Should elevated blood pressure be treated with antihypertensive drug therapy?

Hypertension is the most common modifiable risk factor for cardiovascular events and mortality in the world.1 The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) hypertension guidelines defined a normal blood pressure (BP) as a systolic BP less than 120 mm Hg and a diastolic BP less than 80 mm Hg.2 These hypertension guidelines defined elevated BP as a systolic BP between 120 and 129 mm Hg with a diastolic BP less than 80 mm Hg.2 The 2017 ACC/AHA hypertension guidelines recommended that elevated BP should be treated with lifestyle measures.2, 3 These hypertension guidelines also recommended treatment of elevated BP with antihypertensive drug therapy if the 10-year risk of atherosclerotic cardiovascular disease is 10% or higher.2 A secondary analysis of the Systolic Blood Pressure Intervention Trial (SPRINT)4 supports this recommendation. However, the 2018 European Society of Cardiology/European Society of Hypertension guidelines do not support treating a systolic BP between 120-129 mm Hg with a diastolic BP less than 80 mm Hg with antihypertensive drug therapy.5 Borazjani et al6 performed a secondary analysis of the data from the SPRINT trial7 to investigate whether antihypertensive drug treatment of patients with a high-normal BP to a normal level (systolic BP less than 120 mm Hg) would reduce cardiovascular events and mortality. Of the 9361 patients in SPRINT, 289 high-risk patients with elevated BP (mean atherosclerotic cardiovascular risk in 10 years 24.8% (10%-65%) without prior cardiovascular disease and not receiving antihypertensive drugs were randomized to a systolic BP less than 120 mm Hg or to a systolic BP less than 140 mm Hg. The primary composite outcome was myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes. At 3.06 years of follow-up, a primary outcome event in 361 persons occurred in 3 persons (0.74% per year) in those randomized to a systolic BP less than 120 mm Hg vs 8 persons (1.61% per year) in those randomized to a systolic BP less than 140 mm Hg (hazard ratio 0.19; p = .045). Serious adverse events were not significantly different between the 2 treatment groups. These results were based on a post hoc subgroup analysis of 289 patients from a clinical l trial of 9361 persons. A large clinical trial of high atherosclerotic cardiovascular disease risk patients with a systolic BP between 120 and 129 mm Hg and a diastolic BP less than 80 mm Hg despite lifestyle measures should be performed in which the participants are randomized to treatment with antihypertensive drug therapy to a systolic BP of less than 120 mm Hg vs a systolic blood pressure less than 140 mm Hg is indicated to conclude whether or not these persons should have their systolic BP reduced to less than 120 mm Hg. A study investigated the incidence and risk factors for progression from prehypertension to hypertension in a 12-year Korean cohort study.8 The study included 115 456 middle aged and elderly participants. During follow-up, 48 919 participants developed hypertension. The incidence of hypertension was 45.82 per 1000 person-years in men and 53.57 per 1000 person-years in women. In both men and women, progression to hypertension was predicted by an increased body mass index, family history of hypertension, history of diabetes mellitus, and older age. In men, progression to hypertension was associated with frequent drinking and high alanine aminotransferase levels. In women, progression to hypertension was associated with high hemoglobin levels and low household income.8 The 1999-2000 National Health and Nutrition Examination Survey included 3488 persons aged 20 years and older.9 The age-adjusted prevalence of prehypertension was 39% in men and 23.1% in women. Persons with prehypertension were 1.65 times more likely to have at least one other adverse cardiovascular risk factor than those with a normal BP.9 Numerous studies have demonstrated that elevated BP increases the incidence of cardiovascular events.10-18 A meta-analysis was performed of 61 prospective studies including 1 million adults with no previous cardiovascular disease with 12.7 million person-years at risk.10 Throughout middle and old age, usual BP was strongly and directly related to cardiovascular mortality and to all-cause mortality without any evidence of a threshold down to a BP of at least 115/75 mm Hg.10 A meta-analysis was performed of 1.25 million persons aged 30 years and older who had no previous cardiovascular disease.11 During 5.2 years median follow-up, for each age group (30 years, 60 years, and 80 years), the lowest risk for cardiovascular events occurred in persons with a systolic BP of 90-114 mm Hg and a diastolic BP of 60-74 mm Hg.11 A meta-analysis was performed of 18 studies in 934 106 persons without previous cardiovascular disease with a median follow-up of 8.8 years.12 Prehypertension was associated with a 36% (22%-53%) increased incidence of coronary heart disease which was increased only by 16% if the systolic BP was 120-129 mm Hg.12 A meta-analysis was performed of 29 sudies in 1 010 858 persons without previous cardiovascular disease.13 Compared to a systolic BP less than 120 mm Hg, a systolic BP of 120-129 mm Hg increased the incidence of total cariovascular disease by 24% (10%-39%), stroke by 35% (10%-66%), and myocardial infarction by 43% (10%-86%).13 A meta-analysis was performed of 18 prospective cohort studies of 468, 561 adults without previous cardiovascular disease.14 Prehypertension increased the risk of cardiovascular disease by 55% (41%-71%), coronary heart disease by 50% (30%-74%), and stroke by 71% (55%-89%). A systolic BP between 120 and 129 mm Hg increased the incidence of cardiovascular disease 46% (32%-62%).14 A meta-analysis was performed of 13 studies including 396 200 participants without previous cardiovascular disease with a follow-up of at least 5 years.15 Compared to a systolic BP less than 120 mm Hg, a systolic BP of 120-129 mm Hg increased the incidence of cardiovascular disease by 41% (25%-59%) and of cardiovascular mortality by 18%.15 A meta-analysis was performed of 47 cohort studies including 491, 666 participants without prior cardiovascular disease16 Compared to a systolic BP less than 120 mm Hg and a diastolic BP less than 80 mm Hg, a systolic BP of 120 to 129 mm Hg increased the risk of total cardiovascular disease by 42% (29%-55%), myocardial infarction by 43% (10%-86%), and stroke by 52% (27%-81%). The population-attributable risk for the association of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke with prehypertension (120-139 mm Hg) was 12.09%, 13.26%, 24.60%.15%, and 19.15%, respectively.16 A prospective study was performed in a Chinese rural cohort including 38 765 persons aged 35 years and older without prior cardiovascular disease.17 Median follow-up was 12.5 years. Prehypertension increased the incidence of major adverse cardiovascular events by 34% (19%-51%), cardiovascular mortality by 33% (11%-60%), and stroke by 42% (24%-64%) but did not reduce myocardial infarction.17 A prospective study was performed in 809 persons with prehypertension, mean age 48.5 years in which 409 persons were randomized to candesartan and 400 persons to placebo.18 During the first 2 years, those randomized to candesartan had a 66.3% reduction in the development of hypertension compared to those randomized to placebo. After 4 years, those randomized to candesartan had a 15.6% reduction in the development of hypertension compared to those randomized to placebo. In the placebo group, 63% of patients with prehypertension developed hypertension after 4 years.18 A prospective study was performed in 1008 persons with high-normal office BP who were randomized to treatment with ramipril or to a control group.19 Patients were followed up to 3 years. Hypertension developed in 30.7% in the ramipril group vs 42.9% in the control group (34.4% reduction by ramipril). However, the incidence of cardiovascular events and of cerebrovascular events was not reduced by ramipril.19 A prospective, double-blind, placebo-control trial was performed in 730 Brazilians with prehypertension aged 30-70 years who did not respond to 3 months of lifestyle intervention.20 The patients were randomized to a chlorthalidone/amiloride combination pill or to placebo for 18 months of treatment. The incidence of hypertension was reduced by 44% by chlorthalidone/amiloride from 19.5% to 11.7%.20 On the basis of the available data, persons with elevated BP should be treated with lifestyle measures.2, 3, 21 Weight loss is recommended to reduce BP in adults with elevated BP who are overweight or obese.2, 22 A heart-healthy diet such as the DASH (Dietary Approaches to Stop Hypertension) diet is recommended.2, 23 Sodium reduction is recommended.2, 24 Potassium supplementation, preferably by diet, is recommended unless the patient has chronic kidney disease or is taking drugs that reduce potassium excretion.2, 25 Increased physical activity is recommended.2, 26 Adult men and women with elevated BP should not drink more than 2 or 1 alcoholic drinks per day, respectively.2, 21 In conclusion, elevated BP increases cardiovascular and cerebrovascular events and should be treated with lifestyle measures. A large-scale, randomized trial in patients with elevated BP despite lifestyle measures needs to investigate whether antihypertensive therapy to reduce the systolic BP to less than 120 mm Hg vs less than 140 mm Hg will reduce cardiovascular and cerebrovascular events and mortality. Until we have such data, this author favors treatment of elevated BP with antihypertensive drug therapy to a systolic BP of less than 120 mm Hg if the 10-year risk of atherosclerotic cardiovascular disease is 10% or higher.2. The results reported by Borazjani et al6 from a secondary analysis of the data from the SPRINT trial7 support this recommendation. Dr. Aronow has no conflicts of interest to disclose.