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Cardiovascular disease in inflammatory rheumatic diseases

https://doi.org/10.1016/j.berh.2016.10.006Get rights and content

Abstract

Chronic inflammatory rheumatic diseases (IRD), including rheumatoid arthritis, ankylosing spondylitis, and psoriatic arthritis, are prevalent conditions worldwide, with a considerable burden on healthcare systems. They are associated with increased cardiovascular (CV) morbidity and mortality. In this review, we focused on the epidemiology, traditional CV risk factors, genetics, and the link between chronic inflammation, atherosclerosis, and CV disease. Remarkably, patients with IRD have higher vulnerability to atheromatous plaques. The risk of unstable plaques is higher in patients with rheumatoid arthritis than in controls. Active disease is a characteristic ascribed to vulnerability and rupture of plaques and a cause of thrombosis in IRD. Management of CV risk in patients with IRD includes optimal control of disease activity. CV risk stratification by applying risk charts is also essential. Imaging techniques might be useful to determine the actual CV risk of patients with IRD who are included in the category of intermediate or moderate CV risk.

Introduction

Treatment strategies and outcome of inflammatory rheumatic diseases (IRD) have considerably changed since the application of tight control of the disease and advent of biologic therapies, which are always adjusted to specific therapeutic targets. Presently, patients with chronic IRD die more frequently because of infectious complications and certain comorbidities than because of the disease itself. Within the general comorbidity of IRD, cardiovascular (CV) disease (CVD) is the most relevant.

In this chapter, we will focus on the CV morbidity of the most prevalent IRD: rheumatoid arthritis (RA) and spondyloarthritis, particularly on ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Other diseases included in the group of spondyloarthritis, such as undifferentiated spondyloarthritis and nonradiographic axial spondyloarthritis, are not discussed in this review because of the lack of consistent data on the CV comorbidities in these entities.

The current knowledge on CVD in patients with IRD has been updated. Therefore, a PubMed search of the most relevant literature was performed, particularly studies published in English over the last 10 years.

Section snippets

Epidemiology of cardiovascular disease in inflammatory rheumatic diseases

Standardized mortality ratios (SMRs) in patients with IRD are higher than those in the general population (1.3–2.3 in RA, 1.6–1.9 in AS, and 0.8–1.6 in PsA, respectively). This increased and often premature mortality is mainly due to CV events [1]. A recent cross-sectional study on individuals periodically followed-up at rheumatology outpatient clinics has shown that despite having low disease activity, the prevalence of CVD in patients with IRD remains elevated compared with individuals

Presence of subclinical atherosclerotic disease in patients with inflammatory rheumatic diseases

Several noninvasive methods are available to determine the presence of subclinical atherosclerosis in patients with IRD [21]. Endothelial dysfunction (ED) is as an early step in the development of atherosclerosis. It can be defined by the presence of impaired ability of the artery to dilate in response to physical and chemical stimuli because of decreased release or increased breakdown of nitric oxide. This process can be noninvasively assessed by flow-mediated endothelium-dependent

Traditional cardiovascular risk factors

Traditional CVRFs, such as smoking, DM, obesity, hypertension, and dyslipidemia, are independently associated with subclinical atherosclerosis, CV events, and increased risk of CV mortality in patients with chronic IRD ∗[39], ∗[40], ∗[41].

Smoking is known to be a risk factor for the development of RA, particularly in rheumatoid factor (RF) and anti-CCP-positive RA [42]. A recent meta-analysis showed an increased prevalence of cigarette smoking in patients with RA (OR 1.56, 95% CI 1.34, 1.80)

Risk factors related to the disease itself

Several studies on RA indicate that CV risk is increased from the early phases of the disease [77], [78], and this increase continues throughout its evolution. CV mortality in established disease is known to increase in proportion to disease duration [79]. RF and antinuclear antibodies are considered risk factors for MI, congestive heart failure (CHF), and PAD even in patients without RA [80]. RF and anti-CCP-positive RA patients tend to have more severe joint damage, more extra-articular

Effect of nonsteroidal anti-inflammatory drugs and corticosteroids

Nonsteroidal anti-inflammatory drugs (NSAIDs, including coxibs) are commonly used in IRD. They have been associated with an increased risk of death of CV origin [89]. Nevertheless, a longitudinal cohort study of 17,320 patients with RA followed up for an average of 5 years showed a modest increase in CV risk, which was smaller than the risk observed in the general population [90]. A Cox regression analysis stratified by RA status disclosed that NSAID exposure was associated with a 22% risk

Genetics and cardiovascular risk

A genetic component may influence the risk of CVD in patients with IRD. Most studies on this issue have been conducted using the candidate gene strategy in which a specific polymorphism or a set of genetic variants within certain loci have been genotyped. Such polymorphisms were selected according to their potential biological function or the location in a region previously reported to be associated with disease susceptibility or severity. Overall, the results of these studies indicate that the

Inflammation and cardiovascular disease

A broad body of evidence indicates that inflammation is implicated in the pathogenesis of atherosclerosis and CVD in the general population [105]. A great number of proinflammatory molecules such as CRP, fibrinogen, and diverse cytokines are involved in this process [106]. Proinflammatory cytokines such as TNF, IL-6, and IL-1 play a key role in the development of atherosclerosis in patients with IRD. The levels of these molecules increased in patients with RA and other IRD, which in turn

Management of cardiovascular risk in inflammatory rheumatic diseases

Clinicians and patients must be aware of the increased risk of CVD associated with IRD. Close collaboration and combined efforts between general practitioners, cardiologists, internists, and rheumatologists is important to timely initiate CV risk assessment and management in accordance with current guidelines and recommendations together with optimal control of IRD disease activity ∗[1], [123]. Unfortunately, a recent matched cohort study using primary care electronic health records from a

Summary

Patients with RA and other IRD have an increased risk of CV events and CV mortality. This is mainly the result of the combined effect of traditional CVRFs, a genetic component, and the pivotal presence of a chronic proinflammatory status. CV risk assessment and management are poorly conducted in patients with IRD. Higher physician awareness of the increased CV morbidity in these patients is required. The use of risk charts to stratify the CV risk of patients with IRD is mandatory. Better

Conflict of interest statement

Dr. SC has received grants/research supports from Abbvie, MSD, Pfizer and Roche.

Dr. MTN has received grants/research supports from Abbvie, MSD, Pfizer, BMS, and Roche and received consultation fees/had participated in company-sponsored speaker's bureau from Abbvie, Pfizer, Roche, Janssen, Bristol-Myers, and MSD.

Dr. MAG-G has received grants/research supports from Abbvie, MSD, and Roche and received consultation fees/had participated in company-sponsored speaker's bureau from Abbvie, Pfizer,

Acknowledgements

Prof. González-Gay's research was supported by “Fondo de Investigación Sanitaria” (grants PI06/0024, PS09/00748, PI12/00060, and PI15/00525) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain). It was also partially supported by RETICS Programs RD12/0009 (RIER) from “Instituto de Salud Carlos III” (ISCIII, Health Ministry, Spain).

Glossary of abbreviations

Apo
Apolipoprotein
AS
Ankylosing Spondylitis
BMI
body mass index
CCP
cyclic-citrullinated peptide
CHF
congestive heart failure
CI
Confidence interval
cIMT
carotid artery intima-media wall thickness
CIRT
Cardiovascular inflammation reduction trial
Coxibs
COX-2-selective inhibitors
CRP
C-reactive protein
CV
cardiovascular
CVA
cerebrovascular accident
CVD
cardiovascular disease
CVRF
cardiovascular risk factor
DAS
disease activity score
DM
diabetes mellitus
DMARD
disease-modifying antirheumatic drug
ED
Endothelial dysfunction
ESC

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