The concept that ‘the lower is the better’ in hypertension treatment is increasingly accepted by the medical and scientific community, according to the results of several studies and meta-analyses.
Ettehad and colleagues have shown that the risk of cardiovascular events decreases proportionally to the achieved blood pressure (BP) reduction. A 10 mmHg lowering in SBP has been demonstrated to reduce the risk of major cardiovascular disease events (MACE) by 20%, stroke by 27%, heart failure by 28%, coronary artery disease (CAD) by 17% and all-cause mortality by 13%, independently from baseline estimated cardiovascular risk .
Another large meta-analysis, including 44 989 participants, has demonstrated that a more intensive antihypertensive strategy is associated to a significant reduction in MACE (14%), myocardial infarction (14%), stroke (22%) and albuminuria (10%), although without clear benefits on heart failure, all-cause and cardiovascular death and on end-stage renal disease (ESRD) .
These results are consistent with those reported by Thomoupolos et al. who have documented that a more intensive BP lowering is able to significantly reduce the risk of stroke (29%), CAD (20%), MACE (25%) and death from cardiovascular causes (21%) .
In all the above-mentioned meta-analyses, the greatest absolute benefits have been obtained in patients with the highest cardiovascular risk, such as those with a previous history of atherothrombotic events [1–3].
Although with different approaches and recommendations, the focus on the tighter control of BP in hypertensive patients has been one of the highlights of the American College of Cardiology/American Heart Association (ACC/AHA)  and European Society of Cardiology/European Society of Hypertension (ESC/ESH) Guidelines  in 2017 and 2018, respectively [6,7].
Some important issues, however, remain still debated, such as which BP targets should be achieved to maintain a favorable ratio between the benefits on cardiovascular risk reduction and the risk of therapy-related adverse events, particularly in patients with comorbidities, and at which BP levels a pharmacological treatment should be started.
In such a context, the proportional reduction in the incidence of MACE related to a tighter BP control seems to be lower in individuals affected by diabetes or chronic kidney disease (CKD), probably as a consequence of different methodological characteristics of the studies conducted in these categories of patients, such as length of follow-up and the therapeutic strategies adopted [1,8].
The ACCORD BP (Action to Control Cardiovascular Risk in Diabetes Blood Pressure) trial, which included 4733 participants with type 2 diabetes, demonstrated a significant 39% reduction of the primary composite end-point (nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes) related to an intensive BP control only in the standard glycemia subgroup (A1c target 7–7.9%), but not in patients assigned to an intensive glycemic control (A1c target <6%) . Among the different hypotheses proposed to understand these findings, a plausible explanation is that the reduction of cardiovascular events may be driven by the achievement of target glycemic levels. In these circumstances, the favorable effect of intensive BP-lowering on outcomes may be offset and minimized .
In this complex scenario, the SPRINT (Systolic Blood Pressure Intervention Trial) trial  has added another brick. In this study, which enrolled 9631 individuals with SBP at least 130 mmHg at increased cardiovascular risk, a 25% lower incidence of the primary composite outcome (myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes) and a 27% reduction of all-cause mortality was observed in the intensive treatment group, although with a higher rate of adverse events, such as hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure. Although several relevant criticisms have been raised to SPRINT design and methods, such as the unattended method of BP measurement and the exclusion of patients with diabetes and previous cerebrovascular events, there is no question that this study promotes the concept of a tighter control of BP and had influence on current guidelines . European Guidelines  have indeed reduced BP targets, recommending a goal less than 130/80 mmHg in most patients, especially in those at high or very high cardiovascular risk, and US Guidelines suggest to consider also individuals with BP levels above 130/80 mmHg as hypertensive patients .
In the attempt to provide some additional interpretation to these apparent controversial aspects, in the current issue of Journal of Hypertension, Contreras and colleagues have assessed the benefits of the achievement of an intensive SBP goal less than 120 mmHg compared with standard SBP target less than 140 mmHg on cardiovascular events in the two landmark SPRINT  and ACCORD BP  trials . The rational of the authors in putting together these two studies is only based on the common SBP target of 120 mmHg.
The authors conclude in favor of an intensive antihypertensive treatment in patients with SBP between 130 and 139 mmHg, because of the significant cardiovascular benefits related to a tighter BP control. This post hoc analysis, however, presents some methodological limitations, mostly related to the somewhat risky choice to include two studies with few similarities. In particular, although both SPRINT  and ACCORD BP  aimed to demonstrate the benefits of a SBP goal less than 120 mmHg, they presented some relevant differences in the characteristics of the enrolled populations (nondiabetic vs. diabetic patients) and in the primary composite outcome (heart failure not included in ACCORD BP). In addition, although SBP levels less than 120 mmHg have been reached in the ACCORD BP  intensive-treatment group (119.3 mmHg), this goal has not been fully achieved in the SPRINT  population (121.5 mmHg).
Moreover, even if the results of these trials have influenced the most recent guidelines, driving the reduction of recommended BP targets, the so-called ‘sprintable’ population represents only a 20–30% of the overall hypertensive population who receive drug therapy . Furthermore, in both SPRINT  and ACCORD BP  trials, intensively treated patients experienced a greater number of adverse events, although not serious in most cases, suggesting particular caution in individuals with particular conditions and comorbidities (elderly, CKD, diabetes). Last but not least, the ambitious SBP target less than 120 mmHg may appear often not feasible, requiring complex pharmacological regimens of three or more medications. On the basis of these data, both American and European guidelines suggest a SBP goal less than 130 mmHg, but not less than 120 mmHg, in most hypertensive patients aged less than 65 years [4,5].
Thus, in this difficult scenario, the intensive SBP goal 120 mmHg or less, aimed by the SPRINT  and achieved by the ACCORD BP  trial, should be mitigated by the unavoidable need of an individualized approach, based on a careful assessment of the risk/benefit ratio in each individual and on the fundamental principle of Medicine: ‘primum non nocere’, especially in the most frail patients.
As in the Plato's Allegory, in which the charioteer of the human soul drives a chariot pulled by two winged horses, ‘opposite in breed and character’, physicians, towed by different recommendations, should steer individual clinical decisions toward the right direction .
Further studies, conducted in the cohorts excluded in the SPRINT  and ACCORD BP  trials, may greatly help us to understand, which horse is represented by the SBP goal less than 120 mmHg, if the ‘rational impulse’ or the ‘concupiscent nature’. ‘Therefore, in our case, the driving is necessarily difficult and troublesome’ , as indeed it often happens in the practice of medicine.
Conflicts of interest
There are no conflicts of interest.
1. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet
2. Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, et al. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet
3. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure lowering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels - updated overview and meta-analyses of randomized trials. J Hypertens
4. Whelton PK, Carey RM, Aronow WS, Casey DE Jr, Collins KJ, Dennison Himmelfarb C, 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
5. Williams B, Mancia G, Spiering W, Agabiti Rosei E, Azizi M, Burnier M, et al. ESC Scientific Document Group2018 ESC/ESH Guidelines for the management of arterial hypertension. J Hypertens
6. Volpe M, Gallo G, Battistoni A, Tocci G. Implications of Guidelines for Hypertension Management in Europe. Circ Res
7. Volpe M, Citoni B, Coluccia R, Battistoni A, Tocci G. Hypertension across the Atlantic: a sprint or a marathon? High Blood Press Cardiovasc Prev
8. Parving H-H, Brenner BM, McMurray JJ, de Zeeuw D, Haffner SM, Solomon SD, et al. Cardiorenal end points in a trial of aliskiren for type 2 diabetes. N Engl J Med
9. Study Group ACCORD, Cushman WC, Evans GW, Byington RP, Goff DC Jr, Grimm RH Jr, Cutler JA, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med
10. Wright JT Jr, Williamson JD, Whelton PK, Snyder JK, Sink KM, Rocco MV, et al. The SPRINT Research GroupA randomized trial of intensive versus standard blood pressure control. N Engl J Med
11. Ruiz-Hurtado G, Banegas JR, Sarafidis PA, Volpe M, Williams B, Ruilope LM. Has the SPRINT trial introduced a new blood-pressure goal in hypertension? Nat Rev Cardiol
12. Contreras G, Lu L, Tamariz L, Rocco MV, Papademetriou V, Kostis JB, et al. for the SPRINT Research Group.Outcomes in adults with systolic blood pressure between 130 and 139 mmHg in Action to Control Cardiovascular Risk in Diabetes Blood Pressure trial and Systolic Blood Pressure Intervention Trial. J Hypertens
13. Phaedrus, section 246b, Retrieved 2010-11-17.