Jan Kips

Arterial wave reflections and incident cardiovascular events and heart failure: MESA (Multiethnic Study of Atherosclerosis)

OBJECTIVES This study sought to assess the relationship between central pressure profiles and cardiovascular events (CVEs) in a large community-based sample. BACKGROUND Experimental and physiologic data mechanistically implicate wave reflections in the pathogenesis of left ventricular failure and cardiovascular disease, but their association with these outcomes in the general population is unclear. METHODS Aortic pressure waveforms were derived from a generalized transfer function applied to the radial pressure waveform recorded noninvasively from 5,960 participants in the Multiethnic Study of Atherosclerosis. The central pressure waveform was separated into forward and reflected waves using a physiologic flow waveform. Reflection magnitude (RM = [Reflected/Forward wave amplitude] × 100), augmentation index ([Second/First systolic peak] × 100) and pulse pressure amplification ([Radial/aortic pulse pressure] × 100) were assessed as predictors of CVEs and congestive heart failure (CHF) during a median follow-up of 7.61 years. RESULTS After adjustment for established risk factors, aortic AIx independently predicted hard CVEs (hazard ratio [HR] per 10% increase: 1.08; 95% confidence interval [CI]: 1.01 to 1.14; p = 0.016), whereas PPA independently predicted all CVEs (HR per 10% increase: 0.82; 95% CI: 0.70 to 0.96; p = 0.012). RM was independently predictive of all CVEs (HR per 10% increase: 1.34; 95% CI: 1.08 to 1.67; p = 0.009) and hard CVEs (HR per 10% increase: 1.46; 95% CI: 1.12 to 1.90; p = 0.006) and was strongly predictive of new-onset CHF (HR per 10% increase: 2.69; 95% CI: 1.79 to 4.04; p < 0.0001), comparing favorably to other risk factors for CHF as per various measures of model performance, reclassification, and discrimination. In a fully adjusted model, compared to nonhypertensive subjects with low RM, the HRs (95% CI) for hypertensive subjects with low RM, nonhypertensive subjects with high RM, and hypertensive subjects with high RM were 1.81 (0.85 to 3.86), 2.16 (1.07 to 5.01), and 3.98 (1.96 to 8.05), respectively. CONCLUSIONS Arterial wave reflections represent a novel strong risk factor for CHF in the general population.

Amplification of the Pressure Pulse in the Upper Limb in Healthy, Middle-Aged Men and Women

Central-to-peripheral amplification of the pressure pulse leads to discrepancies between central and brachial blood pressures. This amplification depends on an individuals hemodynamic and (patho)physiological characteristics. The aim of this study was to assess the magnitude and correlates of central-to-peripheral amplification in the upper limb in a healthy, middle-aged population (the Asklepios Study). Carotid, brachial, and radial pressure waveforms were acquired noninvasively using applanation tonometry in 1873 subjects (895 women) aged 35 to 55 years. Carotid, brachial, and radial pulse pressures were calculated, as well as the absolute and relative (with carotid pulse pressure as reference) amplifications. With subjects classified per semidecade of age, carotid-to-radial amplification varied from ≈25% in the youngest men to 8% in the oldest women. Amplification was higher in men (20±14%) than in women (13±12%; P<0.001) and decreased with age (P<0.001) in both. Amplification over the brachial-to-radial path contributed substantially to the total amplification. In univariate analysis, the strongest correlation was found with the carotid augmentation index (−0.51 in women; −0.47 in men; both P<0.001). In a multiple linear regression model with carotid-to-radial amplification as the dependent variable, carotid augmentation index, total arterial compliance, and heart rate were identified as the 3 major determinants of upper limb pressure amplification (R2=0.36). We conclude that, in healthy middle-aged subjects, the central-to-radial amplification of the pressure pulse is substantial. Amplification is higher in men than in women, decreases with age, and is primarily associated with the carotid augmentation index.

Current and projected prevalence of arterial hypertension in sub-Saharan Africa by sex, age and habitat: an estimate from population studies

Introduction In sub-Saharan Africa (SSA), data on hypertension prevalence in terms of urban or rural and sex difference are lacking, heterogeneous or contradictory. In addition, there are no accurate estimates of hypertension burden. Objective To estimate the age-specific and sex-specific prevalence of arterial hypertension in SSA in urban and rural adult populations. Methods We searched for population studies, conducted from 1998 through 2008 in SSA. We extracted data from selected studies on available prevalences and used a logistic regression model to estimate all age/sex/habitat (urban/rural)/country-specific prevalences for SSA up to 2008 and 2025. On the basis of the United Nations Population Fund data for 2008 and predictions for 2025, we estimated the number of hypertensives in both years. Results Seventeen studies pertaining to 11 countries were analysed. The overall prevalence rate of hypertension in SSA for 2008 was estimated at 16.2% [95% confidence interval (CI) 14.1–20.3], ranging from 10.6% in Ethiopia to 26.9% in Ghana. The estimated prevalence was 13.7% in rural areas, 20.7% in urban areas, 16.8% in males, and 15.7% in women. The total number of hypertensives in SSA was estimated at 75 million (95% CI 65–93 million) in 2008 and at 125.5 million (95% CI 111.0–162.9 million) by 2025. Conclusion The estimated number of hypertensives in 2008 is nearly four times higher than the last (2005) estimate of the World Health Organization Regional Office for Africa. Prevalences were significantly higher in urban than in rural populations. Population data are lacking in many countries underlining the need for national surveys.

Ethnic Differences in Arterial Wave Reflections and Normative Equations for Augmentation Index

Data regarding ethnic differences in wave reflections, which markedly affect the central pressure profile, are very limited. Furthermore, because age, heart rate, and body height are strong determinants of augmentation index, relating single measurements to normative data (in which augmentation index values correspond with average population values of its determinants) is challenging. We studied subject-level data from 10 550 adults enrolled in large population-based studies. In a healthy reference sample (n=3497), we assessed ethnic differences in augmentation index (ratio of second/first systolic peaks) and generated equations for adjusted z scores, allowing for a standardized comparison between individual augmentation index measurements and the normative population mean from subjects of the same age, sex, ethnic population, body height, and heart rate. After adjustment for age, body height, heart rate, and mean arterial pressure, African blacks (women: 154%; men: 138%) and Andean Hispanics (women: 152%; men: 133%) demonstrated higher central (aortic) augmentation index values than British whites (women: 140%; men: 128%), whereas American Indians (women: 133%; men: 122%) demonstrated lower augmentation index (all P<0.0001), without significant differences between Chinese and British whites. Similar results were found for radial augmentation index. Nonlinear ethnic/sex-specific equations for z scores were successfully generated to adjust individual augmentation index values for age, body height, and heart rate. Marked ethnic differences in augmentation index exist, which may contribute to ethnic differences in hypertensive organ damage. Our study provides normative data that can be used to complement the interpretation of individual hemodynamic assessments among men and women of various ethnic populations, after removing the effect of various physiological determinants.

Evaluation of Noninvasive Methods to Assess Wave Reflection and Pulse Transit Time From the Pressure Waveform Alone

Accurate quantification of pressure wave reflection requires separation of pressure in forward and backward components to calculate the reflection magnitude as the ratio of the amplitudes backward and forward pressure. To do so, measurement of aortic flow in addition to the pressure wave is mandatory, a limitation that can be overcome by replacing the unknown flow wave by an (uncalibrated) triangular estimate. Another extended application of this principle is the derivation of aortic pulse transit time from a single pulse recording. We verified these approximation techniques for reflection magnitude and transit time using carotid pressure and aortic flow waveforms measured noninvasively in the Asklepios Study (>2500 participants; 35 to 55 years of age). A triangular flow approximation using timing information from the measured aortic flow waveform yielded moderate agreement between reference and estimated reflection magnitude (R2=0.55). Approximating the flow by a more physiological waveform significantly improved these results (R2=0.74). Aortic transit time was assessed using pressure and measured or approximated flow waveforms, and results were compared with carotid-femoral transit times measured by Doppler ultrasound. Agreement between estimated and reference transit times was moderate (R2<0.29). Both for reflection magnitude and transit time, agreement between reference and approximated values further decreased when the approximated flow waveform was obtained using timing information from the pressure waveform. We conclude that, in our Asklepios population, results from pressure-based approximative methods to derive reflection magnitude or aortic pulse transit time differ substantially from the values obtained when using both measured pressure and flow information.

Ultrasound simulation of complex flow velocity fields based on computational fluid dynamics

In this work, a simulation environment for the development of flow-related ultrasound algorithms is presented. Ultrasound simulations of realistic Doppler signals require accurate modeling of blood flow. Instead of using analytically described flow behavior, complex blood movement can be derived from velocity fields obtained with computational fluid dynamics (CFD). By further modeling blood as a collection of point scatterers, resulting RF-signals can be efficiently retrieved using an existing ultrasound simulation model. The main aim of this paper is to elaborate on creating CFD-based phantoms for ultrasound simulations. The coupling of a computed flow field with an ultrasound model offers flexible control of flow and ultrasound imaging parameters, beneficial for improving and developing imaging algorithms. The proposed method was validated in a straight tube with a stationary parabolic velocity profile and further demonstrated by an eccentrically stenosis carotid bifurcation. The estimated flow velocities are in good agreement with the CFD reference, both for color flow imaging and pulsed-wave doppler simulations. The presented method can also be extended to include wall mechanics simulations in future work.

Comparison of central pressure estimates obtained from SphygmoCor, Omron HEM-9000AI and carotid applanation tonometry

Background The Omron HEM-9000AI is the first automated tonometer to provide an estimate of central SBP (cSBP), which is considered to be more predictive of cardiovascular events than brachial pressure. However, considerable differences between the cSBP estimate of Omron and that of SphygmoCor have been reported, but not explained. This study assesses the sources of differences between both cSBP estimates and provides a handle on which estimate is closest to reality. Method For this purpose, aortic cSBP derived from calibrated carotid SBP was used as device- and algorithm-independent reference. Radial, brachial and carotid applanation tonometry were performed in 143 black South Africans, aged 39–91 years. Each individual was measured with an Omron HEM-9000AI and a SphygmoCor. Results When using both devices as advocated by their manufacturers, the corresponding cSBP estimates correlated strongly (r = 0.99, P < 0.001), but the Omron estimate was 18.8 (4.3) mmHg higher than the SphygmoCor estimate. Aortic SBP was in between both estimates: 11.7 (5.5) mmHg lower than cSBP-Omron and 7.1 (5.0) mmHg higher than cSBP-SphygmoCor. Alternative calibration of the radial SphygmoCor-curves with radial instead of brachial pressures yielded a cSBP that was 3.0 (4.2) mmHg lower than aortic SBP. The shape of the recorded pressure waves was similar in both devices: less than 5% of the observed cSBP difference was caused by differences in wave shape. Conclusion The results from this study demonstrate that the considerable difference between the central pressure estimates of Omron HEM-9000AI and SphygmoCor is due to algorithm differences, and suggest that the overestimation by Omron HEM-9000AI is larger than the underestimation by SphygmoCor.

Ambulatory arterial stiffness index does not accurately assess arterial stiffness.

Introduction: The ambulatory arterial stiffness index (AASI), derived from ambulatory blood pressure monitoring (ABPM) recordings, has been proposed as a surrogate marker of arterial stiffness. However, there is controversy to what extent it reflects stiffness or is affected by other parameters. Using a previously validated one-dimensional computer model of the arterial circulation, the relative importance of the different determinants of the AASI was explored. Methods: Arterial distensibility (inverse of stiffness), peripheral resistance, heart rate, maximal cardiac elastance and venous filling pressure were varied from 80 to 120% of their initial value in steps of 10% to generate 3125 BP values, mimicking the daily fluctuations in one theoretical patient. From this dataset, we assessed the confidence with which AASI can be derived in this patient, as well as the influence of different individual parameters on AASI. To assess the ability of AASI to detect large changes in arterial stiffness, two additional patients were simulated with a distensibility of 50 and 25% of the default distensibility, respectively. Results: The distribution of AASI values, obtained from 10 000 ABPM simulations (each using 72 BP values randomly selected among 3125) was normal [AASI = 0.43 ± 0.04 (SD)]. An increase in heart rate, distensibility or resistance from 80 to 120% of its default value caused the AASI to decrease by 37, 21 or 9%, respectively. Whereas there was no overlap in the distensibility ranges for the three theoretical patients, the amount of overlap between the AASI distributions was substantial. Conclusion: The confounding effects of vascular resistance and heart rate seriously limit the use of AASI as a marker of stiffness.

Impaired Cardiovascular Structure and Function in Adult Survivors of Severe Acute Malnutrition

Malnutrition below 5 years remains a global health issue. Severe acute malnutrition (SAM) presents in childhood as oedematous (kwashiorkor) or nonoedematous (marasmic) forms, with unknown long-term cardiovascular consequences. We hypothesized that cardiovascular structure and function would be poorer in SAM survivors than unexposed controls. We studied 116 adult SAM survivors, 54 after marasmus, 62 kwashiorkor, and 45 age/sex/body mass index–matched community controls who had standardized anthropometry, blood pressure, echocardiography, and arterial tonometry performed. Left ventricular indices and outflow tract diameter, carotid parameters, and pulse wave velocity were measured, with systemic vascular resistance calculated. All were expressed as SD scores. Mean (SD) age was 28.8±7.8 years (55% men). Adjusting for age, sex, height, and weight, SAM survivors had mean (SE) reductions for left ventricular outflow tract diameter of 0.67 (0.16; P<0.001), stroke volume 0.44 (0.17; P=0.009), cardiac output 0.5 (0.16; P=0.001), and pulse wave velocity 0.32 (0.15; P=0.03) compared with controls but higher diastolic blood pressures (by 4.3; 1.2–7.3 mm Hg; P=0.007). Systemic vascular resistance was higher in marasmus and kwashiorkor survivors (30.2 [1.2] and 30.8 [1.1], respectively) than controls 25.3 (0.8), overall difference 5.5 (95% confidence interval, 2.8–8.4 mm Hg min/L; P<0.0001). No evidence of large vessel or cardiac remodeling was found, except closer relationships between these indices in former marasmic survivors. Other parameters did not differ between SAM survivor groups. We conclude that adult SAM survivors had smaller outflow tracts and cardiac output when compared with controls, yet markedly elevated peripheral resistance. Malnutrition survivors are thus likely to develop excess hypertension in later life, especially when exposed to obesity.

Experimental and numerical modelling of the ventriculosinus shunt (El-Shafei shunt)

This study assesses malresorptive hydrocephalus treatment by ventriculosinus shunting with the shunt in the antegrade or retrograde position. First, an experimental model of the cerebral ventricles, the arachnoid villi, the cortical veins, and the superior sagittal sinus was built. For this purpose, the compliance of a human cortical vein was measured and then modelled by means of Penrose tubes. The dimensions of the superior sagittal sinus were determined in vivo by measurements on magnetic resonance imaging scans of 21 patients. Second, a numerical model of the cortical veins and the superior sagittal sinus was built. The numerical results were validated with the results from the experimental model. The experimental and numerical pressure difference between the intracranial pressure and the static sinus pressure was small (0–20 Pa) and corresponded to the theoretically expected values. No overdrainage was found in either the antegrade or the retrograde position of the shunt. Blood reflow was only found while mimicking lumbar puncture or changes in position with the experimental model (lowering the intracranial pressure or increasing the sinus pressure rapidly). Optimal results can be obtained with the shunt positioned in the most downstream half of the superior sagittal sinus. The experimental and numerical results confirm the potential of ventriculosinus shunting as therapy for malresorptive hydrocephalus patients. The ventriculosinus shunt thus proves to be a promising technique.