Associations Between Achieved Ambulatory Blood Pressures and Its Changes With Adverse Outcomes in Resistant Hypertension: Was There a J-Curve for Ambulatory Blood Pressures?

Abstract

J-curve associations with adverse outcomes have never been examined in relation to ambulatory blood pressures (BPs). We aimed to investigate the associations between low-achieved BPs and large BP changes during follow-up with major adverse cardiovascular events and mortality in a cohort of 1474 patients with resistant hypertension who performed serial ambulatory BP monitoring. Multivariable Cox regressions with cubic splines examined associations between continuous BP parameters (time-weighted mean relative BP changes and time-updated achieved BPs) with primary (major adverse cardiovascular events and all-cause mortality) and secondary outcomes (cardiovascular mortality, myocardial infarctions, and strokes, separately). Categorical analyses were also performed (subgroups with the largest BP reductions and the lowest achieved BPs). During a median follow-up of 9 years, 299 major adverse cardiovascular events (128 myocardial infarctions and 109 strokes) and 316 all-cause deaths (187 cardiovascular) occurred. In analyses with continuous BP parameters, there were no nonlinear J -curve associations between achieved ambulatory BPs and outcomes ( P of the nonlinear terms >0.18); in general, low-achieved BPs were either neutral or protective (hazard ratios: 0.64–1.01). Otherwise, most of the associations between relative BP changes and outcomes were nonlinear with J - or U -curves. The excess risks of larger BP reductions were more evident in elderly (hazard ratios, 1.00–1.30) and in patients with preexistent cardiovascular diseases (hazard ratios, 1.33–1.52). Categorical analyses were confirmatory. In conclusion, in patients with resistant hypertension, achieving lower ambulatory 24-hour BPs (around 110/60 mmHg) seems safe and probably beneficial, but larger BP reductions might be deleterious, particularly in elderly and in patients with cardiovascular diseases.