# Influence of baseline DBP on the effects of BP lowering on clinical outcomes: A participant level meta-analysis of RCTs

> **NIH NIH R21** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2020 · $114,375

## Abstract

The Systolic Blood Pressure Intervention Trial (SPRINT), a landmark study demonstrated that intensive
systolic blood pressure (SBP) lowering (SBP target <120 versus <140 mmHg) reduced the risk of death and
major cardiovascular disease (CVD) events in persons without diabetes but at high cardiovascular risk. Despite
the success of SPRINT, lowering of diastolic blood pressure (DBP) as a consequence of the SPRINT intensive
therapy intervention has been cited as a cause for concern in adopting SPRINT findings in routine clinical
practice.
 Based on a number of observational reports of J-shaped curves indicating associations of both low and
high DBPs with worse CVD outcomes, strong causal inferences on lowering DBP have been drawn. The
central question is whether the J-curve phenomenon observed in the observational studies reflects a causal
effect of low DBP on cardiovascular outcomes. The most direct and valid method of testing the J-curve
hypothesis is to actively intervene to lower DBP, particularly in those with DBP < 70 mm Hg; if lowering DBP is
deleterious below a certain DBP level, one would expect that the effects of lowering SBP on CVD outcomes
and death would be modified by baseline level of DBP. In a recent SPRINT publication, we identified U-shaped
relationships between baseline DBP and the primary CVD composite outcome and all-cause mortality. In
randomized comparisons, however, intensive SBP lowering that also lowered DBP was beneficial rather than
hazardous. Indeed, intensive SBP lowering seemed to result in similarly beneficial effects across each of the
quintiles of DBP at baseline.
 In the current proposal, we seek to leverage five, large, multi-center NIH funded clinical trials that
randomized participants across a spectrum of baseline characteristics to different BP goals. We will conduct a
participant level meta-analysis to examine the interactions of baseline DBP with the respective BP
interventions on CVD and kidney endpoints and all-cause mortality. The primary hypothesis is that while
baseline DBP has a non-causal U-shaped relationship with CVD endpoints, baseline DBP does not modify the
effect of BP lowering on CVD endpoints. The secondary hypotheses are that despite similar non-causal U-
shaped relationships of baseline DBP with kidney outcomes and all-cause death, baseline DBP does not
modify the effects of BP intervention on these outcomes.
 The proposed study is of public health importance. If the results show that lower baseline DBP does not
moderate the effect of BP lowering interventions on outcomes, this will be reassuring for clinicians and provide
credence to widespread adoption of SPRINT findings. On the other hand, if there are interactions, this study
will provide a basis for caution in application of the SPRINT findings in specific subgroups with a low DBP.

## Key facts

- **NIH application ID:** 9852564
- **Project number:** 5R21HL145494-02
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** SRINIVASAN BEDDHU
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $114,375
- **Award type:** 5
- **Project period:** 2019-02-01 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9852564

## Citation

> US National Institutes of Health, RePORTER application 9852564, Influence of baseline DBP on the effects of BP lowering on clinical outcomes: A participant level meta-analysis of RCTs (5R21HL145494-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9852564. Licensed CC0.

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