Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? A critical appraisal

https://doi.org/10.1016/j.semarthrit.2013.07.007Get rights and content

Abstract

Objective

Arterial hypertension (HTN) is reported to burden up to 74% of systemic lupus erythematosus (SLE) patients and contributes significantly to accelerated atherosclerosis and increased cardiovascular (CV) risk. Current HTN treatment guidelines have not incorporated lupus patients in their recommendations; whether these guidelines can be fully implemented in SLE is doubtful.

Methods

A critical appraisal of the existing HTN guidelines in regard to SLE is presented in this review, based upon clinical and experimental data. Particular issues addressed are the time of antihypertensive therapy initiation, the optimal blood pressure level, the antihypertensive agent of first-choice and the need for reduction of the total cardiovascular risk in SLE.

Results

Antihypertensive therapy should be recommended at levels of 140/90 mmHg (systolic and diastolic BP, respectively) in newly diagnosed lupus patients without overt target organ involvement. In the case of lupus nephritis (LN) or diabetes mellitus (DM), therapy should be implemented at lower levels, such as 130/80 mmHg. Hypertensive lupus patients should be considered at high or very high CV risk and, consequently, the optimal BP level should be less than 130/80 mmHg. Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) seem to be a safe and efficacious first-choice antihypertensive treatment in lupus patients. Total CV risk should be considered and co-morbidities (dyslipidemia, antiphospholipid syndrome, etc.) should be managed promptly.

Conclusions

Current HTN therapeutic guidelines, lacking data from large-scale clinical trials, may not adequately apply to SLE patients. The assessment of the aforementioned recommendations in randomized clinical trials is expected to confirm their value in reducing CV risk in SLE.

Introduction

The use of existing and novel therapeutic modalities in systemic lupus erythematosus (SLE) patients resulted in satisfactory control of disease activity in most cases [1], [2]. However, cardiovascular disease (CVD), primarily coronary artery disease (CAD) and cerebrovascular disease, remains a principal cause of death in these patients [3]. It is now widely accepted that lupus patients are at higher (even 50-fold) CVD risk considerably earlier than the general population, which is mainly attributed to the premature atherosclerosis that is associated with SLE [4], [5], [6], [7]. Accelerated atherosclerosis represents the cumulative effect of traditional (arterial hypertension, HTN, diabetes mellitus, dyslipidemia, smoking, positive family history, obesity, etc.), lupus-related (inflammatory and autoimmune), and possibly other risk factors on the arterial wall [5], [8]. The exact contribution of each of the aforementioned factors to CVD morbidity and mortality in lupus patients has not been thoroughly assessed in prospective, randomized trials. Nevertheless, several studies showed that traditional risk factors account for almost half of the CVD burden in SLE [9], [10], [11].

In this context, current guidelines for the management of lupus patients recommend the vigorous control of modifiable risk factors, such as HTN [12]. However, details on the management of this co-morbidity are not specified, thus relying on existing recommendations for the general population [13], [14], [15], [16]. Whether these guidelines are entirely applicable to lupus patients is the main issue of this review.

Section snippets

Is HTN really a problem in SLE?

The World Health Organization (WHO) reported HTN and its effects on target-organs (heart, kidneys, brain, etc.) to be the first cause of death worldwide [17]. Therefore, HTN evaluation and management should be the primary goal in any patient. The prevalence of HTN in SLE is reported to vary greatly, reaching 74% in certain cohorts [18], [19], [20], [21]. Of note, the prevalence of HTN in non-SLE women is significantly lower, reported to reach 7.7% between 20 and 44 years of age [22]. Even

HTN in SLE: Insights into pathophysiology

Lupus nephritis (LN) along with certain immunological abnormalities, such as anti-dsDNA antibodies and low levels of the complement fragments C3 and C4, occurs in nearly 50% of lupus patients and implies a strong correlation with HTN [23], [24]. Although HTN may develop independently of LN [25], and not all histological forms of LN carry an increased risk for HTN, it can be speculated that even mild forms of nephritis might have a significant impact on renal hemodynamics and tubular function.

When to initiate drug therapy?

Despite the existence of several HTN therapeutic guidelines, mainly from North American and European authorities [13], [14], [15], [16], this issue has not been addressed in SLE; therefore, it is doubtful whether current recommendations can be fully implemented in these patients. In this context, hypertensive lupus patients with early disease and no overt renal and/or cardiovascular involvement are considered either within the general hypertensive population [13], [15] or without compelling

Conclusions

HTN represents a major contributor to accelerated atherosclerosis and CVD in lupus patients. Current therapeutic guidelines, lacking data from large-scale, randomized clinical trials, may not adequately apply to this particular group of patients. However, clinical and experimental data support the use of certain drug classes (i.e., ACEIs or ARBs) in the initial management of HTN in SLE; adjuvant therapy should be individualized according to the underlying organ damage or co-morbidities that may

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