Eoin O'Brien

Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial

BACKGROUND The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic. METHODS Of 19342 hypertensive patients (aged 40-79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10305 with non-fasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat. FINDINGS Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50-0.83], p=0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56-0.96], p=0.024), total cardiovascular events (389 vs 486, 0.79 [0.69-0.90], p=0.0005), and total coronary events (178 vs 247, 0.71 [0.59-0.86], p=0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71-1.06], p=0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up. INTERPRETATION The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Prevention of Coronary and Stroke Events with Atorvastatin in Hypertensive Patients who have Average or Lower-than-Average Cholesterol Concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial— Lipid Lowering Arm (ASCOT-LLA): A Multicentre Randomised Controlled Trial

SummaryBackground The lowering of cholesterol concentrations in individuals at high risk of cardiovascular disease improves outcome. No study, however, has assessed benefits of cholesterol lowering in the primary prevention of coronary heart disease (CHD) in hypertensive patients who are not conventionally deemed dyslipidaemic. Methods Of 19 342 hypertensive patients (aged 40–79 years with at least three other cardiovascular risk factors) randomised to one of two antihypertensive regimens in the Anglo-Scandinavian Cardiac Outcomes Trial, 10 305 with nonfasting total cholesterol concentrations 6.5 mmol/L or less were randomly assigned additional atorvastatin 10 mg or placebo. These patients formed the lipid-lowering arm of the study. We planned follow-up for an average of 5 years, the primary endpoint being non-fatal myocardial infarction and fatal CHD. Data were analysed by intention to treat. Findings Treatment was stopped after a median follow-up of 3.3 years. By that time, 100 primary events had occurred in the atorvastatin group compared with 154 events in the placebo group (hazard ratio 0.64 [95% CI 0.50–0.83], p = 0.0005). This benefit emerged in the first year of follow-up. There was no significant heterogeneity among prespecified subgroups. Fatal and non-fatal stroke (89 atorvastatin vs 121 placebo, 0.73 [0.56–0.96], p = 0.024), total cardiovascular events (389 vs 486, 0.79 [0.69–0.90], p = 0.0005), and total coronary events (178 vs 247, 0.71 [0.59–0.86], p = 0.0005) were also significantly lowered. There were 185 deaths in the atorvastatin group and 212 in the placebo group (0.87 [0.71–1.06], p = 0.16). Atorvastatin lowered total serum cholesterol by about 1.3 mmol/L compared with placebo at 12 months, and by 1.1 mmol/L after 3 years of follow-up. Interpretation The reductions in major cardiovascular events with atorvastatin are large, given the short follow-up time. These findings may have implications for future lipid-lowering guidelines.

Superiority of ambulatory over clinic blood pressure measurement in predicting mortality: the Dublin outcome study.

The purpose of this study was to determine if ambulatory blood pressure measurement predicted total and cardiovascular mortality over and beyond clinic blood pressure measurement and other cardiovascular risk factors; 5292 untreated hypertensive patients referred to a single blood pressure clinic who had clinic and ambulatory blood pressure measurement at baseline were followed up in a prospective study of mortality outcome. Multiple Cox regression was used to model time to total and cause-specific mortality for ambulatory blood pressure measurement while adjusting for clinic blood pressure measurement and other risk factors at baseline. There were 646 deaths (of which 389 were cardiovascular) during a median follow-up period of 8.4 years. With adjustment for gender, age, risk indices, and clinic blood pressure, higher mean values of ambulatory blood pressure were independent predictors for cardiovascular mortality. The relative hazard ratio for each 10-mm Hg increase in systolic blood pressure was 1.12 (1.06 to 1.18; P<0.001) for daytime and 1.21 (1.15 to 1.27; P<0.001) for nighttime systolic blood pressure. The hazard ratios for each 5-mm Hg increase in diastolic blood pressure were 1.02 (0.99 to 1.07; P=NS) for daytime and 1.09 (1.04 to 1.13; P<0.01) for nighttime diastolic pressures. The hazard ratios for nighttime ambulatory blood pressure remained significant after adjustment for daytime ambulatory blood pressure. These results have 2 important clinical messages: ambulatory measurement of blood pressure is superior to clinic measurement in predicting cardiovascular mortality, and nighttime blood pressure is the most potent predictor of outcome.

Blood pressure measuring devices: recommendations of the European Society of Hypertension

There is a large market for blood pressure measuring devices not only in clinical medicine but also among the public where the demand for self measurement of blood pressure is growing rapidly. For consumers, whether medical or lay, accuracy should be of prime importance when selecting a device to measure blood pressure. However, most devices have not been evaluated for accuracy independently using the two most widely used protocols: the British Hypertension Society (BHS) protocol and the standard set by the US Association for the Advancement of Medical Instrumentation (AAMI). 1 2 The Working Group on Blood Pressure Monitoring of the European Society of Hypertension has decided to review blood pressure measuring devices regularly to guide purchasers.3 For this first report devices for which there is published evidence of independent validation using these protocols have been surveyed. Because most blood pressure devices have not been independently validated, only a fraction of the many devices available have been surveyed. Devices that have been validated recently for which results have not yet been published were not included, but this shortcoming should be addressed in future. #### Summary points Two manual sphygmomanometers have been validated, one is recommended Five devices for clinical use in hospitals have been validated, two are recommended 23 devices for self measurement of blood pressure have been validated, five are recommended 24 devices for ambulatory measurement of blood pressure have been validated, 16 are recommended Validations and recommendations will be updated on the BMJ s website ### Validation standards In 1987, the American Association for the Advancement of Medical Instrumentation published a standard for sphygmomanometers which included a protocol for evaluating the accuracy of devices.4 In 1990 a protocol was devised by the British Hypertension Society.5 Both protocols have since been revised. 1 2 Since the two protocols can be reconciled the …

Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults

Working Group on Blood Pressure Monitoring of the European Society of Hypertension International Protocol for validation of blood pressure measuring devices in adults Eoin O’Brien,Thomas Pickering, Roland Asmar, Martin Myers, Gianfranco Parati, Jan Staessen, Thomas Mengden, Yutaka Imai, Bernard Waeber and Paolo Palatini and with the statistical assistance of Neil Atkins and William Gerin, on behalf of the Working Group on Blood Pressure Monitoring of the European Society of Hypertension

Accuracy of the SpaceLabs 90207 determined by the british hypertension society protocol

Results: The three recorders passed the before-use interdevice variability assessment, after which 84% of inflations recorded with these devices during the in-use phase gave valid readings, and the three devices subsequently passed the after-use interdevice variability assessment. The main validation test was carried out on one device in 86 subjects with a wide range of pressures, the results being analysed according to a grading system from A to D. The SpaceLabs 90207 acheived B rating for both systolic and diastolic pressures and also satisfied the criteria for accuracy of the Association for the Advancement of Medical lnstrumentation (AAMI), with an average difference (f s.d.1 of 1 f 7 and 3 f 6 mmHg for systolic and diastolic pressure, respectively. Subject acceptability was good. The manufacturers manual was satisfactory overall, but contained a number of errors and omissions.

Use and interpretation of ambulatory blood pressure monitoring: recommendations of the British Hypertension Society

Over the past 20 years or so, the accuracy of using the conventional Riva-Rocci sphygmomanometer and Korotkoffs sounds to measure blood pressure has been questioned, and efforts have been made to improve measurements with automated devices.1 2 In the same period, the phenomenon of white coat hypertension has been recognised—whereby some patients who apparently have raised blood pressure actually have normal blood pressure when the measurement is repeated away from the medical environment; this has focused attention on methods of measurement that provide profiles of blood pressure rather than rely on isolated measurements made under circumstances that may influence blood pressure.3 These methods have included repeated measurements of blood pressure using the traditional technique, self measurement of blood pressure in the home or workplace, and ambulatory blood pressure measurement using automated devices.2 Ambulatory monitoring is advantageous because it gives multiple measurements throughout the day and night This paper considers only the ambulatory measurement of blood pressure in adults. Its purpose is not to make a case for or against ambulatory measurement; others have already done so.4 5 Although the results of a number of ongoing, longitudinal studies are forthcoming, there is now firm evidence that ambulatory blood pressure measurement is a more sensitive predictor of cardiovascular outcome than conventional measurement.6 We have not considered the complex issues of health economics that the increasing use of ambulatory measurement raises.7 We realise that this technique is being used more often and that doctors who find ambulatory measurement useful in the day to day management of patients with high blood pressure need recommendations from those who have experience. However, regardless of the technique used to diagnose hypertension it is only one factor in determining a patients risk profile and must be assessed in relation to concomitant disease, …

Blood Pressure Lowering in Essential Hypertension With an Oral Renin Inhibitor, Aliskiren

Abstract—Inhibition of the first and rate-limiting step of the renin-angiotensin system has long been an elusive therapeutic goal. Aliskiren, the first known representative of a new class of completely nonpeptide, orally active, renin inhibitors, has been shown to inhibit the production of angiotensin I and II in healthy volunteers and to reduce blood pressure (BP) in sodium-depleted marmosets. The aim of this randomized, double-blind, active comparator trial study was to assess the BP-lowering efficacy and safety of aliskiren. Two hundred twenty-six patients, 21 to 70 years of age, with mild to moderate hypertension, were randomly assigned to receive 37.5 mg, 75 mg, 150 mg, or 300 mg aliskiren or 100 mg losartan daily for 4 weeks. Dose-dependent reductions in daytime ambulatory systolic pressure (mean change, mm Hg [SD of change]; −0.4 [11.7], −5.3 [11.3], −8.0 [11.0], and −11.0 [11.0], P =0.0002) and in plasma renin activity (median change % [interquartile range]; −55 [−64, −11], −60 [−82, −46], −77 [−86, −72], and −83 [−92, −71], P =0.0008) were observed with 37.5, 75, 150, and 300 mg aliskiren. The change in daytime systolic pressure with 100 mg losartan (−10.9 [13.8]) was not significantly different from the changes seen with 75, 150, and 300 mg aliskiren. Aliskiren was well tolerated at all doses studied. This study demonstrates that aliskiren, through inhibition of renin, is an effective and safe orally active BP-lowering agent. Whether renin inhibition results in protection from heart attack, stroke, and nephropathy, similar to angiotensin-converting enzyme inhibition and angiotensin receptor blockade, needs to be researched.

European Society of Hypertension International Protocol revision 2010 for the validation of blood pressure measuring devices in adults.

The Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Ireland, dabl Ltd., Blackrock Co., Dublin, Ireland, Hypertension Center, Third University Department of Medicine, Sotiria Hospital, Athens, Greece, Istituto Scientifico Ospedale San Luca, IRCCS, Instituto Auxologico Italiano, Milan, Italy, Societe Francaise d’Hypertension Arterielle, Filiale de la Societe Francaise de Cardiolgie, Paris, France, The Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Sendai, Japan, Centre for Epidemiological Studies and Clinical Trials, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China, University Clinic Bonn, Department of Internal Medicine, Bonn, Germany and Guy’s and St Thomas’ Hospitals, London, UK

Ambulatory Arterial Stiffness Index Derived From 24-Hour Ambulatory Blood Pressure Monitoring

We hypothesized that 1 minus the slope of diastolic on systolic pressure during 24-hour ambulatory monitoring (ambulatory arterial stiffness index [AASI]) might reflect arterial stiffness. We compared AASI with established measures of arterial stiffness and studied its distribution in Chinese and European populations. We used 90207 SpaceLabs monitors and the SphygmoCor device to measure AASI, central and peripheral pulse pressures, the central (CAIx) and peripheral (PAIx) systolic augmentation indexes, and aortic pulse wave velocity. In 166 volunteers, the correlation coefficient between AASI and pulse wave velocity was 0.51 (P<0.0001). In 348 randomly recruited Chinese subjects, AASI correlated (P<0.0001) with CAIx (r=0.48), PAIx (r=0.50), and central pulse pressure (r=0.50). AASI increased with age and mean arterial pressure but decreased with body height. Both before and after adjustment for arterial wave reflections by considering height and heart rate as covariates, AASI correlated more (P<0.0001) closely with CAIx and PAIx than 24-hour pulse pressure. Among normotensive subjects, the 95th percentile of AASI was 0.55 in Chinese and 0.57 in 1617 Europeans enrolled in the International Database on Ambulatory Blood Pressure Monitoring. The upper boundary of the 95% prediction interval of AASI in relation to age ranged from 0.53 at 20 years to 0.72 at 80 years. In conclusion, AASI is a new index of arterial stiffness that can be easily measured under ambulatory conditions. Pending additional validation in outcome studies, normal values of AASI are probably <0.50 and 0.70 in young and older subjects, respectively.