When diastolic BP falls below 55 mmHg, the risk of CV events increased
Effect of Lowering Diastolic Pressure in Patients With and Without Cardiovascular Disease Analysis of the SPRINT (Systolic Blood Pressure Intervention Trial)Khan NA, Rabkin SW, Zhao Y, et al. - Hypertension. 2018; published online ahead of print
Introduction and Methods
The exact blood pressure (BP) threshold, at which the J-curve phenomenon appears, is not known, and it is not clear whether this threshold differs in patients with obstructive coronary disease [1,2].
In this analysis of SPRINT (Systolic Blood Pressure Intervention Trial), the relationship between lower systolic (SBP) and diastolic BP (DBP) and the risk for CV events was examined in those with and without CV disease. Moreover, clinical predictors for developing low diastolic BP were investigated.
SPRINT was a randomized, open-label, controlled trial that included 9,361 patients aged >50 years with a screening systolic BP of 130 to 180 mmHg and an increased CV risk. Patients with diabetes mellitus, a history of stroke or heart failure were excluded [3,4]. Further exclusion criteria for the present analysis were: patients with a CV event within 30 days of randomization, lack of recorded BPs after randomization, or missing key baseline characteristics.
Patients were stratified by history of clinical CV disease and randomized 1:1 to intensive BP lowering to a systolic target of <120 mmHg versus standard systolic BP lowering of 135 to 139 mmHg. The study was originally planned for a 5-year follow-up, but ended early because of clear evidence of treatment benefit. The median follow-up was 3.26 years. The primary endpoint was a composite of myocardial infarction, acute coronary syndrome, stroke, acute decompensated heart failure, or CV death.
- In the subgroup of individuals without CV disease, the relationship between follow-up SBP and the primary outcome was nonlinear (P=0.03), although a distinct J-shaped relationship was only observed in the standard group.
- In the intensive BP-lowering group, achieving SBP ≤120 mmHg was associated with a significant reduction in CV events, compared with achieved systolic BPs of 121 to 150 mmHg in the standard group (HR: 0.64; 95%CI: 0.48–0.86).
- In the standard treatment group, lowering SBP to ≤120 mmHg was associated with a nonsignificant increase in CV events compared with achieved SBP of 121 to 150 mmHg (HR: 1.38; 95%CI: 0.92–2.06).
- There was a J-shaped association between DBP and the composite CV outcome regardless of intensive or standard treatment strategy (P nonlinearity <0.001; P interaction=0.47).
- The hazards increased when DBP was <55 or >95 mmHg (approximately 25% higher hazard compared with 70 mmHg). The HRs of diastolic BP <55 and >90 mmHg relative to DBP between 55 and 90 mmHg were 1.68 (95%CI: 1.16–2.43) and 1.45 (95%CI: 0.89–2.35), respectively.
- In the subgroup of patients with CVD, the treatment benefit was more evident among those who achieved a lower SBP (intensive vs standard arm HR: 0.74; 95%CI: 0.51–1.07 at 120 mmHg; HR: 1.59; 95%CI: 0.84–3.02 at 160 mmHg). Moreover, the HRs of DBP <55 and >90 mmHg relative to DBP between 55 and 90 mmHg were 1.52 (95%CI: 0.99–2.34) and 0.95 (95%CI: 0.37–2.40), respectively.
- Predictors for very low DBP were intensive antihypertensive treatment, a lower baseline DBP, a widened pulse pressure at baseline, male gender, higher age, a history of CV disease, and elevated creatinine levels.
This post-hoc analysis of SPRINT suggests that intensive BP lowering in patients with hypertension, but not diabetes mellitus, stroke, or heart failure, may increase CV risk if DBP falls to <55 mmHg. These data suggest caution when intensive BP targets are targeted, especially in patients at high risk to develop very low diastolic BP.