By Michael Crawford, MD

Professor of Medicine, Associate Chief for Education, Division of Cardiology, University of California, San Francisco

Dr. Crawford reports no financial relationships relevant to this field of study.

SYNOPSIS: The authors of a large population study found that reducing blood pressure to < 140/90 mmHg is associated with increased mortality, and mortality was highest in those with previous cardiovascular events and age > 80 years.

SOURCES: Douros A, Tölle M, Ebert N, et al. Control of blood pressure and risk of mortality in a cohort of older adults: The Berlin Initiative Study. Eur Heart J 2019;40:2021-2028.

Ewen S, Mahfoud F, Böhm M. Blood pressure targets in the elderly: Many guidelines, much confusion. Eur Heart J 2019;40:2019-2031.

Optimal blood pressure (BP) in elderly hypertensive patients is controversial, partly because there are few randomized trials that have included subjects 75 years of age or older. Investigators from the Berlin Initiative Study (BIS), an ongoing prospective, observational study of eligible Berlin residents ≥ 70 years of age, tested the hypothesis that BP values < 140/90 mmHg during treatment of hypertension would reduce all-cause mortality. Since the focus of the BIS was renal function, those with a kidney transplant or on dialysis were excluded. Douros et al investigated a subgroup treated for hypertension from 2009 until 2011 and followed through 2016. BP values were the mean of two office measurements within 10 minutes after patients were seated quietly for five minutes. Among 2,069 BIS subjects, 79% were treated for hypertension at baseline. Of these, 39% registered BP values < 140/90 mmHg, and 61% registered higher pressures. Antihypertensive treatment consisted of diuretics in 60% of subjects, beta-blockers in 59%, ACE inhibitors in 50%, calcium antagonists in 34%, and ARBs in 30%. Combination therapy was noted in 69%.

After a median follow-up of 73 months, all-cause mortality was highest in the normalized BP group (lower than 140/90 mmHg): 60 vs. 49 per 1,000 person years; adjusted hazard ratio (HR), 1.26; 95% confidence interval (CI), 1.04-1.54. A subgroup analysis showed that the mortality risk was highest in the normalized BP group, particularly for those patients with previous cardiovascular events vs. those without (98 vs. 64 per 1,000 person years; HR, 1.61; 95% CI, 1.14-2.27) and in those > 80 years of age (102 vs. 78 per 1,000 person years; HR, 1.40; 95% CI, 1.12-1.74). Using a BP cutoff of < 150 in the octogenarians attenuated the risk (HR, 1.21). Also, if normalized BP was changed to < 130, mortality risk increased further (HR, 1.42), which was statistically significant at all values < 125.

The authors concluded that reducing BP to lower than 140/90 mmHg in elderly patients or in those with previous cardiovascular (CV) disease is associated with increased mortality.

COMMENTARY

The SPRINT-Senior, the VALISH, and JATOS randomized, controlled trials of BP-lowering in elderly patients with hypertension all demonstrated the superiority of lower than 120 mmHg compared to < 140 mmHg.1-3 However, the generalizability of the studies has been questioned due to their strict inclusion criteria. For example, SPRINT excluded patients with prior stroke, heart failure, diabetes, and dementia. It has been estimated that only about one-third of elderly Americans would qualify for the SPRINT trial. Also, these randomized, controlled trials included a relatively short follow-up period; SPRINT was three years.

In contrast, the BIS study was large, there were few exclusion criteria, and the median follow-up was six years. Also, in addition to adjusting for comorbidities, BIS was adjusted for terminal decline using a one-year lag. Of course, it was an observational study, and there could have been unmeasured confounders that affected the results. For example, other than prior myocardial infarction, Douros et al did not include specific data on coronary artery disease, nor did they include cause of death information. Perhaps the biggest weakness was that BP was only measured at intake into the study.

Nevertheless, the results of the BIS study are in line with other observational studies from the United Kingdom and China with shorter follow-up periods, as well as the older HYVET study, which showed that a target of < 150 mmHg was superior to < 160 mmHg after a short follow-up of 1.8 years.4 The main findings from the BIS study were that the 26% increase in the risk of all-cause mortality with BP < 140 mmHg was mainly driven by the BP < 130 mmHg subgroup, in addition to the increased risk in those age > 80 years and the 61% increase in those with known CV disease. There seems to be some equipoise in the 70- to 79-year-old group, where the < 140 mmHg target was neutral regarding mortality. When these nuances are considered, it may be reasonable to conclude that a BP target of < 140 mmHg is acceptable for those age 60 to 80 years. This would be in line with the recent European Society of Cardiology (ESC) guidelines (2018) but not the American Heart Association/American College of Cardiology (AHA/ACC) guidelines (2017).5,6 In those older than 80 years of age, the ESC moves to less than 160 mmHg, while the AHA/ACC stays at lower than 130 mmHg.

The real issue is discovering the driving pressure needed for optimal organ perfusion in the elderly. This probably depends on the individual. Ideally, one would consider the patient’s biological age, comorbidities, and fitness to decide on what should be the optimal BP target. In those with clear vascular disease, higher thresholds for treatment makes sense, whereas healthy, fit elderly individuals may benefit from a lower target. Also, it is recommended that the introduction of antihypertensive medications and their uptitration should be handled more cautiously in the elderly, with particular attention paid to frailty. Frail individuals are going to be more prone to hypotension, syncope, and falls. Thus, in patients > 60 years of age, antihypertensive therapy should be more individualized rather than following strict BP targets.

REFERENCES

  1. 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;315:2673-2682.
  2. Ogihara T, Saruta T, Rakugi H, et al. Target blood pressure for treatment of isolated systolic hypertension in the elderly: Valsartan in elderly isolated systolic hypertension study. Hypertension 2010;56:196-202.
  3. JATOS Study Group. The Japanese Trial to Assess Optimal Systolic Blood Pressure in Elderly Hypertensive Patients (JATOS): Protocol, patient characteristics, and blood pressure during the first 12 months. Hypertens Res 2005;28:513-520.
  4. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-1898.
  5. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021-3104.
  6. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: A report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017. https://doi.org/10.1161/HYP.0000000000000065.