Editor's Note: Dr. Cushman was a member of the Panel Appointed to the Eighth Joint National Committee (JNC 8) and a co-author of their 2014 report, but this article reflects his opinion and should not be interpreted as necessarily reflecting the opinion of the entire committee.

Starting more than a decade ago, most guidelines for treating hypertension (HTN) recommended blood pressure (BP) goals of <140/90 mm Hg in most adults, and <130/80 mm Hg for adults with diabetes mellitus (DM) or chronic kidney disease (CKD), the latter usually referring to patients with estimated glomerular filtration rates (eGFR) <60 ml/min/1.73 m.² The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) was perhaps most influential in solidifying these recommended goals.¹ However, in the past several years there has been a movement away from these recommended BP goals in some guidelines for some population groups. What is the basis for this change in some recommended goals, and is it appropriate?

In the past, the members of HTN guideline committees were usually quite familiar with the evidence in the medical literature. However, many recommendations in these guidelines were based on the expert opinions of the committee members. These were often heavily influenced by epidemiologic data and the expectation that lower BP levels would lead to reduction in cardiovascular disease (CVD), including stroke, myocardial infarction (MI), heart failure (HF), and CVD death, and renal outcomes. Additionally, they anticipated that a lower recommended goal than randomized controlled trial (RCT) evidence supported would lead to lowering BP to a lower level than was often achieved in practice. However, the relationship of untreated BP levels with CVD and renal outcomes may be quite different than that of treated BP levels.² Therefore, guideline development is becoming more evidence-based by applying more of the principles outlined in the Institute of Medicine Report, "Clinical Practice Guidelines We Can Trust." This evidence-based approach was aspired to in the new "2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8)".³ Many HTN guidelines are now focusing more on the evidence from high quality RCTs and should differentiate between recommendations based on high-quality evidence and those based on expert opinion, where RCT evidence is either lacking or inconclusive.

For systolic BP (SBP) goals, the major 2013-2014 guidelines recommend <140 mm Hg for most adults, but <150 mm Hg either for adults ≥60 years of age (2014 HTN Guideline from the JNC 8 Panel³), ≥65 years of age (2013 European Guidelines⁴), or ≥80 years of age (2013 Canadian Guidelines⁵ and 2013 American Society of Hypertension/International Society of Hypertension Guidelines⁶). The <150 mm Hg goal is based on several trials with SBP goals of <150 or approximately that in patients ≥60 (SHEP, Syst-Eur, HYVET, UKPDS, Syst-China) or ≥80 (HYVET), and two trials showing no benefit in older patients for SBP goal <140 mm Hg (JATOS and VALISH). There are no definitive trials showing benefit for SBP <140 mm Hg at any age, but it was recommended in most guidelines for patients <60-65 (or 80) years of age and for patients with DM or CKD because of achieved SBP levels in many diastolic BP (DBP) HTN trials or control group SBP goals or achieved levels in several DM and CKD trials. In DM, there is only one CVD outcome trial (ACCORD BP)⁷ that tested a SBP goal lower than 150 mm Hg (<120 mm Hg), and, although stroke was significantly reduced, the primary CVD endpoint was not reduced, and stroke was infrequent and one of eight secondary CVD outcomes, and therefore not felt to be conclusive to recommend this SBP goal by all recent guidelines. In patients with recent lacunar strokes, the SPS3 trial did not show reduction in the primary outcome of recurrent stroke. Guidelines that recommend a SBP goal <150 mm Hg for older individuals do not recommend necessarily "backing off" of therapy if SBP is <140 mm Hg if such a patient is already taking a relatively simple well-tolerated regimen.

For DBP goals, there is an abundance of evidence for 90 mm Hg (e.g., VA Morbidity Trial, HDFP, and MRC Trials). The Hypertension Optimal Treatment (HOT) Trial, the only trial testing lower DBP goals in a general HTN population, did not show CVD benefits for DBP goals of <85 or <80 mm Hg vs <90 mm Hg. Therefore, "grade A" evidence supports a DBP goal <90 mm Hg in most HTN patients. For CKD, none of the lower goal trials (essentially equivalent to <130/80 mm Hg) showed benefit for the primary renal outcomes in those trials.⁸ Many of the DBP goal <90 mm Hg trials included patients with DM, but the HOT trial (DBP goal <80 mm Hg arm) and the UKPDS (BP goal <150/85 mm Hg) also showed CVD benefits. The mean achieved DBP in these two trials was 81-82 mm Hg, more consistent with a DBP goal of <85-90 mm Hg. Although several recent guidelines have recommended a DBP goal <80 mm Hg (Canadian, ADA) or <85 mm Hg (European) in DM, based on the HOT and UKPDS trials, the JNC 8 panel considered the HOT (apparent retrospective 8% subgroup analysis) and UKPDS (had combined SBP and DBP goals, with much higher comparison goals) results as insufficient evidence for a recommendation lower than <90 mm Hg. Perhaps any of these three levels (<80, <85, or <90 mm Hg) are appropriate DBP goals in DM, but most patients will have a DBP <80-85 mm Hg when SBP is reduced to <140 mm Hg, as recommended by most guidelines now. I have recently recommended a BP goal <140/85 mm Hg in HTN patients with DM.⁸

Since observational studies suggest that a lower BP is associated with a lower risk for CVD, why should guidelines not recommend lower BP levels than those confirmed by RCTs? First, lowering of BP with drugs might not reduce risk to the level of people with lifelong lower BP. Second, a much larger proportion of adults would be classified as having HTN and would presumably need drug therapy that may not be beneficial. Third, patients already being treated with drugs for HTN defined as ≥140/90 mm Hg would need even more drugs, visits, and monitoring to achieve a lower BP goal. Fourth, if BP is lower with treatment than proven goals in RCTs, CVD events might even increase (the "J-curve effect"). Finally, the addition of potentially unnecessary drugs wastes patients', physicians', and payers' resources and time, and might contribute to reduced adherence to evidence-based drug treatments, including antihypertensives,statins and aspirin.

We have entered a new era of more evidence-based guidelines. Although recommendations, such as those from the JNC panel, are perceived as simpler than older guidelines, this simplicity is actually a product of interpretation of the evidence from RCTs. An even simpler recommendation for BP goals would have been <140/90 mm Hg, or even <150/90 mm Hg, for all adults with HTN, but this was not believed to be consistent with all the evidence available today.

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References

1. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA. 2003;289:2560-71.
2. Kovesdy CP, Bleyer AJ, Molnar MZ, Ma JZ, Sim JJ, Cushman WC, et al. Blood pressure and mortality in U.S. veterans with chronic kidney disease. A cohort study. Ann Intern Med. 2013;159:233-42.
3. Institute of Medicine. Clinical Practice Guidelines We Can Trust.Washington, DC: National Academies Press; 2011. http://www.iom.edu/Reports/2011/Clinical-Practice-Guidelines-We-Can-Trust.aspx. Accessed December 26, 2013.
4. Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the Task Force for the Management of Arterial Hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). Eur Heart J. 2013;34:2159-2219.
5. Hypertension without compelling indications: 2013 CHEP recommendations. Hypertension Canada website. http://www.hypertension.ca/hypertension-without-compelling-indications. Accessed December 26, 2013.
6. Weber MA, Schiffrin EL, White WB. Clinical Practice Guidelines for the Management of Hypertension in the Community: A Statement by the American Society of Hypertension and the International Society of Hypertension. J Clin Hypertens (Greenwich) 2013; [Epub ahead of print].
7. ACCORD Study Group, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, Simons-Morton DG, Basile JN, Corson MA, Probstfield JL, Katz L, Peterson KA, Friedewald WT, Buse JB, Bigger JT, Gerstein HC, Ismail-Beigi F. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575-85.
8. Upadhyay A, Earley A, Haynes SM, Uhlig K. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154:541-8.
9. Ferrannini E, Cushman WC. Diabetes and hypertension: the bad companions. Lancet. 2012;380:601-10.

Keywords: Blood Pressure, Diabetes Mellitus, Blood Pressure Determination, Glomerular Filtration Rate, Hypertension, Renal Insufficiency, Chronic

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