Editor's Note: Commentary based on Delgado J, Masoli JAH, Bowman K, et al. Outcomes of treated hypertension at age 80 and older: cohort analysis of 79,376 individuals. J Am Geriatr Soc 2017;65:995-1003.

Background: Despite numerous randomized clinical trials of hypertension in older adults, outcomes according to on-treatment blood pressure levels have not been well-characterized in the very elderly in routine clinical practice.

Study Question: What is the relationship between on-treatment blood pressure and clinical outcomes among patients 80 years of age or older?

Funding: Supported in part by the National Institute for Health Research (NIHR), School for Public Health Research Ageing Well program, United Kingdom.

Methods

Study Design: Observational cohort study of 79,376 individuals.

Source Population: Primary care practices in England (Clinical Practice Research Datalink [CPRD]).

Study Population: All adults in CPRD 80 years of age or older with diagnosed hypertension and at least three blood measurements during a 3-year period who were prescribed at least one class of antihypertensive medication. All participants were free of dementia, cancer, coronary heart disease, stroke, heart failure, or end-stage renal failure at baseline.

Follow up was for a mean of 4.4 years (maximum follow-up 11.9 years).

Subjects were grouped into on-treatment blood pressure categories with 10 mmHg increments ranging from <125 mmHg to >185 mmHg. For all analyses 145-154 mmHg was defined as the reference range.

Outcomes: The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular events (myocardial infarction, stroke, heart failure) and fragility fractures.

Statistical analysis: Cox proportional hazards models were used to examine associations between blood pressure and mortality. For secondary outcomes, competing risk survival models were used with all-cause mortality included as a competing risk. The main analyses adjusted for multiple covariates, and sensitivity analyses were conducted to evaluate the potential effects of additional confounders.

Results: Mean age was 82.1 years with 69.5% women.

There was a U-shaped relationship between on-treatment blood pressure and mortality, whereby the lowest mortality rates were in patients with blood pressures ranging from 135-154 mmHg. All-cause mortality was higher among patients with blood pressure <135 mmHg (HR 1.25, 95% CI 1.19-1.31), which translated to one extra death for every 13 patients treated to a blood pressure of <135 mmHg (number needed to harm = 13). Adjustment for diastolic blood pressure and pulse pressure did not significantly impact these findings. Mortality outcomes in patients with on-treatment blood pressure >155 mmHg were generally similar to those with blood pressure <135 mmHg.

Risk of myocardial infarction increased progressively with increasing blood pressure, and risk of stroke was higher when the blood pressure was >155 mmHg. Risk of heart failure increased progressively with blood pressures >155 mmHg, but patients with blood pressure <125 mmHg were also at higher risk for incident heart failure. There was no association between blood pressure and fragility fractures; in particular, there was no evidence that lower blood pressure was associated with an increased risk of fractures.

Limitations: Because this is an observational study, there is potential for residual confounding. In particular, data on medications, frailty, and other geriatric syndromes were not included in this analysis. The influence of patient factors such as care preferences and clinical judgment on blood pressure management could also not be ascertained.

Conclusions: In this large population of patients 80 years of age or older with hypertension, on-treatment blood pressures <135 mmHg were associated with increased mortality. Conversely, patients with blood pressures >155 mmHg were at increased risk for death, myocardial infarction, stroke, and heart failure.

Perspective: Optimal blood pressure targets for very old adults with varying burdens of comorbidity remain controversial. The recently completed SPRINT (Systolic Blood Pressure Intervention Trial) randomized trial found that among patients 75 years of age or older, a more aggressive treatment strategy with a goal systolic blood pressure of <120 mmHg was associated with lower mortality and cardiovascular events than the conventional blood pressure target of <140 mmHg.^1,2 However, this was at the expense of an increased risk for electrolyte abnormalities, worsening renal function, hypotension, and syncope (though not injurious falls). In addition, SPRINT excluded patients with diabetes, prior stroke, active heart failure within 6 months, end-stage renal disease, or residence in a nursing home. Thus, the relevance of the SPRINT findings to a large proportion of older adults in routine clinical practice is uncertain. Although the study by Delgado et al. is not definitive due to its observational nature and potential for residual confounding, it does raise a cautionary note that when it comes to treating hypertension in patients 80 years of age or older, lower is not necessarily better, and even blood pressures less than 135 mmHg, which many clinicians consider satisfactory or even excellent, may actually be associated with harm. Clearly, additional studies are needed to clarify these issues and to foster an individualized approach based on each patient's risk profile and treatment goals.

References

1. SPRINT Research Group, Wright JT Jr, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-16.
2. Williamson JD, Supiano MA, Applegate WB, et al. Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial. JAMA 2016;315:2673-82.

Keywords: Geriatrics, Aged, Blood Pressure, Antihypertensive Agents, Proportional Hazards Models, Comorbidity, Accidental Falls, Hypertension, Blood Pressure Determination, Hypotension, Heart Failure, Stroke, Myocardial Infarction, Coronary Disease, Syncope, Diabetes Mellitus, Dementia, Kidney Failure, Chronic, Primary Health Care, Neoplasms, Electrolytes

< Back to Listings