Resistant hypertension and the risk of major adverse cardiac and cerebrovascular events in outpatients

Abstract

Objective: To investigate the prevalence and associated risk of cardiovascular event of resistant hypertension in treated outpatients. Methods: This study was a nationwide multi-center prospective cohort study. The participants were treated outpatients enrolled in the China Nationwide Ambulatory and Home Blood Pressure Registry study of 42 hospitals in 19 provinces across the country from August 2009 to October 2017. Apparent resistant hypertension was defined as uncontrolled office blood pressure (≥140/90 mmHg, 1 mmHg=0.133 kPa) in spite of the use of three antihypertensive drugs or controlled office blood pressure (<140/90 mmHg) with four antihypertensive drugs or more. Subjects diagnosed with uncontrolled office blood pressure were further subdivided as pseudo-resistant hypertension and true resistant hypertension based on 24 h ambulatory blood pressure monitoring. The primary endpoint was fatal and non-fatal cardiovascular and cerebrovascular events, which was a composite endpoint consisting of cardiovascular and cerebrovascular death, ischemic and hemorrhagic stroke, myocardial infarction, coronary artery revascularization, unstable angina, heart failure, and coronary artery stenosis≥50% confirmed by coronary angiography. Secondary outcomes included fatal and non-fatal stroke or cardiac events. Patients with controlled office blood pressure after taking only 1 or 2 antihypertensive drugs were included as control. Kaplan-Meier survival curves, log-rank test, and Cox proportional risk model were used to evaluate the risk of apparent refractory hypertension in relation to cardiovascular and cerebrovascular prognosis. Results: A total of 2 782 treated hypertensive patients, aged (58.1±12.3) years were enrolled, including 1 403 (50.4%) men. The prevalence of apparent and true resistant hypertension was 15.1% (420/2 782) and 10.5% (293/2 782), respectively. Among patients with apparent resistant hypertension, during a median of 5 years follow-up, the cumulative incidence rate was 28.2, 11.2 and 19.1 per 1 000 person-years for fatal and non-fatal cardiovascular events (n=58), stroke (n=24) and cardiac events (n=40), respectively. The Kaplan-Meier curve and log-rank test showed that those patients with true resistant hypertension, had the highest cumulative incidence rate of fatal and non-fatal cardiovascular events, stroke, and cardiac events. Multivariable Cox regression analyses showed that true resistant hypertension was associated with a significantly higher risk of fatal and non-fatal cardiovascular events (HR=1.73, 95%CI 1.17-2.56, P=0.006) and stroke (HR=2.81, 95%CI 1.53-5.17, P=0.001). Conclusion: Resistant hypertension, especially true resistant hypertension, is associated with a higher risk of fatal and non-fatal cardiac and cerebrovascular events.