Prognostic Value of Time in Blood Pressure Target Range Among Patients With Heart Failure

Kangyu Chen, PHD; Chao Li, PHD; Victoria Cornelius, PHD; Dahai Yu, PHD; Qi Wang, MD; Rui Shi, PHD; Zhenqiang Wu, PHD; Hao Su, PHD; Ji Yan, MD; Tao Chen, PHD; Zhixin Jiang, PHD


JACC Heart Fail. 2022;10(6):369-379. 

In This Article

Abstract and Introduction


Background: Blood pressure (BP) is a continuous and dynamic measure. However, standard BP control metrics may not reflect the variability in BP over time.

Objectives: This study assessed the prognostic value of time in BP target range among hypertensive patients with heart failure (HF).

Methods: The authors performed a post hoc analysis of data from the TOPCAT (Treatment of Preserved Cardiac Function HF with an Aldosterone Antagonist) trial and the BEST (Beta-Blocker Evaluation of Survival Trial). Time in target range (TTR) for each patient was calculated using linear interpolation across the study period with the target range of systolic BP between 120 and 130 mm Hg.

Results: A total of 4,789 hypertensive patients (n = 1,654 from BEST and n = 3,135 from TOPCAT) were included. The cumulative incidences of primary endpoint (ie, cardiovascular death or HF hospitalization) were highest among the top quartile of TTR with a dose-dependent manner across quartiles (Ptrend <0.005). The top quartile of TTR was significantly associated with a lower risk of primary outcome using adjusted Cox regression model (HR: 0.71; 95% CI: 0.60–0.82), cardiovascular mortality (HR: 0.68; 95% CI: 0.55–0.84), HF hospitalization (HR: 0.70; 95% CI: 0.58–0.85), all-cause mortality (HR: 0.69; 95% CI: 0.58–0.83), and any hospitalization (HR: 0.76; 95% CI: 0.67–0.85). Further analyses using restricted cubic spline indicated a linear relationship between TTR and primary outcome. Similar patterns were observed in the individual trial. Sensitivity analyses generated consistent results while redefining target range as 110 to 130 mm Hg for systolic BP or 70 to 80 mm Hg for diastolic BP.

Conclusions: TTR could independently predict major adverse cardiovascular events in hypertensive patients with HF.


Hypertension is one of the most common comorbidities and risk factors for cardiovascular disease including heart failure (HF). Numerous studies have confirmed that effective blood pressure (BP) management can prevent the occurrence and progression of HF.[1–3] Despite decades of endeavors in improvement on public awareness, guideline statements, and widely available and inexpensive antihypertension drugs, the prevalence of hypertension among patients with stable HF remains very high (>50%).[4,5]

BP is a continuous and dynamic variable. However, a single or average BP value is often used as a monitoring indicator in clinical practice and studies of hypertension, which makes it difficult to accurately assess the objective state of BP. In 2007, Mancia et al[6] found that continuous and effective BP control could provide additional benefits for hypertension treatment in the International Verapamil SR Trandolapril Study. Therefore, it is recommended that doctors should pay attention to every point of BP monitoring instead of single value of BP.

Recently, researchers have proposed the concept of "time in target range" (TTR) in the field of hypertension management.[7] This measurement can incorporate both the average BP value prevailing during long-term follow-up and the degree of BP variability. Also, it can account for variation both within and outside of target range. A number of limited studies have shown that a higher proportion of BP controlled within the target range was significantly associated with a decreased risk of cardiovascular event or mortality.[7–9] This indicated that TTR may serve as an appropriate performance measure for population level monitoring of BP control or BP control interventions in clinical trials. It remains to be established that this would be a suitable measure for patients with HF given that paradoxical and controversial relationship between BP lowering with clinical outcomes often existed.[4,10,11]

As such, in the present study, we aimed to assess the value of adopting time in BP target range by exploring its association with clinical outcomes among hypertensive patients with HF on the basis of a post hoc analysis of 2 published randomized trials conducted in different centuries.