Apparent treatment resistant hypertension and the risk of recurrent cardiovascular events and mortality in patients with established vascular disease
Introduction
Globally, hypertension affects an estimated 31% (1.4 billion) of the adult population and is an important treatable risk factor for cardiovascular disease (CVD) and mortality [1,2]. Although awareness and treatment have improved considerably, still about 50% of patients medically treated for hypertension do not reach the blood pressure (BP) targets recommended by guidelines [1].
Treatment resistant hypertension (TRH), a particularly severe form of hypertension, has been extensively studied during the last decades. The European Society of Hypertension (ESH) and the European Society of Cardiology (ESC) define TRH as when patients treated with optimal or best-tolerated doses of three or more antihypertensive drugs, which should include a diuretic, fail to achieve office systolic BP and diastolic BP values of <140 mmHg and/or <90 mmHg, respectively [3]. A more liberal definition has been adopted by the American College of Cardiology (ACC) and American Heart Association (AHA) who consider patients resistant when office BP is greater than or equal to 130/80 mmHg despite use of three antihypertensive drugs with complementary mechanisms of action (a diuretic should be 1 component) or when BP control is achieved but requires ≥4 medications [4]. The diagnosis of TRH requires exclusion of pseudo-resistance, including medication non-adherence, improper BP measurement, white coat hypertension, and treatment inertia [5]. After exclusion of pseudo-resistance, the true prevalence of TRH is likely to be <10% of treated patients [3]. Population-based studies often use the term apparent TRH (aTRH) to clarify that pseudo-resistance was not excluded [[6], [7], [8], [9], [10]].
Previous studies among patients with hypertension have shown that patients with resistant hypertension are almost 50% more likely to experience outcomes such as death, myocardial infarction, heart failure, stroke, or chronic kidney disease (CKD) compared with treated hypertensive patients with controlled BP [7,8,10,[11], [12]]. Also, in hypertensive patients with coronary artery disease (CAD) the presence of aTRH was associated with a 27–77% higher risk of all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke compared with treated hypertensive patients with controlled BP [9,13,14].
Although considerable amount of data on the relative risk of (recurrent) major adverse cardiovascular events (MACE) is available, there remains a paucity of data regarding the impact of aTRH on life expectancy (LE) with and without CVD [15,16]. Especially in patients with clinically manifest vascular disease, insight and quantification of the potential gain in life years could be of great value in motivating patients with aTRH to adhere to their risk factor management.
Therefore, the aim of the present study is twofold. First, to examine the risk of aTRH on recurrent MACE and all-cause mortality in patients with established CVD. Second, to evaluate the difference in life expectancy free of recurrent MACE in patients with and without aTRH in a large cohort of hypertensive patients with manifest vascular disease.
Section snippets
Study population
The population in this study originated from the Utrecht Cardiovascular Cohort – Second Manifestations of ARTerial disease (UCC-SMART), a single-center, ongoing prospective cohort study. Since September 1996, patients aged 18–80 referred to the University Medical Center Utrecht (UMCU), the Netherlands with a clinically stable manifestation of arterial disease (coronary artery disease (CAD), cerebrovascular disease (CeVD), peripheral arterial disease (PAD), or abdominal aortic aneurysm (AAA)) or
Clinical characteristics
The study population consisted of 7455 patients, of whom 614 (8%) had aTRH. Compared to patients without aTRH, patients with aTRH had a higher mean age (63.7 ± 9.3 versus 60.7 ± 9.8 years), diabetes mellitus was more prevalent (34% versus 17%) and the average eGFR was lower (68 ± 21 versus 77 ± 18 mL/min/1.73 m2) (Table 1). Baseline cholesterol levels were similar in both groups. Mean number of antihypertensive medications prescribed in patients with aTRH was 3.5 (SD 0.8) compared to 1.5 (SD
Discussion
The present study shows that in patients with a recent manifestation of vascular disease aTRH, based on the ESH/ESC definition, was associated with an increased risk of cardiovascular death and all-cause mortality. At the age of 50 years, compared to patients without aTRH, patients with aTRH, on average had a 4.1 year shorter median life expectancy and a 6.4 year shorter median life expectancy free of recurrent cardiovascular disease.
Results of the present study correspond to results of a
Acknowledgements
We gratefully acknowledge the contribution of the research nurses; R. van Petersen (data-manager); B. van Dinther (study manager) and the members of the Utrecht Cardiovascular Cohort-Second Manifestations of ARTerial disease-Studygroup (UCC-SMART-Studygroup): F.W. Asselbergs and H.M. Nathoe, Department of Cardiology; G.J. de Borst, Department of Vascular Surgery; M.L. Bots and M.I. Geerlings, Julius Center for Health Sciences and Primary Care; M.H. Emmelot, Department of Geriatrics; P.A. de
Conflicts of interest
Folkert Asselbergs is supported by UCL Hospitals NIHR Biomedical Research Centre. The other authors report no conflicts of interest.
Funding
The UCC- SMART study was financially supported by a grant of the University Medical Center Utrecht.
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