Elsevier

The Lancet

Volume 388, Issue 10056, 29 October–4 November 2016, Pages 2142-2152
The Lancet

Articles
Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study

https://doi.org/10.1016/S0140-6736(16)31326-5Get rights and content

Summary

Background

The optimum blood pressure target in hypertension remains debated, especially in coronary artery disease, given concerns for reduced myocardial perfusion if diastolic blood pressure is too low. We aimed to study the association between achieved blood pressure and cardiovascular outcomes in patients with coronary artery disease and hypertension.

Methods

We analysed data from 22 672 patients with stable coronary artery disease enrolled (from Nov 26, 2009, to June 30, 2010) in the CLARIFY registry (including patients from 45 countries) and treated for hypertension. Systolic and diastolic blood pressures before each event were averaged and categorised into 10 mm Hg increments. The primary outcome was the composite of cardiovascular death, myocardial infarction, or stroke. Hazard ratios (HRs) were estimated with multivariable adjusted Cox proportional hazards models, using the 120–129 mm Hg systolic blood pressure and 70–79 mm Hg diastolic blood pressure subgroups as reference.

Findings

After a median follow-up of 5·0 years, increased systolic blood pressure of 140 mm Hg or more and diastolic blood pressure of 80 mm Hg or more were each associated with increased risk of cardiovascular events. Systolic blood pressure of less than 120 mm Hg was also associated with increased risk for the primary outcome (adjusted HR 1·56, 95% CI 1·36–1·81). Likewise, diastolic blood pressure of less than 70 mm Hg was associated with an increase in the primary outcome (adjusted HR 1·41 [1·24–1·61] for diastolic blood pressure of 60–69 mm Hg and 2·01 [1·50–2·70] for diastolic blood pressure of less than 60 mm Hg).

Interpretation

In patients with hypertension and coronary artery disease from routine clinical practice, systolic blood pressure of less than 120 mm Hg and diastolic blood pressure of less than 70 mm Hg were each associated with adverse cardiovascular outcomes, including mortality, supporting the existence of a J-curve phenomenon. This finding suggests that caution should be taken in the use of blood pressure-lowering treatment in patients with coronary artery disease.

Funding

Servier.

Introduction

Lowering blood pressure in patients with hypertension reduces the risk of cardiovascular events and death,1, 2 but the optimum target blood pressure is unresolved.3, 4, 5, 6 Randomised trials did not show a benefit of blood pressure targets of less than 140/90 mm Hg,7, 8 and post-hoc analyses have suggested that the benefit of blood pressure-lowering treatment might even be reversed below a certain threshold,5, 9, 10, 11, 12, 13, 14, 15, 16 the so-called J-curve phenomenon.9 Conversely, a large meta-analysis of trials that randomly assigned participants to intensive versus less-intensive blood pressure-lowering treatment showed that intensive blood pressure-lowering was associated with decreased cardiovascular events, and the SPRINT trial18 showed that targeting a systolic blood pressure of less than 120 mm Hg in high-risk patients was associated with a reduction in blood pressure-related adverse outcomes, rather favouring a lower is better approach.

These contradictory results leave clinicians with uncertainty as to the optimum blood pressure target in patients treated for hypertension. The concern for a J-curve phenomenon is particularly relevant for cardiac events,10 because the heart is perfused during diastole and its perfusion might be compromised at low diastolic blood pressure values, especially in patients with coronary artery disease, both because a coronary stenosis will lower perfusion pressure in the downstream territory and because autoregulation is altered in these patients.19 Our aim was to study the association between achieved blood pressure levels and cardiovascular outcomes in a large cohort of patients with stable coronary artery disease treated for hypertension from the CLARIFY registry.

Section snippets

Study design and participants

The prospective observational longitudinal registry of patients with stable coronary artery disease (CLARIFY) includes 32 703 outpatients receiving standard care. The registry was observational and did not interfere with clinical management or mandate any test, procedure, or treatment.20 Patients were enrolled in 45 countries (excluding the USA). Eligible patients had stable coronary artery disease, defined as at least one of the following: documented myocardial infarction for more than 3

Results

22 672 adult patients with coronary artery disease and hypertension were included in the analysis. Demographic data and baseline characteristics of the patients, overall and for each 10 mm Hg increment blood pressure subgroup, are given in Table 1, Table 2; baseline drugs are shown in the appendix. Mean age at baseline was 65·2 years, 17 019 (75%) patients were men, and 15 190 (67%) patients were white. Compared with patients with high systolic blood pressure, those with a lower systolic blood

Discussion

This observational study, done in real-life stable patients with coronary artery disease treated for hypertension, shows that low systolic (<120 mm Hg) and low diastolic (<70 mm Hg) blood pressures are associated with an increased risk of cardiovascular events, with a steep J-curve not only for the composite of cardiovascular death, myocardial infarction, or stroke, but also separately for cardiovascular death, all-cause death, myocardial infarction, or hospital admission for heart failure.

Our

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