Elsevier

Autoimmunity Reviews

Volume 8, Issue 8, July 2009, Pages 663-667
Autoimmunity Reviews

Cardiovascular risk in rheumatoid arthritis

https://doi.org/10.1016/j.autrev.2009.02.015Get rights and content

Abstract

The increased mortality in rheumatoid arthritis (RA) is mainly due to (atherosclerotic) cardiovascular disease. The cardiovascular morbidity is also increased in comparison with the general population. This increased cardiovascular burden could be caused by 1) an enhanced prevalence of cardiovascular risk factors 2) under treatment of cardiovascular risk factors or 3) RA itself, particularly due to its chronic inflammatory component. Cardiovascular risk factors only partially explain the increased cardiovascular risk and it is becoming increasingly acknowledged that the underlying inflammation in RA plays an essential role. This is probably related to the fact that atherosclerosis also has an inflammatory etiology that is accelerated by RA. Similarly, it can be expected that effective suppression of this inflammatory process by disease modifying antirheumatic drugs and/or biologicals lowers the cardiovascular risk. Altogether, there is accumulating evidence that the increased cardiovascular risk in RA is comparable to that of type 2 diabetes and actually RA should be seen as a new, independent, cardiovascular risk factor for which cardiovascular risk management is essential.

Introduction

The mortality in RA is higher in comparison to the general population and standardized mortality ratio's associated with RA range from 1.3 to 3.0 [1].

This excess mortality is largely attributable to cardiovascular (CV) disease, particularly coronary atherosclerosis. Also the CV morbidity found in RA patients appears to be increased by twofold or more compared to the general population [2], [3].

This increased CV risk in RA could have several causes. First, the prevalence of CV risk factors, such as dyslipidemia, diabetes mellitus, hypertension, higher body mass index (BMI), higher waist to hip-ratio (WHR) or impaired physical fitness, may be increased. Second, in chronic diseases unrelated diseases as CV co-morbidity are under treated frequently which might be another reason explaining the increased CV risk. Third, the chronic inflammatory process in RA, might induce a higher CV risk.

Section snippets

Mortality

Just as in the general population CV disease is the most important cause of death in RA, but not only that, most studies indicate that the chance of dying due to CV disease, particularly coronary heart disease, is increased in comparison to the general population. Investigations assessing the CV mortality are accumulating and recently a meta-analysis of these studies was published [4]. The authors identified 51 observational cohort studies through a “state-of-art” literature search (end of

Cardiovascular morbidity

The last decades several investigations have indicated an amplified rate of CV diseases, i.e. myocardial infarction, congestive heart failure, cerebrovascular disease and peripheral arterial disease in RA patients in comparison to the general population. The magnitude of this increased CV risk was recently investigated by comparing prevalent CV disease in RA with that of diabetes, a well-known CV risk factor, in a prospective Dutch study [5].

Prevalences of coronary, cerebral and peripheral

Preclinical atherosclerosis

Carotid artery intima media thickness (IMT) is an important marker for early, preclinical, atherosclerosis and a predictor of future CV events. IMT is assessed with echocardiographic techniques (carotid ultrasound). One of the landmark studies in 4476 general population persons with a mean age of 73 years and at baseline free from CV disease, followed for 6 years indicated that every 0.20 mm increase of the maximum IMT of the common carotid artery was associated with a 30% increase of new CV

Dyslipidemia

It is well known that increased levels of total cholesterol (TC), low-density-lipoprotein (LDL)-cholesterol and a decreased level of high-density lipoprotein (HDL) cholesterol are associated with an increased risk for CV disease in the general population. The available literature about lipid profiles in patients with RA is contradictory but overall it appears that there is an inverse relationship between disease activity and lipid levels [13]. Early and active RA is associated with an

Under treatment of cardiovascular comorbidity in RA

Generally comorbidity is under treated in chronic diseases [19], and comorbidities in RA are not different than in other chronic diseases [20]. A recent study investigated this topic, in a total of 400 consecutive RA patients and found that hypertension was present 71% of the patients of which only 61% received antihypertensive treatment [21]. Obviously, this area needs further examination.

Atherosclerosis and inflammation

During the last decade it has become increasingly acknowledged that atherosclerosis is a chronic inflammatory process of the artery [22], with, at cellular level, striking similarities with RA [23], [24]. In addition, in both diseases antibodies against heat shock proteins appear to have a role [25]. It has been proposed that the chronic inflammatory state associated with RA translates into a pro-inflammatory state in the vascular wall, resulting in endothelial dysfunction [26], [27], thus

Acetaminophen

From a large prospective investigation it was shown that frequent use, i.e. 22 days/month of acetaminophen was associated with increased risk of CV disease [28]. This might be mediated via cyclo-oxygenase-2 inhibition through induction of hypertension [29].

Glucocorticoids

The net effect of glucocorticoids in RA is a continuing matter of debate in view of their CV side effects, e.g. hypertension, dyslipidemia, insulin resistance and diabetes on one hand but on the other hand glucocorticoids have beneficial

Cardiovascular risk management

As RA appears to be an important, independent, CV risk factor with a similar magnitude as that in type 2 diabetes, RA should be seen as a new CV risk factor, for which CV risk management is mandatory. CV risk management is generally done on the basis of the 10 year absolute risk for a (fatal) CV-event, which is derived from a CV-risk formula based on several CV-risk factors. Examples include the Framingham risk calculator and the Systematic Coronary Risk Evaluation (SCORE). Recently, evidence

Take-home messages

  • RA is a new, independent, cardiovascular risk factor with a similar magnitude as that of diabetes.

  • Traditional cardiovascular risk factors are partly increased in RA.

  • The inflammatory process in RA amplifies atherosclerosis.

  • Cardiovascular risk management is mandatory in RA.

  • Cardiovascular risk management should be aimed at “traditional” cardiovascular risk factors as well as effective suppression of inflammation.

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