Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort studyBMJ 2015; 350 doi: https://doi.org/10.1136/bmj.h158 (Published 05 February 2015) Cite this as: BMJ 2015;350:h158
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Xu W, et al’s paper investigated the optimal systolic blood pressure (BP) goal above which new antihypertensive medications should be added or doses of existing medications increased ("systolic intensification threshold") and to determine the relation between delays in medication intensification and follow-up and the risk of cardiovascular events or death. They observed that systolic intensification thresholds higher than 150 mm Hg, delays of greater than 1.4 months before medication intensification after systolic BP elevation, and delays of greater than 2.7 months before BP follow-up after antihypertensive medication intensification were associated with increased risk of an acute cardiovascular event or death. These findings support the importance of timely medical management and follow-up in the treatment of patients with hypertension.1
Hypertension is the most common risk factor for cardiovascular disease (CVD). Accordingly, to control BP optimally is very important to prevent CVD. In this regard, a meta-analysis of individual data for one million adults in 61 prospective studies reported that throughout middle and old age, usual BP is strongly and directly related to vascular (and overall) mortality, without any evidence of a threshold down to at least 115/75 mm Hg.2 This suggested the lower the systolic blood pressure the lower the risk of CVD. However, recent clinical trials of lower targets failed to show benefit.3 Furthermore, controlling BP to too lower level is hazardous in elderly patients. Therefore, recent European and American guidelines recommend treatment thresholds below 140 mm Hg in patients with hypertension4,5 and below 150 mm Hg in elderly (age> 70 years old) patients with hypertension5.
Despite updated guidelines, several important questions are still unanswered. In this point, the current paper answered these points albeit a retrospective cohort study. They found no evidence of clinical benefit associated with an intensification threshold much below 150 mm Hg, providing strong evidence not enough to outweigh the potentially substantial costs of treating patients with uncomplicated stage 1 hypertension. Also, it suggests that to intensify treatment for raised BP should be completed within six weeks and BP should be measured within the 2.7 months again after treatment intensification.
There are several limitations in this study. First of all, reducing BP has a weaker effect on all cause mortality than on vascular events.6 Hypercholesterolemia and hypertension are both associated with endothelial dysfunction and insulin resistance and their coexistence is associated with an increased incidence of cardiovascular events. Hypercholesterolemia and hypertension have a synergistic deleterious effect on endothelial function, oxidative stress, inflammation, and etc. Statins-based combination treatment with renin-angiotensin-aldosterone system blockades has additive effects- to control BP, lipid profiles, endothelial dysfunction and insulin resistance by both distinct and interrelated mechanisms7-9 that may explain positive outcomes of recent clinical trials10,11. There were no serious adverse effects with statins-based combination treatment, compared with monotherapies. Indeed, various strategies to reduce residual CVD risk in hypertensive patients included treating BP to lower goals and using different classes of antihypertensive medications with limited impact. However, treating moderate cholesterol elevations with low-dose statins reduced CVD 35% to 40%.12
The other is that patients with CVD or high risk should take several medications with high cost on the long-term period. However, low adherence is the big problem. In this regard, use of a combination strategy for BP, cholesterol, and platelet control vs usual care resulted in significantly improved medication adherence at 15 months and statistically significant but small improvements in BP and cholesterol. There were no significant differences in serious adverse events or cardiovascular events between the groups. Evidence existed of larger benefits in patients with lower adherence at baseline.13
Funding: None, Disclosures: None
1. Xu W, Goldberg SI, Shubina M, Turchin A. Optimal systolic blood pressure target, time
to intensification, and time to follow-up in treatment of hypertension: population based
retrospective cohort study. BMJ 2015;350:h158.
2. 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. ACCORD Study Group. Effects of intensive blood-pressure control in type 2 diabetes
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4. Mancia G, Fagard R, Narkiewicz K, Redon J, Zanchetti A, Böhm M, 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). J Hypertens 2013;31:1281-357.
5. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al.
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 (JNC8). JAMA 2014;311:507-20.
6. Blood Pressure Lowering Treatment Trialists’ Collaboration. Effects of different
blood-pressure-lowering regimens on major cardiovascular events: results of
prospectively-designed overviews of randomised trials. Lancet 2003;362:1527-35.
7. Koh KK, Quon MJ, Han SH, et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 2004;110:3687-92.
8. Koh KK, Quon MJ, Han SH, et al. Beneficial vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 2005;45:1088-93.
9. Lee H-Y, Sakuma I, Ihm S-H, et al. Statins and renin-angiotensin system inhibitor combination treatment to prevent cardiovascular disease. Circ J 2014;78:281-7.
10. Athyros VG, Mikhailidis DP, Papageorgiou AA, et al; GREACE Study Collaborative Group. Effect of statins and ACE inhibitors alone and in combination on clinical outcome in patients with coronary heart disease. J Hum Hypertens 2004;18:781-8.
11. Athyros VG, Katsiki N, Karagiannis A, Mikhailidis DP. Combination of statin plus renin angiotensin system inhibition for the prevention or the treatment of atherosclerotic cardiovascular disease. Curr Pharm Des 2014;20:6299-305.
12. Egan BM, Li J, Qanungo S, Wolfman TE. Blood pressure and cholesterol control in hypertensive hypercholesterolemic patients: national health and nutrition examination surveys 1988-2010. Circulation 2013;128:29-41.
13. Thom S, Poulter N, Field J, et al; UMPIRE Collaborative Group. Effects of a fixed-dose combination strategy on adherence and risk factors in patients with or at high risk of CVD: the UMPIRE randomized clinical trial. JAMA 2013;310:918-29.
Competing interests: No competing interests
A recent article published in The BMJ , which investigated optimal systolic blood pressure targets for prescribing antihypertensive medication, is particularly timely in light of the revised blood pressure guidelines recently published by the Eighth Joint National Committee (JNC8). The controversial revisions  include the recommendation for less conservative treatment for older populations and for patients with diabetes and renal disease. These changes are justified by the lack of randomized control trials (RCT) specifically confirming blood pressure threshold targets.
While The BMJ  article, which is a retrospective cohort study, may go some way towards refining guidelines for blood pressure targets, the ambiguity stemming from the JNC8 report indicates the need for a paradigm shift. In particular, peripheral blood pressure measurements may have limited capacity as a single risk factor because they do not accurately reflect the effects of peak blood pressure on centrally located organs. Alternatively, central blood pressure has been reported to be a stronger determinant of cardiovascular events than peripheral blood pressure , and a recent study  reported that monitoring central blood pressure, compared to peripheral blood pressure, led to decreased medication use without adverse effects of left ventricular mass.
Recently, oscillometric pulse wave (PWA) devices have emerged, which are user-friendly and suitable for routine central blood pressure measurements in clinical practice. Therefore, given the known limitations of peripheral blood pressure, the lack of RCTs supporting specific thresholds, and the recent availability of simple PWA devices, perhaps it’s time to advocate longitudinal RCTs to determine the comparative clinical utility of central blood pressure.
1. Xu W, Goldberg SI, Shubina M, Turchin A. Optimal systolic blood pressure target, time to intensification, and time to follow-up in treatment of hypertension: population based retrospective cohort study. BMJ 2015;350:h158.
2. James PA, Oparil S, Carter BL, Cushman WC, Dennison-Himmelfarb C, Handler J, et al. 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). JAMA 2014;311(5):507-20.
3. Peterson ED, Gaziano JM, Greenland P. Recommendations for treating hypertension: what are the right goals and purposes? JAMA 2014;311(5):474-6.
4. Sundstrom J, Arima H, Woodward M, Jackson R, Karmali K, Lloyd-Jones D, et al. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014;384(9943):591-8.
5. Vlachopoulos C, Aznaouridis K, O'Rourke MF, Safar ME, Baou K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with central haemodynamics: a systematic review and meta-analysis. Eur Heart J 2010;31(15):1865-71.
6. Sharman JE, Marwick TH, Gilroy D, Otahal P, Abhayaratna WP, Stowasser M, et al. Randomized trial of guiding hypertension management using central aortic blood pressure compared with best-practice care: principal findings of the BP GUIDE study. Hypertension 2013;62(6):1138-45.
Competing interests: No competing interests