardiovascular risk factors. RESULTS: Regional anthropometric indices were more strongly correlated with PWV than BMI in both sexes. In linear regression analyses, WHtR presented the highest correlation with PWV than other indices in our study population. In adjusted hierarchical regression used, WHtR had the highest additive value on top of BMI while there no additive value of BMI on top of WHtR. These differences remained after adjustment on cardiovascular events. In men WHtR was more closely correlated with PWV than others. In women, waist-hip ratio and WHtR were equally correlated with PWV compared with BMI. CONCLUSION: Regional anthropometric indices are more closely correlated with PWV than BMI in hypertensive patients. WHtR presents the highest correlation with PWV beyond BMI. REGISTRATION: The study was registered in the French National Agency for Medicines and Health Products Safety (No. 2013-A00227-38) and was approved by the Advisory Committee for Protection of Persons in Biomedical Research.

Arterial Stiffness Gradient, Systemic Reflection Coefficient, and Pulsatile Pressure Wave Transmission in Essential Hypertension.

Arterial stiffness and impedance gradients are known to influence pressure wave propagation and macrovascular-microvascular interactions. We studied the association between the carotid-femoral arterial stiffness gradient and the systemic reflection coefficient (N=393); of this population, 246 also underwent assessment of forward/backward pressure wave propagation and microvascular pulsatile pressure transmission (MPPT). Hemodynamic parameters were measured noninvasively. From peripheral vascular resistance and characteristic impedance, we estimated the systemic reflection coefficient and MPPT on peripheral and cardiac microcirculation in age-matched, sex-matched and body mass index-matched individuals with (n=147) or without (n=98) hypertension. The arterial stiffness gradient, systemic reflection coefficient, and correlations between the arterial stiffness gradient and age or blood pressure were similar in both populations. MPPT was higher in hypertension (P<0.0001), and the subendocardial viability (Buckberg) index lower (P<0.0001). In both populations, the systemic reflection coefficient and arterial stiffness gradient were significantly associated with changes in MPPT and the subendocardial viability index. Despite similar systemic reflection coefficients, the carotid reflected pressure and MPPT were higher in hypertension. Maintaining the systemic reflection coefficient within normal ranges was, therefore, insufficient to compensate for higher carotid forward pressure waves which, in hypertension, were associated with increased aortic stiffness (P<0.0001) and higher stroke volume (P=0.0365). Independently of cardiovascular risk, hypertension-induced changes have a weighted effect on MPPT, although insufficient to compensate for increased forward pressure waves. In hypertension, elevated aortic stiffness negatively affects the arterial stiffness gradient and systemic reflection coefficient but positively affects forward pressure.

Application of a decision tree to establish factors associated with a nomogram of aortic stiffness.

Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular (CV) diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. A nomogram of aortic stiffness was evaluated by the calculation of PWV index. Theoretical PWV can be calculated according to age, gender, mean blood pressure, and heart rate, allowing to form an individual PWV index [(measured PWV - theoretical PWV)/theoretical PWV]. The purpose of the present cross-sectional study was to investigate the determinants of the PWV index, by applying a decision tree. A cross-sectional study was conducted from 2012 to 2017, and 597 individuals were included. A training decision tree was constructed based on seventy percent of these subjects (N = 428). The remaining 30% (N = 169) were used as the testing dataset to evaluate the performance of the decision trees. The input variables for the models were clinical and biochemical parameters. The different input variables remained in the model were diabetes, tobacco status, carotid plaque, albuminuria, C-reactive protein, total cholesterol, BMI, and previous CV diseases. For the validation decision model, the sensitivity, specificity, and accuracy values for identifying the related risk factors of PWV index were 70%, 78%, and 0.73. Since determinants of PWV index were all well-accepted CV risk factors, a nomogram of aortic stiffness could be considered as an integrator of CV risk factors on their duration of exposure and could be utilized to develop future programs for CV risk assessment and reduction strategies.

Added value of aortic pulse wave velocity index for the detection of coronary heart disease by elective coronary angiography.

Background: Non-invasive tests leading to elective coronary angiography (CAG) have low diagnostic yield for obstructive coronary heart disease (CHD). Aortic stiffness, an independent predictor of CHD events can be easily measured by pulse wave velocity (PWV). We aimed at retrospectively evaluating the diagnostic accuracy PWV index to detect CHD in consecutive patients with suspected CHD that underwent CAG.Method: In population of 86 healthy patients with available PWV data, a theoretical PWV was derived. In different population of 62 individuals who underwent CAG for suspected CHD, PWV index was calculated as index [(measured PWV - theoretical PWV)/theoretical PWV]. Logistic regression and comparisons between ROC curves were used to add value of CAG indication performance of PWV index.Results: Out of 62, seventeen patients presented obstructive CHD and 22 patients had non-obstructive CHD. PWV index and severity of CHD were positively correlated (p < 0.0001). After applying several models that included classical CHD predictor, the higher performance to detect abnormal CAG was obtained with the combined classifier PWV index/carotid plaque with 87% sensitivity, 93% specificity, 0.92 accuracy and 0.31 threshold. To detect obstructive CAG, individual classifier PWV index presents 94% sensitivity, 91% specificity, 0.95 accuracy and 0.46 threshold.Conclusion: PWV index is individualized approach that optimizes CHD diagnostic strategies and thus might be clinically useful for reducing the rate of unnecessary invasive CAG.

Association between different lipid parameters and aortic stiffness: clinical and therapeutic implication perspectives.

INTRODUCTION: Recommendations about lipid parameters varied from different guidelines. Aortic stiffness is a marker of vascular aging and may reflect occurrence of cardiovascular diseases. Aortic pulse wave velocity (PWV), a marker of aortic stiffness, can be measured by applanation tonometry. The purpose of our study was to test the associations between lipid parameters and aortic stiffness. METHODS: A cross-sectional study was conducted from 2012 to 2017, 603 participants were included: 517 patients and 86 'healthy' individuals used to calculate the theoretical PWV. Lipid parameters, including total cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), non-HDL, total cholesterol/HDL ratio, triglycerides/HDL ratio and LDL/HDL ratio were measured. Theoretical PWV can be calculated according to age, sex, mean blood pressure and heart rate, allowing to form an individual PWV index [(measured PWV - theoretical PWV)/theoretical PWV]. PWV index [(measured PWV -  theoretical PWV)/theoretical PWV] greater than 0 defined aortic stiffness. RESULTS: In multiple linear regression analyses, total cholesterol (P = 0.03), LDL (P = 0.04), non-HDL (P = 0.03), total cholesterol/HDL (P = 0.01) and LDL/HDL (P = 0.03) were significantly correlated with PWV. In multiple logistic regression analyses, non-HDL [OR = 1.12 (1.04-1.20), P = 0.01, R value: 0.224], total cholesterol/HDL [OR = 1.12 (1.02-1.22), P = 0.03, R value: 0.219] and total cholesterol [OR = 1.11 (1.01-1.23), P = 0.03, R value: 0.209] were significantly associated with aortic stiffness. CONCLUSION: Non-HDL, total cholesterol and total cholesterol/HDL were significantly associated with aortic stiffness than others and especially individually lipid parameters. This result should be considered in future clinical lipid-lowering trials.

Coronary heart disease diagnosis by artificial neural networks including aortic pulse wave velocity index and clinical parameters.

BACKGROUND: Cardiovascular disease, such as coronary heart disease (CHD), are the main cause of mortality and morbidity worldwide. CHD is not entirely predicted by classic risk factors; however, they are preventable. Facing this major problem, the development of novel methods for CHD risk prediction is of practical interest. The purpose of our study was to construct an artificial neural networks (ANNs)-based diagnostic model for CHD risk using a complex of clinical and haemodynamics factors of this disease and aortic pulse wave velocity (PWV) index. METHODS: A total of 437 patients were included from 2012 to 2017: 99 CHD and 338 non-CHD patients. Theoretical PWV was calculated, on 93 patients free of hypertension, diabetes and CHD, according to age, blood pressure, sex and heart rate. The results were expressed as an index [(measured PWV - theoretical PWV)/theoretical PWV] for each patient. The original database for ANNs included clinical, haemodynamic and laboratory characteristics. Multilayered perceptron ANNs architecture were applied. The performance of prediction was evaluated by accuracy values based on standard definitions. RESULTS: By changing the types of ANNs and the number of input factors applied, we created models that demonstrated 0.63-0.93 accuracy. The best accuracy was obtained with ANNs topology of multilayer perceptron with three hidden layers for models, parameters included by both biological factors, carotid plaque and PWV index. CONCLUSION: ANNs models including a PWV index could be used as promising approaches for predicting CHD risk without the need for invasive diagnostic methods and may help in the clinical decision.

Added Value of Aortic Pulse Wave Velocity Index in a Predictive Diagnosis Decision Tree of Coronary Heart Disease.

BACKGROUND: Coronary heart disease (CHD) is among the main causes of death in the world. Individual study of cardiovascular risk is an important way to predict CHD risk. The aim of this study was to evaluate the added role of the aortic pulse wave velocity (PWV) index in the prediction of CHD risk. METHODS: A cross-sectional study was conducted from December 2012 to September 2017; 530 patients were included: 99 CHD, 338 non-CHD patients, and 93 nonhypertensives, nondiabetics and non-CHD subjects, whose theoretical PWV were calculated. Theoretical PWV was calculated according to age, blood pressure, gender, and heart rate. The results were expressed as an index ((measured PWV - theoretical PWV)/theoretical PWV) for each patient. The differences observed, the differential diagnostic performance, and the quantification of the added value of diagnostic performance of PWV index were tested using logistic regression, comparisons between receiver operating characteristic (ROC) curves, and decision tree nonlinear methodology. RESULTS: PWV index (P = 0.006), carotid plaque (P = 0.005), and dyslipidemia (P = 0.04) were the independent modulators of CHD diagnosis. PWV index appears to be the highest specific classifier (81%) compared to carotid plaque (75%) and dyslipidemia (78%). For the decision tree, sensitivity, specificity, and area under the ROC curve for CHD diagnosis were 62%, 83%, and 0.87, respectively. CONCLUSIONS: PWV index yielded added value to CHD by assessment of combined classifiers with clinical determinants and decision tree construction and significantly increased the specificity of the differential diagnostic performances of the common risk factors of CHD in daily clinical practice.

[Essential hypertension: Definitions, hemodynamic, clinical and therapeutic review]. / Hypertension artérielle permanente essentielle : définitions et revue hémodynamique, clinique et thérapeutique.

Arterial hypertension is à chronic disease that affects more than 25 % of the French adult population. Increased peripheral resistance combined with normal cardiac output is a special feature of arterial hypertension. The increase in the resistance of arterioles remains an important feature of arterial hypertension while the study of the rigidity of large arterials trunks remains poorly explored. Pulse wave velocity (PWV) measurement has been established as one of the major independent predictors of cardiovascular events in arterial hypertension.

Wave reflections in hypertension: role of sex, metabolic, and ethnic factors.

OBJECTIVES: Although the links between pulsatile hemodynamics and age are widely acknowledged in hypertension, the interactions of sex, ethnicity, and metabolic factors with hemodynamic parameters remain largely unknown. We investigated the effects of body weight, glycemia, and cholesterolemia on the carotid augmentation index (CAI) and potential changes over time, with particular focus on the roles of sex and ethnicity. METHODS: Baseline (V1) and repeat (V2) measurements (at ∼1.7 years) of wave reflections (calculated from CAI), brachial and carotid pulse pressure, and heart rate were assessed in 2530 normotensive and hypertensive men and women living in Paris but born in either France, Africa, or Asia. RESULTS: At V1, and in comparison with French-born individuals, African-born individuals had significantly higher CAI, cardiovascular risk, and body weight, whereas Asian-born individuals had similar CAI but lower body weight, and higher cardiovascular risk, triglyceridemia, and heart rate. Stepwise multiple regression showed similar effects of cholesterolemia on CAI in all populations, whereas only French-born individuals (insulin-resistant men and women) showed associations between hyperglycemia and potential CAI dysfunction. Repeat (V2) measurements highlighted significant interactions (P < 0.008) of sex and ethnicity with changes in CAI over time. In men, CAI changes did not differ as a function of ethnicity, whereas in African-born women, they were lesser than those of Asian-born (P < 0.03) and French-born (P < 0.02) women. CONCLUSION: In the French-born population, CAI changes are affected by diabetes and possibly insulin-resistance, independently of sex. In African-born and Asian-born populations, CAI is sex-specific. Elevated CAI in African-born women calls for close monitoring of cardiovascular risk.

Determinants of pulse pressure amplification in hypertensive and diabetic patients.

Hypertensive diabetic patients remain at high cardiovascular risk despite adequate blood pressure and glycemic control. Pulse pressure amplification (PPA) is expressed as the peripheral-to-central PP ratio and provides complementary information for use in assessing cardiovascular risk. The aim of our study was to determine the clinical and biological determinants of PPA in hypertensive and diabetic patients. A cross-sectional study was conducted in 624 patients. Applanation tonometry was used to determine hemodynamic parameters. Age, gender, and the association between hypertension and diabetes were the independent factors of PPA in our population (N = 624). A threshold of 55 years of age was chosen because of its link with menopause in our analysis. Multivariate regression analyses were performed to evaluate the independent determinants of PPA for hypertensive diabetic and hypertensive nondiabetic male and female patients. HbA1c level is the main factor of increased PPA regardless of age and gender (P < 0.05). Mean BP negatively regulates PPA in the overall study: men > 55 years (P = 0.0001) and women > 55 years (P = 0.03). The threshold calculated glomerular filtration rate (cGFR) < 60 mL/min/1.73 m2 was an independent and negative factor of PPA in hypertensive diabetic men regardless of age (P < 0.05) and in women > 55 years (P = 0.04). Mean BP negatively regulates PPA in hypertensive nondiabetic patients (P < 0.04) regardless of age and gender, except in women > 55 years, where cGFR < 60 (P = 0.04) negatively regulates the modulation of PPA. HbA1c and threshold cGFR < 60 have highly significant impacts on PPA in hypertensive diabetic patients, whereas mean BP appears as the main factor of PPA in hypertensive nondiabetic patients.

Structure and Function of Systemic Arteries: Reflections on the Arterial Pulse.

"Structure and Function of Arteries"-is a topic of great importance to those who deal with arterial hypertension, since it links the source of flow, the left ventricle of the heart (whose output is pulsatile) to the peripheral tissues (whose flow is near continuous). The arterial tree acts passively as a conduit and cushion, and the interaction of heart, arterial tree, and organs is conventionally gauged on the basis of blood pressure measured by cuff in a conveniently located place (the brachial artery). For any precision and perspective to be gained, measurements of brachial systolic and diastolic pressure need be supplemented by other information. When such information is gained, one can understand how beautifully the arterial tree is tuned to the beat of the heart in animals of different size and shape and in humans at age 30 through the first third of a 3 billion beat lifetime. After age 30, the beats themselves progressively destroy the human arteries and their tuning to the heart, with emergence of clinical syndromes. In this review, the subject is tackled quantitatively on the basis of published numerical, physical, physiological, and pathophysiological basis, with principal focus on the beat of the heart, the pulse of the arteries, and their interaction.

Determinants of the aortic pulse wave velocity index in hypertensive and diabetic patients: predictive and therapeutic implications.

OBJECTIVE: Aortic stiffness may provide information to classical risk factors information regarding cardiovascular risk. Aortic pulse wave velocity (PWV) can be measured by applanation tonometry but also theoretical PWV was calculated according to age, blood pressure, heart rate and sex. We aim to highlight biological and hemodynamic determinants of the aortic PWV index, that is the individually calculated [(measured PWV - theoretical PWV)/theoretical PWV] difference, in hypertensive diabetic patients. METHODS: A cross-sectional study was conducted in 514 patients, involving normotensive and hypertensive patients and people with and without diabetes. Biological parameters were measured during day-hospital for cardiovascular screening. Hemodynamic parameters were determined by applanation tonometry. Multivariate regression analyses evaluated the PWV index determinants. RESULTS: Hypertensive and/or diabetic population presents higher PWV index in correlation with the presence of proteinuria (P = 0.0428) and previous cardiovascular events (P = 0.0227). Hypertensive diabetic patients present a higher PWV index than the other patients (P < 0.05). Presence of insulin therapy (P = 0.0101) and the type 1 diabetes (P = 0.0065) were positively and independently modulating PWV index in hypertensive diabetic patients. HDL cholesterol levels (P = 0.0245) and absence of carotid (P = 0.0468) plaques were independently modulating PWV index with a negative correlation in hypertensive without diabetes patients. C reactive protein levels were significantly associated with increased PWV index in hypertensive patients (P = 0.0074) and in hypertensive and/or diabetic population (P = 0.0184). CONCLUSION: PWV index was correlated with numerous cardiovascular risk factors, in addition of being a marker of age and hypertension. Therefore, this index appears as a cardiovascular risk integrator. Its use could be interesting in cardiovascular risk assessment and reduction strategies.

Left Ventricular Torsion Associated With Aortic Stiffness in Hypertension.

BACKGROUND: Left ventricular (LV) torsion plays a key role in cardiac efficiency. In hypertension, aortic stiffening augments cardiac afterload. However, little is known about the links between LV regional contraction and aortic stiffness. We, therefore, investigated these relationships and their contribution to LV diastolic function. METHODS AND RESULTS: The study included normotensive and hypertensive individuals with normal LV ejection. Apical, basal, and global LV rotation rate and LV global longitudinal strain were measured (2-dimensional speckle tracking echocardiography). Aortic stiffness was calculated from carotid-femoral pulse wave velocity, and LV relaxation was calculated from early diastolic mitral annulus motion. The ratio of basal or apical untwist/twist rates was calculated to assess relationships between aortic stiffness and LV torsion parameters. LV twist and untwist rates were greater in hypertensive than normotensive individuals because of increased basal twist (P<0.001) and untwist (P<0.001) rates. LV relaxation was reduced (early diastolic mitral annulus motion=7.4±1.9 versus 10.4±2.3 cm/s; P<0.001). In the whole population, basal untwist rate increased with aortic stiffening (R=0.43; P<0.001) and LV relaxation (R=0.41; P=0.001). The ratio of basal untwist/twist rate was positively correlated with carotid-femoral pulse wave velocity, and in the hypertensive group, was greater than in the control group and positively correlated to carotid-femoral pulse wave velocity(P<0.001). Results were independent of age, treatment, mean blood pressure, and indexed LV mass. CONCLUSIONS: In hypertensive individuals, greater basal LV torsion was associated with increased aortic stiffness and improved diastolic function. These changes may compensate for the deleterious effects of aortic stiffening on LV relaxation.

24-hour aortic blood pressure variability showed a stronger association with carotid damage than 24-hour brachial blood pressure variability: The SAFAR study.

We aim to compare 24-hour aortic blood pressure variability (BPV) with brachial BPV in relation to carotid damage as estimated by carotid intima-media thickness (CIMT) and cross-sectional area (CCSA). Four hundred and forty five individuals received brachial and aortic 24-hour ambulatory BP monitoring with a validated device (Mobil-O-Graph). Systolic BPV was estimated by average real variability (ARV) and time-weighted standard deviation (wSD). In multiple logistic regression analysis, CIMT > 900 µm was significantly and independently associated with aortic ARV (OR = 1.38; 95% CI: 1.04-1.84), aortic wSD (OR = 1.65; 95% CI: 1.19-2.29) and brachial ARV (OR = 1.53; 95% CI: 1.07-2.18), but not with brachial wSD. CCSA > 90th percentile was significantly and independently associated with aortic ARV (OR = 1.50; 95% CI: 1.07-2.10) and wSD (OR = 1.70; 95% CI: 1.12-2.56), but not with brachial BPVs. In receiver operator characteristics curve analysis, aortic wSD identified CCSA > 90th percentile better than brachial wSD (AUC: 0.73 vs 0.68, P < .01). In conclusion, aortic 24-hour systolic BPV showed a slightly stronger association with carotid damage than brachial BPV.