Do current arterial hypertension treatment guidelines apply to systemic lupus erythematosus patients? A critical appraisal
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
References (85)
- et al.
A retrospective analysis of clinical presentation of lupus nephritis
Am J Med Sci
(2011) - et al.
Tubular lesions and tubular cell adhesion molecules for the prognosis of lupus nephritis
Kidney Int
(2001) - et al.
An ACE inhibitor reduces Th2 cytokines and TGF-β1 and TGF-β2 isoforms in murine lupus nephritis
Kidney Int
(2004) - et al.
Resistant hypertension: an overview of evaluation and treatment
J Am Coll Cardiol
(2008) - et al.
Captopril effect on prostaglandin E2, thromboxane B2 and proteinuria in lupus nephritis patients
Prostaglandins Other Lipid Mediat
(2005) Raynaud's phenomenon
Joint Bone Spine
(2007)- et al.
Atenolol-induced lupus erythematosus
J Am Acad Dermatol
(1997) - et al.
Dual effects of statins therapy in systemic lupus erythematosus and SLE-related atherosclerosis: the potential role for regulatory T cells
Atherosclerosis
(2012) The lupus anticoagulant is a risk factor for myocardial infarction (but not atherosclerosis): Hopkins lupus cohort
Thromb Res
(2004)- et al.
Early atheroma in primary and secondary antiphospholipid syndrome: an intrinsic finding
Semin Arthritis Rheum
(2008)
Clinical significance of antiphospholipid syndrome nephropathy (APSN) in patients with systemic lupus erythematosus (SLE)
Rheumatol Clin
Current and novel therapeutics in treatment of SLE
J Allergy Clin Immunol
Novel biological treatments for systemic lupus erythematosus: current and future modalities
Isr Med Assoc J
Mortality in systemic lupus erythematosus
Arthritis Rheum
Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham study
Am J Epidemiol
Cardiovascular disease in systemic lupus erythematosus: the role of traditional and lupus related risk factors
Curr Cardiol Rev
Atherosclerotic vascular events in a multinational inception cohort of systemic lupus erythematosus
Arthritis Care Res (Hoboken)
Cardiovascular co-morbidity in patients with rheumatic diseases
Arthritis Res Ther
The problem of accelerated atherosclerosis in systemic lupus erythematosus: insights into a complex co-morbidity
Thromb Haemost
Evaluation of risk factors that contribute to high prevalence of premature atherosclerosis in Chinese premenopausal systemic lupus erythematosus patients
J Clin Rheumatol
Systemic lupus erythematosus in a multiethnic US cohort (LUMINA). XXIII. Baseline predictors of vascular events
Arthritis Rheum
Prevalence and correlates of accelerated atherosclerosis in systemic lupus erythematosus
N Engl J Med
EULAR recommendations for the management of systemic lupus erythematosus. Report of a Task Force of the EULAR Standing Committee for International Clinical Studies including Therapeutics
Ann Rheum Dis
2007 Guidelines for the management of arterial hypertension. The task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC)
J Hypertens
The 2010 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2—therapy
Can J Cardiol
Hypertension: The Clinical Management of Primary Hypertension in Adults: Update of Clinical Guidelines 18 and 34
Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure
Hypertension
The World Health Report 2002: Risks to Health
Importance of cumulative exposure to elevated cholesterol and blood pressure in development of atherosclerotic coronary artery disease in systemic lupus erythematosus: a proof-of-concept study
Arthritis Res Ther
African-American and Hispanic ethnicities, renal involvement and obesity predispose to hypertension in systemic lupus erythematosus: results from LUMINA, a multiethnic cohort (LUMINAXLV)
Ann Rheum Dis
Cardiovascular risk factors screening in systemic lupus erythematosus
J Rheumatol
Detection of coronary artery disease and the role of traditional risk factors in the Hopkins Lupus Cohort
Lupus
Hypertension in women of reproductive age in the United States: NHANES 1999-2008
PLoS One
Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis
Ann Rheum Dis
The dissociation of arterial hypertension and lupus glomerulonephritis in systemic lupus erythematosus
Blood Press
Correlation of clinical and pathologic findings in patients with lupus nephritis: a five-year experience in Iran
Saudi J Kidney Dis Transpl
Prognostic value of renal hemodynamic characteristics in patients with proliferative lupus nephritis
Kidney Blood Press Res
Renal haemodynamic characteristics in patients with lupus nephritis
Ann Rheum Dis
The pathophysiology of hypertension in systemic lupus erythematosus
Am J Physiol Regul Integr Comp Physiol
Endothelial activation, endothelial dysfunction and premature atherosclerosis in systemic autoimmune diseases
Neth J Med
Quantification of circulating endothelial cells in peripheral blood of systemic lupus erythematosus patients: a simple and reproducible method of assessing endothelial injury and repair
Nephrol Dial Transplant
Circulating endothelial cells and their progenitors in systemic lupus erythematosus and rheumatoid arthritis patients
Rheumatology (Oxford)
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2020, Seminars in Arthritis and RheumatismCitation Excerpt :Impaired renal hemodynamics and tubular function, as well as renal vascular endothelial dysfunction, have all been implicated in the development of hypertension in LN [9,71,72]. However, many hypertensive patients with SLE have normal kidney function [73]. Proposed disease pathways for hyperteniosn development in SLE involve cytokines (e.g., interleukins, type I interferons, TNF-alpha, tumor necrosis factor), oxidative stress, b-cell hyperactivity and autoantibody production [9].
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2019, Autoimmunity ReviewsCardiovascular disease in systemic lupus erythematosus: A comprehensive update
2017, Journal of AutoimmunityCitation Excerpt :A longitudinal study by Kiani et al. investigating the determinants of atherosclerosis progression in 187 SLE patients, identified age and hypertension as independently associated factors with the progression of carotid IMT and plaque [53]. Several studies so far revealed an increased prevalence of arterial hypertension in lupus patients, ranging from 33 to 74% [54–57]. In an effort to investigate potential contributors of HT in a cohort of 112 lupus patients, Sabio et al., identified renal disease, insulin levels and SLE disease activity index (SLEDAI) as independent predictors of hypertension in these individuals.