Blood pressure target in patients with hypertension and type-2 diabetes older than 65 years. Is <130/80 mmHg the right target or an excessive objective preventing from achieving the clinical goals we are aiming at?

In middle-aged and elderly individuals, hypertension and type 2 diabetes are highly prevalent and frequently coexist in the same patient, contributing to increased cardiovascular morbidity and mortality [1]. Thus, according to recent guidelines, most patients with hypertension and type 2 diabetes belong to the high cardiovascular risk category with a > 10%, 10-year risk of developing a cardiovascular events, a category that requires a strict control of blood pressure (BP) [2].

Randomised controlled trials and meta-analyses have clearly documented the clinical benefits of lowering BP in patients with hypertension and type 2 diabetes, but there are still some unresolved issues regarding the risk/benefit ratio of achieving low BP (e.g. a systolic BP <130 mmHg). Importantly, based on the most recent high blood pressure guidelines, the optimal target BP for managing these patients remains confusing, especially for the middle-aged and elderly population when reading the latest guidelines. The American College of Cardiology/American Heart Association (ACC/AHA) hypertension 2107 guidelines [3] target a BP ≤130/80 mmHg independent of comorbidities, level of cardiovascular risk and patient’s age, whereas the European Society of Cardiology/European Society of Hypertension (ESC/ESH) 2018 guidelines recommend a BP of 130–139/70–79 mmHg in patients aged >65 years with hypertension and type 2 diabetes [2]. The most recent ISH hypertension guidelines 2020 [4] have taken an intermediate position, indicating that BP should be lowered if it is >140/90 mmHg and reduced to <130/80 mmHg in younger adults and to <140/80 mmHg in the elderly. Most recently, the 2021 best practice recommendations of the American Diabetes Association [5] recommend individualising the target BP, with a goal of <140/90 mmHg overall and to a target a BP <130/80 mmHg only in patients with a 10-year cardiovascular risk >15%. Today, the only point of agreement for treatment of this group of patients appears to be the benefit of achieving a BP <130/80 mmHg for the prevention of stroke. There is no consensus in terms of prevention of cardiac or renal events. Therefore, new scientific data, preferably prospective, which would help clarify this situation and arrive at a uniform recommendation, are welcome.

Two very interesting post-hoc analyses of the Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial published in the present issue of Blood Pressure provide new insights on the potential cardiovascular benefits of lowering BP to <140/90 mmHg or <130/80 mmHg in middle-aged and elderly patients with hypertension and type 2 diabetes [6,7]. The first paper [7] compares the two target BPs in patients with hypertension and type 2 diabetes (n = 5,250), and the second [6] compares the same two targets in patients with diabetes (n = 5250) versus all study patients (n = 15,245) with a high cardiovascular risk enrolled in VALUE. A novel aspect of these papers is that BP was analysed based on the percentage of on-treatment visits with a BP <140/90 mmHg or <130/80 mmHg up to the occurrence of an event, with a repartition into four subgroups <25%, 25–49%, 50–74% and >75%, as first suggested by Mancia et al. [8]. This approach provides a more accurate assessment of the quality of BP control throughout the study period than BP measured at the time of the event. As expected, the mean on-treatment systolic and diastolic BPs were significantly higher in patients with the shortest time with an achieved BP <140/90 mmHg or <130/80 mmHg, the BP difference between the >75% and the <25% averaging 20–25/8–10 mmHg for systolic and diastolic BP respectively. As observed in previous similar analyses, including VALUE [8,9], the incidence of events increased progressively as the time with BP <140/90 mmHg decreased. This was true for the primary endpoint, as well as for all secondary endpoints in patients with hypertension and type 2 diabetes, as well as in the overall study population. Adjustment for baseline risk factors and comorbidities, including baseline BP did not modify the conclusion. In contrast, when analysing the data with the 130/80 mmHg target, except for stroke, the percentage of visits with a well-controlled BP had no apparent impact on the incidence of cardiovascular events. In fact, in patients with diabetes, a J-shaped relationship was observed, as the incidence of cardiac events increased as the time under more intensive BP control decreased from >75% to 50–74%, but decreased when intensive control was achieved <50% of time. Moreover, when considering the percent changes in risk of morbid and fatal events according to the proportion of time with a BP <130/80 mmHg, for several cardiac endpoints, patients with type 2 diabetes actually benefitted from a higher BP. Of note, diabetic and non-diabetic patients with a BP <130/80 mmHg during <50% ofvisits had an on-treatment mean BP of 131 and 145 mmHg systolic, suggesting that the optimal BP goal could be between 130 and 140 mmHg systolic for patients with hypertension and type 2 diabetes.

What can we learn from these post-hoc analyses? First, these observations tend to support the recommendation of lowering BP <140/90 mmHg in middle-aged and elderly patients with hypertension and type 2 diabetes and to suggest that targeting a BP <130/80 mmHg does not provide any real additional clinical benefit in these patients. Consistent with the conclusions of several previous studies [10] and meta-analyses [11, 12], these data confirm that a sustained BP <130/80 mmHg can be associated with an increased risk of cardiac events in high-risk patients with type 2 diabetes, thus questioning the risk-benefit ratio of achieving a low BP. The only exception may be the prevention of recurrent stroke, as targeting lower BP values was associated with a reduced risk of stroke in the main population of VALUE patients, but not in patients with hypertension and type 2 diabetes.

Second, these data re-emphasise how crucial it is to achieve a sustained rather than intermittent control of BP in patients with high cardiovascular risk. In this context, 75% of visits with an adequately controlled BP is probably still a low cut-off, and it would be of interest to know if cardiovascular risk reduction would be greater in the presence of a controlled BP at >80% or >90% of visits. These findings also underline the need to identify and work on factors interfering with sustained BP control and thereby increasing the visit to visit variability of BP [13], as well as cardiovascular disease risk. Medication adherence [14] and medical inertia [15,16] are recognised as the most important determinants of BP control in the real life management of patients with hypertension [17], including those enrolled in large randomised clinical trials [18]. Even in the context of large randomised controlled outcome trials in hypertension, inertia and the lack of appropriate titration of study drugs to higher doses have been found to be major causes of not reaching BP targets [18].

The third, and probably the most disturbing, but challenging, observation of these two post-hoc analyses is the strikingly low percentage of patients achieving either the <140/90 or the <130/80 mmHg targets throughout the study period, despite all efforts attempting to achieve BP target in all patients. Thus, although about 70% of participants achieved BP control in VALUE, only about one-third of this high cardiovascular risk population had a BP <140/90 during more than 75% of the visits and less than 3 percent of patients with diabetes maintained their BP persistently below 130/80 mmHg. A caveat here is that 130/80 mmHg was not a recommended target at the time of the trial.

Looking at those figures, one wonders if the discussion of targets is really the most relevant issue when facing the poor global management of hypertensive patients using traditional BP targets such as 140/90 mmHg. The real clinical problem does not appear to be the target BP, but rather the low levels of long-term BP control. Importantly, lowering BP with drugs may not reduce cardiovascular disease risk to that of untreated people with lifelong low BP. Experts proposing lower BP targets argue that while focussing on 130/80 mmHg or below, more patients will reach the 140/90 mmHg target. This may be true but still needs to be demonstrated. The deficit of BP control is so huge that the impact might be only marginal.

One must also take into account that much stricter control of BP to lower targets may have several consequences that may limit the reduction of the cardiovascular risk. For example, patients will need more drugs, visits, and monitoring to achieve the new BP goal. The risk of BP dropping too much may occur, with treatment leading to increases in cardiovascular disease events. Further, addition of potentially unnecessary drugs may waste patients’, physicians’, and payers’ resources and time, and may further reduce adherence to the prescribed antihypertensive drugs and increase the number of patients stopping their antihypertensive therapy. Thus, the question is whether setting targets that are not easily achievable and not strongly supported by scientific evidence in high risk patients will prevent doctors from achieving the main therapeutic goal, reduction of cardiovascular morbidity and mortality in the largest number of patients with hypertension. Finally, we should consider the approach recommended by the ESC/ESH and American Diabetes Association [2,5] to lower BP to <140/90–80 mmHg in older patients with hypertension and type 2 diabetes and to individualise BP goals in a shared decision process, taking into consideration the global health and social conditions of the patient and his/her preferences. This appears to be the wisest therapeutic approach. In the end, do we not treat patients rather than numbers?

Disclosure statement

MB, KN and SO are editors of Blood Pressure and report no relevant conflicts of interest to disclose related to this editorial.