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Purpose Obesity clearly increases cardiovascular risk, often inducing high blood pressure (BP), impaired left ventricular (LV) function, and increased arterial stiffness. Intensive weight loss and bariatric surgery induce improvement in hypertension and diabetes for morbid obesity. Carotid artery haemodynamics is a powerful prognostic indicator for stroke and cognitive decline independent of BP. The aim of this study was to evaluate the impact of a 3-stage bariatric strategy of diet, bariatric surgery, and consequent weight loss on carotid haemodynamics and cardiac diastolic function. Material and Methods This prospective study included 26 patients (45 ± 10 years, 4 men) with severe obesity undergoing bariatric surgery without comorbidities (hypertension, diabetes, etc.). Anthropometry, BP, Doppler echocardiography, and common carotid haemodynamics by ultrasound were measured at three times: (1) baseline, (2) after 1-month diet (post-diet), and (3) 8 months after surgery (post-surgery). The lnDU-loop method was used to estimate local carotid pulse wave velocity (ncPWV). Results Baseline BMI was 47.9 ± 7.1 kg/m2 and reduced by 5% and 30% post-diet and post-surgery, respectively. BP decreased only post-diet, without pulse pressure change. However, ncPWV, 6.27 ± 1.35 m/s at baseline, was significantly reduced by 10% and 23% post-diet and post-surgery, respectively, also adjusted for BP changes. The E/A ratio rose from 0.95 ± 0.20 to 1.27 ± 0.31 (p Conclusion Weight loss following diet and bariatric surgery is associated with reduced carotid arterial stiffness and improved LV diastolic function. Diet and bariatric surgery are effective treatments for morbid obesity with its concomitant adverse cardiovascular effects.

OBJECTIVES Arterial stiffness as pulse wave velocity (PWV) predicts cardiovascular events independently of blood pressure (BP). PWV does not distinguish between stiffness in systole and diastole. This cross-sectional study aimed to test the hypothesis that viscous and elastic carotid wall properties differ between systole and diastole, distinguishing effects of ageing, hypertension and T2 diabetes (T2DM). METHODS We examined carotid visco-elasticity in 307 people (180 men), with hypertension alone (n = 69), combined hypertension/T2DM (H-T2DM, n = 99), normotensive (N-T2DM, n = 25) and healthy controls (n = 114). Diameter (D)/pressure (P) waveforms were measured at right /left common carotid arteries, respectively. Local carotid PWV and distensibility in systole and diastole were evaluated by the D2P-loop method, and wall viscosity from hysteresis, the area (HA) within the P--D loop, as a dynamic measure of systolic loading and diastolic unloading. RESULTS Controls' hysteresis fell quadratically with age (R2 = 0.23, P

Aim To test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, versus placebo/doxazosin, to control for blood pressure (BP). Methods A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate-containing beetroot juice or placebo nitrate-depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph®) and carotid lumen area. Data was analysed by modified intention to treat and using mixed-model effect, adjusted for confounders. Results 93 subjects had a baseline evaluation and 86% had follow-up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate-containing versus placebo juice significantly lowered CIMT [-0.06 (95% Confidence Interval -0.12, -0.01), p=0.034], an overall difference of ~8% relative to baseline; but had no effect on carotid diameter (CD) or carotid stiffness (CS). Doxazosin appeared to reduce CS from baseline [-0.34 (-0.62, -0.06)] however, no difference was detected versus spironolactone [-0.15 (-0.46, 0.16)]. No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusion Our results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP-independent effect on carotid structure and function.

Background: Carotid-femoral Pulse Wave Velocity (cfPWV) is the gold-standard measure of arterial stiffness. Accuracy of non-invasive cfPWV as meters per second is impeded by surface estimates of aortic length. Our aim was to compare cfPWV measured using distance estimated from surface measurements with distance traced along the length of the aorta using Magnetic Resonance Imaging (MRI) in a cohort of older women. Methods: Seventy-four women were recruited from the TwinsUK cohort. cfPWV was measured using the SphygmoCor system (SphygmoCor-PWV). The path between carotid and femoral sites was estimated from surface measurements between the sternal notch and femoral artery applanation point. Aortic distance was measured with MRI to obtain MRI-PWV. cfPWV was recalculated using MRI obtained distance. Results: Mean ± standard deviation SphygmoCor-PWV was 9.9 ± 2.1 m/s and MRI-PWV 7.63 ± 1.97 m/s (mean difference 2.2 ± 1.96 m/s, p < 0.001). Distances were considerably higher using surface measures for the SphygmoCor (55.2 ± 3.0, 95% confidence interval 54.4–55.9 cm) compared with MRI (39.9 ± 3.2, 39.2–40.7 cm) with a mean difference of 15.2 cm (14.3–16.2 cm, p < 0.001). Transit times were also marginally longer with the SphygmoCor. When SphygmoCor-PWV was Recalculated using MRI-obtained aortic distance (rec-PWV), the difference between SphygmoCor-PWV and rec-PWV reduced to 0.5 m/s (7.13 ± 1.46 vs. 7.63 ± 1.97 m/s, p = 0.08). Conclusion: In these older women, the PWV difference between SphygmoCor and MRI is substantial but reduced when using MRI length estimates. Important differences between PWV measured by Sphygmocor and MRI are mainly due to accuracy of distance measurements, which may need re-addressing in guidelines.

La hipertensión arterial es una causa modificable muy prevalente de enfermedades cardiovasculares, accidentes cerebrovasculares y muerte. Medir con exactitud la presión arterial es fundamental, dado que un error de medición de 5 mmHg puede ser motivo para clasificar incorrectamente como hipertensas a 84 millones de personas en todo el mundo. En la presente declaración de posición se resumen los procedimientos para optimizar el desempeño del observador al medir la presión arterial en el consultorio, con atención especial a los entornos de ingresos bajos o medianos, donde esta medición se ve complicada por limitaciones de recursos y tiempo, sobrecarga de trabajo y falta de suministro eléctrico. Es posible reducir al mínimo muchos errores de medición con una preparación adecuada de los pacientes y el uso de técnicas estandarizadas. Para simplificar la medición y prevenir errores del observador, deben usarse tensiómetros semiautomáticos o automáticos de manguito validados, en lugar del método por auscultación. Pueden ayudar también la distribución de tareas, la creación de un área específica de medición y el uso de aparatos semiautomáticos o de carga solar. Es fundamental garantizar la capacitación inicial y periódica de los integrantes del equipo de salud. Debe considerarse la implementación de programas de certificación de bajo costo y fácilmente accesibles con el objetivo de mejorar la medición de la presión arterial.

Early vascular aging reflects increased arterial stiffness of central blood vessels at young chronological ages and powerfully predicts cardiovascular events and mortality, independent of routine brachial blood pressure and other risk factors. Since ethnic disparities exist in routine blood pressure, in hypertension and cardiovascular outcomes, this review evaluates major studies comparing arterial stiffness through the life course between different ethnic groups or races (which have no biological definition)—in children, adolescents, young, and middle-aged adults and the very elderly. Most report that compared with white European-origin samples, populations of black African descent have increased central arterial stiffness throughout different life stages, as well as a more rapid increase in arterial stiffness at young ages. Exceptions may include African Caribbean origin people in Europe. Differences in vascular structure and function are clearest, where obesity, socioeconomic, and psychosocial factors are most marked. Few studies evaluate a wider spectrum of ethnic groups or factors contributing to these ethnic disparities. Genetic effects are not obvious; maternal risk and intergenerational studies are scarce. Nevertheless, across all ethnic groups, for given levels of blood pressure and age, some people have stiffer central arteries than others. These individuals are most at risk of vascular events and mortality and, therefore, may benefit from early, as yet untested, preventive action and treatment.

Background Adolescents and young people (10–24 years old) in the Latin America and the Caribbean (LAC) region represent approximately 25% of the region’s population. Since the 2008 global economic crisis, the pace of reduction in poverty and income inequality in the LAC region has stalled. The region is characterised by high levels of inequities and is also vulnerable to many natural disasters. Food systems are changing with increased availability and marketing of packaged and fast foods and sugar-sweetened drinks. Adolescence is a formative phase of the life course with multiple physical, emotional and social changes which can make them vulnerable to health problems. We assess the potential impact of macro-determinants, human and economic development as well as income inequality, on 2 top-ranking regional priorities for adolescent nutrition and mental health, using measures of overweight and suicidal ideation and planning which some have shown to be associated. Methods and findings The Global School-based Health Survey (GSHS) is a nationally representative self-administered, school-based survey. We examined overweight/obesity and suicidal ideation with planning by gross domestic product (GDP) per capita or human development index (HDI) in 10–19-year-old adolescents from 21 LAC countries between 2009 and 2013. Sample sizes varied from 943 in Anguilla to 27,988 in Argentina. A total of 55,295 adolescents had a measure of overweight/obesity status, and 59,061 adolescents reported about suicidal ideation with planning. There was equal representation by sex in the surveys (52% girls and 48% boys). A total of 28.8% of boys and 28.1% of girls had overweight/obesity, and 7.5% of boys and 17.5% of girls reported suicidal ideation with planning over the last 12 months. Adjusted for individual socioeconomic and risk behaviours, and relative to the highest GDP per capita tertile, the middle tertile was associated with 42% (95% confidence interval (CI) 59% to 17%, p = 0.003) and 32% (95% CI 60% to 5%, p = 0.023), and the lowest tertile with 40% (95% CI 55% to 19%, p = 0.001) and 46% (95% CI 59% to 29%, p < 0.001) lower chances of overweight/obesity for girls and boys, respectively. A similar positive effect was seen with HDI, with lowest chances of overweight in the lowest tertile compared with the highest tertile for both sexes. Overweight/obesity was positively related with suicidal ideation with planning for girls (odds ratio (OR) 1.12, 95% CI 1.02 to 1.22, p = 0.009) and weakly related for boys (OR 1.09, 95% CI 0.96 to 1.24, p = 0.182). In contrast to overweight/obesity status, suicidal ideation with planning was not related to macro-level indices despite both outcomes sharing common individual socioeconomic and risk behaviour correlates. Limitations include the dominance of Argentinians in the sample (40%), the exclusion of vulnerable adolescents who dropped out of school, and reporting bias due to stigma of mental health–related issues. Conclusions This study shows that economic and human development were positively associated with adolescent overweight/obesity but not with suicidal ideation with planning. We also observed an interconnectedness between overweight/obesity and suicide ideation with planning among girls. These findings highlight the importance of strategies that engage with both upstream and downstream determinants to improve adolescent nutrition and mental health., Author summary Why was this study done? Adolescents and young people (10–24 years old) in the Latin America and the Caribbean (LAC) region represent over 1 quarter of the region’s population. Adolescent nutrition and mental health are key policy priorities in the region. Despite the considerable diversity across the LAC region in economic development, welfare and health systems, little is known about the influence of level of national development or country-level income inequality on adolescent with overweight and obesity or suicidal ideation and planning. What did the researchers do and find? Using data from 21 LAC countries between 2009 and 2013, we found that adolescents living in more economically developed LAC countries were at higher risk of overweight and obesity. Suicidal ideation and planning was not associated with the level of development, but it was associated with overweight and obesity. What do these findings mean? This study shows that the risk of overweight and obesity is not only limited to individual or household level influences, but also to wider societal influences. Countries in the LAC region need to monitor and prevent adolescent overweight/obesity as they transition from lower to middle- and higher-income status.

AIMS: The aims of the present study were to explore whether a long‐term intervention with dietary nitrate [(NO(3) (−)), a potential tolerance‐free source of beneficial vasoactive nitric oxide] and spironolactone (to oppose aldosterone's potential deleterious cardiovascular effects) improve cardiac structure/function, independently of blood pressure (BP), in patients with/at risk of type 2 diabetes (a population at risk of heart failure). METHODS: A subsample of participants in our double‐blind, randomized, factorial‐design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent‐to‐treat. RESULTS: Nitrate‐containing juice (n = 40) decreased left ventricular (LV) end‐diastolic volume {−6.3 [95% confidence interval (CI) –11.1, –1.6] ml} and end‐systolic volume [−3.2 (95% CI −5.9, –0.5) ml], and increased end‐diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [−0.01 (95% CI −0.02, –0.00)]. Although spironolactone reduced LV mass index relative to baseline [−1.48 (95% CI −2.08, –0.88) g m(–2.7)], there was no difference vs. doxazosin [−0.85 (95% CI −1.76, 0.05) g m(–2.7)]. Spironolactone also decreased the E/A ratio [−0.12 (95% CI −0.19, –0.04)] and increased S′ (a tissue‐Doppler systolic function index) by 0.52 (95% CI 0.05, 1.0) cm s(–1). BP did not differ between the juices, or between the drugs. CONCLUSIONS: Six months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP‐independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic–diastolic function, although confirmatory, were independent of BP.

Aim To test if spironolactone or dietary nitrate from beetroot juice could reduce arterial stiffness as aortic pulse wave velocity (PWVart), a potential treatment target, independently of blood pressure. Methods Daily spironolactone (≤50mg) versus doxazosin (control ≤16mg) and 70mL beetroot juice (‘Beet-It’ ≤11mmol nitrate) versus nitrate-depleted juice (placebo; 0mmol nitrate) were tested in people at risk or with type-2 diabetes using a double-blind, 6-month factorial trial. Vascular indices (baseline, 12, 24 weeks) were cardiac-ankle vascular index (‘CAVI’), a nominally pressure-independent stiffness measure (primary outcome), pulse wave velocity (PWVart) secondary, central systolic pressure and augmentation. Analysis was intention-to-treat, adjusted for systolic pressure differences between trial arms. Results Spironolactone did not reduce stiffness, with evidence for reduced CAVI on doxazosin rather than spironolactone (mean difference [95% confidence intervals]; 0.25[-0.3, 0.5] units, p=0.080), firmer for PWVart (0.37[0.01, 0.7] ms-1, p=0.045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7[-4.8, 3.3]mmHg, p=0.7). Circulating nitrate and nitrite increased on active versus placebo juice, with central systolic pressure lowered -2.6[-4.5, - 0.8]mmHg, p=0.007 more on the active juice, but did not reduce CAVI, PWVart, nor peripheral pressure. Change in nitrate and nitrite concentrations were 1.5-fold [1.1-2.2] and 2.2-fold [1.3, 3.6] higher on spironolactone than on doxazosin respectively; both p

Background Malaria exposure in childhood may contribute to high blood pressure (BP) in adults. We used sickle cell trait (SCT) and α+thalassemia, genetic variants conferring partial protection against malaria, as tools to test this hypothesis. Methods and Results Study sites were Kilifi, Kenya, which has malaria transmission, and Nairobi, Kenya, and Jackson, Mississippi, where there is no malaria transmission. The primary outcome was 24‐hour systolic BP. Prevalent hypertension, diagnosed using European Society of Hypertension thresholds was a secondary outcome. We performed regression analyses adjusting for age, sex, and estimated glomerular filtration rate. We studied 1127 participants in Kilifi, 516 in Nairobi, and 651 in Jackson. SCT frequency was 21% in Kilifi, 16% in Nairobi, and 9% in Jackson. SCT was associated with −2.4 (95% CI, −4.7 to −0.2) mm Hg lower 24‐hour systolic BP in Kilifi but had no effect in Nairobi/Jackson. The effect of SCT in Kilifi was limited to 30‐ to 59‐year‐old participants, among whom it was associated with −6.1 mm Hg (CI, −10.5 to −1.8) lower 24‐hour systolic BP. In pooled analysis allowing interaction by site, the effect of SCT on 24‐hour systolic BP in Kilifi was −3.5 mm Hg (CI, −6.9 to −0.1), increasing to −5.2 mm Hg (CI, −9.5 to −0.9) when replacing estimated glomerular filtration rate with urine albumin to creatinine ratio as a covariate. In Kilifi, the prevalence ratio for hypertension was 0.86 (CI, 0.76–0.98) for SCT and 0.89 (CI, 0.80–0.99) for α+thalassemia. Conclusions Lifelong malaria protection is associated with lower BP in Kilifi. Confirmation of this finding at other sites and elucidating the mechanisms involved may yield new preventive and therapeutic targets., See Editorial by Hotez

PurposeBirth weight (BW) is associated with risk of cardiovascular (CV) disease. The findings form studies examined the association of BW with metabolic markers of CV risk were inconsistent and controversial. We examined the association of BW with insulin resistance and blood lipids using repeated measures up to mid-adulthood.MethodsData from seven screenings of the Bogalusa Heart Study—a longitudinal study of cardiovascular risk factors in Bogalusa, LA, are analyzed using generalized estimation equations method. Participants with birth data and at least one measurement of study outcomes between 18-44 years of age (n=2,034) were included.ResultsBW is inversely associated with insulin resistance, triglycerides and total cholesterol (PConclusionsThe study provides strong evidence of an inverse relationship of BW with adulthood cardiometabolic risk profile. Persons born with low BW are maybe less responsive to preventive interventions aiming at weight reduction.

Aims/hypothesis Progressive decline in functional beta cell mass is central to the development of type 2 diabetes. Elevated serum levels of extracellular nicotinamide phosphoribosyltransferase (eNAMPT) are associated with beta cell failure in type 2 diabetes and eNAMPT immuno-neutralisation improves glucose tolerance in mouse models of diabetes. Despite this, the effects of eNAMPT on functional beta cell mass are poorly elucidated, with some studies having separately reported beta cell-protective effects of eNAMPT. eNAMPT exists in structurally and functionally distinct monomeric and dimeric forms. Dimerisation is essential for the NAD-biosynthetic capacity of NAMPT. Monomeric eNAMPT does not possess NAD-biosynthetic capacity and may exert distinct NAD-independent effects. This study aimed to fully characterise the structure-functional effects of eNAMPT on pancreatic beta cell functional mass and to relate these to beta cell failure in type 2 diabetes. Methods CD-1 mice and serum from obese humans who were without diabetes, with impaired fasting glucose (IFG) or with type 2 diabetes (from the Body Fat, Surgery and Hormone [BodyFatS&H] study) or with or at risk of developing type 2 diabetes (from the VaSera trial) were used in this study. We generated recombinant wild-type and monomeric eNAMPT to explore the effects of eNAMPT on functional beta cell mass in isolated mouse and human islets. Beta cell function was determined by static and dynamic insulin secretion and intracellular calcium microfluorimetry. NAD-biosynthetic capacity of eNAMPT was assessed by colorimetric and fluorescent assays and by native mass spectrometry. Islet cell number was determined by immunohistochemical staining for insulin, glucagon and somatostatin, with islet apoptosis determined by caspase 3/7 activity. Markers of inflammation and beta cell identity were determined by quantitative reverse transcription PCR. Total, monomeric and dimeric eNAMPT and nicotinamide mononucleotide (NMN) were evaluated by ELISA, western blot and fluorometric assay using serum from non-diabetic, glucose intolerant and type 2 diabetic individuals. Results eNAMPT exerts bimodal and concentration- and structure-functional-dependent effects on beta cell functional mass. At low physiological concentrations (~1 ng/ml), as seen in serum from humans without diabetes, eNAMPT enhances beta cell function through NAD-dependent mechanisms, consistent with eNAMPT being present as a dimer. However, as eNAMPT concentrations rise to ~5 ng/ml, as in type 2 diabetes, eNAMPT begins to adopt a monomeric form and mediates beta cell dysfunction, reduced beta cell identity and number, increased alpha cell number and increased apoptosis, through NAD-independent proinflammatory mechanisms. Conclusions/interpretation We have characterised a novel mechanism of beta cell dysfunction in type 2 diabetes. At low physiological levels, eNAMPT exists in dimer form and maintains beta cell function and identity through NAD-dependent mechanisms. However, as eNAMPT levels rise, as in type 2 diabetes, structure-functional changes occur resulting in marked elevation of monomeric eNAMPT, which induces a diabetic phenotype in pancreatic islets. Strategies to selectively target monomeric eNAMPT could represent promising therapeutic strategies for the treatment of type 2 diabetes.

Rationale: Several studies have demonstrated links between infectious diseases and cardiovascular conditions. Malaria and hypertension are widespread in many low- and middle-income countries, but the possible link between them has not been considered. Objective: In this article, we outline the basis for a possible link between malaria and hypertension and discuss how the hypothesis could be confirmed or refuted. Methods and Results: We reviewed published literature on factors associated with hypertension and checked whether any of these were also associated with malaria. We then considered various study designs that could be used to test the hypothesis. Malaria causes low birth weight, malnutrition, and inflammation, all of which are associated with hypertension in high-income countries. The hypothetical link between malaria and hypertension can be tested through the use of ecological, cohort, or Mendelian randomization studies, each of which poses specific challenges. Conclusions: Confirmation of the existence of a causative link with malaria would be a paradigm shift in efforts to prevent and control hypertension and would stimulate wider research on the links between infectious and noncommunicable disease.

The aims of the present study were to explore whether a long-term intervention with dietary nitrate [(NOA subsample of participants in our double-blind, randomized, factorial-design intervention (VaSera) trial of active beetroot juice as a nitrate source (≤11.2 mmol) or placebo (nitrate depleted) beetroot juice, and either ≤50 mg spironolactone or ≤16 mg doxazosin (control), had transthoracic cardiac ultrasounds at baseline (n = 105), and at 3 months and 6 months (n = 87) after the start of the intervention. Analysis was by modified intent-to-treat.Nitrate-containing juice (n = 40) decreased left ventricular (LV) end-diastolic volume {-6.3 [95% confidence interval (CI) -11.1, -1.6] ml} and end-systolic volume [-3.2 (95% CI -5.9, -0.5) ml], and increased end-diastolic mass/volume ratio [+0.04 (95% CI 0.00, 0.07)], relative to placebo juice (n = 47). Spironolactone (n = 44) reduced relative wall thickness compared with doxazosin (n = 43) [-0.01 (95% CI -0.02, -0.00)]. Although spironolactone reduced LV mass index relative to baseline [-1.48 (95% CI -2.08, -0.88) g mSix months' dietary nitrate decreased LV volumes ~5%, representing new, sustained, BP-independent benefits on cardiac structure, extending mechanisms characterized in preclinical models of heart failure. Spironolactone's effects on cardiac remodelling and systolic-diastolic function, although confirmatory, were independent of BP.

We seek to observe the association between childhood obesity by different measures and adult obesity, metabolic syndrome (MetS), and diabetes. Thousand two hundred and nine subjects from "Beijing Blood Pressure Cohort Study" were followed 22.9 ± 0.5 years in average from childhood to adulthood. We defined childhood obesity using body mass index (BMI) or left subscapular skinfold (LSSF), and adult obesity as BMI ≥ 28 kg/m(2). MetS was defined according to the joint statement of International Diabetes Federation and American Heart Association with modified waist circumference (≥ 90/85 cm for men/women). Diabetes was defined as fasting plasma glucose ≥ 7.0 mmol/L or blood glucose 2 h after oral glucose tolerance test ≥ 11.1 mmol/L or currently using blood glucose-lowering agents. Multiple linear and logistic regression models were used to assess the association. The incidence of adult obesity was 13.4, 60.0, 48.3, and 65.1 % for children without obesity, having obesity by BMI only, by LSSF only, and by both, respectively. Compared to children without obesity, children obese by LSSF only or by both had higher risk of diabetes. After controlling for adult obesity, childhood obesity predicted independently long-term risks of diabetes (odds ratio 2.8, 95 % confidence interval 1.2-6.3) or abdominal obesity (2.7, 1.6-4.7) other than MetS as a whole (1.2, 0.6-2.4). Childhood obesity predicts long-term risk of adult diabetes, and the effect is independent of adult obesity. LSSF is better than BMI in predicting adult diabetes.

The potential association between sickle cell trait (SCT) and increased arterial stiffness/blood pressure (BP) has not been evaluated in detail despite its association with stroke, sudden death, and renal disease. We performed 24-hour ambulatory BP monitoring and arterial stiffness measurements in adolescents raised in a malaria-free environment in Kenya. Between December 2015 and June 2016, 938 randomly selected adolescents (ages 11–17 years) who had been continuous residents of Nairobi from birth were invited to participate in the study. Standard clinic BP measurement was performed, followed by 24-hour ambulatory BP monitoring and arterial stiffness measurement using an Arteriograph24 (TensioMed Ltd., Budapest, Hungary) device. SCT status was determined using DNA genotyping in contemporaneously collected blood samples. Of the 938 adolescents invited to participate, 609 (65%) provided complete data for analysis. SCT was present in 103 (15%). Mean 24-hour systolic and diastolic BPs were 116 (standard deviation (SD), 11.5) mm Hg and 64 (SD, 7) mm Hg, respectively, in children with SCT and 117 (SD, 11.4) mm Hg and 64 (SD, 6.8) mm Hg, respectively, in non-SCT children. Mean pulse wave velocity (PWV) was 7.1 (SD, 0.8) m/second and 7.0 (SD, 0.8) m/second in SCT and non-SCT children, respectively. We observed no differences in PWV or in any clinic or ambulatory BP-derived measures between adolescents with and without SCT. These data suggest that SCT does not independently influence BP or PWV.

Background Recent studies have discovered that α‐globin is expressed in blood vessel walls where it plays a role in regulating vascular tone. We tested the hypothesis that blood pressure (BP) might differ between normal individuals and those with α + thalassemia, in whom the production of α‐globin is reduced. Methods and Results The study was conducted in Nairobi, Kenya, among 938 adolescents aged 11 to 17 years. Twenty‐four‐hour ambulatory BP monitoring and arterial stiffness measurements were performed using an arteriograph device. We genotyped for α + thalassemia by polymerase chain reaction. Complete data for analysis were available for 623 subjects; 223 (36%) were heterozygous (−α/αα) and 47 (8%) were homozygous (−α/−α) for α + thalassemia whereas the remaining 353 (55%) were normal (αα/αα). Mean 24‐hour systolic BP ± SD was 118±12 mm Hg in αα/αα, 117±11 mm Hg in −α/αα, and 118±11 mm Hg in −α/−α subjects, respectively. Mean 24‐hour diastolic BP ± SD in these groups was 64±8, 63±7, and 65±8 mm Hg, respectively. Mean pulse wave velocity ( PWV )± SD was 7±0.8, 7±0.8, and 7±0.7 ms −1 , respectively. No differences were observed in PWV and any of the 24‐hour ambulatory BP monitoring‐ derived measures between those with and without α + thalassemia. Conclusions These data suggest that the presence of α + thalassemia does not affect BP and/or arterial stiffness in Kenyan adolescents.

Excess pressure integral (XSPI), a new index of surplus work performed by the left ventricle, can be calculated from blood pressure waveforms and may indicate circulatory dysfunction. We investigated whether XSPI predicted future cardiovascular events and target organ damage in treated hypertensive individuals. Radial blood pressure waveforms were acquired by tonometry in 2069 individuals (aged, 63±8 years) in the Conduit Artery Functional Evaluation (CAFE) substudy of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT). Measurements of left ventricular mass index (n=862) and common carotid artery intima media thickness (n=923) were also performed. XSPI and the integral of reservoir pressure were lower in people treated with amlodipine±perindopril than in those treated with atenolol±bendroflumethiazide, although brachial systolic blood pressure was similar. A total of 134 cardiovascular events accrued during a median 3.4 years of follow-up; XSPI was a significant predictor of cardiovascular events after adjustment for age and sex, and this relationship was unaffected by adjustment for conventional cardiovascular risk factors or Framingham risk score. XSPI, central systolic blood pressure, central augmentation pressure, central pulse pressure, and integral of reservoir pressure were correlated with left ventricular mass index, but only XSPI, augmentation pressure, and central pulse pressure were associated positively with carotid artery intima media thickness. Associations between left ventricular mass index, XSPI, and integral of reservoir pressure and carotid artery intima media thickness and XSPI were unaffected by multivariable adjustment for other covariates. XSPI is a novel indicator of cardiovascular dysfunction and independently predicts cardiovascular events and targets organ damage in a prospective clinical trial.

Objectives The goal of this study was to determine whether aortic pulse wave velocity (aPWV) improves prediction of cardiovascular disease (CVD) events beyond conventional risk factors. Background Several studies have shown that aPWV may be a useful risk factor for predicting CVD, but they have been underpowered to examine whether this is true for different subgroups. Methods We undertook a systematic review and obtained individual participant data from 16 studies. Study-specific associations of aPWV with CVD outcomes were determined using Cox proportional hazard models and random effect models to estimate pooled effects. Results Of 17,635 participants, a total of 1,785 (10%) had a CVD event. The pooled age- and sex-adjusted hazard ratios (HRs) per 1-SD change in log e aPWV were 1.35 (95% confidence interval [CI]: 1.22 to 1.50; p 70 years, respectively; p interaction Conclusions Consideration of aPWV improves model fit and reclassifies risk for future CVD events in models that include standard risk factors. aPWV may enable better identification of high-risk populations that might benefit from more aggressive CVD risk factor management.

We established a maternal birth cohort in Ibadan, Nigeria, where malaria is hyperendemic, to assess how intrauterine exposure to malaria affected infant blood pressure (BP) development. In a local maternity hospital, healthy pregnant women had regular blood films for malaria parasites from booking to delivery. Growth and BP were measured on 318 babies, all followed from birth to 3 and 12 months. Main outcomes were standardized measures of anthropometry and change in BP to 1 year. Babies exposed to maternal malaria were globally smaller at birth, and boys remained smaller at 3 months and 1 year. Change in systolic BP (SBP) during the year was greater in boys than in girls (20.9 versus 15.7 mm Hg; P =0.002) but greater in girls exposed to maternal malaria (18.7 versus 12.7 mm Hg; 95% confidence interval, 1–11 mm Hg; P =0.02). Eleven percent of boys (greater than twice than expected) had a SBP ≥95th percentile (hypertensive, US criteria), of whom 68% had maternal malaria exposure. On regression analysis (β coefficients, mm Hg), sex (boys>girls; β=4.4; 95% confidence interval, 1.1–7.7; P =0.01), maternal malaria exposure (3.64; 0.3–6.9; P =0.03), and weight change (2.4; 0.98–3.8/1 standard deviation score; P =0.001) all independently increased SBP change to 1 year, whereas increase in length decreased SBP (−1.98; −3.6 to −0.40). In conclusion, malaria-exposed boys had excess hypertension, whereas malaria-exposed girls a greater increase in SBP. Intrauterine exposure to malaria had sex-dependent effects on BP, independent of infant growth. Because infant–child–adult BP tracking is powerful, a malarial effect may contribute to the African burden of hypertension.

BACKGROUND: Simple reproducible methods of measuring arterial stiffness, a powerful index of prognosis, are becoming available. AIM: To compare the pulse wave transit time (TT) and pulse wave velocity (PWV) between MRI and an arm cuff-based oscillometric method, the Arteriograph. MATERIALS AND METHODS: MRI phase-contrast data were acquired at the aortic arch and just above the aortic bifurcation in 49 men (age 53+/-6 years). Supine left-arm Arteriograph measurements were made after MRI using the surface sternal notch to symphysis pubis pathway length. RESULTS: MRI TT and PWV covered 86% of aortic root-bifurcation length omitting a mean 4.7 cm of proximal ascending aorta. Arteriograph TT (71+/-9 ms) was 6.6 ms [95% confidence interval (CI) 3.9-9.4] or 10% higher than MRI (64+/-10 ms). Arteriograph PWV (7.9+/-1.3 m/s) was 1.33 m/s (95% CI 0.95-1.70) higher than MRI (6.6+/-1.2 m/s), primarily because the surface aortic length was 70 mm (95% CI 59-81) longer than MRI. Arteriograph-MRI PWV difference decreased to 0.31 m/s (95% CI 0.01-0.61) when Arteriograph PWV was calculated using the MRI aortic path length and to 0.25 m/s (95% CI -0.05 to 0.55) after correcting for the aortic segments omitted in the MRI method. After similar TT corrections for MRI, the Arteriograph-MRI difference in TT reduced to 3.2 ms (95% CI 0.2-6). CONCLUSION: TT estimations by Arteriograph and MRI are close. More accurate length estimation from MRI-derived models improves Arteriograph PWV measurement.

Background The clinical and epidemiological implications of using ambulatory blood pressure monitoring ( ABPM ) for the diagnosis of hypertension have not been studied at a population level in sub‐Saharan Africa. We examined the impact of ABPM use among Kenyan adults. Methods and Results We performed a nested case–control study of diagnostic accuracy. We selected an age‐stratified random sample of 1248 adults from the list of residents of the Kilifi Health and Demographic Surveillance System in Kenya. All participants underwent a screening blood pressure (BP) measurement. All those with screening BP ≥140/90 mm Hg and a random subset of those with screening BP ABPM . Based on the 2 tests, participants were categorized as sustained hypertensive, masked hypertensive, “white coat” hypertensive, or normotensive. Analyses were weighted by the probability of undergoing ABPM . Screening BP ≥140/90 mm Hg was present in 359 of 986 participants, translating to a crude population prevalence of 23.1% (95% CI 16.5–31.5%). Age standardized prevalence of screening BP ≥140/90 mm Hg was 26.5% (95% CI 19.3–35.6%). On ABPM , 186 of 415 participants were confirmed to be hypertensive, with crude prevalence of 15.6% (95% CI 9.4–23.1%) and age‐standardized prevalence of 17.1% (95% CI 11.0–24.4%). Age‐standardized prevalence of masked and white coat hypertension were 7.6% (95% CI 2.8–13.7%) and 3.8% (95% CI 1.7–6.1%), respectively. The sensitivity and specificity of screening BP measurements were 80% (95% CI 73–86%) and 84% (95% CI 79–88%), respectively. BP indices and validity measures showed strong age‐related trends. Conclusions Screening BP measurement significantly overestimated hypertension prevalence while failing to identify ≈50% of true hypertension diagnosed by ABPM . Our findings suggest significant clinical and epidemiological benefits of ABPM use for diagnosing hypertension in Kenyan adults.

Increasing prevalence of hypertension (HTN) in children and adolescents has become a significant public health issue driving a considerable amount of research. Aspects discussed in this document include advances in the definition of HTN in 16 year or older, clinical significance of isolated systolic HTN in youth, the importance of out of office and central blood pressure measurement, new risk factors for HTN, methods to assess vascular phenotypes, clustering of cardiovascular risk factors and treatment strategies among others. The recommendations of the present document synthesize a considerable amount of scientific data and clinical experience and represent the best clinical wisdom upon which physicians, nurses and families should base their decisions. In addition, as they call attention to the burden of HTN in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, these guidelines should encourage public policy makers to develop a global effort to improve identification and treatment of high blood pressure among children and adolescents.

OBJECTIVE To determine associations of gestational diabetes mellitus (GDM) and obesity with adverse pregnancy outcomes in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. RESEARCH DESIGN AND METHODS Participants underwent a 75-g oral glucose tolerance test (OGTT) between 24 and 32 weeks. GDM was diagnosed post hoc using International Association of Diabetes and Pregnancy Study Groups criteria. Neonatal anthropometrics and cord serum C-peptide were measured. Adverse pregnancy outcomes included birth weight, newborn percent body fat, and cord C-peptide >90th percentiles, primary cesarean delivery, preeclampsia, and shoulder dystocia/birth injury. BMI was determined at the OGTT. Multiple logistic regression was used to examine associations of GDM and obesity with outcomes. RESULTS Mean maternal BMI was 27.7, 13.7% were obese (BMI ≥33.0 kg/m2), and GDM was diagnosed in 16.1%. Relative to non-GDM and nonobese women, odds ratio for birth weight >90th percentile for GDM alone was 2.19 (1.93–2.47), for obesity alone 1.73 (1.50–2.00), and for both GDM and obesity 3.62 (3.04–4.32). Results for primary cesarean delivery and preeclampsia and for cord C-peptide and newborn percent body fat >90th percentiles were similar. Odds for birth weight >90th percentile were progressively greater with both higher OGTT glucose and higher maternal BMI. There was a 339-g difference in birth weight for babies of obese GDM women, compared with babies of normal/underweight women (64.2% of all women) with normal glucose based on a composite OGTT measure of fasting plasma glucose and 1- and 2-h plasma glucose values (61.8% of all women). CONCLUSIONS Both maternal GDM and obesity are independently associated with adverse pregnancy outcomes. Their combination has a greater impact than either one alone.

Excess cardiac and vascular disease complicates type 2 diabetes mellitus (T2DM) before diagnosis. Aortic pulse wave velocity (PWV) powerfully predicts mortality in those with and at risk of T2DM independent of blood pressure (BP) [(1)][1]. We tested the hypothesis that spironolactone, dietary

We studied aortic pulse wave velocity (aPWV), a predictor of cardiovascular events independent of blood pressure, in a multiethnic sample of British men, to investigate the roles for blood levels of vitamin D and aldosterone in total and regional aortic stiffness. Total aPWV was estimated noninvasively by the Arteriograph device (aPWV AG ) in 198 men, with its length measure calibrated by magnetic resonance. PWVs over the aortic arch and descending aorta were measured by magnetic resonance in a subsample (n=47). Mean (SE) aPWV AG in South Asians (n=68; age 55±10 years), at known higher coronary disease risk than other groups, was 0.5 m/s (0.2 m/s) higher than in African Caribbeans (n=67; 55±10 years), at lowest coronary disease risk here, and Europeans (n=63; 57±8 years), adjusted for age, systolic blood pressure, and diabetes mellitus ( P =0.01). By magnetic resonance, PWV over the descending aorta in South Asians was 0.7 m/s (0.3 m/s) and 0.8 m/s (0.3 m/s) higher than in African Caribbeans and Europeans, respectively; PWV over the aortic arch was not different. South Asians and African Caribbeans had 21 nmol/L (3 nmol/L) and 14 nmol/L (3 nmol/L) lower mean (SE) 25(OH)D than Europeans ( P AG adjusted for age and systolic blood pressure, as well as weakened or removed ethnic differences in aPWV AG in regression models. These data suggest that aortic stiffness as aPWV parallels coronary disease risk in ethnic groups, descending aortic but not arch PWV has this feature, and serum 25(OH)D is an independent negative correlate of aPWV and may partly account for ethnicity-related differences in aPWV and coronary disease risk.

OBJECTIVE: The goal was to describe the temporal pattern of neonatal plasma glucose levels and associations with maternal glucose levels, cord serum C-peptide levels, and neonatal size and adiposity. METHODS: A total of 17 094 mothers and infants were included in the Hyperglycemia and Adverse Pregnancy Outcome Study (15 centers in 9 countries). Mothers underwent a 75-g, 2-hour, oral glucose tolerance test (OGTT) at 24 to 32 weeks of gestation. Cord blood and neonatal blood samples were collected. Biochemical neonatal hypoglycemia was defined as glucose levels of RESULTS: Plasma glucose concentrations were stable during the first 5 hours after birth. Maternal glucose levels were weakly positively associated with biochemical neonatal hypoglycemia (odds ratios: 1.07–1.14 for 1-SD higher OGTT glucose levels). Frequency of neonatal hypoglycemia was higher with higher cord C-peptide levels (odds ratio: 11.6 for highest versus lowest C-peptide category). Larger and/or fatter infants were more likely to have hypoglycemia (P < .001), and infants with hypoglycemia tended to have a higher frequency of cord C-peptide levels of >90th percentile. CONCLUSIONS: Mean neonatal plasma glucose concentrations varied little in the first 5 hours after birth, which suggests normal postnatal adjustment. Biochemical and clinical hypoglycemia were weakly related to maternal OGTT glucose measurements but were strongly associated with elevated cord serum C-peptide levels. Larger and/or fatter infants were more likely to develop hypoglycemia and hyperinsulinemia. These relationships suggest physiologic relationships between maternal glycemia and fetal insulin production.

Cerebrovascular disease plays an important role in depressive disorder, especially in older adults. An understanding of vascular function in depression is important etiologically and to develop innovative treatments that may improve prognosis by ameliorating vascular damage.This study assessed endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds in 25 elderly subjects with depressive disorder compared with 21 nondepressed control subjects. Subjects underwent pulse wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging. A subset (16 patients and 15 control subjects) had assessment of biopsied small artery dilatation to acetylcholine to further assess endothelial function.The mean sample age was 72.4 years with an average age at onset for depression of 60 years. Mean carotid intima media thickness was significantly higher in depressed subjects (p.01). Pulse wave velocity was 1.6 m/sec higher in depressed subjects (borderline significance). There was a significant reduction in the dilatation response to acetylcholine in preconstricted small arteries (p = .01). On magnetic resonance imaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia (p = .01). Depressed subjects had greater volume of white matter lesions in all regions, but this did not reach statistical significance. There were no baseline differences in vascular risk.Depression in the elderly is associated with poorer endothelial function and more atherosclerosis. This is associated with a greater white matter hyperintensities lesion load and basal ganglia microangiopathy. The use of vasoprotective drugs to improve endothelial function or retard atherosclerosis as depression-modifying agents should be explored.

Aortic stiffness predicts cardiovascular mortality and may be influenced by dietary fat composition. The hypothesis that plasma fat composition influences arterial stiffness and subsequent mortality was tested here in a prospective study. A total of 174 randomly sampled nondiabetic participants aged 45 to 74 years were recruited from local populations, stratified by ethnicity and gender, and followed up for mortality. Aortic pulse wave velocity (PWV), blood pressure, and fatty acid composition of plasma lipids were measured at baseline. PWV was associated with increased cardiovascular mortality and inversely related to the proportions of docosahexaenoic (ρ=−0.22; P =0.02) and arachidonic acids (ρ=−0.25; P

1. This commentary reviews and discusses the association between increased arterial stiffness and indices of glucose and insulin metabolism and diabetes mellitus (DM). 2. Diabetes mellitus is associated with increased cardiovascular events, is an established major independent risk factor for cardiovascular disease and is included in current risk assessment algorithms. Based on Framingham risk assessment, the incremental risk due to DM, at a given level of baseline risk in non-diabetics, is approximately equivalent to 10 years and, at any given level of other major risk factors, DM increases risk three- to fourfold. 3. Increased aortic stiffness has been shown to be an independent risk factor for both cardiovascular and overall mortality in high-risk groups and recently in the general population. Both DM1 and DM2 are associated with accelerated stiffening of the elastic arteries, over and above that associated with normal ageing, and DM can be considered as imparting added biological age and, thus, added cardiovascular risk. 4. Aortic stiffness provides a plausible mechanism relating diabetes to increase cardiovascular disease. 5. A proportion of the increased risk of cardiovascular events in DM is a sequel of stiff arteries. Direct measures of arterial stiffness, such as aortic pulse wave velocity, are likely to be better candidates than pulse wave analysis for refining interventions to improve outcomes in diabetes.

Aortic pulse wave velocity (aPWV), a noninvasive measure of vascular stiffness, is an independent predictor of cardiovascular disease both before and in overt vascular disease. Its characteristics in early life and its relationship to maternal factors have hardly been studied. To test the hypothesis that infant aPWV was positively related to maternal anthropometry and blood pressure (BP) at 28 weeks gestation, after adjusting for neonatal anthropometry and BP, 148 babies born in Manchester were measured 1 to 3 days after birth. A high reproducibility of aPWV, assessed in 30 babies within 3 days of birth, was found with a mean difference between occasions of −0.04 m/s (95% CI: −0.08 to 0.16 m/s). Contrary to our hypothesis, a significant inverse relation was found between neonatal aPWV (mean: 4.6 m/s) and maternal systolic BP (mean: 108.9 mm Hg; r =−0.57; 95% CI: −0.67 to −0.45) but not maternal height nor weight. Neonatal aPWV was positively correlated with birth length, birth weight, and systolic BP. In multiple regression, neonatal aPWV remained significantly inversely associated with maternal systolic BP (adjusted β coefficient: −0.032; 95% CI: −0.040 to −0.024; P

Isolated systolic hypertension is the commonest form of hypertension from middle age onwards. Achieving target systolic blood pressure (BP) control remains difficult in everyday clinical practice and even under clinical trial conditions. Most antihypertensive medicines were designed to lower peripheral vascular resistance, which was considered the haemodynamic determinant of hypertension; most are effective in reducing steady but not pulsatile components of BP. Arterial stiffness, defined via aortic length-specific pulse wave velocity (PWV), is thought to be an important determinant of pulse pressure widening through its effects on the timing and amplitude of pressure wave reflection, and/or the aorta's Windkessel function, or its excess 'reservoir' pressure. Whereas pulse pressure is neither an independent nor consistent cardiovascular risk factor, particularly below the age of about 60 years, PWV has become the most powerful predictor of cardiovascular outcomes including mortality, independent of systolic, pulse, mean or other BP components. PWV is therefore a more direct target for treatment. This review addresses the potential therapeutic options for targeting arterial stiffness and the role of pulse pressure.

Purpose of review Blood lipoprotein profiles in early life are known to be related to and predictive of those in adulthood, but little is known about their determinants. Genetic and environmental influences affect cord blood lipoproteins, but how this occurs and the relative contribution of these influences to the overall profile in healthy newborns remains uncertain. Recent findings This review discusses findings from a range of earlier and more recent studies, and summarizes the key influences on cord blood lipoproteins. In particular, we review the potential contribution of maternal blood total cholesterol levels during pregnancy and the increased maternal transmission in newborns of mothers with diabetes. Summary In cord blood, cholesterol levels are lower than in adults and the relative proportion present in HDL as opposed to LDL is much higher. The currently available evidence suggests that several factors influence the composition of cord blood lipoproteins. Although inheritance of major monogenic disorders can affect cord lipids in general, the genetic contribution appears to be minimal, although effects of the proprotein convertase subtilisin/kexine type 9 gene (PCSK9) need fuller exploration in this regard in certain ethnic groups. Evidence is summarized that maternal lipoprotein levels, particularly those due to diet or induced by pregnancy, influence cord lipid levels. Placental insufficiency and other conditions affecting fetal growth and the mode of delivery may also influence cord lipoprotein concentrations. How maternal glucose tolerance during pregnancy affects cord blood lipoproteins remains unclear. In view of increasing evidence that cardiovascular risk may have prenatal antecedents, this would seem to be an important area for further investigation.

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 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

Arterial distensibility and its converse stiffness have come of age as physiological concepts1 and now as a target for intervention. The central hypothesis sustained so far is that an individual’s “arterial stiffness” measured as aortic pulse wave velocity (PWV) is a convenient, integrated index of vascular pathology over a person’s life course, more precise and reliable than other risk factors individually. For example, blood pressure (BP), whether casual or 24 hour, is more sensitive to stimuli and, therefore, more variable. Arterial distensibility is in part dependent on BP, yet its prognostic power is because of its “independence” from BP, including pulse pressure.2 It appears to indicate the general burden of atherosclerotic disease and subclinical damage from multiple risk factors over time: the “wear and tear” of constant distension and recoil (part of “aging”), effects of smoking, lipid metabolism, (hyper)glycemia, ethnicity, how family history expresses itself, etc.3 European hypertension guidelines now include PWV as a recommended but optional measure. The relationship of arterial distensibility with cardiac function and structure, known as aorto-ventricular coupling, is tantalizing because, as a bioengineering feedback loop, cause and effect are still unclear. Many other key questions remain, most critically related to the natural history of arterial stiffness but also fundamental ones of basic structural biology in the vessel wall. A clue to the natural history of arterial stiffness is published in this issue of Hypertension , an Australian study of 9- to 10-year-old, generally prepubescent schoolchildren.4 The study shows a clear relationship among degree of body fat, physical fitness, and arterial stiffness, measured by carotid-femoral PWV. The link of PWV with fitness was not independent of body fat. Why should this article be of interest, being only cross-sectional, whereby association may well …

Background Blood-vessel dysfunction arises before overt hyperglycemia in type-2 diabetes (T2DM). We hypothesised that a metabolomic approach might identify metabolites/pathways perturbed in this pre-hyperglycemic phase. To test this hypothesis and for specific metabolite hypothesis generation, serum metabolic profiling was performed in young women at increased, intermediate and low risk of subsequent T2DM. Methods Participants were stratified by glucose tolerance during a previous index pregnancy into three risk-groups: overt gestational diabetes (GDM; n = 18); those with glucose values in the upper quartile but below GDM levels (UQ group; n = 45); and controls (n = 43, below the median glucose values). Follow-up serum samples were collected at a mean 22 months postnatally. Samples were analysed in a random order using Ultra Performance Liquid Chromatography coupled to an electrospray hybrid LTQ-Orbitrap mass spectrometer. Statistical analysis included principal component (PCA) and multivariate methods. Findings Significant between-group differences were observed at follow-up in waist circumference (86, 95%CI (79–91) vs 80 (76–84) cm for GDM vs controls, p

Stroke is the fourth leading cause of death in the United States and stroke mortality rates vary by ethnicity. The purpose of this study was to examine the associations between food group consumption and risk of death from stroke among 5 ethnic groups in the United States.The Multiethnic Cohort includes215,000 participants, the majority of whom are African American, Native Hawaiian, Japanese American, Latino, and Caucasian men and women recruited by mail survey in Hawaii and Los Angeles in 1993-1996. Deaths from stroke were identified by linkage to the state death files and the U.S. National Death Index. Diet was assessed using a validated food frequency questionnaire. Associations were examined using multivariable Cox proportional hazards models, stratified by ethnicity and gender.A total of 860 deaths from stroke were identified among the cohort participants. Vegetable intake was associated with a significant reduction in risk for fatal stroke among African American women (relative risk [RR]=0.60; 95% CI: 0.36-0.99). Among Japanese American women only, high fruit intake was significantly associated with a risk reduction for stroke mortality (RR=0.43; 95% confidence interval [CI]: 0.22-0.85), whereas meat intake increased risk (RR=2.36; 95% CI: 1.31-4.26). Among men, a significant reduction in stroke mortality was observed among Native Hawaiians (RR=0.26; 95% CI: 0.07-0.95). After pooling the data for the ethnic groups, the findings support an elevated risk for high meat intake among women overall (RR=1.56; 95% CI: 1.12-2.16); no significant effects of dietary intake on risk for fatal stroke were observed among men.Although some variations were observed for the associations between diet and stroke mortality among ethnic groups, the findings suggest that these differences are not substantial and may be due to dietary intake of specific food subgroups. Additional investigations including dietary subgroups and nutrients sources are needed to clarify these findings.

BACKGROUND: Hypertension is an increasing health issue in sub-Saharan Africa where malaria remains common in pregnancy. We established a birth cohort in Nigeria to evaluate the early impact of maternal malaria on newborn blood pressure (BP). METHODS: Anthropometric measurements, BP, blood films for malaria parasites and haematocrit were obtained in 436 mother-baby pairs. Women were grouped to distinguish between the timing of malaria parasitaemia as 'No Malaria', 'Malaria during pregnancy only' or 'Malaria at delivery', and parasite density as low (

GDM (gestational diabetes mellitus) is associated with later adverse cardiovascular risk. The present study examined the relationship between glycaemia during pregnancy and small artery function and structures approx. 2 years postpartum. Women were originally enrolled in the HAPO (Hyperglycaemia and Adverse Pregnancy Outcome) study from which they were classified by their glycaemic distribution during pregnancy as controls (in the lower half of the distribution), UQ (upper quartile; in the UQ of the glycaemic distribution) or having had overt GDM. Subcutaneous arteries from a gluteal fat biopsy taken at follow-up 2 years later were examined using wire myography. Small artery structure, stiffness and vasoconstrictor responses were similar across groups. Maximal endothelium-dependent dilation in response to carbachol was impaired in arteries from both GDM (43.3%, n=8 and P=0.01) and UQ (51.7%, n=13 and P=0.04) women despite generally ‘normal’ current glycaemia (controls, 72.7% and n=8). Inhibition of NOS (nitric oxide synthase) significantly reduced maximum endothelium-dependent dilation in controls but had no effect on arteries from UQ and GDM women, suggesting impaired NOS activity in these groups. Endothelium-independent dilation was unaffected in arteries from previous GDM and UQ women when compared with the control group. Multiple regression analysis suggested that BMI (body mass index) at biopsy was the most potent factor independently associated with small artery function, with no effect of current glycaemia. Overweight women with either GDM or marginally raised glycaemia during pregnancy (our UQ group) had normal vascular structure and stiffness, but clearly detectable progressively impaired endothelium-dependent function at 2 years follow-up. These results suggest that vascular pathology, which may still be reversible, is detectable very early in women at risk of decline into Type 2 diabetes mellitus.

Examining the relationship between glucose intolerance and dietary intake in genetically similar populations with different dietary patterns and rates of type 2 diabetes may provide important insights into the role of diet in the pathogenesis of this disease. The objective of the present study was to assess the relationship between dietary variables and dysglycaemia/type 2 diabetes among three populations of African origin. The study design consists of a cross-sectional study of men and women of African descent aged 24–74 years from Cameroon (n 1790), Jamaica (n 857) and Manchester, UK (n 258) who were not known to have diabetes. Each participant had anthropometric measurements and underwent a 2 h 75 g oral glucose tolerance test. Habitual dietary intake was estimated with quantitative FFQ, developed specifically for each country. The age-adjusted prevalence of undiagnosed type 2 diabetes in Cameroon was low (1·1 %), but it was higher in Jamaica (11·6 %) and the UK (12·6 %). Adjusted generalised linear and latent mixed models used to obtain OR indicated that each 1·0 % increment in energy from protein, total fat and saturated fats significantly increased the odds of type 2 diabetes by 9 (95 % CI 1·02, 1·16) %, 5 (95 % CI, 1·01, 1·08) % and 16 (95 % CI 1·08, 1·25) %, respectively. A 1 % increase in energy from carbohydrates and a 0·1 unit increment in the PUFA:SFA ratio were associated with significantly reduced odds of type 2 diabetes. The results show independent effects of dietary factors on hyperglycaemia in African origin populations. Whether modifying intake of specific macronutrients helps diabetes prevention needs testing in randomised trials.

In Type 1 and 2 diabetes tissue stiffening is evident from measurements of the gross mechanical properties of the vasculature. Elastic fibers play an important role in the mechanical function of vascular tissue, however, the effects of diabetes on individual elastic fiber components remains poorly defined. Fibrillin microfibrils, a key elastic fiber component, have a ‘beads-on-a-string’ structure with a periodicity of approximately 56 nm. We tested for possible disruption due to diabetes in fibrillin microfibrils isolated from rat aorta using an experimental model of Type 1 diabetes in rats. The isolated fibrillin microfibrils were imaged with atomic force microscopy (AFM) and image analysis techniques were used to characterise the microfibrils. Although there was no significant difference in mean microfibril length (control 23.2 repeats, SEM 6.2 repeats: diabetic 23.6 repeats, SEM 6.1 repeats: Mann Whitney U-test, p=0.391), mean periodicity was significantly reduced in microfibrils isolated from the diabetic rats (52.7 nm, SEM 0.4 nm) compared with age-matched controls (59.5 nm, SEM 0.4 nm) (p

Background Ethnicity is a consistent correlate of excess weight in youth. We examine the influence of lifestyles on ethnic differences in excess weight in early adolescence in the UK.\ud \ud Method Data were collected from 6599 pupils, aged 11–13 years in 51 schools, on dietary practices and physical activity, parental smoking and overweight, and on overweight and obesity (using International Obesity Task Force criteria).\ud \ud Results Skipping breakfast [girls odds ratio (OR) 1.74, 95% confidence interval (CI) 1.30–2.34; boys OR 2.06; CI 1.57–2.70], maternal smoking (girls OR 2.04, CI 1.49–2.79; boys OR 1.63, CI 1.21–2.21) and maternal overweight (girls OR 2.01, CI 1.29–3.13; boys OR 2.47, CI 1.63–3.73) were associated with obesity. Skipping breakfast, more common among girls, was associated with other poor dietary practices. Compared with White UK peers, Black Caribbeans (girls OR 1.62, CI 1.24–2.12; boys OR 1.49, CI 1.15–1.95) and Black Africans (girls OR 1.96, CI 1.52–2.53; boys OR 2.50, CI 1.92–3.27) were more likely to skip breakfast and engage in other poor dietary practices, and Indians were least likely. White Other boys reported more maternal smoking (OR 1.37, CI 1.03–1.82). All these reports were more common among those born in the UK than those born elsewhere. Black Caribbean girls were more likely to be overweight (OR 1.38, CI 1.02–1.87) and obese (OR 1.65, CI 1.05–2.58), Black African girls to be overweight (OR 1.35, CI 1.02–1.79) and White Other boys to be overweight (OR 1.37, CI 1.00–1.88) and obese (OR 1.86, CI 1.15–3.00). Adverse dietary habits and being born in the UK contributed to these patterns.\ud \ud Conclusion These findings signal a potential exacerbating effect on ethnic differences in obesity if adverse dietary habits persist. Combined adolescent and parent-focused interventions should be considered.

The ADVANCE Retinal Measurements (AdRem) Study is a large intervention study evaluating the effects of target driven intensive glucose control and placebo controlled blood pressure lowering on retinal vascular changes. AdRem is a sub-study of the ADVANCE Study (Action in Diabetes and Vascular disease), a 2 x 2 factorial randomized controlled trial with an ACE inhibitor-diuretic combination (perindopril-indapamide) and a gliclazide MR-based regimen in patients with type 2 diabetes mellitus.The AdRem study is based on seven-field stereoscopic retinal photographs of both eyes. These are taken within 3 months after randomization in ADVANCE (baseline), at the biennial and at the final visit. The primary outcome is progression of two or more steps in ETDRS classification. Secondary outcomes include progression of retinal vascular lesions and distortion of retinal vascular geometry. Retinal photographs are made on film and digitized at a central laboratory. The AdRem study uses fully digitized quality control and grading.Between August 2002 and January 2004 1978 patients were included in the AdRem study, from 39 centers in 14 countries. Approximately 85% comply with the strict AdRem quality requirements. Publication of the results is expected in early 2008.The AdRem study is designed to provide reliable evidence on the effects of intensive glucose control and blood pressure lowering on both diabetic retinopathy and abnormalities of retinal vasculature in patients with type 2 diabetes mellitus. (c) 2006 Elsevier Inc. All rights reserved.

Introduction Previous studies have suggested that more intensive initial therapy for hypertension results in better long-term blood pressure (BP) control. We test this hypothesis comparing initial monotherapy with dual therapy in the management of essential hypertension. Methods and analysis The study is a prospective, multicentre, double-blind, active-controlled trial in patients with essential hypertension. Around 50% of patients studied will be newly diagnosed and the others will be known hypertensives who previously received only monotherapy. The trial is divided into three phases as follows: Phase 1 (Week 0–Week 16): Randomised, parallel-group, masked assignation to either combination or monotherapy. Phase 2 (Week 17–Week 32): Open-label combination therapy. Phase 3 (Week 33–Week 52): Open-label combination therapy plus open-label add-on (if BP is above 140/90 mm Hg). Hierarchical primary end points are: a comparison of home BP (home systolic blood pressure (HSBP)) averaged over the duration of phase 1 and 2 in the combination versus monotherapy arms. If combination is superior in this analysis, then the averaged mean HSBP between initial monotherapy and initial combination therapy at the end of phase 2 will be compared. Secondary end points include: BP control at 1 year; the role of age, baseline renin, sodium status, plasma volume, haemodynamic compensation and peripheral resistance on BP control; validation of the National Institute for Clinical Excellence/British Hypertension Society joint guideline algorithm; safety and tolerability of combination therapy; and the impact of combination versus monotherapy on left ventricular mass and aortic pulse wave velocity. A sample size of 536 (268 in each group) will have 90% power to detect a difference in means of 4 mm Hg. Ethics and dissemination PATHWAY 1 was approved by UK ethics (REC Reference 09/H0308/132). Trial results will be published and all participating subjects will be informed of the results. Trial registration number UKCRN 4499 and EudraCT number 2008-007749-29 registered 27/08/2009.

In India, diabetes is endemic, linked to urbanization (1), and its dispersed migrant populations show a particular vulnerability (2,3). For example, in Britain, diabetes is more frequent among Indian migrants than in the general population (4,5), but reported rates appear to equal those in India (6), although diverse dietary and cultural habits across India are also likely to have an impact (7). Rates of glucose intolerance seem to be similar between particular Indian communities living in East Africa, and British population studies provide increasing support for a causal role of nonesterified fatty acids (NEFAs) in the etiology of type 2 diabetes (8,9). Here, using a standardized comparison of culturally specific Gujarati communities between India and Britain, we hypothesized that factors associated with disordered NEFA suppression following glucose challenge would confer greater glucose intolerance in these populations. We compared a Gujarati community who had migrated to Sandwell (West Midlands, Britain) from rural villages around Navsari (Gujarat) with age-, sex-, and caste-matched contemporaries still living in those villages in India (as described elsewhere [10]). Randomly sampled participants from electoral rolls were invited to clinic sessions (beginning 8:30–10:00 a.m.). Participants without known diabetes had glucose tolerance testing (GTT) using …

Insulin-like growth factor (IGF)-I and IGF-II are important in the regulation of metabolism and growth. We previously reported in normoglycemic individuals of normal weight that low circulating IGF-II predicts future weight gain. We subsequently investigated whether such relationships persisted in circumstances of type 2 diabetes.In 224 subjects with type 2 diabetes we assessed the association between baseline IGF-II levels and risk of weight gain (2.0 kg) at the 5-year follow-up.At follow-up, 90 participants (40.2%) gained more than 2.0 kg in body weight. For subjects (body mass index26) at baseline, mean IGF-II levels were significantly lower in those who gained more than 2 kg in weight than in subjects of stable weight, 454 ng/mL (95% confidence interval 349-559) versus 620 ng/mL (534-705) (F=7.4, P=.01). For this subgroup low circulating IGF-II at baseline strongly correlated with weight gain (Spearman rho=-0.52, P.001). With increasing weight, the relationship no longer prevailed. Logistic regression showed that for body mass index less than 26, individuals at baseline for each 100 ng/mL increase in baseline IGF-II there was a 47% decreased risk of gaining 2.0 kg or more in weight. Adjustment for treatment group did not materially alter this relationship. There was no difference in baseline IGF-II by treatment group. There was no difference between the group with weight gain and the group with stable weight in those who additionally received insulin or sulfonylurea treatment in the 5 years between the baseline visit and the follow-up.In subjects of normal weight with type 2 diabetes, baseline IGF-II concentration is inversely related to future weight gain, independent of treatment effect, strengthening the putative role for IGF-II in regulating fat mass. We propose that IGF-II measurement has potential utility in this group for targeting such individuals for early intervention.

The study aim is to investigate differences in birth weights between babies of foreign-born black African, Portugal-born black African, and Portugal-born white mothers.Hospital records for Amadora and Sintra from July 2001 to June 2002 were collated and 2949 Portugal-born white, 461 Portugal-born black African, and 817 foreign-born black African live singleton babies were identified. The impact of biologic and social factors (infant sex, maternal age, parity, gestational age, and maternal smoking, education, and occupational class) and mode of delivery on birth weights was assessed by using multivariable regression models.African mothers were more likely to be of lower socioeconomic status than white Portuguese mothers, among whom rates of smoking were two to three times greater (21% among white Portuguese mothers). Small preterm babies comprised 1.5% of white Portuguese babies, 2.3% of babies of Portugal-born African mothers, and 3.9% of babies of foreign-born African mothers (p0.05 compared with white Portuguese babies). Compared with white Portuguese babies, mean birth weight of term babies, adjusted for sex, among Portugal-born African mothers was -24.6 g (95% confidence interval, -70.1-20.9), and among foreign-born African mothers, was +38.8 g (95% confidence interval, 2.9-74.8). Adjustment for parity, maternal age, and gestational age decreased the significant birth weight advantage of babies of foreign-born African mothers to +2.3 g (95% confidence interval, -31.9-36.5). Among nonsmokers, after adjusting for these factors, white Portuguese babies were heavier (40 g; p0.05) than babies of foreign-born African mothers, but among smokers, they were lighter (163 g; p0.05).Compared with white Portuguese babies, mean birth weight of term babies of foreign-born African mothers was greater, and that of babies of Portugal-born African mothers was intermediate. These differences were related to a combination of biologic factors and smoking.

To study the relationship between low birth weight and the subsequent development of cardiovascular risk factors and to compare this relationship between African-Americans and whites at 7 to 21 years of age.The relationship of birth weight with cardiovascular risk factors, namely, systolic and diastolic blood pressure (BP), BMI, HDL, LDL, triglycerides, and HOMA insulin resistance (HOMA-IR) was examined retrospectively using information on 1155 participants (730 whites and 425 African-Americans) from two cohorts of the Bogalusa Heart Study.Participants with lower birth weight had higher systolic BP, HOMA-IR, triglycerides, and LDL. The association of birth weight with LDL, triglycerides, and HOMA-IR was stronger in African-Americans, while the association with systolic BP was stronger in whites. Subjects with birth weight2500 g were at increased risk of having values of HOMA-IR and LDL in the upper quartile of the observed range compared with those with birth weight2500 g.These results support a relationship between low birth weight and the later development of important cardiovascular risk factors in young African-Americans and white individuals. This relationship tends to be stronger in African-Americans than in whites, except for systolic blood pressure.

Background Arterial stiffness (AS), as pulse wave velocity (PWV), is a powerful independent predictor of cardiovascular events and commonly complicates type 2 diabetes (T2D). This trial aims to test if AS, measured by the VaSera machine as cardio-ankle vascular index (CAVI) and by Arteriograph measuring central PWV, can be reduced by spironolactone and/or inorganic nitrate from beetroot juice independently of blood pressure (BP) in those with or at risk of T2D. Methods A factorial design, double blind, randomised controlled trial in 18–80 year old men and women clinically diagnosed with T2D or at risk of it (body mass index (BMI) ≥ 27 kg m −2 , positive family history or glucose intolerance). The study lasts up to 36 weeks with daily intervention of either ≤50 mg spironolactone (intervention) or ≤16 mg doxazosin (control), and beetroot juice with ≤400 mg (9 mmol) inorganic nitrate (intervention) or placebo beetroot juice, 0 mg nitrate (control). Non-invasive AS measurements are carried out at baseline and then at 12-week intervals thereafter. Results To date, 95 participants have been consented and screened, 19 of these were not suitable or not willing to participate so that 73 have been randomised with 9 participants screened as eligible and awaiting randomisation. 53 participants have completed the study. Mean baseline and follow up measures of cardiac-ankle and cardiac-aortic bifurcation PWV and BP have been straightforward. Conclusion This is a proof-of-principle trial to alter AS independent of BP in a patient sample at high cardiovascular risk. Clinical trial registration information UK Clinical Research Network Portfolio Database: 25003627.