Reducing blood pressure in people of different ages

Abstract

Absolute benefit increases with age and management of overall cardiovascular risk

In the accompanying paper, the Blood Pressure Lowering Treatment Trialists’ Collaboration (BPLTTC) compares the effects of different regimens for reducing blood pressure in different age groups.¹ The meta-analysis found that across 31 trials of more than 190 000 randomised patients, the reduction in blood pressure with various antihypertensive drugs was independent of the patients’ ages.

Previous large scale prospective observational studies and meta-regression analyses have highlighted the role of reducing blood pressure for preventing cardiovascular complications in patients with hypertension.^{2 3 4 5} The new BPLTTC analysis shows that the relative risk reduction of a cardiovascular event with tighter blood pressure control occurs irrespective of the patient’s age.¹

One potential limitation of the BPLTTC analysis is that the age difference between younger and older patients was only about 15 years, and that 65 years was the arbitrary cut off between younger and older patients. However, subsidiary analyses with age fitted as a continuous variable provided better statistical power and reassurance that moderate or large age related effects had not been missed.¹

The BPLTTC analysis provides strong support for the use of blood pressure lowering drugs in elderly patients with hypertension.¹ Because the absolute risk of cardiovascular events is higher in older patients than in younger ones, for a similar relative risk reduction in blood pressure, far fewer patient-years of treatment are needed to prevent one major cardiovascular event in an elderly person. This is especially true in the presence of additional risk factors, such as male sex or a history of previous cardiovascular complications.

In older patients (≥60 years) with isolated systolic hypertension (≥160 mm Hg), antihypertensives reduced systolic blood pressure on average by ~10 mm Hg compared with placebo.⁶ The number of patients needed to treat for five years to prevent one major cardiovascular complication was as low as 18 in men (38 in women), 19 at 70 years or more (39 at 60-69 years), and 16 in patients with previous cardiovascular complications (37 in patients without such a history).⁶

The recently published hypertension in the very elderly trial proved that lowering blood pressure in very old patients (≥80 years) with systolic hypertension (≥160 mm Hg) or diastolic hypertension (90-109 mm Hg) to below 150 mm Hg systolic pressure and 80 mm Hg diastolic pressure reduced the incidence of fatal and non-fatal stroke by 30%.⁷ Fatal stroke declined by 39% and all-cause mortality by 21%. These results dispelled the suspicion that the benefit of antihypertensives in the very elderly in terms of preventing stroke might come at the cost of higher mortality.^{7 8} To prevent one death, only 40 very elderly people had to be treated for two years.

An age oriented strategy in the choice of first line antihypertensive drugs is appealing because it translates certain physiological and pharmacological principles into clinical practice. Examples are the decrease in the activity of plasma renin with age or the age related increase in postsynaptic α adrenoceptor mediated and calcium influx dependent vasoconstriction.

The recently revised British guidelines propose the use of angiotensin converting enzyme inhibitors in people below 55 years and diuretics or calcium channel blockers in older people.⁹ The BPLTTC analysis did not specifically investigate whether the age related blood pressure lowering activity of angiotensin converting enzyme inhibitors or other inhibitors of the renin system differed from that of diuretics or calcium channel blockers.

In the antihypertensive and lipid lowering treatment to prevent heart attack trial,¹⁰ the mean follow-up systolic blood pressure was 2 mm Hg higher in the lisinopril group than in the chlorthalidone group for all participants, 4 mm Hg higher in black people, and 3 mm Hg higher in those 65 years or older. These findings suggest that ethnicity and age have differential effects on the blood pressure lowering efficacy of antihypertensive drugs and therefore support current guidelines.^{9 10 11}

The British and European guidelines emphasise overall cardiovascular risk rather than hypertension as an isolated risk factor.^{9 11} They favour a global approach, with the use of charts for stratifying risk based on additional risk factors, target organ damage, or associated conditions, such as diabetes mellitus or a history of cardiovascular or renal disease.^{9 11} This approach is justified on the basis that hypertension, hypercholesterolaemia, and smoking account for around 85% of the cardiovascular risk that can be modified. The Cholesterol Treatment Trialists Collaboration found that the proportional reduction (~20%) in major vascular events per mmol/l decrease in serum low density lipoprotein cholesterol was similar in people above and below 65 years, but as for blood pressure, the absolute benefit of lowering cholesterol increased with age.¹² Interventions targeted at multiple risk factors hold great potential for efficient prevention of cardiovascular complications.

The BPLTTC analysis strongly supports the early and aggressive management of hypertension, irrespective of age.¹ Clinicians should be aware that similar proportional reductions in risk across the age range translate into much higher absolute benefit in older patients than in younger ones,^{6 7} and that antihypertensive treatment should be embedded within the management of global cardiovascular risk.^{9 11} The BPLTTC analysis did not exclude the possibility that angiotensin converting enzyme inhibitors and other inhibitors of the renin system given as first line treatment in older people might be less efficacious than diuretics or calcium channel blockers.¹