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.

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.

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 ±â€Š0.04 (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.

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.

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.

The influence of tocolytic drugs on cardiac function, large arteries, and resistance vessels.

PURPOSE: Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs, but are associated with cardiovascular side-effects. Atosiban, a newer drug, is a competitive antagonist of oxytocin and has been claimed to have fewer cardiovascular side effects. Until now, there has mainly been a subjective reporting of adverse reactions and few objective cardiovascular data. Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban compared with placebo on cardiac function, large artery properties, blood pressure, and resistance vessels. METHODS: A double-blind, randomized trial was carried out in 20 non-pregnant female volunteers. Hemodynamic measurements were made under standardized conditions during kinetic steady state. Cardiac output was measured with echocardiography, large artery properties with an echo-tracking device. The effect on the microcirculation was estimated using the total peripheral resistance index (TPRI). RESULTS: Atosiban did not differ from placebo. With ritodrine, cardiac function increased by 79% compared with placebo because of a rise in heart rate (91%). TPRI decreased by 48%. Ritodrine increased the distensibility of the common carotid artery by 62% and the compliance by 83%, independent of blood pressure. Compliance of the common femoral artery increased independently of pressure by 33% and the distensibility by 59%. Aortic pulse wave velocity was not influenced by either medication. CONCLUSIONS: The present study shows potential beneficial vascular effects of ritodrine that are counterbalanced by the cardiac effects. Atosiban has no clinically relevant cardiovascular effects and may be a good alternative for ritodrine in pregnant women at risk of cardiovascular complications.

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.

Different effects of tocolytic medication on blood pressure and blood pressure amplification.

BACKGROUND: The importance of tocolysis has been discussed extensively. Beta-2 adrenoceptor agonistic drugs like ritodrine have been the reference tocolytic drugs in most countries. Cardiovascular side-effects are frequent. Atosiban, a newer tocolytic drug, is a competitive antagonist of oxytocin and has fewer cardiovascular side effects. Although large studies exist, there is mainly subjective reporting of adverse reactions with a focus on blood pressure data. OBJECTIVES: Evaluation of the acute effects of therapeutic doses of ritodrine and atosiban in comparison to placebo on central and peripheral blood pressures, central-to-peripheral blood pressure amplification and the augmentation index (AIx) in healthy non-pregnant female volunteers. METHODS: A double-blind, randomized, crossover trial was carried out in 20 healthy non-pregnant female volunteers. Hemodynamic measurements were performed under standardized conditions. RESULTS: At steady state, central and peripheral pressures did not differ from placebo in the atosiban group. During ritodrine -infusion, central SBP increased by 11% versus placebo (p = 0.012) and peripheral SBP by 10% (p = 0.004). In contrast to atosiban and placebo, blood pressure amplification was absent in the ritodrine group. While the AIx did not change in the atosiban group, with ritodrine, the AIx tended to decrease. CONCLUSIONS: The present study shows the significant effects of ritodrine on the cardiovascular system. Atosiban has no significant effects and may be an appropriate alternative to tocolyticum, particularly in cardiovascularly complicated pregnancies.

Evaluation of medication adherence methods in the treatment of malaria in Rwandan infants.

OBJECTIVES: To compare three methods for evaluating treatment adherence in a 7-day controlled treatment period for malaria in children in Rwanda. METHODS: Fifty-six children (< 5 years) with malaria were recruited at the University Hospital of Butare, Rwanda. Patients were treated with quinine sulfate, taste-masked, pellets during seven days: three days in hospital (in-patient) followed by a four-day out-patient period. Three methods to evaluate medication adherence among patients were compared: manual pill count of returned tablets, patient self-report and electronic pill-box monitoring. These pill-boxes were equipped with a microchip registering date and time of every opening. Medication adherence was defined as the proportion of prescribed doses taken. The inter-dose intervals were analysed as well. RESULTS: Medication adherence data were available for 54 of the 56 patients. Manual pill count and patient self-report yielded a medication adherence of 100% for the in- and out-patient treatment periods. Based on electronic pill-box monitoring, medication adherence during the seven-day treatment period was 90.5 +/- 8.3%. Based on electronic pill-box monitoring inpatient medication adherence (99.3 +/- 2.7%) was markedly higher (p < 0.03) than out-patient adherence (82.7 +/- 14.7%), showing a clear difference between health workers' and consumers' medication adherence. CONCLUSION: Health workers' medication adherence was good. However, a significant lower medication adherence was observed for consumers' adherence in the outpatient setting. This was only detected by electronic pill-box monitoring. Therefore, this latter method is more accurate than the two other methods used in this study.

The use of diameter distension waveforms as an alternative for tonometric pressure to assess carotid blood pressure.

Proper non-invasive assessment of carotid artery pressure ideally uses waveforms recorded at two anatomical locations: the brachial and the carotid artery. Calibrated diameter distension waveforms could provide a more widely applicable alternative for local arterial pressure assessment than applanation tonometry. This approach might be of particular use at the brachial artery, where the feasibility of a reliable tonometric measurement has been questioned. The aim of this study was to evaluate an approach based on distension waveforms obtained at the brachial and carotid arteries. This approach will be compared to traditional pulse pressures obtained through tonometry at both the carotid and brachial arteries (used as a reference) and the more recently proposed approach of combining tonometric readings at the brachial artery with linearly or exponentially calibrated distension curves at the carotid artery. Local brachial and carotid diameter distension and tonometry waveforms were recorded in 148 subjects (119 women; aged 19-59 years). The morphology of the waveforms was compared by the form factor and the root-mean-squared error. The difference between the reference carotid PP and the PP obtained from brachial and carotid distension waveforms was smaller (0.9 (4.9) mmHg or 2.3%) than the difference between the reference carotid PP and the estimates obtained using a tonometric and a distension waveform (-4.8 (2.5) mmHg for the approach using brachial tonometry and linearly scaled carotid distension, and 2.7 (6.8) mmHg when using exponentially scaled carotid distension waves). We therefore recommend to stick to one technique on both the brachial and the carotid artery, either tonometry or distension, when assessing carotid blood pressure non-invasively.

Prices of antihypertensive medicines in sub-Saharan Africa and alignment to WHO's model list of essential medicines.

OBJECTIVE: To investigate compliance of National Essential Medicines Lists (NEMLs) with the WHO Essential Medicines List (WHO/EML) in 2007 and to compare prices of antihypertensive drugs in and between 13 sub-Saharan African countries. METHODOLOGY: Data on NEMLs and drug prices were collected from 65 public and 65 private pharmacies (five of each per country). Prices were compared with the International Drug Price Indicator Guide (IDPIG). The cost of drug treatment within a country was calculated using defined daily doses (DDD) and between countries using DDD prices adjusted for purchasing power parity-based gross domestic product per capita. RESULTS: All surveyed countries had a NEML. However, none of these lists were in complete alignment with the 2007 WHO/EML, and 38% had not been updated in the last 5 years. Surveyed medicines were cheaper when on the NEMLs; they were also cheaper in public than in private pharmacies. Prices varied greatly per medicine. A large majority of the public prices were higher than those indicated by the IDPIG. Overall, hydrochlorothiazide is the cheapest drug. CONCLUSION: There are substantial differences in NEML composition between the 13 countries. The proportion of NEMLs not regularly updated was double the global United Nations estimates. Prices of WHO/EML-advised drugs differ greatly between drugs and for each drug within and between countries. In general, the use of drugs on the NEML improves financial accessibility, and these drugs should be prescribed preferentially.

Noninvasive assessment of central and peripheral arterial pressure (waveforms): implications of calibration methods.

OBJECTIVES: Noninvasive estimation of central blood pressure (BP) from radial artery pressure waveforms is increasingly applied. We investigated the impact of radial artery waveform calibration on central BP assessment and calculated pressure amplification, with focus on the one-third rule used to estimate mean arterial BP (MAP). METHODS: Pressure waveforms were noninvasively measured at the radial and carotid arteries in 1873 individuals (age 45.8+/-6.1 years). Radial and carotid artery waveforms were calibrated using brachial artery DBP and SBP, MAP estimated with the one-third rule and MAP estimated as brachial DBP along with 40% of brachial artery pulse pressure. RESULTS: Central SBP obtained via a transfer function was 123.5 +/- 15.7, 117.8 +/- 14.2 and 126.0 +/- 15.4 mmHg (mean +/- SD) following above-mentioned three calibration schemes, respectively. Using the same calibration schemes, carotid artery SBP was 131.4 +/- 15.2, 118.4 +/- 14.4 and 126.8 +/- 15.7 mmHg, respectively. Central-to-brachial amplification was 13.0 +/- 3.6 mmHg using second method as compared with 4.6 +/- 3.8 mmHg with third method. Brachial-to-radial amplification was actually negative (-6.3 +/- 4.5 mmHg) using second method, whereas 3.4 +/- 5.5 mmHg was found with third method. CONCLUSION: Both carotid artery SBP and central SBP obtained via a transfer function are highly sensitive to the calibration of the respective carotid artery and radial artery pressure waveforms. Our data suggest that the one-third rule to calculate MAP from brachial cuff BP should be avoided, especially when used to calibrate radial artery pressure waveforms for subsequent application of a pressure transfer function. Until more precise estimation methods become available, it is advisable to use 40% of brachial pulse pressure instead of 33% to assess MAP.

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 individual's 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 approximately 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.

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 CFDbased 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.

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 (R(2)=0.55). Approximating the flow by a more physiological waveform significantly improved these results (R(2)=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 (R(2)<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.