INTRODUCTION: Individual cohort studies in various populations and study-level meta-analyses have shown interarm differences (IAD) in blood pressure to be associated with increased cardiovascular and all-cause mortality. However, key questions remain, such as follows: (1) What is the additional contribution of IAD to prognostic risk estimation for cardiovascular and all-cause mortality? (2) What is the minimum cut-off value for IAD that defines elevated risk? (3) is there a prognostic value of IAD and do different methods of IAD measurement impact on the prognostic value of IAD? We aim to address these questions by conducting an individual patient data (IPD) meta-analysis. METHODS AND ANALYSIS: This study will identify prospective cohort studies that measured blood pressure in both arms during recruitment, and invite authors to contribute IPD datasets to this collaboration. All patient data received will be combined into a single dataset. Using one-stage meta-analysis, we will undertake multivariable time-to-event regression modelling, with the aim of developing a new prognostic model for cardiovascular risk estimation that includes IAD. We will explore variations in risk contribution of IAD across predefined population subgroups (eg, hypertensives, diabetics), establish the lower limit of IAD that is associated with additional cardiovascular risk and assess the impact of different methods of IAD measurement on risk prediction. ETHICS AND DISSEMINATION: This study will not include any patient identifiable data. Included datasets will already have ethical approval and consent from their sponsors. Findings will be presented to international conferences and published in peer reviewed journals, and we have a comprehensive dissemination strategy in place with integrated patient and public involvement. PROSPERO REGISTRATION NUMBER: CRD42015031227.

BACKGROUND: Previous surveys identified a shift to nurse-led care in hypertension in 2010. In 2011 the National Institute for Health and Care Excellence (NICE) recommended ambulatory (ABPM) or home (HBPM) blood pressure (BP) monitoring for diagnosis of hypertension. AIM: to survey the organisation of hypertension care in 2016 to identify changes, and to assess uptake of NICE diagnostic guidelines. DESIGN AND SETTING: Questionnaires were distributed to all 305 general practices in South West England. METHOD: Responses were compared with previous rounds (2007 and 2010). Data from the 2015 Quality and Outcomes Framework (QOF) were used to compare responders with non-responders, and to explore associations of care organisation with QOF achievement. RESULTS: One-hundred-and-seventeen practices (38%) responded. Responders had larger list sizes and greater achievement of the QOF target BP ≤150/90 mmHg. Healthcare assistants (HCAs) now monitor BP in 70% of practices, compared with 37% in 2010 and 19% in 2007 (P

BACKGROUND: Differences in blood pressure between arms are associated with increased cardiovascular mortality in cohorts with established vascular disease or substantially elevated cardiovascular risk. AIM: to explore the association of inter-arm difference (IAD) with mortality in a community-dwelling cohort that is free of cardiovascular disease. DESIGN AND SETTING: Cohort analysis of a randomised controlled trial in central Scotland, from April 1998 to October 2008. METHOD: Volunteers from Lanarkshire, Glasgow, and Edinburgh, free of pre-existing vascular disease and with an ankle-brachial index ≤0.95, had systolic blood pressure measured in both arms at recruitment. Inter-arm blood pressure differences were calculated and examined for cross-sectional associations and differences in prospective survival. Outcome measures were cardiovascular events and all-cause mortality during mean follow-up of 8.2 years. RESULTS: Based on a single pair of measurements, 60% of 3350 participants had a systolic IAD ≥5 mmHg and 38% ≥10 mmHg. An IAD ≥5 mmHg was associated with increased cardiovascular mortality (adjusted hazard ratio [HR] 1.91, 95% confidence interval [CI] = 1.19 to 3.07) and all-cause mortality (adjusted HR 1.44, 95% CI = 1.15 to 1.79). Within the subgroup of 764 participants who had hypertension, IADs of ≥5 mmHg or ≥10 mmHg were associated with both cardiovascular mortality (adjusted HR 2.63, 95% CI = 0.97 to 7.02, and adjusted HR 2.96, 95% CI = 1.27 to 6.88, respectively) and all-cause mortality (adjusted HR 1.67, 95% CI = 1.05 to 2.66, and adjusted HR 1.63, 95% CI = 1.06 to 2.50, respectively). IADs ≥15 mmHg were not associated with survival differences in this population. CONCLUSION: Systolic IADs in blood pressure are associated with increased risk of cardiovascular events, including mortality, in a large cohort of people free of pre-existing vascular disease.

BACKGROUND: Various prevalence figures have been reported for inter-arm differences in blood pressure (IAD); variation may be explained by differing population vascular risk and by measurement method. AIM: to review the literature to derive robust estimates of IAD prevalence relevant to community populations. DESIGN AND SETTING: Systematic review and meta-analysis. METHOD: MEDLINE, Embase, and CINAHL were searched for cross-sectional studies likely to represent general or primary care populations, reporting prevalence of IAD and employing a simultaneous method of measurement. Using study-level data, pooled estimates of mean prevalence of systolic IADs were calculated and compared using a random effects model. RESULTS: Eighty IAD studies were identified. Sixteen met inclusion criteria: pooled estimates of prevalence for systolic IAD ≥10 mmHg were 11.2% (95% confidence interval [CI] = 9.1 to 13.6) in hypertension, 7.4% (95% CI = 5.8 to 9.2) in diabetes, and 3.6% (95% CI = 2.3 to 5.0) for a general adult population (P

OBJECTIVE: We previously reported the association of inter-arm differences in blood pressure measurements (IAD) with increased cardiovascular and all-cause mortality. Several new large cohorts have been reported since our 2012 meta-analysis. We have therefore updated our meta-analyses to take account of these new data. DESIGN AND METHOD: Systematic review and meta-analysis: Medline, Embase and CINAHL were searched for studies reporting survival data in association with IAD. Study level hazard ratios (HR) were extracted for systolic IADs >=10mmHg and >=15mmHg, and pooled using generic inverse variance in a random effects model. Statistical heterogeneity was assessed using the I statistic. RESULTS: Searches to 12th November 2014 identified 3514 unique citations. Eighty full texts were assessed, and 13 studies (reporting data for 14 unique cohorts) contributed to the analyses, Median follow up ranged from 3 to 13 years. Five cohorts employed a simultaneous method of IAD measurement; the remainder used sequential measurements. Ten cohorts were recruited from community populations, including one hypertensive and one diabetic cohort. Four were selected hospital cohorts at increased vascular risk.Cardiovascular mortality was greater with an IAD >=10mmHg (HR 1.9 (95%CI 1.3 to 2.6; 7 cohorts, 13815 participants; I = 45%) and an IAD >=15mmHg (HR 1.7 (1.2 to 2.4; 9 cohorts; 18241 participants; I = 30%). For all-cause mortality HRs were 1.4 (1.2 to 1.8; 10 cohorts, 17709 participants; I = 62%) for IAD >=10mmHg and 1.4 (1.1 to 1.7; 12 cohorts, 18714 participants; I = 46%) for IAD >=15mmHg. Heterogeneity between studies could be accounted for by stratification according to underlying population cardiovascular risk, with higher HRs seen in populations at elevated risk; cardiovascular mortality with an IAD >=10mmHg: HR 1.4 (1.1 to 1.8; I = 0%) for community based cohorts compared to 3.8 (2.2 to 6.6; I = 0%) for those at elevated cardiovascular risk (p = 0.001; Figure).(Figure is included in full-text article.) CONCLUSIONS: : New studies confirming the association of an IAD with increased cardiovascular and all-cause mortality are consistent with previously published findings. Risks associated with an IAD rise in association with the underlying vascular risk of the population studied.

Differences in blood pressure measurements between arms are commonly encountered in clinical practice. If such differences are not excluded they can delay the diagnosis of hypertension and can lead to poorer control of blood pressure levels. Differences in blood pressure measurements between arms are associated cross sectionally with other signs of vascular disease such as peripheral arterial disease or cerebrovascular disease. Differences are also associated prospectively with increased cardiovascular mortality and morbidity and all cause mortality. Numbers of publications on inter-arm difference are rising year on year, indicating a growing interest in the phenomenon. The prevalence of an inter-arm difference varies widely between reports, and is correlated with the underlying cardiovascular risk of the population studied. Prevalence is also sensitive to the method of measurement used. This review discusses the prevalence of an inter-arm difference in different populations and addresses current best practice for the detection and the measurement of a difference. The evidence for clinical and for vascular associations of an inter-arm difference is presented in considering the emerging role of an inter-arm blood pressure difference as a novel risk factor for increased cardiovascular morbidity and mortality. Competing aetiological explanations for an inter-arm difference are explored, and gaps in our current understanding of this sign, along with areas in need of further research, are considered.

© 2015 Jenkinson et al.; licensee BioMed Central. Background: the NHS Cardiovascular Health Check (NHSHC) programme was introduced in England in 2009 to reduce cardiovascular disease mortality and morbidity for all patients aged 40 to 74 years old. Programme cost-effectiveness was based on an assumed uptake of 75% but current estimates of uptake in primary care are less than 50%. The purpose of this study was to identify factors influencing patients' willingness to attend an NHSHC. For those who attended, their views, experiences and their future willingness to engage in the programme were explored. Method: Telephone or face-to-face interviews were conducted with patients who had recently been invited for an NHSHC by a letter from four general practices in Torbay, England. Patients were purposefully sampled (by gender, age, attendance status). Interviews were audio recorded, transcribed verbatim and analysed thematically. Results: 17 attendees and 10 non-attendees were interviewed. Patients who attended an NHSHC viewed it as worthwhile. Proactive attitudes towards their health, a desire to prevent disease before they developed symptoms, and a willingness to accept screening and health check invitations motivated many individuals to attend. Non-attendees cited not seeing the NHSHC as a priority, or how it differed from regular monitoring already received for other conditions as barriers to attendance. Some non-attendees actively avoided GP practices when feeling well, while others did not want to waste health professionals' time. Misunderstandings of what the NHSHC involved and negative views of what the likely outcome might be were common. Conclusion: While a minority of non-attendees simply had made an informed choice not to have an NHSHC, improving the clarity and brevity of invitational materials, better advertising, and simple administrative interventions such as sending reminder letters, have considerable potential to improve NHSHC uptake.

BACKGROUND: the magnitude of the 'white coat effect', the alerting rise in blood pressure, is greater for doctors than nurses. This could bias interpretation of studies on nurse-led care in hypertension, and risks overestimating or overtreating high blood pressure by doctors in clinical practice. AIM: to quantify differences between blood pressure measurements made by doctors and nurses. DESIGN AND SETTING: Systematic review and meta-analysis using searches of MEDLINE, CENTRAL, CINAHL, Embase, journal collections, and conference abstracts. METHOD: Studies in adults reporting mean blood pressures measured by doctors and nurses at the same visit were selected, and mean blood pressures extracted, by two reviewers. Study risk of bias was assessed using modified Cochrane criteria. Outcomes were pooled across studies using random effects meta-analysis. RESULTS: in total, 15 studies (11 hypertensive; four mixed hypertensive and normotensive populations) were included from 1899 unique citations. Compared with doctors' measurements, nurse-measured blood pressures were lower (weighted mean differences: systolic -7.0 [95% confidence interval {CI} = -4.7 to -9.2] mmHg, diastolic -3.8 [95% CI = -2.2 to -5.4] mmHg). For studies at low risk of bias, differences were lower: systolic -4.6 (95% CI = -1.9 to -7.3) mmHg; diastolic -1.7 (95% CI = -0.1 to -3.2) mmHg. White coat hypertension was diagnosed more frequently based on doctors' than on nurses' readings: relative risk 1.6 (95% CI =1.2 to 2.1). CONCLUSIONS: the white coat effect is smaller for blood pressure measurements made by nurses than by doctors. This systematic difference has implications for hypertension diagnosis and management. Caution is required in pooling data from studies using both nurse- and doctor-measured blood pressures.

OBJECTIVE: to determine whether a difference in systolic blood pressure readings between arms can predict a reduced event free survival after 10 years. DESIGN: Cohort study. SETTING: Rural general practice in Devon, United Kingdom. PARTICIPANTS: 230 people receiving treatment for hypertension in primary care. INTERVENTION: Bilateral blood pressure measurements recorded at three successive surgery attendances. MAIN OUTCOME MEASURES: Cardiovascular events and deaths from all causes during a median follow-up of 9.8 years. RESULTS: at recruitment 24% (55/230) of participants had a mean interarm difference in systolic blood pressure of 10 mm Hg or more and 9% (21/230) of 15 mm Hg or more; these differences were associated with an increased risk of all cause mortality (adjusted hazard ratio 3.6, 95% confidence interval 2.0 to 6.5 and 3.1, 1.6 to 6.0, respectively). The risk of death was also increased in 183 participants without pre-existing cardiovascular disease with an interarm difference in systolic blood pressure of 10 mm Hg or more or 15 mm Hg or more (2.6, 1.4 to 4.8 and 2.7, 1.3 to 5.4). An interarm difference in diastolic blood pressure of 10 mm Hg or more was weakly associated with an increased risk of cardiovascular events or death. CONCLUSIONS: Differences in systolic blood pressure between arms can predict an increased risk of cardiovascular events and all cause mortality over 10 years in people with hypertension. This difference could be a valuable indicator of increased cardiovascular risk. Bilateral blood pressure measurements should become a routine part of cardiovascular assessment in primary care.

BACKGROUND: Previous reviews demonstrate uncertainty about the effectiveness of nurse-led interventions in the management of hypertension. No specific reviews in diabetes have been identified. We have systematically reviewed the evidence for effectiveness of nurse-led interventions for people with diabetes mellitus. METHODS: in this systematic review and meta-analysis, searches of Medline, Embase, CINAHL and the Cochrane Central Trials register were undertaken to identify studies comparing any intervention conducted by nurses in managing hypertension in diabetes with usual doctor-led care. Additional citations were identified from papers retrieved and correspondence with authors. Outcome measures were absolute systolic and diastolic blood pressure, change in blood pressure, proportions achieving study target blood pressure and proportions prescribed anti-hypertensive medication. RESULTS:   Eleven studies were identified. Interventions included adoption of treatment algorithms, nurse-led clinics and nurse prescribing. Meta-analysis showed greater reductions in blood pressure in favour of any nurse-led interventions (systolic weighted mean difference -5.8 mmHg, 95% CI -9.6 to -2.0; diastolic weighted mean difference -4.2 mmHg, 95% CI -7.6 to -0.7) compared with usual doctor-led care. No overall superiority in achievement of study targets or in the use of medication was evident for any nurse-based interventions over doctor-led care. CONCLUSIONS: There is some evidence for improved blood pressure outcomes with nurse-led interventions for hypertension in people with diabetes compared with doctor-led care. Nurse-based interventions require an algorithm to structure care and there is some preliminary evidence for better outcomes with nurse prescribing. Further work is needed to elucidate which nurse-led interventions are most effective.

AIMS: to assess the efficacy of herb and plant extracts in the management of asthma. METHOD: Systematic review and meta-analysis. Multiple database searches identified randomised placebo controlled trials of herbal interventions reporting at least one primary outcome measure. Where possible data were combined for meta-analysis. Primary outcome measures were lung function, exacerbations and reduction in corticosteroid use. Secondary outcome measures were symptoms and symptom scores, use of reliever medications, changes in rates of consultation and adverse effects. RESULTS: Twenty-six studies reporting on 20 herbal preparations were included. Two of six studies reporting change in FEV1 were positive. Little data was available on frequency of exacerbations. For primary outcomes single studies of Boswellia, Mai-Men-Dong-Tang, Pycnogenol, Jia-Wei-Si-Jun-Zi-Tang and Tylophora indica showed potential to improve lung function, and a study of 1.8-Cineol (eucalyptol) showed reduced daily oral steroid dosage. CONCLUSIONS: Improvements in symptoms were not strongly supported by objective changes. Most trials were of small sample size, short duration, and poor methodology. Further adequately powered trials are needed to assess these compounds. Such trials should conform to CONSORT guidance, report standardised spirometry, and use validated symptom and severity scores. No recommendations for herbal treatment of asthma can be made from the current evidence.

Objective: to review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study. Design: Systematic review and meta-analysis. Data sources: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database. Study selection: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults. Data extraction: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken. Data synthesis: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5). Conclusions: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.

OBJECTIVE: to review trials of nurse led interventions for hypertension in primary care to clarify the evidence base, establish whether nurse prescribing is an important intervention, and identify areas requiring further study. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Ovid Medline, Cochrane Central Register of Controlled Trials, British Nursing Index, Cinahl, Embase, Database of Abstracts of Reviews of Effects, and the NHS Economic Evaluation Database. STUDY SELECTION: Randomised controlled trials of nursing interventions for hypertension compared with usual care in adults. DATA EXTRACTION: Systolic and diastolic blood pressure, percentages reaching target blood pressure, and percentages taking antihypertensive drugs. Intervention effects were calculated as relative risks or weighted mean differences, as appropriate, and sensitivity analysis by study quality was undertaken. DATA SYNTHESIS: Compared with usual care, interventions that included a stepped treatment algorithm showed greater reductions in systolic blood pressure (weighted mean difference -8.2 mm Hg, 95% confidence interval -11.5 to -4.9), nurse prescribing showed greater reductions in blood pressure (systolic -8.9 mm Hg, -12.5 to -5.3 and diastolic -4.0 mm Hg, -5.3 to -2.7), telephone monitoring showed higher achievement of blood pressure targets (relative risk 1.24, 95% confidence interval 1.08 to 1.43), and community monitoring showed greater reductions in blood pressure (weighted mean difference, systolic -4.8 mm Hg, 95% confidence interval -7.0 to -2.7 and diastolic -3.5 mm Hg, -4.5 to -2.5). CONCLUSIONS: Nurse led interventions for hypertension require an algorithm to structure care. Evidence was found of improved outcomes with nurse prescribers from non-UK healthcare settings. Good quality evidence from UK primary health care is insufficient to support widespread employment of nurses in the management of hypertension within such healthcare systems.

BACKGROUND: Previous studies have identified a substantial prevalence of a blood pressure difference between arms in various populations, but not patients with type 2 diabetes. Recognition of such a difference would be important as a potential cause of underestimation of blood pressure. AIM: to measure prevalence of an inter-arm blood pressure difference in patients with type 2 diabetes, and to estimate how frequently blood pressure measurements could be erroneously underestimated if an inter-arm difference is unrecognised. DESIGN OF STUDY: Cross-sectional study. SETTING: Five surgeries covered by three general practices, Devon, England. METHOD: Patients with type 2 diabetes underwent bilateral simultaneous blood pressure measurements using a validated protocol. Mean blood pressures were calculated for each arm to derive mean systolic and diastolic differences, and to estimate point prevalence of predefined magnitudes of difference. RESULTS: a total of 101 participants were recruited. Mean age was 66 years (standard deviation [SD] = 13.9 years); 59% were male, and mean blood pressure was 138/79 mmHg (SD = 15/10 mmHg). Ten participants (10%; 95% confidence interval [CI] = 4 to 16) had a systolic inter-arm difference > or =10 mmHg; 29 (29%; 95% CI = 20 to 38) had a diastolic difference >/=5 mmHg; and three (3%; 95% CI = 0 to 6) a diastolic difference > or =10 mmHg. No confounding variable was observed to account for the magnitude of an inter-arm difference. CONCLUSION: a systolic inter-arm difference > or =10 mmHg was observed in 10% of patients with diabetes. Failure to recognise this would misclassify half of these as normotensive rather than hypertensive using the lower-reading arm. New patients with type 2 diabetes should be screened for an inter-arm blood pressure difference.

BACKGROUND: a blood pressure (BP) difference between the upper limbs is often encountered in primary care. Knowledge of its prevalence and importance in the accurate measurement of BP is poor, representing a source of error. Current hypertension guidelines do not emphasize this. OBJECTIVES: to establish the prevalence of an inter-arm blood pressure difference (IAD) and explore its association with other indicators of peripheral vascular disease (PVD) in a hypertensive primary care population. METHODS: This was a cross-sectional study. Primary care, one rural general practice, was the setting of the study. The methods were controlled simultaneous measurement of brachial BPs, ankle-brachial pressure index (ABPI) and tiptoe stress testing in 94 subjects. RESULTS: in all, 18 of 94 [19%, 95% confidence interval (CI) 11-27%] subjects had mean systolic inter-arm difference (sIAD) > or =10 mmHg and seven of 94 (7%, 95% CI 2-12%) had mean diastolic inter-arm difference (dIAD) > or =10 mmHg. Nineteen of 91 (20%, 95% CI 12-28%) had a reduced ABPI. or =20%. CONCLUSIONS: an IAD and asymptomatic PVD are common in a primary care hypertensive population. Magnitude of the IAD is inversely correlated with ABPI, supporting the hypotheses that IADs are causally linked to PVD, and that IAD is a useful marker for the presence of PVD. Consequently, detection of an IAD should prompt the clinician to screen subjects for other signs of vascular disease and target them for aggressive cardiovascular risk factor modification.

Objectives of this study were to measure the prevalence of a difference in blood pressure (BP) between arms and determine whether a difference is associated with increased risk of cardiovascular events or death. A prospective cohort study of 247 patients with hypertension was undertaken in one rural general practice in England. The main outcome measures were mean difference in BP between arms and new episodes of myocardial infarction, cerebrovascular event, onset of angina or peripheral vascular disease or death. A total of 57/247 (23%) patients had a mean difference in systolic BP between arms of >or=10 mm Hg and 8/247 (3%) had a mean difference of >or=20 mm Hg. A total of 15/247 (6%) patients had a mean difference in diastolic BP between arms of >or=10 mm Hg. Survival analysis after 4.7 years (range 3.3-5.9) showed a shorter mean survival time without event or death for patients with a difference in systolic BP of >or=10 mm Hg compared with a difference of

A blood pressure (BP) difference between arms was first reported over 100 years ago. Knowledge of its prevalence and relevance to the accurate measurement of BP remains poor. Current hypertension guidelines do not emphasise it. The objectives of this study were to establish the best estimate of prevalence of the inter-arm difference (IAD) in the population, to consider its implications for accurate BP measurement and treatment, and to discuss its aetiology and potential as a risk marker for cardiovascular disease. Systematic literature review was carried out. The data sources were Medline EMBASE and CINAHL databases, and Index of Theses. Studies reporting prevalence rates of IAD were retrieved and considered for inclusion against explicit methodological criteria. Point prevalence rates were extracted and weighted mean prevalence rates calculated. The main outcome measures were weighted mean prevalences of systolic IAD > or =10 and > or =20 mm Hg and of diastolic IAD > or =10 mm Hg. Thirty-one studies were identified. Most had methodological weaknesses; only four met the inclusion criteria. Pooled prevalences of the IAD from these four studies were 19.6% systolic > or =10 mm Hg (95% CI 18.0-21.3%), 4.2% systolic > or =20 mm Hg (95% CI 3.4-5.1%) and 8.1% diastolic > or =10 mm Hg (95%CI 6.9-9.2%). In conclusion, an IAD is present in a substantial number of patients and should be looked for whenever diagnosis and treatment depend on accurate measurements of BP. The importance of an IAD should be better emphasised in current hypertension management guidelines. There is evidence associating an IAD with peripheral vascular disease, raising the possibility that its presence may predict cardiovascular events.

This module describes recent developments in the management of hypertension, and the practical implications for doctors working in primary care. It covers evidence about measurement of blood pressure, primary prevention, the treatment of mild hypertension, early intensive treatment, and treatment of special groups of patients.