Theodore G. Papaioannou

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.

Non-Invasive Methods and Techniques for Central Blood Pressure Estimation: Procedures, Validation, Reproducibility and Limitations

Hypertension is a major risk factor for a wide range of cardiovascular diseases and is typically identified by measuring blood pressure (BP) at the brachial artery. Although such a measurement may accurately determine diastolic BP, it does not accurately reflect systolic BP. This is mainly attributed to the fact that blood pressure waveform is distorted as it travels outward from the heart due to the presence of wave reflections from the peripheral arteries. Due to this distortion, blood pressure measured at the brachial artery provides an inaccurate measure of central aortic systolic pressure. However, central systolic BP is an important factor determining cardiac function and work, while central diastolic BP may determine coronary flow. Consequently central (aortic and carotid) pressures are pathophysiologically more relevant than peripheral pressures and thus their non-invasive accurate estimation is challenging and clinically necessary. The purpose of this review is to present methods and techniques that are used for the estimation of central blood pressures and to describe and discuss issues regarding methodological procedures, reproducibility, validity and limitations.

Postprandial Improvement of Endothelial Function by Red Wine and Olive Oil Antioxidants: A Synergistic Effect of Components of the Mediterranean Diet

Objective: Consumption of olive oil may cause postprandial impairment of endothelial function, while acute ingestion of red wine seems to improve it. The purpose of the present study was to investigate the combined postprandial effects of two essential components of the Mediterranean diet, red wine and olive oil, on endothelial function. Methods: Fifteen healthy subjects were enrolled in the study, which was comprised of 4 study days. Subjects were asked to consume a standard meal at each study day containing 50gr of olive oil and 250 ml of wine. Two types of wine (red and white; rich and poor in antioxidants respectively) and two types of olive oil (green and refined; rich and poor in antioxidants respectively) were used in a 2*2 design. Endothelium dependent, flow mediated dilatation (FMD) was measured with a B-Mode ultrasound device at fast and 1, 2 and 3 hours postprandially. Results: Combined consumption of red wine and green olive oil (both rich in antioxidants) improved FMD postprandially (p = 0.002, ANOVA for repeated measures), which remained significant 1 hour (p = 0.002) and 2 hours (0.037) following the meal compared to fasting levels. No other combination of wine and olive oil caused any significant alteration on FMD. Conclusion: Acute consumption of both red wine and green olive oil, rich in antioxidants, led to an improvement in the postprandial endothelial function in healthy subjects. These findings provide an additional favorable effect of components of the Mediterranean diet and of their antioxidant substances on endothelial function, at the postprandial state.

Non-invasive 24 hour ambulatory monitoring of aortic wave reflection and arterial stiffness by a novel oscillometric device: The first feasibility and reproducibility study

BACKGROUND Surrogates of aortic wave reflection and arterial stiffness, such as augmentation index (AIx), augmentation pressure, pulse wave velocity (PWV) and pulse pressure amplification (PPampl) are independent predictors of cardiovascular risk. A novel ambulatory, brachial cuff-based oscillometric device has been recently developed and validated, yielding 24-h assessment of the aforementioned parameters (Mobilo-O-Graph). Aim of this study was to investigate the feasibility and reproducibility of wave reflection and arterial stiffness estimation by pulse wave analysis using this device. METHODS Thirty treated or untreated hypertensives (mean age: 53.6 ± 11.6 years, 17 men) had test-retest 24-h monitoring one week apart using the test device. RESULTS Mean numbers of valid aortic readings per subject, between test and retest, were comparable. Approximately 12 aortic readings per subject (17%) were not feasible or valid. No differences were observed for any 24-h parameter between the two assessments. Bland-Altman plots showed no systemic difference, while the limits of agreement for each parameter indicated high reproducibility (AIx: -7.2 to 8.2%, AP: -3.7 to 4.1mm Hg, PWV: -0.39 to 0.41 m/s, PPampl: -0.08 to 0.06). This was further verified by intraclass correlation coefficients which were >0.8 for each parameter. CONCLUSIONS Non-invasive 24-h estimation of wave reflection and arterial stiffness indices, derived by the test device, appear to be highly reproducible. Future studies should investigate whether these measurements have additive prognostic value for cardiovascular risk stratification, beyond common brachial blood pressure measurements or single estimations of wave reflection and PWV at office settings.

Hour-to-hour and week-to-week variability and reproducibility of wave reflection indices derived by aortic pulse wave analysis: implications for studies with repeated measurements.

Background Wave reflections are implicated increasingly in clinical research. Aims The purpose of the present study was to investigate whether wave reflection indices are reproducible when measured repeatedly (more than twice) at longer time intervals, namely hour-to-hour and week-to-week, in healthy subjects; something that has not yet been examined. Methods Bland–Altman plots, the interclass correlation coefficients (ICC) and coefficient of variation were used for this purpose. Two series, with measurements repeated in triplicate, were performed in 22 healthy subjects: the first at intervals of 1 h and the second at 1-week time intervals. Augmentation index (AIx), heart rate-corrected AIx (AI@75) and arrival time of reflected waves at the central aorta (tr) were calculated by aortic pulse wave analysis. Results AIx and AI@75 presented very good to excellent reproducibility (ICC = 0.86) for hour-to-hour repeated measurements, while tr was also highly reproducible (ICC = 0.79). AIx, AI@75 and tr were substantially reproducible when measured repeatedly with 1-week intervals, providing ICCs greater than 0.70. Bland–Altman plots confirmed these results, indicating that more than 90% of AIx, AI@75 and tr measurements fell within two standard deviations of the mean difference. Conclusions Wave reflections are substantially reproducible even when measurements repeated in triplicate are performed at longer time intervals (hours and weeks). A quantifiable amount of variation was reported, which should be taken carefully into consideration in interventional studies with repeated measurements and in observational studies investigating differences or correlations of these indices.

Methodology and technology for peripheral and central blood pressure and blood pressure variability measurement: Current status and future directions - Position statement of the European Society of Hypertension Working Group on blood pressure monitoring and cardiovascular variability

Office blood pressure measurement has been the basis for hypertension evaluation for almost a century. However, the evaluation of blood pressure out of the office using ambulatory or self-home monitoring is now strongly recommended for the accurate diagnosis in many, if not all, cases with suspected hypertension. Moreover, there is evidence that the variability of blood pressure might offer prognostic information that is independent of the average blood pressure level. Recently, advancement in technology has provided noninvasive evaluation of central (aortic) blood pressure, which might have attributes that are additive to the conventional brachial blood pressure measurement. This position statement, developed by international experts, deals with key research and practical issues in regard to peripheral blood pressure measurement (office, home, and ambulatory), blood pressure variability, and central blood pressure measurement. The objective is to present current achievements, identify gaps in knowledge and issues concerning clinical application, and present relevant research questions and directions to investigators and manufacturers for future research and development (primary goal).

Combined acute effects of red wine consumption and cigarette smoking on haemodynamics of young smokers

Objective Red wine seems to improve haemodynamic variables, while smoking provokes adverse effects. The haemodynamic effects of their combined use is unknown. The purpose of the present study was to examine the acute effects of red wine and its constituents, in combination with the smoking of one cigarette, on haemodynamic parameters, such as blood pressure and wave reflections, in a group of smokers. Methods Twenty smokers (12 males, eight females) participated in a double-blind, crossover study comprised of 3 study days. All subjects either smoked one cigarette, or smoked and drank 250 ml of red wine, or 250 ml of de-alcoholized red wine (containing the same type and similar concentration of antioxidants). Applanation tonometry and generalized transfer functions were used to estimate aortic pressure waveforms at baseline and 30, 60 and 90 min after each trial. The augmentation index (AIx) was used to express wave reflections. Results Smoking increased peripheral systolic blood pressure (P < 0.005) 30 min later, but simultaneous consumption of either type of red wine caused no such effect. Additionally, smoking caused no overall effect on AIx, while smoking and drinking either regular or de-alcoholized red wine reduced AIx (P < 0.001). The reduction of AIx after red wine consumption was significantly greater than the respective reduction after de-alcoholized red wine (P = 0.004). Conclusion Antioxidant substances in red wine counteracted the smoking–induced increase in peripheral systolic blood pressure. Both alcohol and antioxidants in red wine decrease wave reflections in uncomplicated habitual smokers postprandially, indicating an additional favourable effect of red wine.

Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension

Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67±2.94 vs 6.06±4.91% and 145.8±22.7 vs 135.7±20.3%, P<0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52±4.29 vs 10.73±5.77% and 139.5±21.7 vs 124.5±17.0%, P<0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837–0.99, P=0.04 and OR:1.023, 95%CI:1.023–1.040 P=0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (−2 log likelihood=139.368, change of χ2=4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.

Quantitative analysis of carotid plaque vasa vasorum by CEUS and correlation with histology after endarterectomy

BACKGROUND Intraplaque neovascularization and vasa vasorum (VV) proliferation contribute in the progression and rupture of atherosclerotic lesions. Contrast enhanced ultrasonography (CEUS) has been reported to attain data regarding intraplaque neovessels and VV. However, whether the detection of microbubbles by CEUS within atherosclerotic plaques truly represents microvessels is a point of concern. We aimed to evaluate stable and unstable carotid artery plaque (CAP) VV pattern by CEUS and its correlation with histology and immunochemistry. PATIENTS AND METHODS Patients with CAP scheduled for plaque endarterectomy were enrolled. CAP was initially identified by conventional ultrasonography and subsequently CEUS (harmonic ultrasound imaging with simultaneous intravenous contrast agent injection) was performed. The recorded image loops were evaluated by a semi-automated method. Plaque specimens were excised and underwent histological and immunochemical (for CD34, Vascular Endothelial Growth Factor, CD68 and CD3 antibodies) analysis. RESULTS Fourteen patients (67.6 ± 10.2 years, 10 males) with a 86.9 ± 11.5 % degree of carotid artery stenosis were evaluated. Histology showed that half of the plaques were unstable. Enhancement of plaque brightness on CEUS was significant for both stable and unstable plaque subgroups (p = 0.018 for both). Immunochemistry showed that microvessels, as assessed by CD34 antibody, were more dense in unstable vs. stable plaques (36.6 ± 17.4 vs. 13.0 ± 7.2 respectively, p = 0.002). However, correlation between plaque brigthness enhancement on CEUS and microvessel density was significant only for stable (r = 0.800, p = 0.031) plaques. CONCLUSIONS The identification of brightness enhacement during CEUS in carotid atherosclerotic plaques may not always reflect the presence of VV.

The effect of antihypertensive drugs on central blood pressure beyond peripheral blood pressure. Part I: (Patho)-physiology, rationale and perspective on pulse 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. In the present review (Part I) we deal with the mechanisms underlying: (i) the genesis and recording of BP difference between central and peripheral arteries (pressure amplification), (ii) the rational of differential effect of antihypertensive drugs on pressure amplification, (iii) the pathophysiological role of pressure amplification on cardiovascular disease as well as its clinical and research implications.