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Volume 27 Supplement 1 September 2013 www.nature.com/jhh Annual Scientific Meeting of the British Hypertension Society 9th–10th September 2013 Greenwich University, London, UK Editor in Chief David A Calhoun Alabama, USA Editor: UK Editor: Asia Pacific Sunil Nadar Wolverhampton, UK Michael Stowasser Brisbane, Australia Editorial Board Larry J Appel Baltimore, MD Stanley S Franklin Los Angeles, CA Pantelis Sarafidis Thessaloniki, Greece Edouard Battegay Zurich, Switzerland Ehud Grossman Tel-Hashomer, Israel Sheldon Tobe Toronto, Canada Robert Brook Ann Arbor, MI Kazuomi Kario Shimotsuke, Japan James R Sowers Columbia, MO Ellen Burgess Calgary, Canada Gregory YH Lip Birmingham, United Kingdom Jan A Staessen Leuven, Belgium Michael Bursztyn Jerusalem, Israel Robert J Macfadyen Birmingham, United Kingdom George Stergiou Athens, Greece David Calhoun Birmingham, AL Graham A MacGregor London, United Kingdom Rhian Touyz Montreal, Canada Renata Cifková Prague, Czech Republic Frank H Messerli New York, NY Hirotsugu Ueshima Shiga, Japan Paul R Conlin Boston, MA John P Middleton Durham, NC Hector Ventura New Orleans, LA Michael Davidson Chicago, IL Trefor O Morgan Melbourne, Australia Paolo Verdecchia Perugia, Italy Prakash Deedwania San Francisco, CA Carl J Pepine Gainesville, FL Matthew Weir Baltimore, MD Giovanni De Simone Naples, Italy Neil R Poulter London, United Kingdom Jackson Wright Case Western, OH Brent M Egan Charleston, SC Michel Safar Paris, France Volume 27 Supplement 1 September 2013 Annual Scientific Meeting of the British Hypertension Society 9th –10th September 2013 Greenwich University, London, UK Conference Organizer: Hampton Medical Conferences Ltd Sponsor statement: Funding for the publication of this supplement was provided by the British Hypertension Society for the advancement of knowledge and dissemination of information concerning the pathophysiology, epidemiology, detection, investigation and treatment of arterial hypertension and related vascular diseases. India: Tel: +91 124 288 1054. Fax: +91 124 288 1053. E-mail: [email protected] Rest of the World: Tel: +44 (0) 20 7843 4759. Fax: +44 (0) 20 7843 4998. E-mail: [email protected] Journal of Human Hypertension is published by Nature Publishing Group, a division of Macmillan Publishers Ltd. Scope Journal of Human Hypertension is published monthly. The editors will consider for publication all suitable papers dealing directly or indirectly with clinical aspects of hypertension, including epidemiology. The journal aims to perform the dual role of increasing knowledge in the field of high blood pressure as well as improving the standard of care of patients. This journal is covered by Current Contents, Chemical Abstracts, Current Contents Clinical Medicine, SCIExpanded, EMBASE/Excerpta Medica and Index Medicus/MEDLINE. Editorial Manuscripts should be submitted online at http://mts-jhh. nature.com. Detailed instructions to authors are available at this website. 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Journal of Human Hypertension (ISSN 0950-9240) is published 12 times a year by Nature Publishing Group, a division of Macmillan Publishers Ltd. US Mailing Agent: Mercury Airfreight International Inc., 365 Blair Road, Avenel, NJ 07001, USA. Periodicals postage paid at Rahway, NJ. POSTMASTER: Send address changes to Journal of Human Hypertension, Nature Publishing Group, c/o Mercury Airfreight International Inc., 365 Blair Road, Avenel, NJ 07001, USA. Whilst every effort is made by the publishers and editorial board to see that no inaccurate or misleading data, opinion or statement appears in this Journal, they wish to make it clear that the data and opinions appearing in the articles and advertisements herein are the responsibility of the contributor or advertiser concerned. Accordingly, the publishers, the editorial committee and their respective employees, officers and agents accept no liability whatsoever for the consequences of any such inaccurate or misleading data, opinion or statement. Whilst every effort is made to ensure that drug doses and other quantities are presented accurately, readers are advised that new methods and techniques involving drug usage, as described within this Journal, should only be followed in conjunction with the drug manufacturer’s own published literature. Printed on acid-free paper, effective with Volume 8, Issue 1, 1994 Contents S1 2A.1. What blood pressure reduction should we expect from renal denervation? Insights from office vs. ambulatory pressure reductions in uncontrolled and blinded placebo-controlled drug trials of 4121 patients JP Howard, AN Nowbar and DP Francis S2 2A.2. Blood pressure-variability is independently associated with all-cause mortality among incident haemodialysis patients V Selvarajah, L Pasea, S Ojha, IB Wilkinson and LA Tomlinson S2 2A.3. MRI is a safe and effective imaging strategy in the investigation of resistant hypertension AE Burchell, LEK Ratcliffe, EC Hart, LQ Stewart, A Lee, JRF Paton, NE Manghat and AK Nightingale S3 2A.4. Relationship between air pollutants and blood pressure control and survival following hypertension diagnosis S Robinson, CE Hastie, R Gilmore, J Dawson, S Muir, AF Dominiczak, R Touyz and S Padmanabhan S3 2A.5. Maybe it’s time for something a little different? The extent to which current pharmacotherapy practice conforms to national guidelines for primary for cardiovascular disease prevention JP Sheppard, K Fletcher, RJ McManus and J Mant S4 2A.6. Ethnic differences in adherence, adverse effects and beliefs about hypertension and anti-hypertensive medicines E Emanuwa, A Ferro, J Weinman and SHD Jackson S4 3A.1. Detection of mutations in KLHL3 and CUL3 in families with Familial Hyperkalaemic Hypertension (FHH or Gordon syndrome) M Glover, J Ware, A Henry, M Wolley, S Xu, S Cook, I Hall, W van’t Hoff, R Gordon, M Stowasser and K O’Shaughnessy S5 3A.2. Ethnic differences in central haemodynamics and central arterial stiffness CM Park, T Tillin, K March, N Chaturvedi and AD Hughes S5 3A.3. Predictors of QTc and QTc prolongation in the generation scotland family study CE Brown, CE Hastie, J Alghamdi, C Schulz, LJ Hocking, M Luciano, D Porteous, A Morris, BH Smith, AF Dominiczak, ES Tobias, C Delles and S Padmanabhan S6 3A.4. Left ventricular pre-ejection wall stress is an independent predictor of mortality in treated hypertensive patients L McCallum, D Varghese, J Dawson, S Muir, AF Dominiczak, S Padmanabhan, Glasgow Blood Pressure Group For University of Glasgow, Glasgow, United Kingdom S6 3A.5. Microvascular autoregulatory response to ischaemia in the skin and association with mean blood oxygen saturation DD Adingupu, C Thorn, F Casanova, S Elyas, PE Gates, WD Strain and AC Shore S7 3A.6. The PlA1/A2 polymorphism of glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a meta-analysis CN Floyd and A Ferro S7 3B.1. Allied health professional-led interventions for improving control of blood pressure in patients with hypertension: systematic review and meta-analysis CE Clark, LFP Smith, LG Glynn, RS Taylor, JL Campbell and L Cloutier S8 3B.2. Genome sequencing and gene expression analysis in the stroke-prone spontaneously hypertensive rat M Dashti, K Maritou, S Atanur, TJ Aitman, AF Dominiczak, D Graham, R Breitling, JD McClure and MW McBride S8 3B.3. Systolic arterial blood flow is underestimated by auscultation compared with doppler return-to-flow S Hussain, A Ali, E Glassey and PS Lewis S9 3B.4. Ward blood pressure measurement (BPM) standards are required to improve National Early Warning Score (NEWS) reliability M Holland, J Burke, JA Morris and PS Lewis S9 4A.1. Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): a randomised controlled trial RJ McManus, J Mant, MS Haque, EP Bray, S Greenfield, MI Jones, S Jowett, P Little, C O’Brien, MC Penaloza-Ramos, C Schwartz, H Shackleford, J Varghese, B Williams and FDR Hobbs S9 4A.2. Quantifying capillary rarefaction in pregnancy accurately and independently predicts preeclampsia TFT Antonios, V Nama, D Wang and IT Manyonda S10 4A.3. Ischemic preconditioning promotes intrinsic vascularisation and enhances growth of cardiac tissue SY Lim S10 8.1. The inter-arm blood pressure difference in people with diabetes: measurement, vascular, and mortality implications CE Clark, AM Steele, RS Taylor, AC Shore, OC Ukoumunne and JL Campbell S11 8.2. High rates of non-adherence to antihypertensive treatment in patients from a specialist cardiovascular centreFthe results of high-performance liquid chromatography-tandem mass spectrometry urine analysis CMJ White, P Patel, N Masca, R Damani, J Hepworth, NJ Samani, P Gupta, W Madira, AG Stanley, B Williams and M Tomaszewski S11 8.3. Clinic and ambulatory blood pressure measurements in white British, South Asian and African-Caribbean individuals with and without a diagnosis of hypertension U Martin, P Gill, S Wood, S Greenfield, M Sayeed Haque, J Mant, M Mohammed, G Heer, A Gohal, R Kaur, C Schwartz and R Mcmanus S12 8.4. Real world experience of renal denervation in the United KingdomFa two centre study I Dasgupta, AH Taylor, R Watkin, JS Freedman, J Moss, AJ Brady, P Crowe and PB Mark S12 PA.1. Is it safe to wake up? Defining the prognostic value of the morning blood pressure surge in clinical practice JP Sheppard, J Hodgkinson, R Riley, U Martin and RJ McManus S13 PA.2. Urinary proteomics can be predictive of cardiovascular events CE Brown, H Mischak, A Abalat, W Mullen, N Sattar, NS McCarthy, AD Hughes, S Thom, J Mayet, A Stanton, P Sever, AF Dominiczak and C Delles S13 PA.3. Gender and regional differences in the treatment for hypertension: A pharmacoepidemiological analysis of the General Practice Research Database (GPRD) in the context of hypertension in atrial fibrillation (AF) patients T Childs, A Scowcroft and S Todd S14 PA.4. End organ damage in new referrals to a hypertension clinic LEK Ratcliffe, AE Burchell, NE Manghat, JRF Paton and AK Nightingale S14 PA.5. Pulse pressure is more strongly associated with incident coronary heart disease in South Asians than in Europeans. A cohort follow-up study T Tillin, C Tuson, E Coady, N Chaturvedi and AD Hughes S15 PA.6. Non-invasive estimates of cardiac output: Comparison of pulse waveform analysis and inert gas re-breathing methods JE Middlemiss, IB Wilkinson and CM McEniery S15 PA.7. Education session specifically for patients from black African and Caribbean background who have hypertension and diabetes AE Denver S16 PA.8. Is it possible to transmit sounds through the arterial system as a means of measuring blood pressure? A Ali, S Hussain, E Glassey and P Lewis S16 PB.1. Beat to beat variability in newly diagnosed hypertension M Agarwal, MJ Parkes and U Martin S17 PB.2. Night-time blood pressure and subclinical target organ damage: findings from an irish primary care based population sample AM O’Flynn, RJ Curtin, IJ Perry and PM Kearney S17 PB.3. Prognostic significance of short term blood pressure variability in a tertiary referral centre population C Huang, F Ng, V Kapil, M Caulfield and M Lobo S17 PB.4. Comparison of the Vicorder and SphygmoCor devices in routine, community-based blood pressure assessment JC Smith, JK Woodcock-Smith, LM Day, KM Miles, IB Wilkinson and CM McEniery S18 PB.5. Raised central pulse pressure in hypertension is predominately driven by changes in forward pressure wave H Fok, A Guilcher, B Jiang and P Chowienczyk S18 PC.1. Microvascular autoregulatory response to ischaemia and pulse pressure DD Adingupu, S Elyas, F Casanova, PE Gates, AC Shore and WD Strain S19 PD.1. MO25b has no physiological role in electrolyte homeostasis or systemic blood pressure maintenance in the mouse K Siew, P de los Heros, DR Alessi, KM O’Shaughnessy S19 PD.2. Deficient uterine artery remodelling in the SHRSP during pregnancy is not improved by nifedipine treatment H Small, S Totten, E Beattie, D Graham S20 PE.1. Declining renal function is associated with increased visit-to-visit blood pressure variability in primary care D Lasserson, N Scherpbier de Haan, V van Gelder, W de Grauw, M Biermans, J Wetzels and C O’Callaghan S20 PE.2. Phaeochromocytoma-paraganglioma syndrome presenting as a para-renal mass: A case report PJ Robinson, FL Ng, MD Lobo, S Akker, WM Drake, D Cavlan and MJ Caulfield Journal of Human Hypertension (2013) 27, S1–S21 & 2013 Macmillan Publishers Limited All rights reserved 0950-9240/13 www.nature.com/jhh Oral abstracts Journal of Human Hypertension (2013) 27, S1–S21; doi:10.1038/jhh.2013.72 2A.1. What blood pressure reduction should we expect from renal denervation? Insights from office vs. ambulatory pressure reductions in uncontrolled and blinded placebo-controlled drug trials of 4121 patients Howard JP, Nowbar AN and Francis DP International Centre for Circulatory Health, National Heart and Lung Institute, London, United Kingdom Background: Trials of renal denervation report drops of B30 mm Hg in office systolic blood pressure, yet reductions in ambulatory pressures appear to be B3-fold smaller. It has been claimed this disparity is seen in antihypertensive drug trials. We examine this office-ambulatory discrepancy though meta-analysis of drug trials reporting office and ambulatory pressures. Methods and Results: We tested the hypothesis that office pressure drops overestimate ambulatory drops by meta-analysis of both one-armed and double-blinded placebo-controlled drug trials. DRUG TRIALS: 31 drug trials enrolling 4121 patients met the criteria. Office blood pressure drop per unit ambulatory pressure drop was 1.46 (95% CI 1.23–1.68) in uncontrolled trials, but only 0.96 (95% CI 0.81–1.12) for blinded placebo-controlled trials. DENERVATION: 23 trials enrolling 720 patients were analysed. Office pressure drops were 7.64 mm Hg vs. pre-treatment and 26.6 mm Hg vs. controls in open label trials. Ambulatory pressure drops averaged 15.7 mm Hg. No randomized blinded results are available. Conclusion: In drug trials only unblinded uncontrolled studies demonstrate office pressure drops to be larger than ambulatory drops. The officeambulatory pressure drop discrepancy in renal denervation trials may therefore be absent from future double-blinded trials. Persistence of the discrepancy would only be possible if renal denervation managed to abolish the alerting response, or ‘white coat effect’, implying that the alerting response is mediated by the renal sympathetic nerves. Figure 1 Mortality for patients with high versus low variability of SBP. Abstracts S2 2A.2. Blood pressure-variability is independently associated with all-cause mortality among incident haemodialysis patients Selvarajah V1, Pasea L2, Ojha S1, Wilkinson IB3 and Tomlinson LA3 1 Department of Nephrology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 2Centre for Applied Medical Statistics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom and 3Cambridge Clinical Trials Unit, University of Cambridge, Cambridge, United Kingdom Introduction: Visit-to-visit systolic blood pressure variability (SBPV) is an independent risk factor for mortality and cardiovascular (CV) events in the general population. Studies in haemodialysis (HD) populations are confounded by inclusion of prevalent patients. We investigated the effects of SBPV on all-cause mortality in incident HD patients. Methods: We performed a longitudinal observational study of patients commencing HD between 2005 and 2011 in our region. We excluded patients with CV events within 6 months of starting HD. The exposure was SBPV assessed by standard deviation, coefficient of variation and variation independent of the mean (VIM) using short-gap, pre-dialysis SBP readings between 3–6 months after commencing HD. Results: 203 patients were included aged 66±15 years, 66% male, 33% with previous CV disease, BP 144±16/75±10 mm Hg taking a mean of 2.0±1.3 antihypertensives. 37(18.2%) patients died during a follow-up of 2.0±1.3 years. The HR for mortality adjusted for diabetes, CV disease, SBP and DBP was 1.09 (95%CI 1.02–1.16) for a one-unit increase of VIM. Those with VIM of SBP above the median were 2.4 (95%CI 1.17–4.74) times more likely to die during follow-up than those below the median (Fig. 1). Findings were similar for all measures of SBPV. Further adjustment for type of dialysis access, use of antihypertensives and mean intradialytic weight change did not alter these findings. Discussion: Variability of SBP is a strong and independent predictor of all-cause mortality in incident HD patients. Further research is needed to understand the mechanism as this may form a therapeutic target or focus for management. 2A.3. MRI is a safe and effective imaging strategy in the investigation of resistant hypertension Burchell AE1,3, Ratcliffe LEK1,3, Hart EC1,3, Stewart LQ1,3, Lee A3, Paton JRF1,3, Manghat NE2 and Nightingale AK1,2,3 1 Bristol CardioNomics Group, Bristol, United Kingdom; 2Bristol Heart Institute, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom and 3University of Bristol, Bristol, United Kingdom Background: In patients with early onset or drug resistant hypertension (HTN) exclusion of secondary causes with imaging and endocrine testing is recommended. Magnetic resonance imaging (MRI) is non-invasive, non-ionising and is the gold standard imaging modality for the quantification of cardiac volumes and masses. We proposed that a single MRI visit could provide all the imaging required in routine evaluation of patients with HTN. Methods: Patients attending a specialist hypertension clinic with early onset (o40 years), drug resistant or challenging drug intolerant HTN underJournal of Human Hypertension went a Hypertension Protocol MRI scan assessing for end organ damage and secondary causes. This included imaging of the renal arteries, adrenals, aorta and heart as well as cerebral vessels. Data presented as mean±s.e.m. Results: 56 patients (29 male), aged 54±2 years, had an office blood pressure of 179±4/101±2 mm Hg on 3.9±0.3 antihypertensive medications. We identified 1 hypertrophic cardiomyopathy, 1 multinodular goitre, 2 renal artery stenoses, 4 adrenal masses and 3 cerebral microaneurysms. 15% had X1 accessory renal artery and 31% had X1 hypoplastic vertebral artery. 75% of patients had Abstracts S3 left ventricular hypertrophy by left ventricular mass index (95.8±3.7 g/m2). Conclusion: MRI is a safe and effective method of screening for secondary causes of HTN and could replace the combination of echocardiography, renal ultrasound and CT imaging. It also provides additional information for patients being considered for renal denervation and is likely to be a cost effective first line investigation for patients with possible secondary causes of hypertension. 2A.4. Relationship between air pollutants and blood pressure control and survival following hypertension diagnosis Robinson S, Hastie CE, Gilmore R, Dawson J, Muir S, Dominiczak AF, Touyz R and Padmanabhan S University of Glasgow, Glasgow, United Kingdom Objective: There is evidence that air pollution, in the form of particulate matter (PM2.5 and PM10), nitrogen oxides (NOX), sulphur dioxide (SO2), and carbon dioxide (CO2) is associated with blood pressure and in some cases mortality. We investigated the effect of these and other components of air pollution on blood pressure change and mortality. Methods: We studied 6040 patients attending the Glasgow Blood Pressure Clinic (GBPC) between 1990 and 2011, with 21 year follow-up for mortality outcomes. Geocoding using patient postcode enabled mapping of each subject to 25 air pollutants. Cox proportional hazards models were used to explore the multivariate-adjusted associations between individual pollutants and cause-specific mortality. Generalised estimating equations were used to estimate the effect of individual pollutants on follow-up systolic blood pressure (SBP). Results: Over 21 years of follow up there were 670 deaths, of which 324 had a cardiovascular (CV) cause. PM2.5 and PM10 were significantly associated with all-cause, CV, and non-CV mortality risk (Po0.001, Po0.001, and Po0.05, respectively), and with SBP change over time (Po0.05). Eight other pollutants (butadiene, benzene, carbon monoxide, CO2, copper, NOX, selenium, and vanadium) were highly correlated (coefficient 40.80) with PM2.5 and PM10. Two independent, i.e. not correlated with any others, pollutants (dioxins and volatile organic compounds) were also significantly associated with increasing SBP and mortality outcomes. Conclusions: Our data indicate that there are components of air pollution other than those previously reported that contribute to the progression of blood pressure and mortality outcomes. 2A.5. Maybe it’s time for something a little different? The extent to which current pharmacotherapy practice conforms to national guidelines for primary for cardiovascular disease prevention Sheppard JP1, Fletcher K1, McManus RJ2 and Mant J3 University of Birmingham, Birmingham, United Kingdom; 2University of Oxford, Oxford, United Kingdom and 3University of Cambridge, Cambridge, United Kingdom 1 Introduction: Screening for cardiovascular disease (CVD) risk is an important part of CVD prevention in UK clinical practice. The success of screening is dependent on the rigour with which treatments are subsequently prescribed. We studied the extent to which current pharmacotherapy practice conforms to national guidelines for CVD prevention. Methods: A cross-sectional study of anonymised patient records (aged 40–74) from 19 general practices was conducted. Data relating to patient characteristics, including CVD risk factors and prescribed medication were extracted. CVD risk (thus eligibility for treatment) was calculated using the Framingham equation. Descriptive statistics were used to define guideline adherence and comparisons by age and disease type were made using Chi-squared tests. Results: Of the 34 975 patients included in this study, 2550 (7%) had existing CVD and 12 349 (35%) had recorded CVD risk factors or were on treatment. For primary prevention, 6621 (54%) patients were receiving appropriate treatment. Guideline adherence was higher in younger patients (5149 [57%] aged 40–64 years vs. 1472 [45%] aged 65–74 years, Po0.001). For secondary prevention, guideline adherence was highest in patients with ischaemic heart disease (IHD) (866 patients with IHD [52%] vs. 288 patients with stroke [46%] vs. 276 patients with other CVD [39%], Po0.001). Conclusions: Our data suggest there is scope for improvement in treatment for both primary and secondary prevention of CVD. Uptake of these evidence based treatments may be inhibited by the wide-ranging and contradictory guidance available to clinicians. One solution could be the introduction blanket treatment for CVD prevention using a Polypill. Journal of Human Hypertension Abstracts S4 2A.6. Ethnic differences in adherence, adverse effects and beliefs about hypertension and anti-hypertensive medicines Emanuwa E1, Ferro A2, Weinman J2 and Jackson SHD1 1 Kings Health Partners, London, United Kingdom and 2King’s College London, London, United Kingdom Introduction: Ethnic minorities in Britain have a higher incidence of vascular complications of hypertension. Evidence suggests that this may in part be due to lower treatment adherence. Illness perception, medication beliefs and adverse effects have been shown to relate to adherence. This study therefore investigated whether a relationship between ethnicity, illness perception, self reported adherence and adverse effects could be observed among hypertension patients. Methods: This questionnaire based study utilised validated questionnaires to assess illness perception(1), medication beliefs(2), adherence and adverse effects(3) measured using arbitrary units. 95 participants (47.4% Black, 45.3% White) were recruited from hypertension clinics at King’s College and St Thomas’ Hospitals. Results: Black participants reported poorer scores for adherence (P ¼ 0.004), which may well have arisen from differences in their illness and treatment beliefs since they perceived their hypertension to be less chronic (P ¼ 0.001), had greater concerns about their medication (P ¼ 0.001) and more adverse effects (P ¼ 0.036). For the whole sample lower adherence was associated with greater medication concerns (P ¼ 0.002) and a lower perceived need for treatment (P ¼ 0.007). Conclusion: Statistically significant ethnic differences in adherence, illness perception, medication beliefs and adverse effects were identified. This could contribute to an understanding of why black patients have worse outcomes. Further work is needed to confirm these findings and as a basis for developing effective interventions to improve adherence and clinical outcome. 1. Broadbent E et al. (2006) Journal of Psychosomatic Research, 60:631–637. 2. Horne R, Weinman J. (2002) Psychology and Health, 17:17–32. 3. Weinman J et al. (1996) Psychology and Health, 11:431–5. 3A.1. Detection of mutations in KLHL3 and CUL3 in families with Familial Hyperkalaemic Hypertension (FHH or Gordon syndrome) Glover M1, Ware J3, Henry A1, Wolley M2, Xu S2, Cook S3, Hall I1, van’t Hoff W5, Gordon R2, Stowasser M2 and O’Shaughnessy K4 University of Nottingham, Nottingham, United Kingdom; 2University of Queensland, Brisbane, Australia; Imperial College, London, United Kingdom; 4University of Cambridge, Cambridge, United Kingdom; 5Great Ormond Street Hospital, London, United Kingdom and 6University of Leicester, Leicester, United Kingdom 1 3 FHH, a salt-dependent hypertension, is a genetically heterogeneous condition caused by mutations in regulators of the thiazide-sensitive NaCl cotransporter, NCC, and is effectively treated by thiazide diuretics and/or dietary salt restriction. Variation in at least four genes can cause FHH, including ‘With No lysine (K)’ kinases (WNK1 and WNK4) and, more recently, KeLcH-Like3 (KLHL3) and CULlin3 (CUL3). Here we report the genetic analysis of 25 affected individuals from 16 families with FHH who had already been screened and found negative for WNK1/4 mutations. CUL3 and KLHL3 were sequenced using Fluidigm/ HiSeq technologies. GATK variant calling followed by within family filtering was used to prioritise variants. Sanger sequencing was used to validate NGS results. PCR amplification of CUL3 RNA from PBMCs was undertaken. Journal of Human Hypertension Affecteds (n ¼ 16) from 10 of 16 families were found to have CUL3 or KLHL3 variants not reported in the general population. Seven families (2 with CUL3, 5 with KLHL3 mutations) demonstrated mutations previously associated with FHH. Previously undescribed mutations were discovered in three families. CUL3 mutations were shown to affect splicing of exon 9. Our results confirm recent findings of CUL3 and KLHL3 mutations in FHH and identify novel disease-causing variants. This strengthens the argument that these gene products are physiologically important regulators of distal nephron NaCl reabsorption, and hence are potentially interesting novel anti-hypertensive drug targets. As only 63% of our non-WNK FHH families were found to contain plausible CUL3 or KLHL3 variants, there are likely to be additional, as yet undiscovered, regulators of thiazide-sensitive pathways. Abstracts S5 3A.2. Ethnic differences in central haemodynamics and central arterial stiffness Park CM, Tillin T, March K, Chaturvedi N and Hughes AD ICCH, Imperial College London, London, United Kingdom Background: Ethnic minorities in UK experience markedly different risks of coronary heart disease (CHD), but this remains unexplained. Central blood pressure is a strong predictors of CHD. We investigated whether there are ethnic differences in central haemodynamics and arterial stiffness. Methods: 1312 participants (70±6 yrs, 618 European (E), 475 South Asian (SA) and 219 African Caribbean (AC)) underwent radial applanation tonometery to estimate central systolic blood pressure (cSBP) and pulse pressure (cPP). The outgoing pressure wave (P1), augmentation pressure (Paug) and total arterial elastance (TAE) were calculated. Data are mean±s.e. Results: After adjusting for age, sex and heart rate (Table 1) SBP and cSBP were similar in all ethnic groups. PP and cPP were significantly higher in SA compared to E and AC. cPP was significantly lower in AC compared to E. P, Paug and TAE were highest in SA and lowest in AC. After further adjustment for diabetes and blood pressure treatment cPP, Paug and TAE all remained significantly higher in SA and lower in AC compared to E. Conclusions: Compared to E, SA have unfavourable and AC have favourable central haemodymanics. SA have increased cPP and central arterial stiffness compared to E and AC. This may contribute ethnic differences in rates of CHD. Table 1 *Po0.05,**Po0.01 compared to E, yPo0.05, yyPo0.01 compared to AC by post-hoc test after ANCOVA SBP, mm Hg PP, mm Hg cSBP, mm Hg cPP, mm Hg P1, mm Hg PAug, mm Hg TAE, mm Hg/ml European South Asian 142±0.7 57±0.4 133±0.6 47±0.5 32.2±0.3 14.9±0.3 0.87±0.01 143±0.7 59±0.6**yy 133±0.7 50±0.5**yy 33.4±0.4**yy 16.2±0.3**yy 0.97±0.02**yy African Caribbean P value 144±1.1 56±0.9 134±1.1 45±0.8* 31.5±0.5 13.7±0.4* 0.80±0.02* 0.2 0.0001 0.08 o0.0001 0.002 o0.0001 o0.0001 3A.3. Predictors of QTc and QTc prolongation in the generation scotland family study Brown CE1, Hastie CE1, Alghamdi J1, Schulz C1, Hocking LJ2, Luciano M3, Porteous D3, Morris A4, Smith BH4, Dominiczak AF1, Tobias ES1, Delles C1 and Padmanabhan S1 1 3 University of Glasgow, Glasgow, United Kingdom; 2University of Aberdeen, Aberdeen, United Kingdom; University of Edinburgh, Edinburgh, United Kingdom and 4University of Dundee, Dundee, United Kingdom Objective: Heart-rate adjusted prolongation of cardiac repolarisation (QTc interval) is variably associated with cardiac death in the general population. We analysed QTc interval from a large cohort of families to determine the prevalence of QTc prolongation in the Scottish population and its predictors. Methods: The Generation Scotland Family Health Study is a nationwide cohort of families recruited between 2006 and 2011. 17 733 individuals in 5401 families had ECG and e-prescribing data available. Exclusion criteria were- use of QT prolonging medication at least two months prior to recruitment, QRS4120 ms, atrial fibrillation or pacemaker. Prolongation of QT interval was defined as QTc 4450 ms (males) and 4460 ms (females). Results: 13 722 individuals (5082 families) were included in the analyses—mean age 47 (s.d. ±15) years, QTc 411±23 ms and 60% females. Prevalence of QTc prolongation was 3.3%. 1% of the overall population (without exclusions) were on multiple QT prolonging drugs concurrently (50% antipsychotic/anti-depressant, 33% antibiotics, 12% dopamine antagonists). After accounting for family correlation, QTc was significantly associated with age, sex, height, waist circumference, P-wave duration, PR interval and QRS duration. Prolonged QTc interval in one parent was associated with an increased risk of QTc prolongation in the offspring (OR ¼ 2.44 [95% CI 1.16;5.12]). Each 1 ms increase in QRS duration and each year increase in age were associated with a 6% (1.06 [1.04;1.09]) and 4% (1.04[1.01;1.06]) increased risk of QT prolongation respectively. Conclusions: Parental QTc prolongation, QRS duration and age are the main predictors of QTc prolongation. Concurrent use of multiple QT prolonging drugs is low. Journal of Human Hypertension Abstracts S6 3A.4. Left ventricular pre-ejection wall stress is an independent predictor of mortality in treated hypertensive patients McCallum L, Varghese D, Dawson J, Muir S, Dominiczak AF, Padmanabhan S, Glasgow Blood Pressure Group For University of Glasgow, Glasgow, United Kingdom University of Glasgow, Glasgow, United Kingdom Objective: The echocardiographic measurements associated with outcomes in hypertensive patients include left ventricular (LV) mass and ejection fraction. Measures of LV wall stress have not been studied as predictors of outcomes. Methods: We studied 2179 patients attending the Glasgow Blood Pressure Clinic (GBPC), who had an echocardiogram performed within 1 year of initial clinic visit, with 10 year follow-up for mortality outcomes. Left ventricular circumferential wall stress at end-diastole (preload, LVPEWS) and at the end of isovolumic left ventricular contraction (afterload, LVWT) was calculated by using left ventricular internal dimensions and wall thickness measured by quantitative echocardiography and systolic and diastolic blood pressures. Cox-proportional hazards models were used to explore the multivariate adjusted associations between LVPEWS, LVWT and mortality. Results: The mean age was 57(s.d.:15), 48% were men and 47% smokers. Over a 10 year follow up there were 106 deaths. The mean LVPEWS was 188.8 dyne/cm2 (s.d.:50.8) and 189.6(53.8) for men and women respectively. The lowest quartile of LVPEWS was associated with the highest and the third quartile associated with the lowest 10 year mortality on univariate (KM plot; Figure) and multivariate (HR for Q3 Vs Q1: 0.41;95% CI:0.19– 0.86) analyses. LVWT was not associated with mortality (log-rank P ¼ 0.7). Conclusions: Left ventricular pre-ejection wall stress is an independent risk factor for all-cause mortality in treated hypertension patients and has clinical implications. 3A.5. Microvascular autoregulatory response to ischaemia in the skin and association with mean blood oxygen saturation Adingupu DD, Thorn C, Casanova F, Elyas S, Gates PE, Strain WD and Shore AC Diabetes and Vascular Medicine, University of Exeter Medical School, Exeter, United Kingdom Introduction: We have previously described three distinct cutaneous microvascular responses to an ischaemic stimulus using laser Doppler fluximetry. These are associated with a gradation of cardiovascular risk. 1) ‘normal response’ with a controlled graded rise to peak at B10–15 s, 2) ‘non-dominant early peak (NDEP),’ with an abnormal early peak within 2 s of lower amplitude than the subsequent ‘normal’ graded rise to peak, 3) ‘dominant early peak (DEP)’ within 2 s of cuff release with maximum amplitude, which declines rapidly and is then followed by a lesser ‘normal’ peak. Exact mechanism involved in abnormal peak responses is unclear. Aims: To explore associations between microvascular autoregulatory responses and cutaneous blood oxygenation (SO2, %). Journal of Human Hypertension Methods: Post occlusive reactive hyperaemia of the microcirculation was assessed on the foot of participants with cardiovascular disease (CVD), diabetes (DM), both (DM þ CVD) or neither (controls) using laser Doppler fluximetry and Oxygen to See, which measures blood oxygen saturation in the first 1 mm of skin. All participants underwent basic demographic & biochemical screening. Results: 232 participants were studied, 76 controls, 106 with CVD, 34 with DM and 16 with DM þ CVD. Results were stratified by peak response groups. In keeping with previous reports, there was an increase in CVD, diabetes and CVD risk factors across peak response groups. Area under the curve of oxygen saturation was incrementally lower in those with impaired autoregulation. After adjustment for CVD, diabetes, blood pressure, heart rate and Abstracts S7 BMI, this remained strongly negatively associated with abnormal peak responses, geometric mean (95% CI) normal 1459(1364–1554) vs. NDEP 1212(1132–1292) (P ¼ 0.001) vs. DEP 1142(1040– 1245) (Po0.001). Conclusion: These data suggest that the previously described abnormal peak responses have significant consequences in the delivery of oxygen as they are independently associated with reduced mean oxygen saturation post ischaemia. 3A.6. The PlA1/A2 polymorphism of glycoprotein IIIa in relation to efficacy of antiplatelet drugs: a meta-analysis Floyd CN, Ferro A King’s College London, London, United Kingdom Introduction: The PlA1/A2 polymorphism of glycoprotein IIIa (GPIIIa) has been associated with both antiplatelet drug resistance and increased cardiovascular events. Here we present the first metaanalysis examining the impact of carriage of the PlA2 allele on the efficacy of the antiplatelet drugs aspirin and clopidogrel. Methods: Electronic databases (MEDLINE and EMBASE) were searched for all articles evaluating genetic polymorphisms of GPIIIa. For studies where antiplatelet resistance was measured using validated techniques, pooled odds ratios (ORs) were calculated using fixed-effect and random-effect models. Results: 16 studies were eligible for statistical analysis and included 1650 PlA1 homozygous subjects and 668 carriers of the PlA2 allele. For carriers of the PlA2 allele, OR 0.924 (n ¼ 2318; 95% CI 0.743–1.151; P ¼ 0.481) was observed for resis- tance to either drug, OR 0.862 (n ¼ 2085; 95% CI 0.685–1.086; P ¼ 0.208) for resistance to aspirin and OR 1.429 (n ¼ 233; 95% CI 0.791–2.582; P ¼ 0.237) for resistance to clopidogrel. In the aspirin cohort, sub-group analysis revealed no statistical association in either healthy subjects or those with cardiovascular disease. PlA2 carriage was marginally associated with aspirin sensitivity using the fixed-effect model when identified by the PFA-100 assay (n ¼ 1151; OR 0.743, 95% CI 0.558–0.989; P ¼ 0.041) but with significant heterogeneity (I2 ¼ 55%; P ¼ 0.002); significance was lost with analysis using a random-effect model. Conclusions: The totality of published data does not support an association between carriage of the PlA2 allele and antiplatelet drug resistance. Significant heterogeneity indicates the need for larger studies using validated assays. 3B.1. Allied health professional-led interventions for improving control of blood pressure in patients with hypertension: systematic review and meta-analysis Clark CE1, Smith LFP1, Glynn LG2, Taylor RS1, Campbell JL1 and Cloutier L3 1 University of Exeter Medical School, Exeter, United Kingdom; 2Department of General Practice, National University of Ireland, Galway, Ireland and 3Department of Nursing, Université du Québec à Trois-Rivières, Trois-Rivières, Canada Background: Nurse or pharmacist led care are promising methods of improving control of hypertension. We present findings from our current Cochrane review (A115), addressing the evidence for allied health professional led interventions in the management of hypertension. Methods: We searched multiple bibliographic databases to November 2011 for randomised controlled trials. We included any nursing, pharmacist, or allied health professional-led intervention designed to improve control of blood pressure (BP), compared to usual care in hypertension. Primary outcome measures were systolic and diastolic BP, and achievement of study target BP. Two authors independently identified eligible studies and assessed study quality using Cochrane criteria. Intervention effects were pooled using odds ratios (OR) or weighted mean differences (WMD). Results: We identified 506 potential unique citations, and 195 for full-text assessment. At present we have assessed 71 papers and 49 have met inclusion criteria. Compared to usual care, nurseled interventions achieve lower final systolic (WMD 4.1 mm Hg [6.4 to 1.8]; 11 studies) and diastolic (WMD 2.1 mm Hg [2.9 to 1.2]; 13 studies) BP, and meet study BP targets more frequently (OR 1.5 [1.2 to 1.9]; 13 studies). Pharmacist-led interventions achieve lower final diastolic BP (WMD 2.8 mm Hg [3.8 to 1.7]; 8 studies) and meet study BP targets more frequently (OR 4.2 [3.0 to 5.9]; 6 studies). Study quality is moderate; 50% of judgements assess risk of bias as low. Conclusions: Nurse and pharmacist-led interventions appear effective in lowering BP more than usual care approaches. An up to date analysis will be presented to the meeting. Journal of Human Hypertension Abstracts S8 3B.2. Education session specifically for patients from black African and Caribbean background who have hypertension and diabetes Denver AE1,2 1 Whittington Health, London, United Kingdom and 2University College London, London, United Kingdom Aim: To enable our Black African and Caribbean patients to become more equal partners in achieving good blood pressure control by increasing their understanding of hypertension and its self-management. Method: 500 patients were identified from our diabetes database. Their level of interest in learning about high BP was assessed by sending a letter to160 patients who were asked to return an pre-paid reply slip. 97 were returned and they were invited to attend a Hypertension Information session which would cover: What is BP? What is High BP? What the associated risks if they have High BP? What changes can people make to their diet to lower their BP? This concentrated specifically on salt in the Black African/Caribbean diet Results: 64 said ‘yes’ to invite; 50 (M23:F27) signed in, 3 didn’t. 6 did not attend. 47 feedback forms were returned. In response to the statement 00 I am glad that that I attended this event and would recommend similar future events to others00 , 71% Strongly Agree, 27% Agree, and 2% (1 person) Strongly Disagree. 39% correctly identified that 6 g is the UK maximum RDI of salt. An audit of attendees v non-attendees showed pre session BP 146/76 v 142/77; post session 145/76 v 151/78 respectively. Conclusion: Although no significant improvement in the BP of those who attended the session, patients said that they found the session informative and helpful. Feedback in clinic has been positive and we are planning a further session this August. 3B.3. Systolic arterial blood flow is underestimated by auscultation compared with doppler return-to-flow Hussain S, Ali A, Glassey E and Lewis PS University of Manchester, Manchester, United Kingdom Introduction: Systolic blood pressure (SBP) is a key indicator of cardiovascular risk. It is therefore important to measure blood pressure accurately to aid diagnosis and research. Methods: We studied 24 females and 32 males aged between 18–85 years. With subjects in a sitting position with their left arm supported horizontal at level of shoulder, an A and D Medical UA 767 PC semi-automated blood pressure monitor was used to inflate and deflate an appropriately sized cuff placed on the upper arm. Three readings were taken at 1 min intervals. SBP was assessed, during cuff deflation, by simultaneous auscultation of first Korotkoff sound (K1) heard over brachial artery with the bell of a Littmann stethoscope and by the point of return of arterial blood flow measured by flat-bed Doppler probes placed over the brachial and radial arteries. Results: SBP measurements differed significantly between methods. The pressure at which arterial blood flow returned at the brachial Doppler was 5.58 mm Hg higher than K1 (95% CI 1.85 to 9.32, P value ¼ 0.004). The point of return of radial Doppler flow was 2.44 mm Hg higher than K1 (95% CI 0.66 to 4.21, P value ¼ 0.008). Conclusion: The traditional auscultatory method of blood pressure measurement underestimates systolic blood pressure compared with Doppler return-toflow whether measured at the brachial or radial arteries, leading to potential errors in assessing cardiovascular risk. 3B.4. Ward blood pressure measurement (BPM) standards are required to improve National Early Warning Score (NEWS) reliability Holland M1, Burke J2, Morris JA3 and Lewis PS1 1 Blood Pressure & Heart Research Centre, Stockport NHS Foundation Trust, Stockport, United Kingdom; University of Manchester Medical School, Manchester, United Kingdom and 3University Hospital of South Manchester, Wythenshawe, United Kingdom 2 We audited BPM procedures in 100 adult in-patients against office BPM standards. In 35 patients automated ward BPMs were taken three times at Journal of Human Hypertension each of four time points to compare the potential contribution of a single vs. multiple BPMs on NEWS. Abstracts S9 Because single readings and poor standardisation compromise the reproducibility of in-patient BPM, we recommend standardising ward BPM techniques to improve the reliability of NEWS. 4A.1. Targets and self-management for the control of blood pressure in stroke and at risk groups (TASMIN-SR): a randomised controlled trial McManus RJ1, Mant J2, Haque MS3, Bray EP3, Greenfield S3, Jones MI3, Jowett S3, Little P4, O’Brien C3, Penaloza-Ramos MC3, Schwartz C3, Shackleford H3, Varghese J3, Williams B5 and Hobbs FDR1 1 University of Oxford, Oxford, United Kingdom; 2University of Cambridge, Cambridge, United Kingdom; 3University of Birmingham, Birmingham, United Kingdom; 4University of Southampton, Southampton, United Kingdom and 5University College London, London, United Kingdom Introduction: Self-monitoring of blood pressure with self-titration of antihypertensives (self-management) results in lower blood pressure in hypertension but there are no data in high risk groups. This trial assessed the added value of self-management in stroke and other high cardiovascular risk groups compared to usual care. Design and setting: Pragmatic primary care, unblinded, randomised controlled trial of selfmanagement of blood pressure (BP) vs. usual care. Eligible patients had BP4130/80 mm Hg, a history of stroke, coronary heart disease, diabetes or chronic kidney disease and were individually randomised to usual care or self-management. Self-management comprised self-monitoring of blood pressure combined with an individualised self-titration algorithm agreed at baseline. A target of 130/80 mm Hg adjusted for home measurement was used in all groups. The primary outcome was the difference in office SBP between intervention and control at 12 months. Results: 552 patients were randomised from 58 General Practices. After 12 months, primary outcome data were available from 450 patients (82%). Baseline blood pressure was 143.1/80.5 mm Hg (intervention) and 143.6/79.5 mm Hg(control). After 12 months this had dropped to 128.2/73.1 mm Hg (intervention) and 137.8/76.3 mm Hg(control), a difference of 9.7 mm Hg (95%CI 8.6 to 10.8) in systolic and 2.5 mm Hg (1.4 to 3.5) in diastolic following correction for baseline blood pressure and covariates. Conclusions: Self-monitoring with self-titration of antihypertensive medication is feasible and effective for those at high risk of cardiovascular disease through co-morbidities. Patients with stroke and other high risk conditions whose blood pressure is above target should be offered self-management to control their blood pressure. 4A.2. Quantifying capillary rarefaction in pregnancy accurately and independently predicts preeclampsia Antonios TFT1, Nama V1,2, Wang D3 and Manyonda IT2 St. George’s, University of London, London, United Kingdom; 2St. George’s Healthcare Trust, London, United Kingdom and 3London School of Hygiene & Tropical Medicine, London, United Kingdom 1 Background: Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. We have recently reported that women who later on in pregnancy developed preeclampsia had significant reduction in their skin capillary density (i.e. rarefaction) before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. Methods: We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive Caucasian women, of which 305 subjects completed the study. Results: We found that structural capillary rarefaction at 20–24 weeks gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cut-off of 2 capillaries/field with the Area Under the Curve of the Receiver Operating Characteristic (ROC AUC) value of 0.70 whilst capillary rarefaction at 27–32 weeks gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cut-off of 8 capillaries/field with ROC AUC value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariate analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension, in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of Journal of Human Hypertension Abstracts S10 preeclampsia was capillary rarefaction at 27–32 weeks. Conclusion: Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia. Acknowledgement: The British Heart Foundation funded the study. 4A.3. Genome sequencing and gene expression analysis in the stroke-prone spontaneously hypertensive rat Dashti M1, Maritou K2, Atanur S2, Aitman TJ2, Dominiczak AF1, Graham D1, Breitling R3, McClure JD1 and McBride MW1 1 Insitute of Cardiovascular & Medical Science, University of Glasgow, Glasgow, UK, Glasgow, United Kingdom; 2MRC Clinical Science Centre, Faculty of Medicine, Imperial College, London, United Kingdom and 3 Computation & Evolutionary Biology, University of Manchester, Manchester, United Kingdom Introduction: The stroke-prone spontaneously hypertensive rat (SHRSP) is an excellent model for human cardiovascular disease. Quantitative trait loci were previously identified on chromosomes 2, 3 and 14 for blood pressure and cardiac mass and validated by construction of congenic strains. This study aims to identify positional candidate genes which contribute to the SHRSP phenotype by analysing whole genome sequencing and gene expression data. Method: Sequencing SHRSP and WKY reads were mapped to rat reference genome with Burrows Wheeler Aligner. Genome Analysis Toolkit was used to discover sequence variants and annotated with Ensembl Variant Effect Predictor. Significantly differentially expressed positional candidate genes were identified by Parteks (FDRo0.05) and protein coding sequence variants were prioritised. Further candidate genes were identified by BiolayoutExpress3D cluster analyses. Results: E90% of reads were mapped to the BN reference genome for SHRSP at 27 and WKY at 26 coverage. Genomic difference distribution of 1 163 332 single nucleotide polymorphisms and 213 130 insertions or deletions of DNA segments between SHRSP and WKY were not uniform. There were 769 non-synonymous coding, 5 stop gained, 24 frame shift coding variants within the congenic regions and significantly differently expressed genes were prioritised. This identified Gstm1, a previously validated positional and functional candidate for hypertension in SHRSP. Furthermore, Gstm7, Ampd2, Atp11b, Pik3r1 were positional candidate genes identified in the cluster analysis of Gstm1’s. Conclusion: The integration of sequence variants and gene expression data has implicated and prioritised positional candidate genes that may contribute to blood pressure regulation and cardiac mass in the SHRSP. 4A.4. Ischemic preconditioning promotes intrinsic vascularisation and enhances growth of cardiac tissue Lim SY Shiang Y Lim, Victoria, Australia Objective: Ischemic preconditioning (IPC) is a powerful endogenous protective mechanism which involves release of paracrine factors that promote cell survival and angiogenesis. We aim to determine whether in vivo IPC might promote the growth and development of cardiac tissue in an in vivo tissue engineering setting. Methods: We employed a vascularized tissue engineering strategy where polyacrylic chambers were placed subcutaneously in the groin, enclosing the femoral vessels. IPC was induced by 3 cycles of 5 min femoral artery occlusion interspersed with 5 min reperfusion. Results: When chambers were implanted they filled with new vascularized tissue formed by outgrowth Journal of Human Hypertension from the femoral vessels. Rats subjected to IPC generated bigger tissue constructs at 7 and 28 days (B50% increased in weight and volume vs. control, Po0.05) with higher microcirculatory vascular volume (B100% increased in lectin-positive blood vessels, Po0.05). To investigate the cytoprotective effect of IPC, neonatal rat cardiomyocytes (rCM) were implanted with fibrin gel into chambers. IPC significantly reduced apoptosis of rCM at 3 days post-implantation (B50% reduction in TUNEL positive and cleaved caspase-3 positive cells, Po0.05). At 28 days post-implantation, tissue constructs contracted spontaneously and IPC significantly increased the cardiac muscle volume, which was correlated with increased vascular volume. Abstracts S11 Conclusion: In vivo IPC promotes survival of implanted cardiomyocytes and is associated with enhanced angiogenesis. As neither genetic modification nor exogenous substances were required to achieve this beneficial effect, IPC may represent a new clinically adaptable approach to optimize tissue engineering of heart and other tissues with implanted cells. 8.1. The inter-arm blood pressure difference in people with diabetes: measurement, vascular, and mortality implications Clark CE, Steele AM, Taylor RS, Shore AC, Ukoumunne OC and Campbell JL University of Exeter Medical School, Exeter, United Kingdom Background: Differences in blood pressure between arms are associated with vascular disease and increased mortality in cohorts at elevated cardiovascular risk. The implications of an inter-arm difference (IAD) in diabetes, also a condition with increased cardiovascular risk, have not been reported. Uncertainty exists concerning how best to initially check for an IAD. We assessed a pragmatic measurement technique against gold standard in a community cohort with and without diabetes, and explored vascular associations of an IAD in diabetes. Methods: People with diabetes and spouse-controls recruited to the Diabetes Alliance for Research in England (DARE) had repeated brachial blood pressures measured simultaneously at recruitment. Mean IADs were examined for prospective mortality differences and cross-sectional associations. The data were used to inform a pragmatic measurement strategy. Results: 8.6% of 514 participants with diabetes and 2.9% of 238 controls had a systolic IAD X10 mm Hg. Single pairs of blood pressure measurements had high negative predictive values (0.97 to 0.99) for excluding an IAD. In diabetes systolic IADs were associated with diabetic retinopathy (X10 mm Hg and X15 mm Hg), peripheral arterial disease (X10 mm Hg), and chronic kidney disease (X15 mm Hg) at recruitment. After 41 months systolic IADs were associated with increased cardiovascular mortality (hazard ratios 4.6 (1.2 to 17.6) for X10 mm Hg and 10.9 (2.3 to 51.3) for X15 mm Hg). Conclusions: Systolic IADs can be excluded on a single pair of measurements. In diabetes preliminary findings suggest that systolic IADs are associated with increased risk of mortality. Blood pressure should be measured in both arms during initial assessment in diabetes. 8.2. High rates of non-adherence to antihypertensive treatment in patients from a specialist cardiovascular centre—the results of high-performance liquid chromatography-tandem mass spectrometry urine analysis White CMJ1,2,3, Patel P3, Masca N1,2, Damani R1, Hepworth J1, Samani NJ1,2, Gupta P3, Madira W3, Stanley AG3, Williams B4 and Tomaszewski M1,2 1 Department of Cardiovascular Sciences, University of Leicester, Leicester, United Kingdom; 2The NIHR Leicester Biomedical Research Unit in Cardiovascular Disease, Leicester, United Kingdom; 3University Hospitals of Leicester NHS Trust, Leicester, United Kingdom and 4Institute of Cardiovascular Science, and NIHR University College London Hospitals Biomedical Research Centre, UCL, London, United Kingdom Background: Non-adherence to therapy is an important cause of suboptimal blood pressure [BP] control and resistant hypertension. Few practical tools exist to accurately determine its prevalence. We used a simple urine-based assay to audit the prevalence of antihypertensive treatment non-adherence and its impact on BP, in a specialist cardiovascular centre. Method: 208 hypertensive patients [125 new referrals, 66 follow-ups with inadequate BP control, 17 renal denervation [RD] referrals] underwent biochemical screening for non-adherence to antihypertensive treatment. Spot urine sample analysis was performed at clinic visits, using high-performance liquid chromatography-tandem mass spectrometry [HPLC-MS/MS] to detect any of 40 of the most commonly prescribed antihypertensive medications (or their metabolites). Results: 25% of patients were non-adherent to antihypertensive treatment [total non-adherence: 10.1%, partial non-adherence: 14.9%]. The greatest prevalence of partial and total non-adherence was amongst follow-up patients with inadequate BP control [28.8%] and those with ‘resistant hypertension’ referred for RD [23.5%], respectively. There was a linear relationship between BP and the numerical difference between prescribed and detected medications; every unit increase in this difference was associated with 3.0 (1.1) mm Hg increase in clinic SBP, 3.1 (0.7) mm Hg increase in DBP and 1.9 (0.7) mm Hg increase in 24-hour Journal of Human Hypertension Abstracts S12 mean daytime DBP (P ¼ 0.0051, P ¼ 8.62 106, P ¼ 0.0057), respectively. Conclusions: Non-adherence to anti-hypertensive therapy is much more common than previously recognised, particularly in those with suboptimal BP control or referred for RD. HPLC-MS could be used to exclude non-adherence and stratify further diagnostic and therapeutic needs. 8.3. Clinic and ambulatory blood pressure measurements in white British, South Asian and African-Caribbean individuals with and without a diagnosis of hypertension Martin U1, Gill P1, Wood S1, Greenfield S1, Sayeed Haque M1, Mant J3, Mohammed M1, Heer G1, Gohal A1, Kaur R1, Schwartz C1 and Mcmanus R1 1 University of Birmingham, Birmingham, United Kingdom; 2University of Oxford, Oxford, United Kingdom and 3University of Cambridge, Cambridge, United Kingdom Guidance on the use of blood pressure (BP) monitoring is largely based on research in white populations. This validation study was performed to compare reference ambulatory monitoring (ABPM) (daytime mean, X14 measurements) with office (first reading, first day (Clinic1) and mean of second and third blood pressure readings taken on three occasions (clinic23)) in white British (WB), South Asian (SA) and African-Caribbean (AC) groups. Participants were recruited from 28 practices from the Primary Care Research Network. The primary outcome was the difference between the reference standard (mean daytime ABPM), clinic1 and clinic23 in people with and without a diagnosis of hypertension (HT). 301 WB, 229 AC and 241 SAs completed the study. In the WB group the difference in systolic BP between clinic1 and ABPM demon- strated the expected white coat effect (WCE) (132 vs. 128 mm Hg normotensive group, 136 vs. 132 mm Hg, HT group). People with diagnosed hypertension, but not normotensive, SA and AC groups had significantly greater differences between both measurements compared with WB, indicative of more marked WCE (142 (clinic1) vs. 134 mm Hg (ABPM) P ¼ 0.01, both SA and AC groups). With repeat clinic measurements the WCE disappeared and systolic day time ABPM was higher than clinic23 in WB and SA but equivalent in the AC HT group (132 mm Hg (ABPM) vs. 133 mm Hg (clinic23) P ¼ 0.04, compared with WB). WCE is more pronounced amongst diagnosed hypertensives in SA and AC groups than WB. Additional clinic measurements reduce this effect and therefore should be undertaken before adjusting medication in SA and AC hypertensives. 8.4. Real world experience of renal denervation in the United Kingdom- a two centre study Dasgupta I1, Taylor AH2, Watkin R1, Freedman JS1, Moss J4, Brady AJ3, Crowe P1 and Mark PB2 1 Heart of England Foundation Trust, Birmingham, United Kingdom; 2BHF Cardiovascular Research Centre, University of Glasgow, Glasgow, United Kingdom; 3Glasgow Royal Infirmary, Glasgow, United Kingdom and 4 Western Infirmary Glasgow, Glasgow, United Kingdom Background: Renal denervation (RDN) is a promising therapy for resistant hypertension and has been shown to be effective in clinical trials. The role of RDN in routine clinical practice is less well established. We studied outcomes of pilot studies of RDN in two large tertiary referral centres for hypertension in the United Kingdom. Methods: Patients with office blood pressure (BP) X160/90 mm Hg on X3 antihypertensive agents and no secondary cause for hypertension were considered eligible for RDN. All patients underwent ambulatory blood pressure monitoring (ABPM) prior to and six months after RDN. Baseline and follow up medication and laboratory data were analysed. Results: 20 consecutive patients were studied (45% male, mean age 50.1 years). At baseline the mean clinic BP was 189/110 mm Hg with ABPM of 172/ 100 mm Hg. The median number of antihypertensive Journal of Human Hypertension agents was 6 (range 4–8) At baseline therapy all patients received either angiotensin converting enzyme inhibitor or angiotensin receptor blocker, calcium channel blocker in 95% and diuretic in 90%. A wide range of renal function was studied (median creatinine 74 mmol/l, range 57–246). At six months following RDN, there was a significant fall in clinic systolic BP of 18 mm Hg (Po0.05) and systolic BP at ABPM of 9 mm Hg (Po0.05). There was a reduction in number of antihypertensives prescribed (median 4, Po0.01). There were no significant changes in renal function. 5 patients required extended hospital stay for symptomatic groin haematoma. Conclusions: Renal denervation is an effective treatment for resistant hypertension, although the effect observed was less than reported in previous studies. Abstracts S13 Poster abstracts PA.1. Is it safe to wake up? Defining the prognostic value of the morning blood pressure surge in clinical practice Sheppard JP1, Hodgkinson J1, Riley R1, Martin U1 and McManus RJ2 1 University of Birmingham, Birmingham, United Kingdom and 2University of Oxford, Oxford, United Kingdom Introduction: An exaggerated morning blood pressure surge (MBPS) may be associated with ‘wake-up’ stroke and other cardiovascular events, but the threshold at which it becomes pathological is unclear. This study aimed to systematically review the existing literature to establish the most appropriate definition of pathological MBPS. Methods: A systematic review was conducted searching MEDLINE and 15 other databases aiming to capture all studies relating an exaggerated MBPS to cardiovascular endpoints. Estimates (adjusted hazard ratios [HR]) of the association between MBPS and cardiovascular endpoints were extracted and entered into a meta-analysis. Results: The search strategy identified 3653 articles of which 15 fulfilled the eligibility criteria. Six different definitions of MBPS were found; the most common was the ‘prewaking surge’ (mean blood pressure for 2 h after wake-up minus mean blood pressure for 2 h prior to wake-up) (6 studies). A meta-analysis demonstrated no significant association with prewaking MBPS and all cardiovascular (HR 0.94, 95% CI 0.39– 2.28) or stroke events (HR 1.26, 95% CI 0.92–1.71) when the surge was defined by a predetermined threshold (425–55 mm Hg). However, each 10 mm Hg increase in MBPS, analysed as a continuous variable, was associated with an increased risk of all stroke events (HR 1.11, 95% CI 1.03–1.20). Conclusions: These findings do not support the hypothesis that patients with a MBPS above a predetermined threshold are at increased cardiovascular risk. Some evidence was found of an association between increasing levels of MBPS and stroke risk but further studies are needed to accurately define this relationship. PA.2. Urinary proteomics can be predictive of cardiovascular events Brown CE1, Mischak H1, Abalat A1, Mullen W1, Sattar N1, McCarthy NS2, Hughes AD3, Thom S3, Mayet J3, Stanton A2, Sever P3, Dominiczak AF1 and Delles C1 Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom; 2Royal College of Surgeons in Ireland Medical School, Dublin, Ireland and 3Imperial College London, London, United Kingdom 1 Objectives: We previously demonstrated associations between the urinary proteome profile and coronary artery disease (CAD). Here we evaluated the potential of urinary proteomics as a predictor of CAD in the ‘Hypertension Associated Cardiovascular Disease’ sub-study population of the ASCOT study. Methods: Thirty-seven cases with the primary endpoint CAD were selected and matched for sex and age within þ /2 years to controls who had not reached a CAD endpoint during the study. Subjects with cardiovascular disease at baseline were not included. A spot urine sample collected at 1–1.5 years post randomisation was analysed using capillary electrophoresis (CE) coupled to Micro-TOF mass spectrometry (MS). The previously developed model for CAD and three unrelated models (chronic kidney disease, CKD; heart failure, HF; stroke) were assessed for their predictive values, and a classifier was calculated for each sample for each model. Results: Sixty urine samples (32 cases; 28 controls; 88% male, mean age 64±5 years) passed quality control. Classifiers were not different between cases and controls respectively for the CKD (0.069±0.388 vs. 0.095±0.236, P ¼ 0.752), HF (0.282±0.663 vs. 0.114± 0.569, P ¼ 0.301) and stroke models (0.114±0.679 vs. 0.140±0.528, P ¼ 0.868). There was a trend towards lower values for the CAD model (0.432±0.326 vs. 0.587±0.297, P ¼ 0.062), and the CAD model showed statistical significance on Kaplan-Meier survival analysis (P ¼ 0.021). Conclusions: Due to limited sample size this proofof-concept study cannot evaluate the predictive value of proteomics compared to other traditional risk factors. We have, however, shown that a CAD specific urinary proteome panel predicts CAD endpoints in a prospective study. Journal of Human Hypertension Abstracts S14 PA.3. Gender and regional differences in the treatment for hypertension: A pharmacoepidemiological analysis of the General Practice Research Database (GPRD) in the context of hypertension in atrial fibrillation (AF) patients Childs T1, Scowcroft A2 and Todd S1 University of Reading, Reading, United Kingdom and 2Boehringer Ingelheim Ltd., Bracknell, United Kingdom 1 Background: A recent study1 utilising GPRD data showed that male AF patients in the UK are more likely to receive anticoagulation treatment than female patients. Recent work builds on this study to explore the treatment patterns of hypertension in AF patients. Objectives: The key objective of this research was to identify factors that influence the likelihood of AF patients with hypertension receiving hypertension treatment. As hypertension can be defined differently, this work also sought to identify the most appropriate classification of hypertension for use in future epidemiological studies. Methods: Logistic regression was applied to GPRD data to model the likelihood of hypertension treatment; a sensitivity analysis was applied to identify the most suitable definition of hypertension. Results: After adjusting for other factors, overweight or diabetic individuals were more likely to receive treatment. Female patients were 30% more likely to be treated, while patients in the Midlands were about 30% less likely than those in Southern England to get treated. Finally the classification of hypertension as ‘either diagnosis by GP or at least two blood pressure records in excess of 140/ 90 mm Hg in a twelve-month period’ was identified as the most suitable for epidemiological studies. Conclusions: This study confirmed the influence of known risk factors of BMI and diabetes on the treatment of hypertension. Regional variations in hypertension treatment may exist. Contrary to the gender bias in anticoagulation of AF patients in favour of men, women were more likely to receive treatment for hypertension. 1. Lee et al. BMJ Open 1, e000269. PA.4. End organ damage in new referrals to a hypertension clinic Ratcliffe LEK1,3, Burchell AE1,3, Manghat NE2, Paton JRF1,3 and Nightingale AK1,2,3 Bristol CardioNomics Group, Bristol, United Kingdom; 2Bristol Heart Institute, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom and 3University of Bristol, Bristol, United Kingdom 1 The Bristol Hypertension Clinic was recently established to manage difficult-to-treat hypertension. Evidence of end organ damage (EOD) is sought at first visit, in accordance with NICE recommendations. Our experience over the last 8 months is reviewed. Demographics: 74 new patients (33 men; mean age 57 years, range 21–82 years) were seen. The mean office systolic blood pressure was 157 mm Hg (range 104–217 mm Hg) in men and 175 mm Hg (range 121– 248 mm Hg) in women. The mean number of antihypertensive medications prescribed was 3.2 (range 0–8). The main reasons for referral were drugresistant hypertension (43.2%), difficult-to-control hypertension (14.9%), young-onset hypertension (14.9%) and multiple drug intolerances (12.2%). There was a high prevalence of diabetes mellitus (18.9%), ischaemic heart disease (16.2%), cerebrovascular disease (17.6%), and peripheral vascular disease (10.8%). Journal of Human Hypertension Left ventricular hypertrophy (LVH): LVH was present in 38/69 (55.1%) patients, assessed by one or more of electrocardiography (ECG), echocardiography and magnetic resonance imaging (MRI). 24.6% (17/69) patients had ECG changes of LVH. In patients without ECG evidence of LVH, 23/35 demonstrated LVH on imaging. Renal function and proteinuria: Estimated glomerular filtration rate (eGFR) was calculated in 70/74 and proteinuria quantified in 55/74 patients. The renal function was normal (490 ml/min/1.73 m2) in 20% of patients. 24.3% of patients had eGFR o60 ml/ min/1.73 m2. Microalbuminuria was detected in 32.7% of patients and macroalbuminuria/proteinuria in a further 10.9%. Conclusion: We found a high prevalence of EOD in patients referred. Patients are predominantly referred to achieve target blood pressure, but the importance of detecting EOD and escalating treatment accordingly must not be lost. Abstracts PA.5. Pulse pressure is more strongly associated with incident coronary heart disease in South Asians than in Europeans. A cohort follow-up study S15 Tillin T, Tuson C, Coady E, Chaturvedi N and Hughes AD Background: South Asian populations across the world are at greater risk of coronary heart disease(CHD) compared with Europeans. Pulse pressure (PP), an indicator of arterial stiffness, is known to be predictive of cardiovascular events in Europeans, but it is not known whether it is equally predictive in South Asians. Methods: We used competing risks regression to study ethnicity-specific associations between baseline PP and incident CHD studied in a west London population-based cohort with 20 years of follow-up. At baseline (1988–91) participants, then aged 40–70, completed a health and lifestyle questionnaire and underwent fasting blood tests, anthropometry and blood pressure measurements. We excluded those with treated hypertension or known cardiovascular disease at baseline. CHD events were identified from primary care medical record review and death certificates. Results: Follow-up data were available for 1380/ 2023 (68%) Europeans and 916/1393 (66%) South Asians. Incident CHD events occurred in 226 (16%) Europeans and 273 (30%) South Asians (subhazard ratio for South Asians vs. Europeans ¼ 2.16; Po0.001). In models adjusted for baseline risk factors, including diabetes, both PP and mean arterial pressure (MAP) were independently asso- Predicted CHD incidence/1000 person years Imperial College London, London, United Kingdom 20 15 10 5 20 30 40 50 60 70 80 90 Baseline pulse pressure, mm Hg European South Asian ciated with CHD (P ¼ 0.048 and o0.001 respectively). PP was more strongly associated with CHD in South Asians (interaction P ¼ 0.033). There was no evidence of an ethnicity interaction with MAP. Conclusion: Mid-life pulse pressure is substantially more strongly associated with incident CHD in South Asians than in Europeans, possibly indicative of the adverse effects of arterial stiffening. Earlier and tighter control of blood pressure may be required in South Asian people. PA.6. Non-invasive estimates of cardiac output: Comparison of pulse waveform analysis and inert gas re-breathing methods Middlemiss JE, Wilkinson IB and McEniery CM University of Cambridge, Cambridge, United Kingdom Non-invasive, cuff-based systems have recently become available for the assessment of central haemodynamic parameters. The aim of the current study was to compare measurements of cardiac output (CO) derived from one such device (Vicorder) with an established inert gas re-breathing method (Innocor). Comparisons were made at rest and in response to postural change (study 1) and mild exercise (study 2). Study 1 included 16 subjects, (mean age±s.d. 35±9 years). Haemodynamic indices (brachial blood pressure, CO, stroke volume (SV) and heart rate) were measured with both devices after 10 min each of supine and standing rest. Study 2 included 22 subjects (mean age 35±8 years). Haemodynamic indices were measured at Figure 1 Comparison of CO between 2 devices during rest, and cycling at 20 and 35 rpm. Journal of Human Hypertension Abstracts S16 rest and following 4 min of steady-state cycling on an upright cycle ergometer, at 20 rpm and 35 rpm, corresponding to 12 and 20 watts, respectively. Overall, the devices were significantly correlated for CO and SV; (r ¼ 0.43, P ¼ 0.001) and (r ¼ 0.32, P ¼ 0.001), respectively. There was a reasonable agreement between devices with a mean difference in CO of 0.6±1.4 l/minute (supine) and 1.0±1.2 l/ minute (standing). Similarly, in study 2, the mean difference was 0.4±1.2 l/minute (rest), 0.03±1.8 l/ minute and 1.1±3 l/minute cycling at 20 rpm and 35 rpm respectively (Figure 1). The Vicorder produces reasonable estimates of SV and CO compared to inert gas rebreathing, both at rest and in response to physiological challenges. Moreover, the Vicorder is simple-to-use and costeffective for comprehensive haemodynamic monitoring. PA.7. Is it possible to transmit sounds through the arterial system as a means of measuring blood pressure? Ali Aisha1, Hussain Sabeera1, Glassey Ewan1 and Lewis Phillip2 1 The University of Manchester, Manchester, United Kingdom and 2Stepping hill hospital, Manchester, United Kingdom Background: We aim to study how vibrations propagate along the arterial system and whether a new non invasive method of measuring blood pressure in patients with arrhythmias is achievable. Method: 59 participants were included in the study, 18 had a normal BMI, 5 were underweight and 31 were considered moderately obese. Measurements with a doppler ultrasound were made at the brachial and radial arteries. A sensitive microphone was mounted within the acoustic pathway of a stethoscope. Artificial sounds were produced at the subclavian artery and detected by the three probes. Recordings were made on the left arm at three positions and two time intervals (cuff deflated and inflated.) The difference of the amplitude of sound waves during cuff deflation and inflation (VD1–VI1) and the difference of the frequency (FI1–FD1) was calculated. Results: A significant attenuation of sound was caused by the restriction of blood flow through the brachial and radial artery. The microphone (VD1– VI1) was on average 66.45 mV (95% CI 23.9–52.9.) The (FI1–FD1) recorded by the microphone during the two time intervals was 5.03 Hz (95% Cl 7.6– 2.45.) Indicating that frequency of sound waves rises with cuff pressure. Conclusion: The attenuation of artificial sounds during cuff inflation demonstrates that sound waves conduct through the arterial blood supply. This often coincides in time with the Korotkoff sounds. These observations suggest that the production of regular rhythmic vibrations may be used in addition to Korotkoff sounds as an audible criterion for recognising systolic pressure in patients with AF. PB.1. Beat to beat variability in newly diagnosed hypertension Agarwal M, Parkes MJ and Martin U University of Birmingham, Birmingham, United Kingdom Increased blood pressure (BP) variability is known to be associated with poor outcomes in patients with hypertension. Blood pressure variability is traditionally assessed using standard office and/or home BP measurements. Fluctuations in BP between each heart beat have not been studied but baroreflex sensitivity (BRS) has been shown to be reduced in hypertension, which might affect beat to beat variability. Seventeen newly diagnosed hypertensives (HT) (mean daytime ambulatory blood pressure monitoring (ABPM) 4135/85 mm Hg) and seventeen age-matched normotensive (NT) controls had beat to beat variability measured non-invasively using finger plethysmography (Finapres) while resting over a 1 h period. Data was analysed for the absolute sizes (mm Hg) of systolic beat-to-beat fluctuations. BRS was assessed using spontaneous Journal of Human Hypertension baroreflex analysis techniques. The relationship of BP measured by Finapres to ABPM and clinic measurements was studied. The sizes of beat-to-beat fluctuations were similar in HT and NT ((mean± standard error) 3.6±0.3 vs. 3.3±0.3 mm Hg, P40.05). However, for each period of measurement there were a greater number of fluctuations in the HT group due to a significantly faster heart rate (72±2 vs. 65±2 beats/min). Baroreflex sensitivity was significantly reduced (Po0.001) in HT compared with NT in both expiration and inspiration. There were significant differences between mean Finapres and daytime ABPM measurements in some conditions. Beat-to-beat variability measured over 1 h does not appear to differ in unmedicated hypertensive patients compared to normotensive subjects despite reduced BRS. Abstracts PB.2. Night-time blood pressure and subclinical target organ damage: findings from an irish primary care based population sample S17 O’Flynn AM1,2, Curtin RJ1,2, Perry IJ1 and Kearney PM1 1 University College Cork, Cork, Ireland and 2Cork University Hospital, Cork, Ireland Introduction: The prognostic significance of nocturnal blood pressure (BP) is well recognised. The dipping phenomenon was first described in 1988. More recently the focus has been on absolute BP levels to classify hypertension. Our aim is to determine whether absolute night-time BP levels or dipping status are better associated with subclinical target organ damage (TOD). Methods: The Mitchelstown Cohort was established to examine cardiovascular health in a middle-aged Irish adult population based sample recruited from one large primary care centre. Of 2047 participants 1207(response rate 59%), under-went 24 h ambulatory BP monitoring. We excluded 135 studies due to incomplete data. Night-time BP was classified by absolute levels and dipping status. Subclinical TOD was defined by Cornell Product ECG left ventricular hypertrophy (LVH) voltage criteria and urine albumin:creatinine ratio (ACR) 41.1 mg/mmol. Multi-variable logistic regression analysis was used to assess the association between night-time BP and TOD. Results: Of 1072 patients, 255 (24%) had day-night hypertension and 64 (6%) had isolated nocturnal hypertension [94% of these were non-dippers or reverse dippers]. 165 (28%) of dippers had elevated night-time BP. In multivariable analysis each 10 mm Hg rise in night-time systolic BP resulted in an approximate doubling of risk for TOD. Odds ratio (OR) for ACR ¼ 1.84(95% CI 1.05–3.23) and OR for LVH ¼ 2.20(95% CI 1.13–4.27). Discussion: Nocturnal hypertension rather than dipping status may be a better way to classify night-time BP. Further interventional studies are required to determine if there is a benefit in reducing absolute night-time BP levels. PB.3. Prognostic significance of short term blood pressure variability in a tertiary referral centre population Huang C, Ng F, Kapil V, Caulfield M and Lobo M Barts and the London, London, United Kingdom Background: Blood pressure variability (BPV) is increasingly recognised as an independent risk factor for vascular events and mortality. Given that ambulatory blood pressure monitoring (ABPM) is now mandated in hypertension diagnosis, we examined the prognostic significance of BPV using ABPM in our clinic population. Methods: 440 patients attending our Hypertension clinic, underwent ABPM in 2008 with variability measured as the standard deviation of the daytime mean systolic blood pressure. We collected data on baseline patient demographics, medications and biochemistry, together with outcomes data for cardiovascular events and mortality from electronic records with a median follow-up time of 2.9 years. Results: Increasing age was associated with increasing BPV (Po0.001). Additionally, patients with CKD (eGFRo60, n ¼ 49) had higher SBP s.d. compared to those without (n ¼ 177) (14.3±4.4 mm Hg vs. 12.9±3.4 mm Hg; Po0.05). There was no association with gender, ethnicity or diabetes. Treatment naı̈ve subjects had lower BPV compared to those on treatment (11.4±3.3 mm Hg vs. 13.2±3.6 mm Hg, Po0.001) and there was an increase in variability with number of medications (slope 0.50 mm Hg CV per additional antihypertensive, Po0.001). In this cohort there was no statistically significant effect of BP variability on the combined outcomes of cardiovascular events and death, and rate of eGFR decline. Conclusion: To our knowledge this is the first study of BP variability in a heterogeneous UK clinic population.Our dataset did not detect an association of BPV with cardiovascular events, eGFR decline or mortality. However, there may be a relationship with increasing number of antihypertensive medications, which has not previously been described. PB.4. Comparison of the Vicorder and SphygmoCor devices in routine, communitybased blood pressure assessment Smith JC, Woodcock-Smith JK, Day LM, Miles KM, Wilkinson IB, McEniery CM Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom Estimates of central systolic blood pressure (cSBP) using the Vicorder have recently been validated. The aim of the study was to compare estimates of cSBP obtained with the Vicorder Journal of Human Hypertension Abstracts S18 and SphygmoCor, in a routine, community-based setting. Paired Vicorder and SphygmoCor estimates of cSBP were available in 1032 individuals, aged 20–93 years. Brachial BP was assessed using the Vicorder and cSBP derived from brachial waveforms recorded with the same device. Brachial pressure was also measured using an Omron 705CP and radial pressure waveforms recorded using the SphygmoCor. Both approaches used the respective brachial systolic and diastolic BP for peripheral waveform calibration, and the order in which Vicorder and SphygmoCor measurements were made was random. Brachial BP measured with the Vicorder and Omron devices were highly correlated (r ¼ 0.80, Po0.001, systolic; r ¼ 0.74, Po0.001, diastolic) and in reasonable agreement, with a mean difference (±s.d.) between devices of 4±11 mm Hg for systolic (Po0.001) and 5±7 mm Hg for diastolic (Po0.001). Estimates of cSBP were highly correlated (r ¼ 0.82, Po0.001) and in reasonable agreement (mean difference 2±10 mm Hg, Po0.001). In younger individuals, Vicorder-derived cSBP tended to underestimate SphygmoCor-derived values (Figure). Figure 1 Estimates of cSBP obtained with the Vicorder and SphygmoCor devices across the age range. Used in routine practice, the Vicorder and SphygmoCor produced similar estimates of cSBP, although a greater disparity tended to be present in younger individuals. The ease of a cuffbased system for estimating cSBP is likely to be better suited to community-based screening programmes. PB.5. Raised central pulse pressure in hypertension is predominately driven by changes in forward pressure wave Fok H, Guilcher A, Jiang B, Chowienczyk P Department of Clinical Pharmacology, King’s College London, London, United Kingdom Central pulse pressure (cPP), an important determinant of cardiovascular outcome, is determined by ventricular-vascular interaction. The extent to which pulsatile pressure waveform is determined by the forward and backward components is disputed. We decomposed cPP into components due to forward pressure waves (cPPFPW) and backward pressure waves (cPPBPW) generated by the ventricle and arterial tree respectively in hypertensive subjects (mean age±s.e. 47.4±3.0 years, BP: 158.5±6.2/98.7±3.2 mm Hg, n ¼ 20) and normotensive controls (mean age±s.e. 52.2±2.7 years, BP:108.7±2.7/ 71.8±1.7 mm Hg, n ¼ 20) and examined effects of dobutamine (to increase myocardial contractility) and norepinephrine (to increase peripheral arteriolar tone) on FPW and BPW in a subset of normotensive controls (n ¼ 10). Wave decomposition was performed on central pressure and flow waveforms obtained from carotid tonometry and aortic root Doppler flow velocity waveforms. cPPFPW was 50.4±3.4 and 35.2±1.8 mm Hg in hypertensives and controls respectively (Po0.001) and cPPBPW 8.9±1.7 and 1.6±0.4 mm Hg in hypertensives and controls respectively (Po0.002). After dobutamine (7.5 mg/min) cPPFPW increased from 36.4±3.7 to 57.3±3.0 mm Hg (Po0.001) but cPPBPW did not change significantly (1.5±1.0 and 2.6±0.4 mm Hg at baseline and after dobutamine respectively, P ¼ NS). After norepinephrine (50 ng/min) cPPFPW did not change significantly (35.3±1.6 and 39.0±3.3 mm Hg at baseline and after norepinephrine respectively, P ¼ NS) but cPPBPW increased significantly from 2.0±1.0 to 5.6±1.6 mm Hg (Po0.02). These data are consistent with cPPFPW and cPPBPW being determined by the left ventricle and peripheral arterial tree respectively. They suggest that in hypertension increased cPP results both from an increased ventricular and peripheral artery component but that the former dominates. PC.1. Microvascular autoregulatory response to ischaemia and pulse pressure Adingupu DD, Elyas S, Casanova F, Gates PE, Shore AC and Strain WD Diabetes and Vascular Medicine, University of Exeter Medical School, Exeter, United Kingdom Introduction: Microvascular dysfunction is increasingly recognised in the transmission of higher systolic Journal of Human Hypertension pressures to tissue beds, where it leads to hypertensive target organ damage. We have described three Abstracts S19 distinct cutaneous microvascular peak responses to an ischaemic stimulus using laser Doppler fluximetry which are associated with a clear gradation of cardiovascular risk. A ‘normal peak’ with a controlled graded rise to peak, ‘non-dominant early peak (NDEP),’ with an early peak within 2 s but which was lower than the subsequent ‘normal’ graded rise to peak, and ‘dominant early peak (DEP)’ within 2 s of cuff release, which declined rapidly and was then followed by a lesser ‘normal’ peak. Aims: To determine if there was association between pulse pressure and abnormal peak responses. Methods: Microvascular assessment post occlusive reactive hyperaemia (PORH) was performed on 126 participants with history of cardiovascular disease (CVD), 204 with type 2 diabetes and 111 controls, using laser Doppler DRT4 (Moor instruments, UK). Pulse pressure was calculated as systolic minus diastolic brachial blood pressure. Results: Data was stratified by PORH peak response morphology, 148 classified as normal peak, 183 NDEP and 91 DEP responses. There was no difference in resting systolic and diastolic blood pressures and heart rate across peak response groups. There was a difference in pulse pressure between peak response group’s normal, NDEP and DEP (mean±s.d. 54±11, 56±12, 59 ± 13 respectively, P ¼ 0.0042), with higher pulse pressure in DEP response group compared with normal peak response (P ¼ 0.004) and a trend for higher pulse pressure compared with NDEP (P ¼ 0.066). Conclusions: These data show that participants with more abnormal peak response morphology DEP have higher pulse pressure compared with more normal responses. The mechanisms underlying this association need further investigation. PD.1. MO25b has no physiological role in electrolyte homeostasis or systemic blood pressure maintenance in the mouse Siew K1, de los Heros P2, Alessi DR2, O’Shaughnessy KM1 1 Clinical Pharmacology Unit, Department of Medicine, University of Cambridge, Cambridge, United Kingdom and 2MRC Protein Phosphorylation Unit, College of Life Sciences, University of Dundee, Dundee, United Kingdom Introduction: Recently mouse protein-25 alpha (MO25a) was identified as a master regulator of SPAK; which forms a cascade with WNKs regulating the Na þ -Cl Cotransporter (NCC) involved in blood pressure (BP) & renal Na þ homeostasis (1–2). MO25a has been shown to colocalise with NCC & increase SPAK activity B100-fold independent of WNKs in vitro, which in turn enhances NCC activity & Na þ reabsorption (2–4). However MO25a-KO mice die in utero, so KO mice for the paralog MO25b were used to test the hypothesis that MO25 deficiency could produce a hypotensive salt-wasting phenotype. Methods: MO25b-KO mice aged 2–4 months were fed either a 0.25% or 3% Na þ diet for 10 days before switching to a 0.03% Na þ diet. Urine was collected at various time-points post-switch and the carotid BP was measured directly by manometry followed by terminal blood & tissue collection. Data represents mean±s.e.m.; Po0.05 was considered statistically significant (Student’s t-test). Results: There were no differences between KO vs. wildtype mean BP on 0.25% Na þ [80.2±2.4 (n ¼ 4) vs. 79.0±2.3 mm Hg (n ¼ 3)] or 0.03% Na þ diets [80.0±1.2 (n ¼ 11) vs. 80.7±1.1 mm Hg (n ¼ 11)]. No significant differences were detected for urine or plasma levels of creatinine, Na þ , K þ , Cl, Ca2 þ , on either diet except for Mg2 þ on Mg2 þ or PO3 4 þ 0.25% Na diet. We conclude that MO25b does not play a significant role in BP or electrolyte homoeostasis in vivo in the mouse. References [PMID] (1) 20091762; (2) 23034389; (3) 21423148; (4) 22977235 PD.2. Deficient uterine artery remodelling in the SHRSP during pregnancy is not improved by nifedipine treatment Small H, Totten S, Beattie E, Graham D University of Glasgow, Glasgow, United Kingdom Background: To meet the needs of the developing foetus during normal pregnancy, the blood supply to the uterus increases through circumferential enlargement (remodelling) of the uterine blood vessels. Insufficient remodelling is linked to high risk pregnancy conditions. The aim of this study was to investigate the impact of antihypertensive treatment on uterine vascular function, morphology and Journal of Human Hypertension Abstracts S20 blood flow in the pregnant SHRSP rat, a model of spontaneous deficient uterine artery remodelling. Methods: Female SHRSP were treated with nifedipine (25 mg/kg/day) or vehicle prior to and during pregnancy, and compared to female WKY controls. Blood pressure was measured by radiotelemetry and uterine artery blood flow by echo Doppler. Uterine artery structure and function were measured by wire and pressure myography at gestational day 18. Oxidative stress was measured by MDA assay in the placental/mesometrial unit. Results: WKY rats demonstrate normal adaptations to pregnancy with reduced contractile response to noradrenaline (Po0.01 v non-pregnant WKY), outward hypertrophic remodelling (Po0.001 v non- pregnant WKY) and reduced vascular stiffness (Po0.01 v no-pregnant WKY). These normal vascular responses to pregnancy were significantly blunted in SHRSP. SHRSP also demonstrate adverse blood flow parameters including increased resistance index, reduced diastolic volume and evidence of notching. Nifedipine treatment significantly reduced systolic blood pressure prior to and during pregnancy in SHRSP (Po0.001 v untreated SHRSP), however there were no significant improvements in abnormal uterine artery remodelling, blood flow or placental unit oxidative stress. Conclusion: Deficient uterine artery remodelling in the pregnant SHRSP is genetically determined and independent of blood pressure level. PE.1. Declining renal function is associated with increased visit-to-visit blood pressure variability in primary care Lasserson D1, Scherpbier de Haan N2, van Gelder V2, de Grauw W2, Biermans M2, Wetzels J2 and O0 Callaghan C3 Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom; 2Radboud University Nijmegen Medical Centre, Nijmegen, Netherlands and 3Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom 1 Background: Visit-to-visit variability in office BP measurements identifies patients at high risk of vascular events. Chronic kidney disease (CKD) is strongly associated with cardiovascular risk, largely due to comorbid diabetes and hypertension. However, renal impairment predicts vascular events even after controlling for known risk factors. The mechanism underlying this additional risk is unclear. We hypothesised that impaired renal function is associated with greater variability in visit-to-visit BP in primary care. Methods: From the CONTACT telenephrology study in 47 general practices in Nijmegen, Netherlands, eGFR was calculated from creatinine and BP measurements taken as part of routine care between 2007 and 2012. Multiple linear regression was used to analyse the influence of renal function on measures of systolic BP variability adjusted for age, sex, diabetes, and antihypertensive use. Variability measures were calculated from X7 BP measurements and included standard deviation, successive variation, absolute residual variation (before and after transformation to independence of mean). Results: Of 63 073 adult patients, 19 175 had X7 blood pressure measurements. Multiple linear regressions demonstrated a consistent, significant positive relationship between declining eGFR and all measures of BP variability (all at Po0.001). This relationship was not seen with mean BP. Indices of variability in patients with stage 4 CKD were similar to those reported previously in patients with TIA. Conclusion: Worsening renal function is associated with increased visit-to-visit BP variability; this effect is independent of age, sex, diabetes and antihypertensive use. This may be a mechanism whereby CKD raises the risk of cardiovascular events. PE.2. Phaeochromocytoma-paraganglioma syndrome presenting as a para-renal mass: A case report Robinson PJ1, Ng FL1,2, Lobo MD1,2, Akker S2, Drake WM2, Cavlan D2 and Caulfield MJ1,2 1 2 William Harvey Research Institute & Barts NIHR Biomedical Research Unit, London, United Kingdom and Barts & The London, Queen Mary University of London, London, United Kingdom A 48 year old female presented with recently diagnosed diabetes and a 22 year history of resistant hypertension, in part due to intolerance (amlodipine/ thiazides). Renal ultrasound revealed a 4 cm mass within the left renal pole. CT guided biopsy was planned and she was referred to the hypertension clinic for BP management. Journal of Human Hypertension Her mother had a stroke but there was no other cardiovascular history amongst her six siblings and four children. She had no flushing, palpitations or dizziness. Renal function was mildly impaired (eGFR 55 ml/ min). Electrolytes were normal. Ambulatory daytime BP was 155/99 and clinic BP 164/90, taking Abstracts S21 spironolactone 25 mg od and irbesartan 300 mg od. 24 h urine metanephrines were abnormal, with metadrenaline 3866 nmol (Normal o2000) and normetadrenaline 52985 nmol (normal o4000). MRI scan showed a left para-aortic mass encasing the left renal vessels, and a second left para-aortic mass inferiorly. MIBG scan showed intense tracer uptake within the left para-aortic mass with a further focal area of intense uptake seen just inferior to mass. She underwent pre-operative a- and b-blockade, followed by adrenalectomy and splenectomy. She required 5 litres of fluid intraoperatively. Histopathology was consistent with a phaeochromocytoma and a paraganglioma. Six months post op, her daytime ABP was 147/93 on no antihypertensive medication. Her glucose intolerance had improved. Genetic studies are awaited. This case illustrates the need to exclude phaeochromocytoma prior to biopsy of a para-renal mass, and the need to re-investigate patients with a history of resistant hypertension to exclude a new or undetected secondary cause. Journal of Human Hypertension Advance Online Publication From Nature Publishing Group What is Advance Online Publication (AOP)? How do I use the DOI in a reference? AOP gives you the research you need faster. Papers are published online as soon as they are ready, so you do not have to wait for the print publication. AOP articles are the definitive versions of the paper and can be cited immediately using the Digital Object Identifier (DOI). All NPG journals now have AOP. It’s simple. Instead of giving the volume and page number, you can give the paper’s DOI at the end of the citation. What is a Digital Object Identifier (DOI)? DOIs enable citation of research that is published online before in print. They are markers assigned to editorial content to provide a unique and persistent identifier for that item. The DOI system is administered by the International DOI Foundation and CrossRef maintains a lookup system, making the DOI a reference standard and enabling cross-publisher linking. 12932-06NPG_AOP_AJFP4C.indd 1 Does MEDLINE use DOIs? MEDLINE currently captures DOIs with online publication dates and is developing an enhanced level of support for the DOI system. How do I get to AOP content? Simple, just visit any nature.com journal homepage – a list of journals by subject is available at www.nature.com. 11/5/07 1:10:13 pm
