Editor's Note: Please see the associated Expert Analysis, "The 2017 Hypertension Guidelines: Approaches to Mild Hypertension and Combination Therapy."

We appreciate the author's compliments on the content of our recent blood pressure (BP) guideline and are happy to explain our rationale for treatment recommendations in adults with stage 2 hypertension (systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg) as well as comment on our recommendations for combination drug therapy.¹

Throughout the guideline, we have endeavored to underscore the importance of environmental factors such as poor diet, insufficient physical activity and excessive alcohol consumption as a cause for high BP and management of these exposures as a core element of prevention and treatment of hypertension. In the section detailing treatment of adults with stage 2 hypertension who have no history of cardiovascular disease and a 10-year risk of atherosclerotic cardiovascular disease (ASCVD) <10%, our text states "for those for whom nonpharmacological therapy has been ineffective, antihypertensive drug treatment should be added in patients with an SBP ≥140 mm Hg or a DBP ≥90 mm Hg, even in adults who are at lower risk than those included in RCTs." The guideline writing committee was concerned that leaving systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg could result in cardiovascular disease complications in adults with a 10-year risk of ASCVD <10%, especially in younger adults who would be exposed to uncontrolled levels of BP over many years. Higher levels of BP are consistently associated with an increased risk of CVD across the entire spectrum of age,^2,3 even at an index age of 30 years,³ and the pattern for relative risk is similar across groups that differ in their level of absolute risk for CVD.² Randomized controlled trials have demonstrated that antihypertensive drug treatment results in a similar reduction in relative risk of CVD events across a wide spectrum of baseline absolute risk for CVD and low-dose diuretic therapy in adults with a baseline systolic BP between 120-139 mm Hg or diastolic BP between 80-89 mm Hg has led to a reduction in left ventricular mass.^4-7 In aggregate, these data led the writing committee to recommend antihypertensive drug therapy in adults with stage 2 hypertension who had no history of CVD and a 10-year risk of ASCVD <10%. This was deemed to be a "strong" recommendation that merited a class (strength) of recommendation (COR) of I, but it was recognized that the quality of the evidence was limited, resulting in a level (quality) of evidence (LOE) of C-LD.

We emphasized the primacy of BP lowering over specific choice of drugs, with two qualifications. Some adults with comorbid disease merit treatment with drugs from specific classes that concurrently lower BP. For example, treatment with a beta-blocker in adults with hypertension who have had a myocardial infarction or use of an angiotensin converting enzyme (ACE) inhibitor in adults with hypertension and stable ischemic heart disease. In addition, simultaneous use of an ACE inhibitor, angiotensin receptor blocker (ARB), and/or renin inhibitor is potentially harmful and was not recommended for treatment of adults with hypertension. We encouraged combination drug therapy, especially in adults with stage 2 hypertension and in black adults with hypertension. We recommended combination drug therapy, including fixed-dose combinations, with agents that are deemed to provide complementary effects. For example, diuretics may stimulate the renin-angiotensin-aldosterone system. Combining a diuretic with an ACE inhibitor or ARB which lower BP by inhibiting the renin-angiotensin-aldosterone system is logical and likely to result in greater BP lowering that one might expect from the BP lowering effects of each agent on its own. Likewise, the combination of a calcium channel blocker with an ACE inhibitor or ARB was deemed to be sensible. However, the writing committee as a whole was not convinced that the available randomized controlled trials that have compared different antihypertensive drug combinations provide compelling evidence for the superiority of a particular combination.^8,9 In adults with hypertension, we felt that the focus should be on choice of agents that provide logical combinations and, above all, reduction in BP to a SBP/DBP target of <130/80 mm Hg (SBP <130 mm Hg in older adults).

References

1. 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. J Am Coll Cardiol 2018;71:e127-248.
2. Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies. Lancet 2002;360:1903-13.
3. Rapsomaniki E, Timmis A, George J, et al. Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1.25 million people. Lancet 2014;383:1899-911.
4. Blood Pressure Lowering Treatment Trialists' Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014;384:591-8.
5. van Dieren S, Kengne AP, Chalmers J, et al. Effects of blood pressure lowering on cardiovascular outcomes in different cardiovascular risk groups among participants with type 2 diabetes. Diabetes Res Clin Pract 2012;98:83-90.
6. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 3. Effects in patients at different levels of cardiovascular risk—overview and meta-analysis of randomized trials. J Hypertens 2014;32:2305-14.
7. Fuchs SC, Poli-de-Figueiredo CE, Figueiredo Neto JA, et al. Effectiveness of chlorthalidone plus amiloride for the prevention of hypertension: the PREVER-Prevention Randomized Clinical Trial. J Am Heart Assoc 2016;5.
8. Dahlof B, Sever PS, Poulter NS, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding Bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicenter randomized controlled trail. Lancet 2005;366:895-906.
9. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2009;359:2417-28.

Keywords: Adrenergic beta-Antagonists, Angioedema, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Blood Pressure, Blood Pressure Determination, Calcium Channel Blockers, Calcium Channels, Coronary Artery Disease, Diabetes Mellitus, Exercise, Goals, Drug Therapy, Combination, Cholesterol, Health Personnel, Hypertension, Hypertension, Pulmonary, Hypotension, Life Style, Myocardial Infarction, Myocardial Ischemia, Peptidyl-Dipeptidase A, Risk, Risk Factors, Syncope, Primary Prevention, Secondary Prevention

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