Author + information
- aASH Comprehensive Hypertension Center, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois
- bDivision of Cardiovascular Diseases, Mayo Clinic, Rochester, Minnesota
- ↵∗Address for correspondence:
Dr. George Bakris, ASH Comprehensive Hypertension Center, Department of Medicine, The University of Chicago Medicine, 5841 South Maryland Avenue, MC 1027, Chicago, Illinois 60637.
Approximately 70% of women and 65% of men above age 65 years have hypertension (1). Individuals age >65 years are also more likely to have isolated systolic hypertension and to have higher cardiovascular risk. Several randomized trials provide evidence of benefit from blood pressure (BP)–lowering treatment in older patients, including individuals over age 80 years with predominant isolated systolic hypertension (2–6).
In the SHEP (Systolic Hypertension in the Elderly Program), hypertensive patients, mean age of 72 years, were randomized to chlorthalidone or placebo and attained a mean BP of 143/68 mm Hg. This resulted in a lower incidence of cardiovascular events across all age subgroups (2). In very old individuals (above age 80 years) with moderate to severe hypertension, HYVET (Hypertension in the Very Elderly Trial) showed that reducing BP below 150/80 mm Hg with a low-dose thiazide diuretic agent with or without an ACE inhibitor reduced all-cause mortality and especially heart failure risk (3).
There is an important distinction, however, between outcome trial designs that treat to target versus treating to an achieved BP. A recent meta-analysis of 123 randomized trials of antihypertensive therapy demonstrated that a lower achieved systolic BP is associated with better cardiovascular outcomes across all age groups, regardless of the initial systolic BP (6).
Only 4 trials have randomized BP to different target goals in older individuals, and the results are inconsistent. The VALISH (Valsartan in Elderly Isolated Systolic Hypertension) study and JATOS (Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients) (7,8) were prospective randomized, open-label, intermediate-risk trials with blinded endpoints. Both trials failed to show a benefit of a systolic BP target below 140 mm Hg compared with SBP targets below 150 and 160 mm Hg, respectively. Both trials reported a >20 mm Hg SBP reduction in treatment groups and low event rates.
Target BP in hypertensive subjects over age 75 years was robustly examined in SPRINT (Systolic Pressure Intervention Trial) (9). Among approximately 2,600 nondiabetic patients with hypertension, one-third of whom were classified as frail, systolic BP reduction to a target of <120 mm Hg (mean achieved systolic BP of 123.4 mm Hg) resulted in lower rates of the primary cardiovascular endpoint and all-cause mortality, even in frail individuals. Most of the individuals enrolled in the SPRINT trial had controlled hypertension at baseline and maintained a diastolic BP above 60 mm Hg. This suggests that the SPRINT cohort had less stiff arteries than some people and were capable of tolerating lower BPs. However, these results raise the concern that the benefits of BP lowering in older individuals are underestimated and that with the addition of ∼1 antihypertensive medication, a meaningful and well-tolerated reduction of BP can be achieved.
In this issue of the Journal, Bavishi et al. (10) performed a systematic-review and a random-effects meta-analysis of the 4 currently available trials with treat-to-target designs involving 10,857 older hypertensive patients with a mean follow-up of 3.1 years. Three of the 4 studies included Japanese and Chinese elderly hypertensive patients with achieved BP in the intensive systolic BP groups of ∼135 mm Hg. Coincidently, this is approximately the BP achieved in the standard BP arm of the SPRINT study. Intensive BP control (systolic BP <140 mm Hg) decreased major adverse cardiovascular events, including cardiovascular mortality and heart failure, without a significant difference in the incidence of serious adverse events but with higher rates of renal failure when analyses with a fixed-effects model were performed.
The results of this meta-analysis are mainly driven by the SPRINT trial results that reported higher cardiovascular event rates than the other 3 included studies. The results are subject to limitations inherent to any meta-analysis on the basis of pooling of data from different trials with different inclusion criteria, different designs, variable follow-up duration with differing attrition rates, different patient populations, and different methods for measuring BP. Moreover, given the lack of patient-level data from each trial, the results are not adjusted for adherence to assigned therapy. Finally, the antihypertensive regimens and dosages used in individual studies were different and may have differential effects on outcomes and safety measures.
The principal question remains, however, whether the results of SPRINT can be extrapolated to a broader older hypertensive population. The second but equally important question is whether the results of SPRINT and the current meta-analysis are applicable to patients with isolated systolic hypertension who constitute at least two-thirds of the elderly hypertensive patients (11). In a recent analysis of data from NHANES (National Health and Nutrition Examination Survey), 34.6% of individuals age ≥75 years met the SPRINT eligibility criteria (12). However, sex- and ethnicity-related disparities exist with fewer patients of African descent and fewer females meeting the study eligibility criteria. Last, a critically important difference among the studies is the method by which BP was measured. The SPRINT trial differs from all other trials in older people in that BP measurements were performed using an automated office BP device after 5 min of rest. These values are 5 to 10 mm Hg lower than achieved in routine office readings (13). Therefore, treating all older hypertensive patients to a systolic BP target of <120 mm Hg using non-SPRINT methodology is equal to a BP between 110 and 115 mm Hg by SPRINT methods. This may not be beneficial and could actually be harmful.
Older people constitute a heterogeneous population. Frail patients are under-represented in trials, and the participation of “healthier” less representative elderly individuals may lead to a discrepancy between “recommended evidenced-based” and “optimal individualized” approaches. However, this subset in SPRINT did very well at lower BP values (9). Moreover, a previous report from NHANES notes that systolic and diastolic BPs were not associated with mortality in frail adults (14).
In closing, we support lower pressures in older people who can tolerate them; however, we emphasize 1 of the authors’ conclusions from this meta-analysis: “Data on adverse events were limited but suggested an increased risk of renal failure. When considering more intensive BP control in the elderly, clinicians should carefully balance benefits against potential risks” (10).
↵∗ Editorials published in the Journal of the American College of Cardiology reflect the views of the authors and do not necessarily represent the views of JACC or the American College of Cardiology.
Both authors have reported that they have no relationships relevant to the contents of this paper to disclose. P.K. Shah, MD, served as Guest Editor-in-Chief for this paper.
- American College of Cardiology Foundation
- Bavishi C.,
- Bangalore S.,
- Messerli F.H.
- Bress A.P.,
- Tanner R.M.,
- Hess R.,
- Colantonio L.D.,
- Shimbo D.,
- Muntner P.
- Bakris G.L.