Elsevier

Atherosclerosis

Volume 209, Issue 1, March 2010, Pages 255-260
Atherosclerosis

Target organ damage in patients with rheumatoid arthritis: The role of blood pressure and heart rate

https://doi.org/10.1016/j.atherosclerosis.2009.08.047Get rights and content

Abstract

Background

Rheumatoid arthritis (RA) is characterised by increased cardiovascular morbidity and mortality. Even though hypertension (HT) is highly prevalent in RA, the extent of target organ damage (TOD) caused by it remains unknown. Inflammation and sympathetic overdrive may also associate with TOD. We investigated the prevalence and associations of TOD in RA.

Methods

In this cross-sectional, observational study, 251 RA patients with no overt cardiovascular or renal disease had extensive clinical and laboratory evaluations, including a 12-lead electrocardiogram and urine albumin:creatinine ratio. Pulse pressure (PP) was used as a proxy of arterial stiffness and heart rate (HR) of autonomic activity. TOD was defined as described in the European guidelines for the management of arterial hypertension. Binary logistic regression analysis was used to evaluate the independence of the variables that associated with the presence of TOD.

Results

TOD prevalence was 23.5% (59/251). Of the 59 patients with TOD, 45.8% had suboptimally controlled HT, whereas 32.3% had undiagnosed HT. In univariable analysis, TOD was significantly associated with higher age (64.2 ± 11.7 years vs. 58.0 ± 12.4 years, p = 0.001), HT prevalence (89.8% vs. 60.4%, p < 0.001), systolic blood pressure (SBP) (150.3 ± 18.8 mmHg vs. 139.7 ± 20.7 mmHg, p = 0.001), PP (70.6 ± 16.6 mmHg vs. 60.3 ± 17.3 mmHg, p < 0.001), HR (77.1 ± 15.4 bpm vs. 72.2 ± 12.2 bpm, p < 0.001), serum uric acid (320.6 ± 88.8 μmol/l vs. 285.0 ± 74.9 μmol/l, p = 0.03) and type 2 diabetes mellitus prevalence (13.6% vs. 4.7%, p = 0.019). Binary logistic regression analysis revealed that only hypertension indices and HR associated independently with TOD.

Conclusions

TOD is highly prevalent in patients with RA and associates independently with hypertension, arterial stiffness and heart rate. Further prospective studies are needed to confirm these findings and examine the role of beta-blockers in this particular population.

Introduction

One of the individualized cardiovascular risk assessment tools is the cardiovascular continuum which was originally proposed by Dzau et al. [1]. This “cardiovascular disease (CVD) ladder” extends from the well established CVD risk factors (hypertension, dyslipidemia, obesity, smoking, diabetes) to intermediate phenotypes such as endothelial dysfunction and target organ damage (TOD), to established, clinically overt CVD. By TOD, most authorities refer to subclinical injury or dysfunction of different organs, including the heart and kidneys. Left ventricular hypertrophy (LVH) is one of the earlier manifestations of TOD and constitutes a powerful predictor of cardiovascular events [2]. Microalbuminuria, an integrated marker of cardiovascular risk, has also been added to the CVD risk factor panel [3], [4] and constitutes another element of TOD.

The main drive for TOD in the general population is hypertension [5], diabetes mellitus, obesity [6] and the other components of the metabolic syndrome [7]. Pulse pressure [8] and serum uric acid levels [9] have also been implicated as markers of subclinical TOD in hypertensive subjects. Of note, several studies have shown an association between increased heart rate and hypertension [10], showing that central influences act consensually on the heart and the arterioles and prevail over homeostatic mechanisms. Sympathetic overactivity, which is reflected by increased heart rate, has also been implicated in the pathogenesis of several cardiovascular risk factors (hypertension, dyslipidaemia, insulin resistance) and the evolution of cardiovascular hypertrophy [10]. A study by Marinakis et al. [11] has demonstrated a relationship between heart rate variability and TOD, thus highlighting its importance in the genesis of subclinical CVD. Recently [12], inflammation, and in particular tumor necrosis factor-α (TNF-α), has been implicated in the cascade leading to TOD in patients with essential hypertension [12].

Rheumatoid arthritis (RA) is a chronic inflammatory disease, characterised by erosive symmetrical polyarthritis and associated systemic features involving other organs. RA is the most common inflammatory arthritis, affecting 0.8% of the adult population in the UK [13], and has been associated with subclinical atherosclerosis (aortic pulse wave velocity [14], carotid intima media thickness [15]). Despite the increased prevalence [16] and poor control of hypertension in RA [17], no studies exist in the literature assessing the prevalence and associations of TOD. Furthermore, patients with RA are characterised by increased systemic inflammation [18] and increased sympathetic drive [19], factors that could contribute to an increased incidence of TOD.

The present study aimed to investigate the prevalence and associations of TOD in patients with RA.

Section snippets

Patients and methods

In the present study, we assessed a subgroup of the Dudley Rheumatoid Arthritis Comorbidity COhort (DRACCO), detailed characteristics of which have been described in previous papers [17], [20]. All patients of the cohort, without established cardiovascular or renal disease as defined by the European guidelines for the management of hypertension [21] were included in this study (N = 251).

Blood pressure (BP) was the mean of three measurements taken at 5-min intervals on the right arm with the

Results

Two hundred and fifty-one patients with RA fulfilled the inclusion criteria of the present study. Mean age was 59.5 ± 12.5 years and 78.5% (197/251) were females. TOD was present in 23.5% of the studied population (59/251). The prevalence of LVH was 12.4% (31/251), of mild renal impairment 4.8% (12/251) and of microalbuminuria 12% (30/251). Of the 59 RA patients with prevalent TOD, 7 (11.9%) had their HT optimally controlled, 6 (10.2%) had normal blood pressure, 27 (45.8%) had poorly controlled

Discussion

The present study suggests a high prevalence of TOD amongst patients with RA who have no overt cardiovascular or renal disease. However, almost 80% of RA patients with TOD had either undiagnosed or uncontrolled HT, highlighting the importance of early recognition and treatment of high blood pressure in this patient group. In the univariable analysis TOD associated with hypertension indices, heart rate, SUA levels, type 2 DM, while a trend was present for the use of oral glucocorticosteroids.

References (50)

  • R. Pedrinelli et al.

    Microalbuminuria, an integrated marker of cardiovascular risk in essential hypertension

    J Hum Hypertens

    (2002)
  • H.L. Hillege et al.

    Microalbuminuria is common, also in a nondiabetic, nonhypertensive population, and an independent indicator of cardiovascular risk factors and cardiovascular morbidity

    J Intern Med

    (2001)
  • A. Adler

    Obesity and target organ damage: diabetes

    Int J Obes Relat Metab Disord

    (2002)
  • G. Leoncini et al.

    Metabolic syndrome is associated with early signs of organ damage in nondiabetic, hypertensive patients

    J Intern Med

    (2005)
  • F. Viazzi et al.

    Pulse pressure and subclinical cardiovascular damage in primary hypertension

    Nephrol Dial Transplant

    (2002)
  • F. Viazzi et al.

    Serum uric acid and target organ damage in primary hypertension

    Hypertension

    (2005)
  • P. Palatini et al.

    Heart rate and the cardiovascular risk

    J Hypertens

    (1997)
  • A.G. Marinakis et al.

    Heart rate and blood pressure variability are predictors of target organ damage in arterial hypertension

    Am J Hypertension

    (2003)
  • J.F. Navarro-Gonzalez et al.

    Association of tumor necrosis factor-alpha with early target organ damage in newly diagnosed patients with essential hypertension

    J Hypertens

    (2008)
  • D. Symmons et al.

    The prevalence of rheumatoid arthritis in the United Kingdom: new estimates for a new century

    Rheumatology

    (2002)
  • K.M. Maki-Petaja et al.

    Rheumatoid arthritis is associated with increased aortic pulse-wave velocity, which is reduced by anti-tumor necrosis factor-alpha therapy

    Circulation

    (2006)
  • C. Gonzalez-Juanatey et al.

    Increased prevalence of severe subclinical atherosclerotic findings in long-term treated rheumatoid arthritis patients without clinically evident atherosclerotic disease

    Medicine (Baltimore)

    (2003)
  • V.F. Panoulas et al.

    Hypertension in rheumatoid arthritis

    Rheumatology (Oxford)

    (2008)
  • V.F. Panoulas et al.

    Prevalence and associations of hypertension and its control in patients with rheumatoid arthritis

    Rheumatology (Oxford)

    (2007)
  • J.C. Dekkers et al.

    Elevated sympathetic nervous system activity in patients with recently diagnosed rheumatoid arthritis with active disease

    Clin Exp Rheumatol

    (2004)
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