Hypertension affects approximately 46% individuals nationwide and is the most common reason for pharmacologic therapy in the United States.^1,2 Additionally, hypertension is one of the most powerful contributors to cardiovascular disease (CVD) and accounts for more CVD deaths than any other modifiable risk factor.^3-5 Though updated American College of Cardiology/American Heart Association (ACC/AHA) hypertension guidelines were recently published in 2017, the diagnosis and treatment of hypertension remains central to clinical practice.

Similar to prior guidelines, the current ACC/AHA guidelines define a normal blood pressure of ≤120/80. However, different from the Seventh Report of the Joint National Committee (JNC7) is the definition of stage 1 and stage 2 hypertension; moreover, the threshold to treat is lower with stage 1 hypertension now defined as systolic blood pressure (SBP) of 130-139 or a diastolic blood pressure (DBP) of 80-89 mmHg and stage 2 hypertension correlating to the previous JNC7 report definition of stage 1 hypertension.⁵ Thus, with evolving guidelines and now a lower recommended threshold to treat hypertension that will affect millions of patients nationwide, an important question arises of how low to treat blood pressure in a cost-effective manner.

Though there is no doubt that controlling blood pressure results in a reduction of CVD events, the debate over SBP treatment target largely centers on the J-curve phenomenon of CVD outcomes described in the literature.^6-9 This phenomenon is based on observational studies with the possible explanations being that too low of a diastolic blood pressure does not perfuse critical organs or that perfusion pressure too low in plaque-laden vessels.¹⁰

The Systolic Blood Pressure Intervention Trial (SPRINT) published in 2015 was a landmark trial that examined whether intensive blood pressure control (<120 mmHg) is superior to routine management with a target of <140 mmHg in patients without diabetes and an increased risk of CVD. The trial was terminated early due to a 25% reduction in the primary outcome of myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or CVD death and a 27% reduction in total mortality.¹¹

In contrast, the Heart Outcomes Prevention Evaluation-3 Trial (HOPE-3) noted no benefit for aggressive blood pressure treatment among patients with a mean baseline SBP of 138 who were intermediate risk for coronary artery disease. The investigators found that only those patients with an SBP >140 had a reduction in atherosclerotic cardiovascular disease (ASCVD) risk.¹² Thus, while SPRINT supports intensive BP control in high risk patients, HOPE-3 suggests that less stringent BP targets may be suitable for intermediate risk patients. On the other hand, the average amount of SBP lowering in HOPE-3 was much more modest than in SPRINT (6 mmHg vs. 13 mHg).

In this context, there has been an emerging body of literature evaluating the use of "net benefit targeted therapy" for the treatment of hypertension, dyslipidemia, and diabetes mellitus. Such net benefit-driven therapy has been deemed the natural evolution of CVD prevention guidelines instead of "treatment targeted therapy" due to increased cost-effectiveness and less adverse events.¹⁵ More specifically, the use of ASCVD risk to guide blood pressure targets leads to a progressively greater absolute risk reduction in lowering blood pressure as baseline risk increases.¹³

McEvoy and colleagues specifically assessed if coronary artery calcium scoring (CAC) is useful in risk assessment for determining BP goals and found that in persons with SBP <160, CAC stratified risk for events and the estimated NNT for SBP goal of 120 mmHg varied substantially according to CAC levels when ASCVD risk was <15% and SBP was <160 mmHg.¹⁴ Thus, assessment of CAC may inform more personalized BP goals specifically among persons who are intermediate risk and have a BP ranging from 120-140 mmHg.

In conclusion, there remains controversy surrounding optimal blood pressure targets despite recent publication and endorsement by the ACC/AHA for stricter blood pressure control and overall lower blood pressure targets. Similar to the management of dyslipidemia, the future is a risk based assessment for determination of blood pressure targets and subsequent pharmacologic therapy.

References

1. Egan BM, Zhao Y, Axon RN. US trends in prevalence, awareness, treatment, and control of hypertension, 1988-2008. JAMA 2010;303:2043-50.
2. Muntner P, Carey RM, Gidding S, et al. Potential U.S. population impact of the 2017 ACC/AHA high blood pressure guideline. J Am Coll Cardiol 2018;71:109-18.
3. Padwal R, Straus SE, McAlister FA. Evidence based management of hypertension. Cardiovascular risk factors and their effects on the decision to treat hypertension: evidence based review. BMJ 2001;322:977-80.
4. Kannel WB. Blood pressure as a cardiovascular risk factor: prevention and treatment. JAMA 1996;275:1571-6.
5. 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 2017. [Epub ahead of print]
6. Hong KN, Fuster V, Rosenson RS, Rosendorff C, Bhatt DL. How low to go with glucose, cholesterol, and blood pressure in primary prevention of CVD. J Am Coll Cardiol 2017;70:2171-85.
7. Vidal-Petiot E, Ford I, Greenlaw N, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet 2016;388:2141-52.
8. Bhatt DL. Troponin and the J-curve of diastolic blood pressure: when lower is not better. J Am Coll Cardiol 2016;68:1723-6.
9. Bohm M, Schumacher H, Teo KK, et al. Achieved blood pressure and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials. Lancet 2017;389:2226-37.
10. Kang YY, Wang JG. The J-curve phenomenon in hypertension. Pulse (Basel) 2016;4:49-60.
11. SPRINT Research Group, Wright JT, Williamson JD, et al. A randomized trial of intensive versus standard blood-pressure control. N Engl J Med 2015;373:2103-16.
12. Lonn EM, Bosch J, Lopez-Jaramillo P, et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med 2016;374:2009-20.
13. 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.
14. McEvoy JW, Martin SS, Dardari ZA, et al. Coronary artery calcium to guide a personalized risk-based approach to initiation and intensification of antihypertensive therapy. Circulation 2017;135:153-65.
15. Sussman J, Vijan S, Hayward R. Using benefit-based tailored treatment to improve the use of antihypertensive medications. Circulation 2013;128:2309-17.

Keywords: Blood Pressure, Coronary Artery Disease, Risk Factors, Acute Coronary Syndrome, Numbers Needed To Treat, Cost-Benefit Analysis, Research Personnel, Hypertension, Risk Assessment, Atherosclerosis, Blood Pressure Determination, Stroke, Diabetes Mellitus, Myocardial Infarction, Dyslipidemias, Heart Failure

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