Optimization of diastolic BP associated with reduced CV risk, even at optimal systolic BP
Achieved diastolic blood pressure and pulse pressure at target systolic blood pressure (120–140mmHg) and cardiovascular outcomes in high-risk patients: results from ONTARGET and TRANSCEND trials
Introduction and methods
Guidelines recommend a target systolic blood pressure (SBP) <140 mmHg and a target diastolic blood pressure of <90 mmHg for the prevention of cardiovascular (CV) events [1-3]. The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET) and the Telmisartan Randomized AssessmeNt Study in ACE iNtolerant participants with cardiovascular Disease (TRANSCEND) trials , reported the lowest CV event rate in patients with an SBP of 120 to <140 mmHg. Moreover, SBP <120 mmHg was associated with an increased risk for CV and all-cause death.
It is hypothesized that within the optimal range of SBP 120 - <140 mmHg, a DBP-risk association might exist. In this secondary analysis of the ONTARGET and TRANSCEND studies, the associations between DBP levels and CV outcomes were explored in patients with SBP 120 to <140 mmHg.
In ONTARGET, patients with stable coronary artery disease were randomly assigned to oral ramipril 10mg per day, telmisartan 80mg per day or both. In TRANSCEND, patients at high CV risk were randomly assigned to telmisartan 80mg per day or placebo. The primary outcome was a composite of CV death, non-fatal myocardial infarction (MI), stroke, or hospitalization for heart failure (hHF). Secondary outcomes included the individual components of the composite, as well as all-cause death. Out of a total of 31,546 patients randomized in both studies, those with SBP <120 or >140 mmHg, and those with missing data of interest were excluded, leaving a sample of 16,099 patients for the present analysis.
- The lowest risk for all CV outcomes was achieved at DBP of 70 to <80mmHg. The yearly event rates (YER) for the primary outcome were 2.70 for DBP 70 - <80, vs 4.29 for DBP <70, 3.18 for DBP 80 - <90, and 6.35 for DBP ≥90 mmHg.
- YER for CV death were 1.18 for DBP: 70 - <80, vs 1.70 for DBP <70, 1.33 for DBP 80 - <90, and 1.79 for DBP ≥90.
- YER for MI were 0.79 for DBP 70 - <80, vs. 1.41 for DBP <70, 0.89 for DBP 80 - <90, and 2.24 for DBP ≥90.
- YER for stroke were 0.65 for DBP 70 - <80, vs. 0.77 for DBP <70, 0.92 for DBP 80 - <90, and 1.83 for DBP ≥90.
- Similar J-shaped curves were found for hHF and all-cause death.
- Patients with DBP >80mmHg had an increased risk for the primary outcome, stroke, and hHF (DBP ≥80mmHg) and for MI (DBP ≥90mmHg).
- Patients with DBP <70mmHg had an increased risk for the primary endpoint, MI, hHF, and all-cause death but not for CV death and stroke.
In patients at a high CV risk with well-controlled SBP (between 120 and <140 mmHg), a DBP between 70 and <80 mmHg was associated with a lower risk of adverse outcomes, as compared to DBP lower than 70 and higher than 80 mmHg. These findings support DBP-control, also when optimal SBP control is achieved in high-risk CV patients.