Apparent resistant hypertension and the risk of recurrent cardiovascular events and mortality after a first manifestation of vascular disease
Authors: Groenland E.H , Bots M.L , Asselbergs F.W , De Borst G.J , Kapelle L.J , Visseren F.L.J , Spiering W 
Published: November 2020

Abstract

Background
Previous studies have shown that patients with resistant hypertension carry a higher risk of developing cardiovascular disease than patients with non-resistant hypertension. However, little is known about the prognosis of apparent resistant hypertension in patients with symptomatic vascular disease.

Purpose
The aim of this study was to examine the relation between different stages of hypertension and the risk of recurrent cardiovascular events and mortality in a cohort of hypertensive patients with symptomatic vascular disease.

Methods
Hypertensive patients (n=7280) with symptomatic vascular disease (cerebrovascular disease, coronary heart disease, peripheral artery disease or abdominal aortic aneurysm) were included from the ongoing SMART cohort between 1996 and 2018. Patients were classified into three groups according to baseline office blood pressure (BP): controlled (BP &lt;140/90 mmHg and a hypertension diagnosis or on 1 to 3 antihypertensive drugs), uncontrolled (BP ≥140/90 mmHg on ≤2 drugs) and apparent resistant (BP ≥140/90 mmHg despite treatment with three or more antihypertensive drugs including a diuretic or treatment with four or more antihypertensive medications irrespective of BP status). Cox proportional hazard models were used to quantify the relation between the different stages of hypertension and the risk of recurrent major adverse cardiovascular events (MACE including stroke, myocardial infarction and vascular death) and death from any cause. Models were adjusted for age, sex, current smoking, body mass index, renal function and diabetes. In addition, survival according to the different stages of hypertension was plotted, taking competing risk of non-vascular mortality into account by using the Fine and Gray method.

Results
In total 3123 patients (43%) had controlled hypertension, 3354 patients (46%) had uncontrolled hypertension and 803 (11%) had apparent resistant hypertension. A total of 1498 MACE and 1762 deaths occurred in 64,469 person-years (median follow-up of 8.6 years, IQR 4.6–12.7 years). Compared to patients with controlled hypertension patients with apparent resistant hypertension were at increased risk of recurrent MACE (HR 1.32; 95% CI 1.11–1.58) and death from any cause (HR 1.46; 95% CI 1.25–1.72). At the age of 60 years, patients with apparent resistant hypertension after a first cardiovascular event on average had a recurrent cardiovascular event 10 years earlier than patients with controlled or uncontrolled hypertension (Figure 1).

Conclusions
Irrespective of age at first cardiovascular event, apparent resistant hypertension is related to a higher risk of recurrent vascular events and death from any cause. These findings support the need for greater efforts toward improving blood pressure control and treatment of other cardiovascular risk factors among patients with apparent resistant hypertension.
Figure 1

Funding Acknowledgement
Type of funding source: Private hospital(s). Main funding source(s): UMC Utrecht