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REGARDS: Optimal blood pressure levels in elderly persons in the reasons for geographic and racial differences in stroke (REGARDS) cohort study


Presenter abstract
Discussant report
All the Scientific resources on ESC Congress 365


By Manciej Banach
Other authors: Dr. Samantha Bromfield (USA), Prof. George Howard (USA), Prof. Virginia J. Howard (USA), Prof. Alberto Zanchetti (Italy), Prof. Wilbert S. Aronow (USA), Prof. Ali Ahmed (USA), Prof. Monika M. Safford (USA), Prof. Paul Muntner (USA)
In recent years there has been extensive discussion on the effective management of hypertension in the elderly population. Despite more and more data we still do not know what should be the optimal levels of blood pressure (BP) in these persons. Therefore we aimed to search for the optimal BP levels in elderly persons on the basis of the data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.

We analyzed 13,948 subjects with treated hypertension without any previous cardio- and cerebrovascular history, which were divided into 3 groups: 55-64 (pre-elderly), 65-74 and ≥75 years old. Then all 3 groups were divided according to the baseline treated systolic BP (SBP) levels: <120, 120-129, 130-139, 140-149, and >150 mmHg. The primary outcome was an incident CV event (stroke, coronary heart disease [CHD], cardiovascular disease [CVD]), and all-cause mortality.

Relative to those with BP <120 mmHg, in pre-elderly patients with BP >150 and between 120-129 mmHg were at the highest risk of CVD (adjusted hazard ratio [aHR] 1.36, 95%Cl 0.82-2.28; and 1.57, 95%Cl 0.79-3.09, respectively), whereas the optimal BP was 130-139 mmHg (aHR 0.88; 95%Cl 0.50-1.57). For all other endpoints there was a “lower the better” trend, especially noticed for stroke and CHD events (p=0.028). For 65-74-year old patients the highest risk for CVD events was observed for BP >150 mmHg (aHR 2.33, 95%Cl 1.37-3.97), and BP<120 mmHg was characterized by the lowest risk for CVD events (p<0.001). Similar results were obtained for CHD (aHR 2.74, 95%Cl 1.50-5.04; p<0.001) and all-cause mortality (aHR 1.67, 95%Cl 1.27-2.21; p<0.001). The highest risk for stroke in this group was observed for BP >140 mmHg, and the optimal BP level for this outcome was 120-129 mmHg (aHR 0.92, 95%Cl 0.57-1.49). The caution concerning all endpoints should be kept for BP values <110 mmHg. For the oldest patients the optimal BP level for all analyzed endpoints was <140 mmHg (CVD: 130-139 mmHg [aHR 0.69; 95%Cl 0.39-1.24; p<0.001], CHD: 120-129 mmHg [aHR 0.60, 95%Cl 0.28-1.28, p<0.001], stroke: <140 mmHg [with the further reduction for BP<120 mmHg], and all cause-mortality: 130-139 mmHg [aHR 0.78, 95%Cl 0.62-0.99]) with significant increase of CV events above this value. However, the large caution should be kept for BP values <110 mmHg, especially for CHD events and all-cause mortality.   

The results suggest that for all patients above 55 the recommended level of SBP should be <140 mmHg, including the oldest patients (>75 years old), with the most reasonable values between 120-139 mmHg. The intensive hypertension therapy (with targeted BP<120 mmHg) should be a matter of further investigations.

Discussant Report

Christi Deaton
The value of large population based longitudinal cohort studies such as REGARDS is tremendous, especially when they include large numbers of high risk and often hard to reach groups as in this study. 
These studies provide insight and ideas for further research, and the data from REGARDS have already generated a number of interesting observations and hypotheses. 
This analysis set out to determine optimal blood pressure related to cardiovascular disease (CVD) risk among 13,948 people aged 55 and older with treated hypertension in the REGARDS cohort.
Patients were divided into 3 age cohorts and outcomes were assessed over a median 4-6 year period by telephone interview and subsequent medical record review for incident cardiovascular events, stroke, coronary heart disease (MI or CHD death) and all-cause mortality (adjusted for age, race, gender, region of residence, income, education, dyslipidemia, diabetes, current smoking, atrial fibrillation and diastolic blood pressure). 
Limitations acknowledged in the analysis were that only baseline BP measurements (2 measurements on a single occasion) were available, with potential misclassification of patients, and the relatively low number of stroke and CHD incidents in some sub-groups.  Importantly there are no data regarding blood pressure control during the years of follow-up.
Hazard ratios for incident CVD and CHD increased with increased levels of baseline blood pressure, and were significant for baseline systolic BP > 150 mm Hg for the different age groups (except for incident CVD in those less than 65 years), although confidence intervals were wide for some.
Interestingly there was not a significant increase in hazard ratio for stroke incidence with increased blood pressure at any age, and hazard ratio for all cause mortality was significant only for SBP > 150 mmHg in persons < 75 years old.  The authors concluded that the results of the REGARDS cohort study generate a hypothesis that for all patients >55 years the recommended level of SBP should be <140 mmHg with optimal values possibly between 120-139 mmHg.  This is a bold hypothesis from these data, although it does highlight our need for continuing research in this area.   
The 2013 European Guidelines for the Management of Arterial Hypertension(1) recommend a systolic BP treatment target between 150 and 140 mmHg in elderly patients less than age 80 (Class I, level of evidence A) although a target < 140 may be considered in the fit elderly (Class IIb, level C).  The recommendation for hypertensive patients older than 80 is for a target between 150 and 140 mmHg (Class I, level B).  Most of the current evidence for BP lowering in the elderly cited in the guidelines shows an improvement in CVD events and death for achieving SBP targets between 140 – 145 mHg. 
Only the sub-group analysis of elderly in the FEVER study showed a benefit for lowering SBP just below 140 compared to 145.(2)  The issue of blood pressure control in the elderly has often been contentious; decades ago we thought that isolated systolic hypertension in the elderly was expected and well tolerated.
The 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension also advocate a holistic approach to assessing and managing patients, including broad assessment of cardiovascular risk.  In another analysis of the REGARDS cohort, investigators found a significant reduction in stroke risk for patients (mean age 65) meeting more targets for a greater number of cardiovascular risk factors (the Lifestyle 7).(3) In the absence of definitive evidence regarding BP targets < 140 mmHg especially in the elderly, it is worth remembering that risk of cardiovascular disease events and death may be lowered through attention to all risk factors.  The analysis presented here adjusted for many, but not all risk factors in the Lifestyle 7 score.   
We can agree with the REGARDS investigators that large well-designed intervention trials in older patients are needed before we can set lower blood pressure targets than currently recommended in the guidelines.   Indeed, the 2013 European Guidelines for the Management of Arterial Hypertension(1) calls for research focusing on optimal BP targets to be achieved by treatment especially for elderly hypertensive patients.  Treatment of any patient needs to include a holistic assessment, attention to all cardiovascular risk factors, and for the elderly, assessment of frailty or fragility.

1. The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).  The 2013 ESH/ESC Guidelines for the Management of Arterial Hypertension. European Heart Journal. 2013; 34: 2159 – 2219.

2. Zhang Y, Zhang X, Liu L, Zanchetti A.  Is a systolic blood pressure target < 140 mmHg indicated in all hypertensives?  Subgroup analyses of findings from the randomised FEVER trial.  European Heart Journal. 2011; 32: 1500 – 1508.

3. Kulshreshtha A, Vaccarino V, Judd SE, Howard VJ, McClellan WM, Muntner P, Hong Y, Safford MM, Goyal A, Cushman M.  Life's Simple 7 and Risk of Incident Stroke: The Reasons for Geographic and Racial Differences in Stroke Study.  Stroke 2013;44:1909-1914. doi: 10.1161/STROKEAHA.111.000352




REGARDS: Optimal blood pressure levels in elderly persons in the reasons for geographic and racial differences in stroke (REGARDS) cohort study

The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.