Prognostic Impact of Home Blood Pressures for Adverse Cardiovascular Outcomes and Mortality in Patients With Resistant Hypertension: A Prospective Cohort Study

Home blood pressure (HBP) monitoring has been increasingly used in hypertension management. We aimed to evaluate the prognostic importance of HBP parameters in patients with resistant hypertension in relation to office and ambulatory blood pressures (BPs). Three hundred thirty-three patients with resistant hypertension performed 24-hour ambulatory and HBP monitoring at baseline and were followed up for a median of 5.6 years. Primary outcomes were total cardiovascular events, major adverse cardiovascular events, and all-cause and cardiovascular mortality. Associations between HBPs (total mean, morning and evening BPs, analyzed as continuous and as dichotomical variables) and outcomes were assessed by multivariable-adjusted Cox analyses. Improvement in risk discrimination with HBP was evaluated by C statistics and the Integrated Discrimination Improvement index. During follow-up, there were 48 cardiovascular events (42 major adverse cardiovascular events) and 43 all-cause deaths (26 cardiovascular). Continuous HBP parameters were associated with significantly higher risks of all adverse outcomes, with hazard ratios varying from 1.7 to 2.1, after adjustments for office and ambulatory BPs. In dichotomical analyses, uncontrolled HBP was associated with significantly higher risks of all outcomes, except for the evening HBP. Morning HBP was associated with the highest risks. HBP parameters improved risk discrimination, with increases in C statistics of up to 0.044 and relative Integrated Discrimination Improvements up to 42%, equivalent to those obtained from ambulatory BPs, except for all-cause and cardiovascular mortalities, in which ambulatory BPs provided greater improvements than HBPs. In conclusion, higher/uncontrolled HBP levels are predictive of adverse cardiovascular outcomes and mortality and improve risk discrimination in patients with resistant hypertension.

Associations Between Achieved Ambulatory Blood Pressures and Its Changes With Adverse Outcomes in Resistant Hypertension

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.

Prognostic Importance of On-Treatment Clinic and Ambulatory Blood Pressures in Resistant Hypertension

The prognostic importances of on-treatment clinic and ambulatory blood pressure (BP) levels have never been investigated in individuals with resistant hypertension. We aimed to evaluate them for the occurrence of incident cardiovascular and mortality outcomes in a prospective cohort of 1726 patients with resistant hypertension. Clinic and ambulatory BPs were measured at baseline and serially during follow-up (analyzed as time-varying and as mean cumulative BPs) and also categorized as controlled/uncontrolled as defined by the traditional and new 2017 American College of Cardiology/American Heart Association criteria. Multivariate Cox analyses examined the associations between BP parameters and the occurrence of total cardiovascular events, major adverse cardiovascular events, and cardiovascular and all-cause mortalities. C statistics and the integrated discrimination improvement indexes evaluated the improvement in risk discrimination. Over a median follow-up of 8.3 years, 417 total cardiovascular events occurred (358 major adverse cardiovascular events) and 391 individuals died (233 cardiovascular deaths). All single systolic BP (SBP) parameters significantly predicted all outcomes, but the associations were stronger for ambulatory SBPs than for clinic SBPs and for on-treatment SBPs (particularly for mean cumulative) than for baseline SBPs, and both improved risk discrimination (with increases in C statistic of up to 0.021 and integrated discrimination improvements of up to 19.7%). These findings were consistent for diastolic BPs. Uncontrolled ambulatory BPs were associated with higher risks for all outcomes, whereas uncontrolled clinic BPs were not. In conclusion, mean cumulative ambulatory BPs during follow-up were the best prognostic markers of adverse cardiovascular outcomes and mortality in patients with resistant hypertension. Serial ambulatory BP monitoring shall be more widely used in resistant hypertension management.