Older adults with low blood pressure, particularly those who are moderately or severely frail, may have increased all-cause mortality, UK researchers have found. The results of a large data analysis suggest that international blood pressure guidelines may have to be reviewed.
However, the implication of the findings remains an open question, as experts do not agree on the significance or meaning of the associations.
Guidelines Need Updates
Dr Jane Masoli, a geriatrician and PhD student at the University of Exeter, and colleagues looked at data on more than 415,000 individuals aged 75 years or over, stratifying them by degree of frailty.
They found the expected increased risk of cardiovascular incidents with increasing blood pressure. However the research, published by the journal Age and Ageing on March 5th, indicated that individuals aged over 85 years, and those between 75 and 84 with moderate to severe frailty, had a lower all-cause mortality risk if their systolic blood pressure (SBP) was ≥150 mmHg.
"Internationally, guidelines are moving towards tight blood pressure targets, but our findings indicate that this may not be appropriate in frail older adults," Dr Masoli said in a news release.
"We need more research to ascertain whether aggressive blood pressure control is safe in older adults, and then for which patient groups there may be benefit, so we can move towards more personalised blood pressure management in older adults."
She added: "We know that treating blood pressure helps to prevent strokes and heart attacks and we would not advise anyone to stop taking their medications unless guided by their doctor."
Confirming Concerns
Jeremy Pearson, PhD, associate medical director at the British Heart Foundation, who was not involved in the research, told Medscape News UK that the study "confirms that high blood pressure in old age increases your risk of heart attack, heart failure and stroke".
He added: "Previous research has shown that taking steps to lower your blood pressure in old age can also reduce your risk of heart and circulatory diseases." He emphasised that patients should continue their blood pressure lowering medications "unless your doctor says otherwise".
However, Kazem Rahimi, associate professor of cardiovascular medicine at the University of Oxford, questioned the conclusions reached by the researchers and said in a statement that the study is "problematic from several points of view".
Study Details
While hypertension is the commonest chronic disease in older adults, with a prevalence of more than 75% in people aged over 80 years, the team notes that an individual’s prognosis for a given blood pressure remains unclear.
Trials targeting blood pressure in older adults have reached conflicting conclusions, with the result that blood pressure limits for older adults in international guidelines range from ≤130/80 mmHg to ≤150/90 mmHg. Moreover, few trials have included frail older adultsTo gain a better understanding of the associations between baseline blood pressure, all-cause mortality and cardiovascular outcomes, the researchers gathered data from the UK clinical practice research datalink.
For the period 2000 to 2014, they identified individuals aged 75 years or over who had undergone at least three blood pressure measures in the previous 3 years, stratifying them by baseline score on the electronic frailty index.
In all, 415,980 adults with an average age of 79.5 years and up to 10 years of follow-up were included. Of those, 62.5% were deemed non-frail, 33.1% had mild frailty, 4.1% moderate frailty, and 0.2% severe frailty.
A hypertension diagnosis at baseline was found in 55.1% of non-frail individuals, rising to 65.8% in those with mild frailty, 71.5% in people with moderate frailty, and 75.6% in those categorised as severely frail.
Increasing age was found to have a greater effect on all-cause mortality than increasing frailty, the team reports, at a hazard ratio with increasing SBP of 3.01 versus 1.55 for frailty.
However, high SBP, even ≥180 mmHg, was not associated with an increased mortality risk in adults aged over 85 years or those with severe frailty, and there was even evidence of a lower risk with increasing SBP.
For example, compared with an SBP of 130–139 mmHg, adults aged 75–84 years with an SBP of 150–159 mmHg who were non-frail had a hazard ratio for all-cause mortality of 0.94, which fell to 0.84 if they had moderate or severe frailty.
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However risks of cardiovascular outcomes increased with SBPs >150mmHg across all categories of frailty.
Practice Implications
The team writes that: "the data presented confirm trial evidence from younger groups that SBPs >150 mmHg increase the risk of cardiovascular outcomes.
"However, the data also suggest that BP-attributable cardiovascular outcomes have limited impact on overall mortality in frail older people of 75–84 and all above 85 years.
"This may be due to complexities of co-existing morbidity." For example, they have previously shown that in adults above 70 years chronic kidney disease is more strongly predictive of mortality than BP.
The researchers say: "Our findings, therefore, imply that management of non-cardiovascular morbidities may be relatively more important for many older frail patients."
Prof Rahimi said "the key issue" with the study is that, "by design, the investigators included all patients irrespective of their health status at baseline".
"This all-comer design in an observational study is highly prone to bias and limits the interpretation of the results to a simple association.
"Therefore, I do not see how this study could challenge the international guideline recommendations that are largely based on unbiased evidence from randomised clinical trials."
He added that, the authors "are right in pointing out that randomised evidence in frail elderly people is limited, but unfortunately this paper does not provide any novel or compelling answers to this question".
Calling for more research into the area, Prof Rahimi continued: "I do not see how the findings from this study could lead to the conclusion that more personalised blood pressure management is needed.
"In my view, we should be very careful with such statements as they could lead to unwarranted variation in practice or low adherence rates against guideline recommendations."
However, Peter Sever, professor of clinical pharmacology & therapeutics, Imperial College London, questioned the value of evidence from randomised trials when applied to the overall population."
He was one of several experts to comment via the Science Media Centre. he continued: "Whilst clinical trials remain the gold standard for evaluating the effects of treatment in various patient groups, the results of these trials should be viewed with caution when extrapolating to patients unrepresentative of those recruited into the trials," he said.
"Based on the Masoli paper, the take home message for practitioners is that the biological age of the patient, incorporating his or her general and cardiovascular health, should determine whether or not tighter blood pressure control should be attempted."
Prof Sever added: "For the frail, including those with previous stroke, coronary heart disease or dementia, higher blood pressures may be more acceptable and, in all patients, careful evaluation of drug use and potential side effects should be undertaken."
For Prof David Paterson, president-elect of The Physiological Society and professor of physiology, University of Oxford, the study makes "an important association between blood pressure and mortality in frail elderly adults, and challenges the accepted dogma of what is ‘normal’ when treating blood pressure".
"If a cause-and-effect relationship is established between poor cardiovascular outcomes and what is currently considered normal blood pressure in this population, then guidelines will need to be re-thought."
Prof Paterson also called for basic research to establish whether autoregulation of blood flow to essential organs like the heart, brain and kidney is shifted in the elderly, since the body has a built in control system to keep blood flow constant to these areas over a range of perfusion pressures.
"Low blood pressure is as dangerous as high pressure, and it is becoming clear that what is normal may be age-dependent."
The study was funded by the National Institute for Health Research.
No conflicts of interest declared.
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