Nicola J. Goodson

Patterns of cardiovascular risk in rheumatoid arthritis

Background: Although it is known that rheumatoid arthritis is associated with an increased risk of cardiovascular disease (CVD), the pattern of this risk is not clear. This study investigated the relative risk of myocardial infarction, stroke and CVD mortality in adults with rheumatoid arthritis compared with adults without rheumatoid arthritis across age groups, sex and prior CVD event status. Methods: We conducted a cohort study among all residents aged ⩾18 years residing in British Columbia between 1999 and 2003. Residents who had visited the doctor at least thrice for rheumatoid arthritis (International Classification of Disease = 714) were considered to have rheumatoid arthritis. A non-rheumatoid arthritis cohort was matched to the rheumatoid arthritis cohort by age, sex and start of follow-up. The primary composite end point was a hospital admission for myocardial infarction, stroke or CVD mortality. Results: 25 385 adults who had at least three diagnoses for rheumatoid arthritis during the study period were identified. During the 5-year study period, 375 patients with rheumatoid arthritis had a hospital admission for myocardial infarction, 363 had a hospitalisation for stroke, 437 died from cardiovascular causes and 1042 had one of these outcomes. The rate ratio for a CVD event in patients with rheumatoid arthritis was 1.6 (95% confidence interval (CI) 1.5 to 1.7), and the rate difference was 5.7 (95% CI 4.9 to 6.4) per 1000 person-years. The rate ratio decreased with age, from 3.3 in patients aged 18–39 years to 1.6 in those aged ⩾75 years. However, the rate difference was 1.2 per 1000 person-years in the youngest age group and increased to 19.7 per 1000 person-years in those aged ⩾75 years. Among patients with a prior CVD event, the rate ratios and rate differences were not increased in rheumatoid arthritis. Conclusions: This study confirms that rheumatoid arthritis is a risk factor for CVD events and shows that the rate ratio for CVD events among subjects with rheumatoid arthritis is highest in young adults and those without known prior CVD events. However, in absolute terms, the difference in event rates is highest in older adults.

Cardiovascular admissions and mortality in an inception cohort of patients with rheumatoid arthritis with onset in the 1980s and 1990s

Background: There is increased cardiovascular disease mortality in rheumatoid arthritis. This may reflect an increased prevalence of cardiovascular disease or an increased case fatality in patients with rheumatoid arthritis. Objectives: To examine whether rheumatoid patients with disease onset in the 1980s–1990s have increased mortality, and to compare cardiovascular admission rates in rheumatoid patients with those of the general population. Methods: An inception cohort of 1010 rheumatoid patients attending Stockport rheumatology clinics between 1981 and 1996 was followed up to December 2002 through the Office for National Statistics. Standardised mortality ratios (SMR) were calculated for all-cause and cause specific mortality, using the population of Stockport as reference. Cardiovascular disease admission rates were ascertained for a subgroup of patients using national hospital episode statistics; standardised cardiovascular disease admission rates (SAR) and SMRs were calculated for this subgroup. Results: 470 patients (48%) died during a median follow up of 11.4 years. All-cause mortality was increased in men (SMR = 1.45 (95% confidence interval, 1.22 to 1.71)) and women (SMR = 1.84 (1.64 to 2.05)), as was cardiovascular disease mortality in men (SMR = 1.36 (1.04 to 1.75) and women (SMR = 1.93 (1.65 to 2.26)). No difference in cardiovascular disease admission rates was observed in men (SAR 1.20 (0.89 to 1.58) or women (SAR = 1.10 (0.88 to 1.36)), despite excess cardiovascular disease mortality in this subgroup. Conclusions: Patients with rheumatoid arthritis have reduced life expectancy and excess cardiovascular disease mortality. Nevertheless, standardised admission rates for cardiovascular disease were not raised. This suggests either that cardiovascular disease in rheumatoid arthritis has a higher case fatality than in the general population or that it often goes unrecognised before the fatal event.

Association of the HLA-DRB1 Gene With Premature Death, Particularly From Cardiovascular Disease, in Patients With Rheumatoid Arthritis and Inflammatory Polyarthritis

Objective To examine the role of the variants of the PTPN22 and HLA–DRB1 genes as predictors of mortality in inflammatory polyarthritis (IP) and rheumatoid arthritis (RA). Methods Patients were recruited from a primary care–based inception cohort of patients with IP and were followed up prospectively. For patients who died, the cause and date of death was obtained. Cox proportional hazards regression models were used to assess the association of the HLA–DRB1 (including the shared epitope [SE]) and PTPN22 genes with the risk of death from all causes and from cardiovascular disease (CVD) and to assess the interactions between SE, smoking, and anti–cyclic citrullinated peptide (anti-CCP) status, adjusted by age at symptom onset and sex. Results DNA samples were available from 1,022 IP patients. During followup, 751 of them (74%) satisfied the American College of Rheumatology 1987 criteria for RA, and 242 of them (24%) died. Carriage of 2 copies of SE alleles predicted death from all causes (hazard ratio [HR] 1.57 [95% confidence interval (95% CI) 1.1–2.2]) and from CVD (HR 1.68 [95% CI 1.1–2.7]). This effect was most marked for individuals with the HLA–DRB1*01/*04 combination. An interaction of smoking, SE alleles, and anti-CCP antibodies was observed and was associated with the greatest risk of death from CVD (HR 7.81 [95% CI 2.6–23.2]). No association of the PTPN22 gene with mortality was detected. Conclusion SE alleles, particularly compound heterozygotes, are associated with death from all causes and from CVD, independently of autoantibody status. However, the combination of SE, smoking, and anti-CCP antibodies is associated with a high risk of premature death in patients with IP and RA, which raises the possibility of a targeted strategy to prevent CVD in these patients.

Coronary artery disease and rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have a reduced life expectancy when compared with the general population. Cardiovascular death is considered the leading cause of mortality in patients with RA; it is responsible for approximately half the deaths observed in RA cohorts. The prevalence of cardiovascular comorbidity is difficult to assess accurately, because cardiovascular disease (CVD) has a tendency to remain silent in the rheumatoid patient. It is not clear why rheumatoid patients have higher rates of coronary disease. Traditional cardiovascular risk factors do not seem to be wholly responsible for the increased cardiovascular risk. Novel cardiovascular risk factors, including inflammatory markers, have been identified over the past few years. It may be that these new cardiovascular risk factors are responsible for accelerating coronary heart disease in patients with RA. This article reviews recent literature relating to the epidemiology of cardiovascular disease in the context of RA.

Non-Steroidal Anti-Inflammatory Drug use does not appear to be associated with increased cardiovascular mortality in patients with inflammatory polyarthritis: Results from a primary care based inception cohort of patients.

Objectives: There is controversy about the effects of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular disease (CVD) mortality. The aim of this study was to explore associations between NSAID use and mortality in patients with inflammatory polyarthritis (IP). Subjects and methods: A total of 923 patients with new onset (IP), recruited to the UK Norfolk Arthritis Register (NOAR) between 1990–1994, were followed up to the end of 2004. Current medication was recorded annually for the first 6 years and then every 2–3 years. Rheumatoid factor (RF) and C-reactive protein (CRP) were measured. Logistic regression was used to calculate all cause and CVD mortality odds ratios (OR) for NSAID use at baseline and during follow-up, adjusting for gender and time-varying covariates: RF, CRP, joint counts, smoking, steroid use, DMARD use and other medication use. Results: By 2004 there were 203 deaths, 85 due to CVD. At baseline, NSAIDs were used by 66% of patients. In final multivariate models, baseline NSAID use was inversely associated with all cause mortality (adjusted OR 0.62, 95% CI 0.45 to 0.84) and CVD mortality (adjusted OR 0.54, 95% CI 0.34 to 0.86). Interval NSAID use had weaker mortality associations: all cause mortality (adjusted OR 0.72, 95% CI 0.52 to 1.00), CVD mortality (adjusted hazard ratio (HR) 0.66, 95% CI 0.40 to 1.08). Conclusion: No excess CVD or all cause mortality was observed in NSAID users in this cohort of patients with IP. This is at variance with the literature relating to NSAID use in the general population. It is unclear whether this represents unmeasured confounders influencing a doctor’s decision to avoid NSAIDs in the treatment of IP.

Cardiovascular co-morbidity in early rheumatoid arthritis

Rheumatoid arthritis (RA) is associated with increased morbidity and mortality due to cardiovascular disease (CVD), mostly accelerated atherosclerotic CVD, and there is evidence that this occurs early in the inflammatory disease process. Both traditional and novel CVD risk factors as well as the effects of the RA disease process and its treatment interact and contribute to the development of CVD in RA. In this review we discuss the evidence for co-morbid CVD complicating early RA. This includes examining studies of mortality outcome and CVD events in cohorts of early RA patients as well as studies using surrogate markers for atherosclerotic CVD in RA. The evidence for shared risk factors for RA and CVD is presented. Screening and modification of CVD risk factors should be an integral part of care for any patient diagnosed with RA. Novel methods to diagnose CVD in high-risk asymptomatic RA patients need to be evaluated.

Cardiovascular involvement in rheumatoid arthritis.

Cardiovascular (CV) disease morbidity and mortality are increased in patients with rheumatoid arthritis (RA) and much of the excess CV disease morbidity appears to be due to atherosclerosis. The pathogenesis of atherosclerosis (ATS) in RA is complex and there is increasing evidence that many factors including novel and traditional cardiovascular risk factors, RA treatments and the RA inflammatory disease process are involved in the development of CV disease in these patients. Of particular interest are the effects of chronic inflammation and immune dysregulation associated with RA. These have been shown to be associated with endothelial dysfunction, which is an early, potentially reversible, functional abnormality of the arterial wall. However, as several CV disease risk factors and drug prescribing are also influenced by RA disease severity it is very difficult to separate out the effects of the inflammatory disease burden on the cardiovascular system in RA.

Magnetic resonance imaging and musculoskeletal ultrasonography detect and characterize covert inflammatory arthropathy in systemic sclerosis patients with arthralgia

OBJECTIVES Arthropathy, particularly synovial inflammation in SSc, is not well characterized. We explored the role of MRI and musculoskeletal ultrasonography (MSUS) in detecting and characterizing synovial inflammation in SSc patients with arthralgia while comparing the two imaging modalities. METHODS Seventeen SSc patients with arthralgia and no overt inflammatory arthritis had a baseline MSUS of their hands. Six months later, 13 unselected patients had a second MSUS and 8 of these 13 patients also had MRI with gadolinium of their most symptomatic hand. RESULTS Of the eight patients undergoing MRI scan, all (100%) patients had synovitis and 88% of patients had tenosynovitis. MRI also showed erosions in 75% of patients. On MSUS, on baseline and second scans, tenosynovitis was seen in 46% and 47% of the patients and synovitis in 6% and 23%, respectively. No erosions were identified. Applying the RAMRIS system (a semi-quantitative MRI scoring system used in RA), the mean values for synovitis, oedema and erosions fell within the range seen in RA. CONCLUSIONS This study demonstrates the presence of a persistent inflammatory, erosive, peripheral arthropathy, similar to that seen in RA, in SSc patients with arthralgia without overt inflammatory joint disease. While both MRI and MSUS are useful in characterizing synovial inflammation in SSc, MRI is clearly more sensitive than MSUS in this setting. Further studies to establish the clinical and radiological musculoskeletal outcomes over time in this group of patients are required in order to identify the appropriate management of arthralgia in SSc.

Cardiovascular risk factors associated with the metabolic syndrome are more prevalent in people reporting chronic pain: Results from a cross-sectional general population study

Summary The prevalence of cardiovascular risk factors and metabolic syndrome are increased in chronic pain. This may contribute to the reduced life expectancy in these patients. ABSTRACT To explore whether chronic pain is associated with cardiovascular risk factors and identify whether increased distribution or intensity of pain is associated with cardiovascular risk, participants in Generation Scotland: The Scottish Family Health study completed pain questionnaires recording the following: presence of chronic pain, distribution of pain, and intensity of chronic pain. Blood pressure, lipids, blood glucose, smoking history, waist–hip ratio, and body mass index were recorded; Framingham 10‐year coronary heart disease (CHD) risk scores were calculated and a diagnosis of metabolic syndrome derived. Associations between chronic pain and cardiovascular risk were explored. Of 13,328 participants, 1100 (8.3%) had high CHD risk. Chronic pain was reported by 5209 (39%), 1294 (9.7%) reported widespread chronic pain, and 707 (5.3%) reported high‐intensity chronic pain. In age‐ and gender‐adjusted analyses, chronic pain was associated with elevated CHD risk scores (odds ratio 1.11, 95% confidence interval 1.01–1.23) and the metabolic syndrome (odds ratio 1.42, 95% confidence interval 1.24–1.62). Multivariate analyses identified dyslipidaemia, age, gender, smoking, obesity, and high waist–hip ratio as independently associated with chronic pain. Within the chronic pain subgroup, widespread pain did not confer any additional cardiovascular disease risk. However, cardiovascular disease risk factors contributing to metabolic syndrome were more prevalent in those reporting high‐intensity chronic pain. This large population‐based study has demonstrated that chronic pain, and in particular high‐intensity chronic pain, is associated with an increased prevalence of cardiovascular risk factors and metabolic syndrome. The 10‐year CHD risk score and metabolic syndrome correlate well with increased pain intensity, but not with widespread pain.

The cardiovascular manifestations of rheumatic diseases.

Purpose of reviewTo review the cardiovascular manifestations of several more common rheumatic conditions in the light of the recent reported literature. Recent findingsEvidence that chronic inflammation is associated with the occurrence of cardiac events in people both with and without chronic inflammatory joint disease is emerging. Both atherosclerosis and rheumatic diseases, however, have a complicated cause, and it is likely that inflammation contributes to other environmental and host risk factors in these patients. Treatments used to suppress inflammation in many rheumatic conditions have the potential to reduce cardiovascular disease morbidity as well as improve musculoskeletal function. SummaryCardiovascular morbidity and mortality have been found to be increased in association with many of the rheumatic diseases. In particular, coronary heart disease seems to be associated with inflammatory rheumatic conditions. Whilst it is likely that chronic systemic inflammation promotes accelerated atherosclerosis in these patients, the mechanisms by which this occurs are complex and the effects of treatment and other cardiovascular risk factors need to be considered.