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CARDIOVASCULAR JOURNAL OF AFRICA • Volume 29, No 5, September/October 2018
AFRICA
317
Rheumatoid arthritis and risk of cardiovascular disease
Pieter WA Meyer, Ronald Anderson, James A Ker, Mahmood TM Ally
Abstract
In developing countries, rheumatoid arthritis (RA) remains
a seriously under-prioritised disease, particularly among the
underprivileged, often resulting in presentation of patients
late in the course of their disease, further complicated by
limited therapeutic options and inconsistent follow up. The
consequences are often severe with irreversible disability,
increased frequency of co-morbidities, especially cardiovas-
cular disease (CVD), and higher mortality rates, relative to
developed countries. Despite addressing traditional cardio-
vascular risk factors, the impact of subclinical or ‘residual’
inflammation from uncontrolled RA needs to be considered.
This narrative review explores the prevalence and pathogen-
esis of CVD in RA, including the impact of tobacco use. It
discusses pitfalls in the risk assessment of CVD in patients
with RA, and the effect of disease-modifying anti-rheumatic
therapy on cardiovascular co-morbidity.
Keywords:
cardiovascular risk, chronic inflammation, rheuma-
toid arthritis, tobacco usage, effects of drug treatment
Submitted 28/6/17, accepted 11/3/18
Published online 27/3/18
Cardiovasc J Afr
2018;
29
: 317–321
www.cvja.co.zaDOI: 10.5830/CVJA-2018-018
Overall mortality in rheumatoid arthritis (RA)
Despite innovative advances made in the management of
patients with RA, premature mortality from co-morbid diseases
remains a significant challenge. The disease is not only more
common in females (gender ratio of 3:1), but they also tend to
have more active disease and impaired function than males.
1
A systematic review and meta-analysis of 11 longitudinal
studies published in 2013, which covered the period 1955–1995,
encompassing five different developed countries (theNetherlands,
Spain, Sweden, UK and USA) and a total of 51 819 patients
with RA, concluded that ‘mortality has decreased among RA
patients over the past decades but remained higher than in the
general population as assessed by the incident mortality rate and
the standardised mortality over time’.
2
This trend has continued
in developed countries according to more recent studies from
Canada,
3
France
4
and the UK,
5
all confirming a sustained
increased mortality rate in RA sufferers relative to the general
population.
6
According to the findings of the aforementioned
systematic review and a meta-analysis reported by Dadoun
et al.
,
the standardised mortality ratio is 1.47, meaning that patients
with RA have a 47% higher risk of premature mortality relative
to the general population when matched for age and gender,
2
with a decreased life expectancy of three to 10 years or more.
7
A recent study from Spain covering the period 1994–2013
identified the following major independent risk factors for poor
survival in RA: male gender, older age at diagnosis, the presence
of rheumatoid factor (RF), [testing for anti-cyclic citrullinated
peptide antibodies (ACPA) was unavailable in the early years
of the study], higher number of hospital admissions, greater
disease activity, and more severe radiographic joint damage.
8
In addition, genetic predisposition in Caucasian populations
contributes significantly to the development and severity of,
as well as mortality from, RA, this being conferred by the
susceptibility genes known as the
HLA-DRB1
shared epitope
(SE) alleles.
9
The influence of genetic susceptibility is particularly
evident in RA patients who smoke, increasing the propensity for
the development of ACPA-seropositive disease.
9
Indeed cigarette
smoking, and possibly exposure to other types of inhaled
irritants/toxicants, particularly in the context of expression
of SE alleles, appears to promote the formation of ACPA by
mechanisms that have been reviewed in detail.
10,11
Causes of mortality in RA
Cardiovascular disease (CVD) is well recognised as the most
common cause of mortality in patients with RA, being
associated with endothelial dysfunction and arterial stiffness
due to inflammation-associated loss of elasticity of the vascular
wall. This results from alterations in the structural proteins,
Department of Immunology, Faculty of Health Sciences,
University of Pretoria, and Tshwane Academic Division of
the National Health Laboratory Service of South Africa,
Pretoria, South Africa
Pieter WA Meyer, PhD,
Pieter.Meyer@up.ac.zaDepartment of Immunology, Faculty of Health Sciences,
University of Pretoria, Pretoria, South Africa
Ronald Anderson, PhD
Department of Internal Medicine, Faculty of Health
Sciences, University of Pretoria, Pretoria, South Africa
James A Ker, MB ChB, MD
Division of Rheumatology, Department of Internal
Medicine, Faculty of Health Sciences, University of
Pretoria, Pretoria, South Africa
Mahmood TM Ally, PhD
Review Articles