Athanase D. Protogerou

Expert consensus document on the measurement of aortic stiffness in daily practice using carotid-femoral pulse wave velocity

Stiffness of elastic arteries like the aorta predicts cardiovascular risk. By directly reflecting arterial stiffness, having the best predictive value for cardiovascular outcome and the ease of its measurement, carotid-femoral pulse wave velocity is now considered the gold standard for arterial stiffness assessment in daily practice. Many different measurement procedures have been proposed. Therefore, standardization of its measurement is urgently needed, particularly regarding the distance measurement. This consensus document advises on the measurement procedures in general and provides arguments for the use of 80% of the direct carotid-femoral distance as the most accurate distance estimate. It also advises the use of 10 m/s as new cut-off value for carotid-femoral pulse wave velocity.

Role of Pulse Pressure Amplification in Arterial Hypertension Experts’ Opinion and Review of the Data

Arterial hypertension is a major modifiable cardiovascular (CV) risk factor worldwide based on observational studies of brachial artery blood pressure (BP). In the latest guidelines of the European Society of Hypertension1 for the management of arterial hypertension, aortic stiffness was introduced as an index of target organ damage. Three additional cardinal features of BP were also acknowledged: (1) systolic BP and pulse pressure (PP) may differ between the brachial artery and central arteries (ie, the aorta and its proximal branches), (2) the effects of antihypertensive drug treatment on brachial BP does not invariably reflect those seen on central BP, and (3) central BP is significantly related to CV events. Moreover, the guidelines acknowledged that noninvasive methods exist for the assessment of central hemodynamic parameters, such as central PP, and highlighted the need for large scale interventional studies that will further confirm the prognostic importance of central BP. Two years ago, coincident with the 6th International Workshop on the “Structure and Function of the Vascular System,” in Paris, a consensus document on the role of central BP in arterial hypertension was published.2 It concluded that there is “mounting evidence suggesting that central BP and indices correlate more closely with intermediate markers of CV risk than brachial BP”. It was also suggested that clinicians and researchers need to become familiarized with the disparity between peripheral and central BPs, ie, the phenomenon of pressure wave amplification. The present document is designed to address this need. The left ventricle consumes energy by ejecting blood into the arterial system, thereby creating arterial blood flow and pressure. This phenomenon is easily conceived as a propagating pulse along the arterial bed. In daily clinical practice the arterial pulse, at a distinct site of the arterial tree (eg, at the brachial artery), is quantified as the …

Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation.

Diastolic Blood Pressure and Mortality in the Elderly With Cardiovascular Disease

Isolated systolic hypertension is predominantly observed in the elderly because of increased arterial stiffness. Aggressive treatment leads to excessive lowering of diastolic blood pressure and favors the presence of a J-shaped curve association with mortality. We investigated whether, in the elderly, this pattern of association is a simple epiphenomenon of increased arterial stiffness and impaired cardiac function. In a cohort of 331 hospitalized subjects >70 years old (mean age±SD: 85±7 years), aortic pulse wave velocity and pressure wave reflections, by pulse wave analysis, and cardiac function, by ultrasound, were assessed. During a 2-year follow-up period, 110 subjects died. No association of prognosis with systolic pressure, pulse pressure, or pulse wave velocity was observed. A J-shaped association between diastolic pressure and overall and cardiovascular mortality was observed. Unadjusted Cox regression analysis showed that patients in the first tertile of diastolic pressure (≤60 mm Hg) had higher mortality. In Cox regression analysis, diastolic pressure ≤60 mm Hg was a predictor of mortality independently from cardiac–vascular properties, cardiovascular risk factors, and drug treatment. Multivariate regression analysis showed that increased age and low total peripheral resistance, but not left ventricular function, were the cardinal determinants of low diastolic pressure. An “optimal” diastolic pressure of 70 mm Hg in subjects with isolated systolic hypertension was found. We showed that, in the frail elderly, a value of diastolic blood pressure ≤60 mm Hg is associated with reduced survival, independent from large artery stiffness and left ventricular function, suggesting that more rational antihypertensive therapy, not only based on systolic pressure level, is needed.

The Effect of Antihypertensive Drugs on Central Blood Pressure Beyond Peripheral Blood Pressure. Part II: Evidence for Specific Class-Effects of Antihypertensive Drugs on Pressure Amplification

The blood pressure (BP) waveform varies substantially between the peripheral conduit (brachial) and the central elastic (aorta) arteries mainly do a gradual increase of systolic BP, as the wave propagates distally. This phenomenon is called BP amplification and is principally generated by the presence of arterial stiffness gradient and wave reflections along the arterial bed. More and more clinical studies suggest that central BP may provide additional information regarding cardiovascular risk beyond peripheral BP. Arterial properties and thus pressure amplification, are modulated by age, cardiovascular risk factors, vasoactive substances and drugs. Recent evidence suggests, beyond any doubt, that antihypertensive drugs affect peripheral and central BP differentially and alter pressure amplification. The aim of the present review (Part II) is to summarize the available evidence regarding: (i) the specific class-effect of antihypertensive drugs on central BP beyond peripheral BP, as well as the potential underlying hemodynamic mechanisms, (ii) head to head comparison of the effect of different classes of antihypertensive drugs on central BP, (iii) the effect of combination drug treatment on central BP. Finally to attempt an interpretation of the clinical trials in hypertension, which classically record brachial BP, based on the results of studies which assessed central BP. Several conclusions were drawn. First, it is clear that there are important differences between the classes of antihypertensive drugs regarding their effects on BP amplification. Second, it seems that the newer antihypertensive drugs [angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers and dihydropyridine calcium blockers], as well as nitrates, have a more beneficial effect on BP amplification than the older drugs (diuretics and BBs). Third, there is compelling evidence regarding the detrimental effect of BBs (mainly atenolol) on central BBs and convincing evidence that ACEIs increase BP amplification.

Central blood pressures: do we need them in the management of cardiovascular disease? Is it a feasible therapeutic target?

It is well established that in young and healthy individuals central (aortic or carotid) systolic and pulse pressures are different from peripheral (brachial) corresponding pressures as a consequence of progressive changes in arterial stiffness and pressure wave reflections along the arterial tree. There is evidence indicating that in interventions with pharmaceutical and non-pharmaceutical agents, central pressures are subjected to greater changes than peripheral pressures, and they are more closely related to the pathophysiology of end-organ damage or cardiovascular risk. Therefore central blood pressures may be of higher clinical importance than peripheral pressures. The present review aims to provide an insight into the (patho)physiology of central blood pressures, to present the most accurate techniques for their estimation, and to discuss the available experimental and epidemiological data that support the emerging need for the evaluation of central blood pressures in clinical practice.

Blood pressure response under chronic antihypertensive drug therapy: the role of aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study.

OBJECTIVES We sought to evaluate the role of arterial stiffness on blood pressure (BP) response to drug treatment. BACKGROUND Increased arterial stiffness (pulse wave velocity [PWV]) is associated with increased systolic blood pressure (SBP). Antihypertensive drug therapy achieves better control of diastolic blood pressure (DBP) than SBP does, implying that increased PWV might be a predictor of the SBP response to treatment. METHODS The REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study is a randomized, double-blind trial comparing atenolol versus perindopril/indapamide; 375 patients with hypertension, with BP and PWV measurements at baseline and after 12 months of treatment, were divided into 3 tertiles according to baseline PWV and included in a post-hoc analysis. RESULTS After 12 months of treatment, BP differed significantly between PWV tertiles (the third having the lowest response, p < 0.05). Factors related to smaller BP decline were low baseline BP, high baseline PWV, need for a double dose of treatment, use of atenolol (only for SBP response), and age (only for DBP). Although DBP control did not differ in the PWV tertiles, SBP control was significantly associated with PWV level (p = 0.001) as well as with the use of perindopril/indapamide (p < 0.001). The predictive value of PWV on BP response was independent of age, sex, mean BP, and cardiovascular risk factors. CONCLUSIONS Baseline PWV is a significant predictor of BP response to antihypertensive treatment, independent from age, the need for increasing drug dosage, and the presence of cardiovascular risk factors. Achievement of SBP control appears to be influenced by aortic stiffness as well as by angiotensin-converting enzyme inhibition.

Hypertension and vascular dynamics in men and women with metabolic syndrome.

Metabolic syndrome (MetS), an important component of insulin resistance and cardiovascular (CV) risk, is defined by 3 or more of the following characteristics: abdominal obesity, hyperglycemia, hypertension, hypertriglyceridemia, and hypo-high-density lipoprotein cholesterolemia. Based on the previously published age- and sex-mediated DESIR (Data from an Epidemiological Study on the Insulin Resistance Syndrome) cohort and parallel central hemodynamic measurements, our goal was to evaluate the effects of MetS on brachial central pulse pressure (PP), PP amplification, aortic stiffness, and wave reflections. These data were then compared with those of patients with essential hypertension but without MetS for the same mean arterial pressure. Increased aortic stiffness, a major mechanical factor predicting CV risk, has been well identified as playing a role in MetS. Its age progression is proportional to the number of risk factors involved in MetS and is responsible for increased systolic blood pressure and decreased diastolic blood pressure with increasing age, the principal hallmarks of hypertension in the elderly. Beyond brachial pressure measurements, central hemodynamic parameters involve increased aortic stiffness, reduced wave reflections, and increased PP amplification, a parameter commonly associated with increased heart rate. With the exception of arterial stiffness, all these findings are opposite in direction to those observed in essential hypertension, in which MetS is absent. A divergent behavior of wave reflections and PP amplification, but not of arterial stiffness, is observed when hypertension is studied alone or when compared with MetS for the same mean arterial pressure. This pulsatile hemodynamic abnormality contributes independently to increase age- and sex-mediated CV risk, justifying new research regarding Framingham scores and drug treatment.

Left-ventricular hypertrophy is associated better with 24-h aortic pressure than 24-h brachial pressure in hypertensive patients: the SAFAR study.

Objective: To test the hypothesis that left-ventricular hypertrophy (LVH) is better associated with aortic, than brachial, 24-h average blood pressure (BP) in individuals with hypertension. Background: The office aortic BP is associated better with organ damage, such as LVH, than the office brachial BP; whether the 24-h average aortic BP associates better with LVH, than the 24-h average brachial BP, has never been tested. Methods: Aortic ambulatory BP monitoring (ABPM) was performed with a novel validated oscillometric cuff-based BP recording device, also used for simultaneous brachial ABPM, and the application of pulse wave analysis method. Office brachial and aortic BP were assessed with validated oscillometric recording device and pulse wave analysis, respectively; left-ventricular mass was measured by ultrasound. Results: Regression analysis performed in 229 individuals (aged 54.3 ± 14.6 years; 56% men; 75% hypertensive patients) showed that the 24-h average aortic SBP was significantly better associated with left-ventricular mass index and LVH than the 24-h average brachial, as well as, office (brachial or aortic) SBP, independently of age, sex, obesity or treatment. Receiver operator characteristics curve analysis showed a higher discriminatory ability of 24-h average aortic than brachial SBP to detect the presence of LVH (area under the curve: 0.73 versus 0.69; P = 0.007). A high degree of interindividual overlap regarding aortic 24-h average SBP level was found in individuals in whom the corresponding brachial measurements denoted different hypertension levels. Conclusion: These data suggest that aortic ABPM, when compared to brachial ABPM, improves the individualized assessment of the BP-associated heart damage.

Arterial stiffness and central hemodynamics in treated hypertensive subjects according to brachial blood pressure classification.

Background International recommendations have classified brachial blood pressure (BP) in subgroups enabling better cardiovascular risk stratification. Central BP is an independent predictor of cardiovascular risk, differing from brachial BP through the predominant influence of arterial stiffness and wave reflections. Central BP has never been studied in relation to international guidelines for brachial BP classification. Methods In 580 chronically treated hypertensive subjects we measured: carotid–femoral pulse wave velocity (PWV), carotid artery augmentation index (AI) and carotid blood pressures, using applanation tonometry and pulse wave analysis, and using brachial BP for carotid pressure wave calibration. Results For each given brachial value, carotid systolic blood pressure (SBP) and PP were significantly lower than the corresponding brachial SBP and PP. This pressure amplification was significantly lower in the ‘optimal’ and ‘normal’ BP ranges (6.8–7.4 mmHg) than in the higher BP ranges (10.1–11.3 mmHg), mainly depending on heart rate (HR) and PWV levels. PWV gradually increased as a function of brachial BP classification and was a significant predictor of this classification independently of age, drug treatment, atherosclerotic lesions and even mean BP. Finally, PWV was a highly sensitive marker of the effective BP control throughout all decades of age. Conclusion Under chronic antihypertensive therapy, central BP does not strictly parallel the corresponding brachial BP classification, depending on differences in aortic stiffness and HR. Whether aortic PWV might predict the brachial BP classification and/or the presence of effective BP control, as suggested in this study, needs further confirmation.