Association of different timepoint and threshold of time-in-target-range and MACEs: insight from the SPRINT study

Abstract Objective To evaluate the prognostic value of different timepoint and threshold of systolic blood pressure (SBP) Time in Target Rang (TTR) in Major Adverse Cardiovascular Events (MACEs). Method This is a post-hoc analysis of the SPIRNT (Systolic Blood Pressure Intervention Trial). Participants with complete record of BP values and no adverse events occurred in the initial 2-years follow-up were enrolled. Different SBP TTR indexes was calculated by different timepoint (3 month,12 month,24 month) and threshold (110-130mmHg;110-140mmHg;110-130mmHg for intensive treatment group and 120-140mmHg for standard treatment group) (Fig 1). The primary outcome was major adverse cardiovascular events (MACEs) occurred 2 years later, defined as the composite of myocardial infarction, stroke, heart failure and cardiovascular death. Results A total of 7134 participants in SPIRNT were enrolled in this study. Those SBP TTR indicators with independent predictive value of MACEs were selected by a multivariable COX model adjusted for traditional cardiovascular risk factors (Fig 2). SBP TTR calculated with 110-140mmHg window in 3 months (3month SBP TTR110-140) was considered to be the best predictor of MACEs occurred 2 years later among selected SBP TTR indexes according to c statistics and relative informativeness (Table1). The restricted cubic spline plot was used to evaluate the nonlinear trend of the TTR indicator. In addition, we obtain the cut-off value by looking for the point in the RCS curve with the largest slope change. 0.65 was considered to be the best truncation for 3month SBP TTR110-140(Fig 3). Patients with 3month TTR110-140 greater than 0.65 had 23.9% lower incidence of MACEs than patients with TTR less than or equal to 0.65 (HR 0.761[0.592-0978], P=0.033).(Table 2) In addition, for patients with early SBP control (3month SBP TTR110-140 >0.65), there was no significant difference in mean SBP between 110-130 mmHg and 130-140 mmHg (Fig4 Group1 Vs Group2). Lasso regression also suggests that TTR110-140 has more informatics advantages than TTR110-130 in cox model at different timepoints (Fig5). Conclusions 3month SBP TTR110-140 was considered to be the best predictor of MACEs occurred 2 years later in different SBP TTR indexes, which indicated the importance of early SBP control. This study also proposed 0.65 as the critical value of 3-month SBP TTR110-140 for prevention of the incident of MACEs. In the future, more cohort studies are needed to expend these findings.