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OBJECTIVES Hypertension phenotypes differ between Africans and Europeans, with a greater prevalence of low renin salt-sensitive hypertension and greater predisposition to adverse cardiac remodelling in Africans. To elucidate the roles of inheritance and environment in determining hypertension phenotypes in sub-Saharan Africans and white-Europeans, we compared phenotypes in white individuals in the UK (n = 132) and in African individuals in the UK (n = 158) and Nigeria (n = 179). METHODS Biochemistry, blood pressure, left ventricular structure (echocardiography) and 24-h urinary collections of sodium and potassium were measured. RESULTS Twenty-four-hour urinary sodium/potassium ratio was lower in individuals living in Europe (both African and white: 2.32 ± 0.15 and 2.28 ± 0.17) than in individuals in Nigeria (4.09 ± 0.26, both P

The estimation of central aortic blood pressure is a cardinal measurement, carrying effective physiological, and prognostic data beyond routine peripheral blood pressure. Transfer function‐based devices effectively estimate aortic systolic and diastolic blood pressure from peripheral pressure waveforms, but the reconstructed pressure waveform seems to preserve features of the peripheral waveform. We sought to develop a new method for converting the local diameter distension waveform into a pressure waveform, through an exponential function whose parameters depend on the local wave speed. The proposed method was then tested at the common carotid artery. Diameter and blood velocity waveforms were acquired via ultrasound at the right common carotid artery while simultaneously recording pressure at the left common carotid artery via tonometer in 203 people (122 men, 50 ± 18 years). The wave speed was noninvasively estimated via the lnDU‐loop method and then used to define the exponential function to convert the diameter into pressure. Noninvasive systolic and mean pressures estimated by the new technique were 3.8 ± 21.8 (p = 0.015) and 2.3 ± 9.6 mmHg (p = 0.011) higher than those obtained using tonometery. However, differences were much reduced and not significant in people >35 years (0.6 ± 18.7 and 0.8 ± 8.3 mmHg, respectively). This proof of concept study demonstrated that local wave speed, estimated from noninvasive local measurement of diameter and flow velocity, can be used to determine an exponential function that describes the relationship between local pressure and diameter. This pressure‐diameter function can then be used for the noninvasive estimation of local arterial pressure., The noninvasive determination of local arterial pressure is of great interest to both clinicians and physiologists. In this work we present a novel technique for the determination of arterial pressure using direct and noninvasive local measurements. The results are encouraging and warrant further investigation to establish the full extent of benefits of this method.

High blood pressure (BP) is a highly prevalent modifiable cause of cardiovascular disease, stroke, and death. Accurate BP measurement is critical, given that a 5-mmHg measurement error may lead to incorrect hypertension status classification in 84 million individuals worldwide. This position statement summarizes procedures for optimizing observer performance in clinic BP measurement, with special attention given to low-to-middle-income settings, where resource limitations, heavy workloads, time constraints, and lack of electrical power make measurement more challenging. Many measurement errors can be minimized by appropriate patient preparation and standardized techniques. Validated semi-automated/automated upper arm cuff devices should be used instead of auscultation to simplify measurement and prevent observer error. Task sharing, creating a dedicated measurement workstation, and using semi-automated or solar-charged devices may help. Ensuring observer training, and periodic re-training, is critical. Low-cost, easily accessible certification programs should be considered to facilitate best BP measurement practice.

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.

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.

BACKGROUND: Vascular and lung function develop and decline over the life course; both predict cardiovascular events and mortality but little is known of how they develop over time. We analysed their relationship in a multiethnic cohort study to test whether lung function from early adolescence to young adulthood affected vascular indices.METHODS: 'DASH' (http://dash.sphsu.mrc.ac.uk) included 6643 children aged 11-13 years in 2003; a representative 10% sample (n = 665) participated in a pilot follow-up in 2013. Psychosocial, anthropometric, blood pressure (BP), and lung function measures were collected in both surveys; aortic pulse wave velocity (PWV) and augmentation index (AIx) were measured at aged 21-23 years. Relationships between forced expiratory volume Z-scores in 1 s (zFEV1), after global initiative-ethnic adjustments and BP, PWV, and AIx were tested in linear regression and general estimating statistical models.RESULTS: In total, 488 people with complete data were included. At 11-13 years, SBP was positively associated with zFEV1 (coefficient = 1.90, 95% confidence interval 1.11-2.68, P 0.05).CONCLUSION: Forced expiratory volume change is positively and independently associated with SBP change from adolescence to young adulthood, suggesting earlier lung function plays important roles in SBP development. Vascular indices were unrelated to lung function or its change.

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

Epidemiology suggests that melanin inhibits cutaneous vitamin D3 synthesis by UVR. Laboratory investigations assessing the impact of melanin on vitamin D production have produced contradictory results. We determined the effect of melanin on vitamin D3 photosynthesis in healthy young volunteers (n = 102) of Fitzpatrick skin types II-VI (white to black). Participants, irrespective of skin type, were exposed to the same suberythemal UVR dose, to 85% body surface area, using solar simulated UVR or narrowband UVB (311 nm). This was repeated five times with intervals of 3–4 days between UVR exposures. Blood was taken before, during, and after the irradiation and assessed for serum 25-hydroxyvitamin D3 (25[OH]D3) as a marker of vitamin D3 status. Linear UVR dose-dependent increases in 25(OH)D3 were highly significant (P ≤ 7.7 x 10-11). The ratios of regression slopes of the different skin type groups were compared, and only skin type II was significantly steeper than the other groups. Comparisons between extreme skin types II and VI showed melanin inhibition factors of approximately 1.3–1.4, depending on the UVR source. We conclude that the inhibitory effect of melanin on vitamin D3 synthesis is small, compared with erythema, but that this difference may be sufficient to explain the epidemiological data.

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.

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.

Data from randomized controlled trials to guide antihypertensive agent choice for chronic hypertension in pregnancy are limited; this study aimed to compare labetalol and nifedipine, additionally assessing the impact of ethnicity on treatment efficacy. Pregnant women with chronic hypertension (12 +0 –27 +6 weeks’ gestation) were enrolled at 4 UK centers (August 2014 to October 2015). Open-label first-line antihypertensive treatment was randomly assigned: labetalol- (200–1800 mg/d) or nifedipine-modified release (20–80 mg/d). Analysis included 112 women (98%) who completed the study (labetalol n=55, nifedipine n=57). Maximum blood pressure after randomization was 161/101 mm Hg with labetalol versus 163/105 mm Hg with nifedipine (mean difference systolic: 1.2 mm Hg [−4.9 to 7.2 mm Hg], diastolic: 3.3 mm Hg [−0.6 to 7.3 mm Hg]). Mean blood pressure was 134/84 mm Hg with labetalol and 134/85 mm Hg with nifedipine (mean difference systolic: 0.3 mm Hg [−2.8 to 3.4 mm Hg], and diastolic: −1.9 mm Hg [−4.1 to 0.3 mm Hg]). Nifedipine use was associated with a 7.4-mm Hg reduction (−14.4 to −0.4 mm Hg) in central aortic pressure, measured by pulse wave analysis. No difference in treatment effect was observed in black women (n=63), but a mean 4 mm Hg reduction (−6.6 to −0.8 mm Hg; P =0.015) in brachial diastolic blood pressure was observed with labetalol compared with nifedipine in non-black women (n=49). Labetalol and nifedipine control mean blood pressure to target in pregnant women with chronic hypertension. This study provides support for a larger definitive trial scrutinizing the benefits and side effects of first-line antihypertensive treatment. Clinical Trial Registration— URL: https://www.isrctn.com . Unique identifier: ISRCTN40973936.

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.

Background: Epidemiological and animal studies suggest the potential of dietary nitrate (NO 3−) to inhibit atherogenesis. Spironolactone may improve arterial stiffness. We tested if 6 months’ intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness versus placebo/doxazosin, to control for blood pressure (BP), in a population with or at risk of type 2 diabetes [1]. Methods: A subgroup of participants in our double-blind, randomized-controlled, factorial VaSera trial were randomized to nitrate-containing beetroot juice or nitrate-depleted juice, and spironolactone or doxazosin. Ultrasound for carotid diameter (CD, mm) and intima-media thickness (CIMT, mm) was performed at baseline, 3- and 6-months. Carotid stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph®) and carotid lumen area. Data was analysed by modified intention-to-treat and mixed-model effect, adjusted for confounders. Results: 93 participants had a baseline evaluation; 86% had follow-up data. No statistical interactions occurred between the juice and drug arms. BP was similar between the juices and between the drugs. CIMT was significantly lower following nitrate-containing, compared with placebo juice [−0.06 (95% Confidence Interval −0.12, −0.01), p = 0.022], with no effect on CD. CS reduction was similar between juices [−0.38(−0.67, −0.10) with placebo, −0.13 (−0.42, 0.16) with active juice] and the drugs [−0.30(−0.58, −0.02) with doxazosin, −0.21(−0.51, 0.09), with spironolactone]. No differences were detected between spironolactone or doxazosin on CIMT and CD. Conclusion: 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.

Aim: Patients with HIV have increased cardiovascular risk and pulmonary defects. We investigated the association between impaired pulmonary function (IPF) and arterial stiffening measured by the cardio-ankle vascular index (CAVI) in Ghanaian HIV patients. Method: Spirometry was used to measure pulmonary indices; forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC) in 79 HIV patients on treatment, 75 HIV treatment naïve patients and 78 non-HIV controls. We also used FEV1/FVC < lower limit of normal as a further index. Arterial stiffness was measured as CAVI using the Vasera device. Results: Compared to non-HIV controls, CAVI was higher in treatment naïve (6.9 ± 1.4 vs 6.3 ± 1.1 units, p < 0.01) and HIV patients on treatment (8.1 ± 1.4, vs 6.3 ± 1.1, p < 0.01). IPF was detected in 12 (15.2%) HIV patients on treatment, 8 (10.7%) treatment naïve HIV patients and 5 (6.4%) non-HIV controls. Compared to those without IPF, IPF patients had higher CAVI in non-HIV controls (6.5 ± 1.1 vs 5.7 ± 0.8, p < 0.01), treatment naïve HIV patients (7.1 ± 1.8 vs 6.6 ± 1.4, p = 0.023) and HIV patients on treatment (7.8 ± 1.4 vs 8.7 ± 1.2, p < 0.01). In multivariable logistic regression analysis, IPF was independently associated with CAVI [adjusted OR = 1.33 (1.15 – 1.89), p = 0.037] after adjustment for age [1.21 (0.98 – 2.14), p = 0.11], male sex [0.42 (0.32 – 0.91), p = 0.035], current/former smoking status [1.43 (0.47 – 4.01), p = 0.75] and history of tuberculosis infection [1.96 (1.08 – 3.12), p < 0.01]. Conclusion: Ghanaian HIV patients have a high prevalence of impaired respiratory function and arterial stiffening, and these indices are associated with each other.

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.

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.

different ethnic groups with varying cardiovascular risk☆ Mohammad-Reza Rezai , Satheesh Balakrishnan Nair , Brett Cowan , Alistair Young , Naveed Sattar , Joseph D. Finn , Frederick C. Wu , J. Kennedy Cruickshank a,⁎ a Cardiovascular Research Group, University of Manchester, Manchester Academic Health Science Centre, UK b Wellcome Trust Clinical Research Facility, Manchester, UK c Auckland MRI Research Group, University of Auckland, New Zealand d Institute of Cardiovascular and Medical Sciences, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, UK e Andrology Research Unit, Developmental & Regenerative Biomedicine Research Group, University of Manchester, Manchester Academic Health Science Centre, UK

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.

Adiponectin, high-density lipoprotein cholesterol (HDL-C) and insulin concentrations may be important in the pathophysiology of cardiovascular disease.We tested the hypothesis that serum adiponectin rather than insulin differs from early life, between South Asians and Europeans, with a potentially key role in excess cardiovascular risk characteristic of adult South Asians.We conducted a longitudinal study of 215 British-born children of European (n = 138) and South Asian (n = 77) origin, from birth to 3 yr.Serum adiponectin, insulin, proinsulin and HDL-C concentrations were assessed in relation to ethnic group and growth in anthropometric variables from 0-3 yr of age.Serum adiponectin was lower in South Asian children, despite their smaller size, notable at age 3-6 months (9.5 vs. 11.8 mg/liter; P = 0.04), with no ethnic differences in serum lipids or insulin or proinsulin. In mixed-effects longitudinal models for HDL-C, determinants were adiponectin (P = 0.034), age (P0.001), and body mass index (P0.001) but not ethnicity. None of these or growth variables affected either insulin or proinsulin. In a fully adjusted mixed-effects longitudinal model including age, sex, insulin, and proinsulin, the independent determinants of serum adiponectin were height [21.3 (95% confidence interval = 31.7-10.8 cm lower, for every 1 mmol/liter increase in adiponectin, P0.001], HDL-C [2.8 (1.3-4.2) mmol/liter higher, P0.0001], body mass index (lower, P = 0.03), and South Asian ethnicity (lower, P = 0.01).These British South Asian-origin infants have lower serum adiponectin but no differences in HDL-C or insulin molecules. In South Asians, factors affecting adiponectin metabolism in early life, rather than insulin resistance, likely determine later excess cardiovascular 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.

Context: Adiponectin is a recognized protective risk marker for cardiovascular disease in adults and is associated with an optimal lipid profile. The role of adiponectin at birth is not well understood, and its relationship with the neonatal lipid profile is unknown. Because ethnic disparities in cardiovascular risk have been attributed to low adiponectin and its associated low high-density lipoprotein cholesterol (HDL-C), investigation at birth may help determine the etiology of these risk patterns. Objective: Our objective was to investigate the relationship between neonatal adiponectin and lipid profile at birth in two ethnic groups in cord blood. Design, Setting, and Participants: Seventy-four healthy mothers and their newborns of South Asian and White European origin were studied in this cross-sectional study at St. Mary’s Hospital, Manchester, United Kingdom. Main Outcome Measures: Serum adiponectin, total cholesterol, HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride levels were measured in umbilical venous blood at birth and in maternal blood collected at 28 wk gestation. Results: Cord adiponectin was significantly inversely associated with cord LDL-C (r = −0.32; P = 0.005) but not HDL-C. In a multiple regression analysis, cord LDL-C remained the most significant association of cord adiponectin (β = −0.13; P < 0.001). We did not find any significant ethnic differences in cord adiponectin or lipids with the exception of triglycerides, which were significantly lower in South Asian newborns (P < 0.05). Conclusion: This is the first report of an inverse relationship between cord adiponectin and LDL-C at birth. In contrast to adult studies, we found no significant association between adiponectin and HDL-C in cord blood. Our results and the strong independent association between adiponectin and HDL-C observed in adult studies suggest a role for adiponectin in lipid metabolism. Ethnic differences in adiponectin may arise after birth.

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

Aims: To study the effect of the insulin-like growth factor (IGF) system on growth, adiposity and systolic blood pressure (SBP) in early life in British-born South Asian (SA) and White European (WE) children. Methods: The effect of IGF-1 and insulin-like growth factor-binding protein 3 (IGFBP-3) over the first 4 years in 204 healthy SA and WE children was investigated by mixed linear regression modelling. This enabled inclusion of all follow-up observations and adjustment for repeated measures. Results: At birth, SA babies were shorter and lighter than WE babies. Over 4 years, SA ethnicity was associated with lower height, weight and body mass index (BMI) standard deviation score (SDS), higher subscapular/triceps skinfold thickness (Ss/Tr SFT) and lower SBP (all p < 0.01). IGF-1 was associated with greater height (p = 0.03), weight (p < 0.001) and BMI SDS (p < 0.001), and IGFBP-3 with greater weight SDS (p < 0.001), BMI SDS (p = 0.001), Ss/Tr SFT (p = 0.003) and SBP (p = 0.023). Conclusions: Over this first 4-year period of life, SA ethnicity was associated with being shorter, lighter, having more superficial truncal adiposity and lower SBP. IGFBP-3 (and not IGF-1) was independently associated with both superficial truncal adiposity and SBP, suggesting that IGFBP-3 is a potential metabolic and cardiovascular marker in healthy children in the early years of life.

Objective: Systemic lupus erythematosus (SLE) is a chronic inflammatory disease associated with vascular derangement [1]. Leptin and adiponectin are adipokines with immunomodulatory and vascular functions [2]. We studied the association between arterial stiffness and plasma leptin and adiponectin levels in SLE patients in Ghana. Methods: In a case control design involving 80 SLE patients and 90 non-SLE controls, arterial stiffness was assessed by cardio-ankle vascular index (CAVI) and heart-ankle pulse wave velocity (haPWV) using Vasera 1500N. Circulating levels of leptin, adiponectin, insulin and C-reactive protein (CRP) were measured by ELISA. Results: Compared to non-SLE controls, SLE patients had higher levels of CAVI (7.3±1.1 vs 6.1±1, p < 0.001), haPWV (7.7±1.3 vs 6.5±0.8 m/s, p =

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.

BACKGROUND Some studies suggest that blood pressure (BP)-lowering effects of commonly used antihypertensive drugs differ among ethnic groups. However, differences in the response to second-line therapy have not been studied extensively. METHODS In the BP-lowering arm of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT-BPLA), BP levels of European (n = 4,368), African (203), and South-Asian-(132) origin patients on unchanged monotherapy (atenolol or amlodipine) and/or on second-line therapy (added thiazide or perindopril) were compared. Interaction between ethnicity and BP responses (defined as end BP minus start of therapy BP) to both first-and second-line therapies were assessed in regression models after accounting for age, sex, and several other potential confounders. RESULTS BP response to atenolol and amlodipine monotherapy differed among the three ethnic groups (interaction test P = 0.05). Among those allocated atenolol monotherapy, black patients were significantly less responsive (mean systolic BP (SBP) difference +1.7 (95% confidence interval: -1.1 to 4.6) mm Hg) compared to white patients (referent). In contrast, BP response to amlodipine monotherapy did not differ significantly by ethnic group. BP responses to the addition of second-line therapy also differed significantly by ethnic group (interaction test P = 0.004). On adding a diuretic to atenolol, BP lowering was similar among blacks and South-Asians as compared to whites (referent). However, on addition of perindopril to amlodipine, BP responses differed significantly: compared to whites (SBP difference -1.7 (-2.8 to -0.7) mm Hg), black patients had a lesser response (SBP difference 0.8 (-2.5 to 4.2) mm Hg) and South-Asians had a greater response (SBP difference -6.2 (-10.2 to -2.2) mm Hg). CONCLUSIONS We found important differences in BP responses among ethnic groups to both first-and second-line antihypertensive therapies.

The cause of ethnic differences in cardiovascular disease remains a scientific challenge. Blood pressure tracks from late childhood to adulthood. We examined ethnic differences in changes in blood pressure between early and late adolescence in the United Kingdom. Longitudinal measures of blood pressure, height, weight, leg length, smoking, and socioeconomic circumstances were obtained from London, United Kingdom, schoolchildren of White British (n=692), Black Caribbean (n=670), Black African (n=772), Indian (n=384), and Pakistani and Bangladeshi (n=402) ethnicity at 11 to 13 years and 14 to 16 years. Predicted age- and ethnic-specific means of blood pressure, adjusted for anthropometry and social exposures, were derived using mixed models. Among boys, systolic blood pressure did not differ by ethnicity at 12 years, but the greater increase among Black Africans than Whites led to higher systolic blood pressure at 16 years (+2.9 mm Hg). Among girls, ethnic differences in mean systolic blood pressure were not significant at any age, but while systolic blood pressure hardly changed with age among White girls, it increased among Black Caribbeans and Black Africans. Ethnic differences in diastolic blood pressure were more marked than those for systolic blood pressure. Body mass index, height, and leg length were independent predictors of blood pressure, with few ethnic-specific effects. Socioeconomic disadvantage had a disproportionate effect on blood pressure for girls in minority groups. The findings suggest that ethnic divergences in blood pressure begin in adolescence and are particularly striking for boys. They signal the need for early prevention of adverse cardiovascular disease risks in later life.

Hypertension in children and adolescents has been gaining ground in cardiovascular medicine, mainly due to the advances made in several areas of pathophysiological and clinical research. These guidelines arose from the consensus reached by specialists in the detection and control of hypertension in children and adolescents. Furthermore, these guidelines are a compendium of scientific data and the extensive clinical experience it contains represents the most complete information that doctors, nurses and families should take into account when making decisions. These guidelines, which stress the importance of hypertension in children and adolescents, and its contribution to the current epidemic of cardiovascular disease, should act as a stimulus for governments to develop a global effort for the early detection and suitable treatment of high pressure in children and adolescents. J Hypertens 27:1719-1742 Q 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins.2010 Asociaci?n Espa?ola de Pediatr?a. Published by Elsevier Espana. All rights reserved.

Background— Statins reduce the risk of cardiovascular events in people with hypertension. This benefit could arise from a beneficial effect of statins on central aortic pressures and hemodynamics. The Conduit Artery Function Evaluation–Lipid-Lowering Arm (CAFE-LLA) study, an Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) substudy, investigated this hypothesis in a prospective placebo-controlled study of treated patients with hypertension. Methods and Results— CAFE-LLA recruited 891 patients randomized to atorvastatin 10 mg/d or placebo from 5 centers in the United Kingdom and Ireland. Radial artery applanation tonometry and pulse-wave analysis were used to derive central aortic pressures and hemodynamic indices at repeated visits over 3.5 years of follow-up. Atorvastatin lowered low-density lipoprotein cholesterol by 32.4 mg/dL (95% confidence interval [CI], 28.6 to 36.3) and total cholesterol by 35.1 mg/dL (95% confidence interval, 30.9 to 39.4) relative to placebo. Time-averaged brachial blood pressure was similar in CAFE-LLA patients randomized to atorvastatin or placebo (change in brachial systolic blood pressure, −0.1 mm Hg [95% CI, −1.8 to 1.6], P =0.9; change in brachial pulse pressure, −0.02 mm Hg [95% CI, −1.6 to 1.6], P =0.9). Atorvastatin did not influence central aortic pressures (change in aortic systolic blood pressure, −0.5 mm Hg [95% CI, −2.3 to 1.2], P =0.5; change in aortic pulse pressure, −0.4 mm Hg [95% CI, −1.9 to 1.0], P =0.6) and had no influence on augmentation index (change in augmentation index, −0.4%; 95% CI, −1.7 to 0.8; P =0.5) or heart rate (change in heart rate, 0.25 bpm; 95% CI, −1.3 to 1.8; P =0.7) compared with placebo. The effect of statin or placebo therapy was not modified by the blood pressure–lowering treatment strategy in the factorial design. Conclusions— Statin therapy sufficient to significantly reduce cardiovascular events in treated hypertensive patients in ASCOT did not influence central aortic blood pressure or hemodynamics in a large representative cohort of ASCOT patients in CAFE-LLA.