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 >or=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 >or=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 >or=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.     

Severe extra-articular disease manifestations are associated with an increased risk of first ever cardiovascular events in patients with rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis is associated with increased cardiovascular mortality and morbidity. OBJECTIVE: To assess the effect of severe extra-articular rheumatoid arthritis (ExRA) manifestations on the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis. METHODS: Patients with ExRA (n = 81) according to predefined criteria and controls (n = 184) without evidence of extra-articular disease were identified from a large research database of patients with rheumatoid arthritis. In a structured review of the medical records, the occurrence and the date of onset of clinically diagnosed CVD events were noted. Cox proportional hazards models were used to estimate the effect of ExRA on the risk of first ever CVD events after the diagnosis of rheumatoid arthritis. ExRA manifestations were modelled as time-dependent covariates, with adjustment for age, sex and smoking at the diagnosis of rheumatoid arthritis. Onset of erosive disease and rheumatoid factor seropositivity were entered as time-dependent variables. Patients were followed until onset of CVD, death or loss to follow-up. RESULTS: ExRA was associated with a significantly increased risk of first ever CVD events (p<0.001), and also with an increased risk of new-onset coronary artery disease, adjusted for age, sex and smoking (hazard ratio (HR): 3.16; 95% confidence interval (95% CI: 1.58 to 6.33). The association between ExRA and any first ever CVD event remained significant when controlling for age, sex, smoking, rheumatoid factor and erosive disease (HR: 3.25; 95% CI: 1.59 to 6.64). CONCLUSION: Severe ExRA manifestations are associated with an increased risk of CVD events in patients with rheumatoid arthritis. This association is not due to differences in age, sex, smoking, rheumatoid factor or erosive joint damage. It is suggested that systemic extra-articular disease is a major determinant of cardiovascular morbidity in rheumatoid arthritis.     

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.     

Usefulness of risk scores to estimate the risk of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have an excess burden of cardiovascular (CV) disease (CVD). CV risk scores for the general population may not accurately predict CV risk for patients with RA. A population-based inception cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA from 1988 to 2007 was followed until death, migration, or December 31, 2008. CV risk factors and CVD (myocardial infarction, CV death, angina, stroke, intermittent claudication, and heart failure) were ascertained by medical record review. Ten-year predicted CVD risk was calculated using the general Framingham and the Reynolds risk scores. Standardized incidence ratios were calculated to compare observed and predicted CVD risks. The study included 525 patients with RA aged ≥30 years without previous CVD. The mean follow-up period was 8.4 years, during which 84 patients developed CVD. The observed CVD risk was 2-fold higher than the Framingham risk score predicted in women and 65% higher in men, and the Reynolds risk score revealed similar deficits. Patients aged ≥75 years had observed CVD risk >3 times the Framingham-predicted risk. Patients with positive rheumatoid factor or persistently elevated erythrocyte sedimentation rates also experienced more CVD events than predicted. In conclusion, the Framingham and Reynolds risk scores substantially underestimated CVD risk in patients with RA of both genders, especially in older ages and in patients with positive rheumatoid factor. These data underscore the need for more accurate tools to predict CVD risk in patients with RA.     

Decreasing mortality in patients with rheumatoid arthritis: results from a large population based cohort in Sweden, 1964-95

OBJECTIVE: To assess changes in mortality in patients with rheumatoid arthritis (RA) from 1964 to 1995. METHODS: A population based cohort of 46,917 patients with RA was identified from 1964 to 1994, using the Swedish Hospital Discharge Register, and followed until 1995 through linkage to the Cause of Death Register. Mortality was separately analyzed in each inclusion period (1964-75, 1975-84, 1985-94). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference RESULTS: All-cause mortality was increased twice the expected (SMR = 2.03, 95% CI 2.00, 2.05). Coronary artery disease was the major cause of death and mortality was increased by 80% (SMR = 1.79, 95% CI 1.75, 1.83). Females with RA aged 20-39 at first discharge had a more than 5-fold increased risk of coronary death (SMR = 5.48, 95% CI 3.45-5.71). From 1975 patients with RA had decreasing all-cause mortality. This decline was most pronounced in patients aged 40-59 at first discharge, where SMR was 2.68 (95% CI 2.45, 2.92) from 1964 to 1974 compared to SMR 1.63 (95% CI 1.37, 1.92) from 1985 to 1994. CONCLUSION: The elevated mortality rates in RA patients compared to the general population have decreased during the last 20 years, possibly due to an increased access to specialized rheumatology care. An excess risk for death in coronary artery disease was, however, present in RA patients, especially patients with early onset of disease.     

Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964-95

OBJECTIVE: Although short term prognosis has improved in patients with systemic lupus erythematosus (SLE) during the early disease course, less is known about the longterm prognosis. METHODS: A cohort of 4737 patients with a diagnostic code of SLE was identified 1964-94 in the Swedish Hospital Discharge Register and followed by linkage to the Cause of Death Register until the end of 1995. Mortality was separately analyzed in 3 different calendar periods (1964-75, 1975-84, 1985-95). The relative risk of death was estimated as standardized mortality ratio (SMR) using the Swedish population as a reference. RESULTS: In total 2314 patients were deceased. Mortality was 3-fold increased (SMR = 3.63, 95% CI 3.49, 3.78) and cardiovascular disease (CVD) was the major cause of death. Patients aged 20-39 years at the first discharge had a 16-fold increased risk of death from coronary heart disease (SMR = 15.99, 95% CI 10.4, 23.6). All-cause mortality had decreased since 1975 and the reason for this decrease was entirely due to a decrease in causes attributed to SLE, but not CVD. Patients aged 20-39 years at the first discharge had a pronounced decrease in mortality, with SMR 33.59 (95% CI 24.3, 45.3) before 1975 compared with SMR 14.23 (95% CI 8.70, 22.0) after 1984. CONCLUSION: Cardiovascular disease was the major cause of death in patients with SLE and young patients had a pronounced increased risk of death. Even if all-cause mortality had declined during the last 2 decades due to causes attributed to SLE, the risk of cardiovascular death remained unchanged.     

Circulating levels of tumor necrosis factor receptors are highly predictive of mortality in patients with rheumatoid arthritis

OBJECTIVE: To investigate whether circulating levels of soluble tumor necrosis factor receptors (sTNFR) are predictive of mortality in rheumatoid arthritis (RA). METHODS: Levels of sTNFRI and sTNFRII at study entry were quantified using enzyme-linked immunosorbent assays in sera from 401 white patients with RA followed up for 13 years. Patients were tracked via the National Health Service Central Register, and the relationship between sTNFR levels and mortality was analyzed using a Cox proportional hazards regression model. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated. RESULTS: At the end of the followup period, 132 (32.9%) of 401 patients had died. Of these, 64 (48.5%) died of cardiovascular disease (CVD). Significant associations between all-cause mortality and baseline levels of sTNFRI and sTNFRII were identified in men (HR 1.7 [95% CI 1.2-2.4] and HR 1.18 [95% CI 1.05-1.32], respectively) and women (HR 1.33 [95% CI 0.99-1.8] and HR 1.14 [95% CI 1.02-1.28], respectively). Analysis including levels of both sTNFRI and sTNFRII indicated that the sTNFRII level was the best overall predictor of mortality. Multivariate analysis also revealed that the sTNFRII level was a predictor of all-cause and CVD mortality independently of age, sex, disease duration, C-reactive protein level, erythrocyte sedimentation rate, rheumatoid factor, nodular disease, modified Health Assessment Questionnaire score, taking CVD drugs, and smoking. CONCLUSION: Our data indicate that serum levels of sTNFR are powerful predictors of mortality in RA. Elevated levels are particularly associated with mortality due to CVD and may be useful for identifying patients at increased risk of premature death.     

Antibodies against human 60 kDa heat shock protein are not associated with cardiovascular disease in patients with rheumatoid arthritis

BACKGROUND: Rheumatoid arthritis is associated with an unexplained increased risk of cardiovascular disease (CVD). Antibodies against human 60 kDa heat shock protein (anti-HSP60) are associated with the presence and severity of CVD. OBJECTIVES: To investigate whether anti-HSP60 antibodies are associated with prevalent CVD in patients with rheumatoid arthritis. METHODS: In a nested case-control design, anti-HSP60 antibody levels were measured in the serum samples of 192 rheumatoid patients. In a regression analysis the association between prevalent CVD and anti-HSP60 antibodies was examined, along with the possible influence on this association of several demographic, rheumatoid arthritis, and CVD related variables. RESULTS: In a random sample of 326 patients with rheumatoid arthritis, 48 cases were identified who also suffered from CVD. Three controls per case with rheumatoid arthritis but without CVD (n = 144) were matched for sex, age, disease duration, and smoking habits. A regression analysis showed no significant association between prevalent CVD and anti-HSP60 antibodies (odds ratio = 1.00 (95% confidence interval, 0.997 to 1.004)). After correcting for possible confounding variables, still no association was found. CONCLUSIONS: In contrast to the general population, anti-HSP60 antibody titres are not associated with prevalent CVD in patients with rheumatoid arthritis. These findings could be the result of an altered immune response to HSP60 in rheumatoid arthritis.     

Disability and Incident Coronary Heart Disease in Older Community‐Dwelling Adults: The Three‐City Study

OBJECTIVES: To prospectively assess the association between disability and incident fatal and nonfatal coronary heart disease (CHD) in older adults free of cardiovascular disease (CVD). DESIGN: A French multicenter prospective population‐based cohort of 9,294 subjects, aged 65 and older at baseline, recruited between 1999 and 2001 and followed for 6 years. SETTING: Three cities in France: Bordeaux in the southwest, Dijon in the northeast, and Montpellier in the southeast. PARTICIPANTS: Seven thousand three hundred fifty‐four participants with no history of CVD and with available information on disability status. Subjects were categorized at baseline as having no disability, mild disability (mobility only), and moderate or severe disability (mobility plus activities of daily living or instrumental activities of daily living). MEASUREMENTS: Incident fatal and nonfatal coronary events (angina pectoris, myocardial infarction, revascularization procedures, and CHD death). RESULTS: At baseline, the mean level of the risk factors increased gradually with the severity of disability. After a median follow‐up of 5.2 years, 264 first coronary events, including 55 fatal events, occurred. After adjustment for cardiovascular risk factors, participants with moderate or severe disability had a 1.7 times (95% confidence interval (CI)=1.0–2.7) greater risk of overall CHD than nondisabled subjects, whereas those with mild disability were not at greater CHD risk. An association was also found with fatal CHD, for which the risk increased gradually with the severity of disability (hazard ratio (HR)_{mild disability}=1.7, 95% CI=0.8–3.6; HR_{moderate/severe disability}=3.5, 95% CI=1.3–9.3; P for trend=.01). CONCLUSION: In older community‐dwelling adults, the association between disability and incident CHD is mostly due to an association with fatal CHD.     

Causes of death in patients with celiac disease in a population-based Swedish cohort

BACKGROUND: Patients with celiac disease have an increased risk of death from gastrointestinal malignancies and lymphomas, but little is known about mortality from other causes and few studies have assessed long-term outcomes. METHODS: Nationwide data on 10 032 Swedish patients hospitalized from January 1, 1964, through December 31, 1993, with celiac disease and surviving at least 12 months were linked with the national mortality register. Mortality risks were computed as standardized mortality ratios (SMRs), comparing mortality rates of patients with celiac disease with rates in the general Swedish population. RESULTS: A total of 828 patients with celiac disease died during the follow-up period (1965-1994). For all causes of death combined, mortality risks were significantly elevated: 2.0-fold (95% confidence interval [CI], 1.8-2.1) among all patients with celiac disease and 1.4-fold (95% CI, 1.2-1.6) among patients with celiac disease with no other discharge diagnoses at initial hospitalization. The overall SMR did not differ by sex or calendar year of initial hospitalization, whereas mortality risk in patients hospitalized with celiac disease before the age of 2 years was significantly lower by 60% (95% CI, 0.2-0.8) compared with the same age group of the general population. Mortality risks were elevated for a wide array of diseases, including non-Hodgkin lymphoma (SMR, 11.4), cancer of the small intestine (SMR, 17.3), autoimmune diseases (including rheumatoid arthritis [SMR, 7.3] and diffuse diseases of connective tissue [SMR, 17.0]), allergic disorders (such as asthma [SMR, 2.8]), inflammatory bowel diseases (including ulcerative colitis and Crohn disease [SMR, 70.9]), diabetes mellitus (SMR, 3.0), disorders of immune deficiency (SMR, 20.9), tuberculosis (SMR, 5.9), pneumonia (SMR, 2.9), and nephritis (SMR, 5.4). CONCLUSION: The elevated mortality risk for all causes of death combined reflected, for the most part, disorders characterized by immune dysfunction.     

Survival and cause specific mortality in patients with inflammatory bowel disease: a long term outcome study in Olmsted County, Minnesota, 1940-2004

BACKGROUND AND AIMS: We followed a population based cohort of patients with inflammatory bowel disease (IBD) from Olmsted County, Minnesota, in order to analyse long term survival and cause specific mortality. Material and METHODS: A total of 692 patients were followed for a median of 14 years. Standardised mortality ratios (SMRs, observed/expected deaths) were calculated for specific causes of death. Cox proportional hazards regression was used to determine if clinical variables were independently associated with mortality. RESULTS: Fifty six of 314 Crohn's disease patients died compared with 46.0 expected (SMR 1.2 (95% confidence interval (CI) 0.9-1.6)), and 62 of 378 ulcerative colitis (UC) patients died compared with 79.2 expected (SMR 0.8 (95% CI 0.6-1.0)). Eighteen patients with Crohn's disease (32%) died from disease related complications, and 12 patients (19%) died from causes related to UC. In Crohn's disease, an increased risk of dying from non-malignant gastrointestinal causes (SMR 6.4 (95% CI 3.2-11.5)), gastrointestinal malignancies (SMR 4.7 (95% CI 1.7-10.2)), and chronic obstructive pulmonary disease (COPD) (SMR 3.5 (95% CI 1.3-7.5)) was observed. In UC, cardiovascular death was reduced (SMR 0.6 (95% CI 0.4-0.9)). Increased age at diagnosis and male sex were associated with mortality in both subtypes. In UC but not Crohn's disease, a diagnosis after 1980 was associated with decreased mortality. CONCLUSIONS: In this population based study of IBD patients from North America, overall survival was similar to that expected in the US White population. Crohn's disease patients were at increased risk of dying from gastrointestinal disease and COPD whereas UC patients had a decreased risk of cardiovascular death.     

Metabolic syndrome is common among middle-to-older aged Mediterranean patients with rheumatoid arthritis and correlates with disease activity: a retrospective, cross-sectional, controlled, study

OBJECTIVES: Patients with rheumatoid arthritis have an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)-a major contributor to CVD-in a cohort of patients with rheumatoid arthritis and its relationship with rheumatoid arthritis related factors is investigated here. METHODS: 200 outpatients with rheumatoid arthritis (147 women and 53 men), with a mean (standard deviation (SD)) age of 63 (11) years, and 400 age and sex-matched controls were studied. MetS was assessed according to the adult treatment panel III criteria and rheumatoid arthritis disease activity by the disease activity score of 28 joints (DAS28). A standard clinical evaluation was carried out, and a health and lifestyle questionnaire was completed. RESULTS: The overall prevalence of MetS was 44% in patients with rheumatoid arthritis and 41% in controls (p = 0.5). Patients with rheumatoid arthritis were more likely to have low high-density lipoprotein cholesterol compared with controls (p = 0.02), whereas controls were more likely to have increased waist circumference or raised blood pressure (p = 0.001 and 0.003, respectively). In multivariate logistic regression analysis adjusting for demographics and rheumatoid arthritis treatment modalities, the risk of having moderate-to-high disease activity (DAS28>3.2) was significantly higher in patients with MetS compared with those with no MetS components (OR 9.24, 95% CI 1.49 to 57.2, p = 0.016). CONCLUSION: A high, albeit comparable to the control population, prevalence of MetS was found in middle-to-older aged patients with rheumatoid arthritis. The correlation of rheumatoid arthritis disease activity with MetS suggests that the increased prevalence of coronary heart disease in patients with rheumatoid arthritis may, at least in part, be attributed to the inflammatory burden of the disease.     

Baseline levels of C-reactive protein and prediction of death from cardiovascular disease in patients with inflammatory polyarthritis: a ten-year followup study of a primary care-based inception cohort

OBJECTIVE: To test the hypothesis that the C-reactive protein (CRP) concentration at baseline is an independent predictor of death from cardiovascular disease (CVD) in newly diagnosed patients with inflammatory polyarthritis (IP). METHODS: Patients with IP (n = 506) who were recruited from the Norfolk Arthritis Register between 1990 and 1992 were followed up to the end of 2001, and complete data on mortality were obtained. At baseline, subjects underwent a structured interview and joint examination and completed a Health Assessment Questionnaire (HAQ). Blood was obtained and analyzed for rheumatoid factor (RF) and CRP concentration. Cox regression was used to calculate hazards ratios (HRs) for risk of death from CVD. RESULTS: The median followup was 10.1 years (interquartile range 9.3-10.8). There were 104 deaths, 40 of which were the result of CVD. Elevated CRP levels (> or=5 mg/liter) predicted death from CVD in univariate analyses: HR 3.9 (95% confidence interval [95% CI] 1.2-13.4) for men, and HR 4.22 (95% CI 1.4-12.6) for women. After adjusting for age and sex, the CVD mortality association was strongest in the subgroup of patients who were RF positive at baseline (adjusted HR 7.4 [95% CI 1.7-32.2]). Multivariate analysis revealed that elevated CRP levels remained a significant independent predictor of death from CVD, even after adjusting for age, sex, smoking status, HAQ score, RF positivity, and swollen joint counts (HR 3.3 [95% CI 1.4-7.6]). CONCLUSION: The CRP concentration at baseline is an important predictor of subsequent death from CVD in patients with new-onset IP and is independent of other indicators of disease severity. This supports the theory that CRP may play a direct role in the pathogenesis of CVD.     

Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study

OBJECTIVE: To study the association between silica exposure and rheumatoid arthritis and how it is modified by cigarette smoking. METHODS: Data were analysed from 276 male cases and 276 male controls aged 18 to 70 years, included in a Swedish population based study between May 1996 and June 2001. A case was defined as a person recently diagnosed with rheumatoid arthritis according to the ACR criteria. Controls were selected from the study base as a stratified random sample accounting for age, sex, and residency. Men with a self reported history of work with rock drilling, stone crushing, or exposure to stone dust in general were defined as silica exposed. Rheumatoid factor (RF) status among cases was recorded. RESULTS: Silica exposed men had increased risk of rheumatoid arthritis, with an odds ratio (OR), adjusted for age, residential area, and smoking, of 2.2 (95% confidence interval, 1.2 to 3.9) among men aged 18 to 70 years, and 2.7 (1.2 to 5.8) among those aged 50 to 70 years. Men who had worked with rock drilling or stone crushing (regarded as highly exposed) had a slightly greater increase in risk of rheumatoid arthritis than silica exposed men in general, with an OR of 3.0 (1.2 to 7.6). The joint effects of silica exposure and smoking were compatible with synergy between these two exposures in the development of rheumatoid arthritis but this was not conclusive. CONCLUSIONS: Silica exposure is associated with increased risk of developing rheumatoid arthritis. This association is not explained by smoking habits.     

Treatment with tumor necrosis factor blockers is associated with a lower incidence of first cardiovascular events in patients with rheumatoid arthritis

OBJECTIVE: To investigate the risk of cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA) treated with tumor necrosis factor (TNF) inhibitors, compared to a standard RA population. METHODS: Patients were recruited from a regional register, which includes over 90% of patients with RA started on TNF blockers in 1999 or later, and a local community based cohort of RA patients, established in 1997. Of a total of 983 patients in the combined cohort, 531 received treatment with etanercept or infliximab during the study period. The total cohort (n = 983) was linked with national registers for inpatient care and cause of death through December 31, 2001. CVD was defined as the first inpatient care or death from CVD without inpatient care for CVD prior to study entry. First CVD events in those treated versus not treated with TNF blockers were estimated, using age and sex adjusted incidence density computations with treatment and disease severity markers as time-dependent covariates. RESULTS: In the anti-TNF-treated patients, the age-sex adjusted incidence rate of first CVD event was 14.0/1000 person-years at risk (95% CI 5.7-22.4), compared with 35.4/1000 person-years (95% CI 16.5-54.4) in those not treated. Controlling for disability, the age-sex adjusted rate ratio was 0.46 (95% CI 0.25-0.85, p = 0.013) in anti-TNF-treated versus not treated. CONCLUSION: These findings suggest that the risk of developing CVD is lower in patients with RA treated with TNF blockers. This is compatible with the hypothesis that inflammation contributes to the development of cardiovascular events.     

Differences in atherosclerotic coronary heart disease between subjects with and without rheumatoid arthritis

OBJECTIVE: Patients with rheumatoid arthritis (RA) are at increased risk for cardiovascular diseases (CVD). We compared the histologic features of coronary artery disease in patients with RA and non-RA controls. METHODS: Forty-one RA patients who died and underwent autopsy between 1985 and 2003 were matched to 82 non-RA controls of the same age and sex with similar history of CVD and autopsy date. Coronary arteries were submitted for histologic evaluation. The grade of stenosis was evaluated in each artery. The numbers of vulnerable plaques and acute coronary lesions were counted. The composition of a representative stable and vulnerable plaque from each vessel was evaluated. Chi-square tests were used to compare differences between groups. RESULTS: Patients and controls had similar age at death (mean 79 yrs) and 61% were female in both groups. Overall, there was no significant difference in grade of stenosis or number of acute coronary lesions. Among subjects with CVD, 54% of controls had grade 3-4 lesions in left main artery versus only 7% of patients (p = 0.023). Vulnerable plaques in left anterior descending (LAD) artery were significantly more common in patients than controls (p = 0.018). Inflammation was observed more frequently in patients, in both the media of left circumflex (p = 0.005) and adventitia of LAD artery (p = 0.024). Similar trends were seen for subjects with heart failure. CONCLUSION: There was less histologic evidence of atherosclerosis but greater evidence of inflammation and instability in RA patients compared to controls. These differences suggest that the mechanisms responsible for cardiovascular morbidity and mortality may be different in patients with RA.     

Death rates and causes of death in patients with rheumatoid arthritis: a population-based study

OBJECTIVE: To assess the mortality and causes of death in a cross-sectional population-based study of 1042 patients with rheumatoid arthritis (RA). METHODS: In 1988, 604 RA patients [470 females (F), 134 males (M)] and 457 age- and sex-matched controls (352 F, 105 M) were examined prospectively (participants) and 438 (183 F, 81 M) non-participant RA patients retrospectively. In 1999, vital status and causes of death were determined. Mortality in the total RA population was compared to that in the general population, and that among participant RA patients to their matched controls. RESULTS: A total of 384 (37%) RA patients and 71 (16%) controls died. RA patients had increased mortality compared to the general population (standardized mortality ratios SMR 2.64) or controls (1.71). This was observed in both sexes. Over 40% of deaths in all groups were due to cardiovascular diseases. RA patients were at increased risk of dying of urogenital, gastrointestinal, respiratory and cardiovascular diseases, infections, and cancers when compared to the general population or controls. CONCLUSIONS: Our results show that a cross-sectional cohort of RA patients had an increased risk of death from various causes.     

Subgroup analyses to determine cardiovascular risk associated with nonsteroidal antiinflammatory drugs and coxibs in specific patient groups

OBJECTIVE: To explore the extent to which clinical characteristics influence the association between cyclooxygenase 2 inhibitors (coxibs) and/or nonselective nonsteroidal antiinflammatory drugs (NSAIDs) and increased cardiovascular disease (CVD) risk in specific patient subgroups. There is substantial concern regarding the potential cardiovascular adverse effects of selective coxibs and nonselective NSAIDs, but many patients with arthritis experience important clinical benefits from these agents. METHODS: The study population consisted of Medicare beneficiaries also eligible for a drug benefits program for older adults during the years 1999-2004. We calculated the relative risk (RR) for CVD events (myocardial infarction [MI], stroke, congestive heart failure, and cardiovascular death) among users of coxibs or nonselective NSAIDs in the prior 6 months compared with nonusers. We assessed biologic interaction between these medication exposures and important patient characteristics. RESULTS: In the primary cohort, we identified 76,082 new users of coxibs, 53,014 new users of nonselective NSAIDs, and 46,558 nonusers. Compared with nonusers, the adjusted RR of CVD events for new users of each agent increased for rofecoxib (RR 1.22, 95% confidence interval [95% CI] 1.14, 1.30) and decreased for naproxen (RR 0.79, 95% CI 0.67, 0.93). Several patient characteristics were found to increase the risk of CVD events among users of some agents in both the primary and secondary cohorts, including age >/=80 years, hypertension, prior MI, prior CVD, rheumatoid arthritis, chronic renal disease, and chronic obstructive pulmonary disease. Rofecoxib and ibuprofen appeared to confer an increased risk in multiple patient subgroups. CONCLUSION: Many nonselective NSAIDs and coxibs are not associated with an increased risk of CVD events. However, several patient characteristics identify important subgroups that may be at an increased risk when using specific agents.     

Excess recurrent cardiac events in rheumatoid arthritis patients with acute coronary syndrome

BACKGROUND: Cardiovascular mortality is increased in rheumatoid arthritis. Possible reasons include an increased incidence of ischaemic heart disease or worse outcome after acute coronary syndrome (ACS). OBJECTIVES: To assess the outcome of ACS in rheumatoid arthritis compared with case matched controls in the context of underlying cardiac risk factors, clinical presentation, and subsequent management. METHODS: 40 patients with rheumatoid arthritis and ACS identified from coronary care admission registers between 1990 and 2000 were case matched as closely as possible for age, sex, classical cardiovascular risk factors, type and severity of ACS, and admission date (+/-3 months) with 40 controls. A standardised proforma was used for detailed case note review. RESULTS: Age, sex, other cardiovascular risk factors, and type and severity of presenting ACS were not significantly different between cases and controls. Recurrent cardiac events were commoner in rheumatoid arthritis (23/40, 57.5%) than controls (12/40, 30%) (p = 0.013); there were 16/40 deaths in rheumatoid arthritis (40%) v 6/40 (15%) in controls (p = 0.012). Recurrent events occurred earlier in rheumatoid arthritis (log rank survival, p = 0.05). Presentation with chest pain occurred in all controls compared with 33/40 rheumatoid patients (82%) (p = 0.006); collapse occurred in one control (2.5%) v 7/40 rheumatoid patients (17.5%) (p = 0.025). Treatment during the ACS was not significantly different in the two groups. CONCLUSIONS: Recurrent ischaemic events and death occur more often after ACS in rheumatoid arthritis. Atypical presentation is commoner in rheumatoid arthritis. There is an urgent need to develop identification and intervention strategies for ACS specific to this high risk group.     

北京地区25～64岁人群高血压左心室肥厚与心血管事件和死亡的关系

目的 分析北京地区25～64岁人群基线时高血压伴左心室肥厚与随访期间发生急性心血管病事件和死亡的关系.方法 本研究对1984-1993年在北京地区采取分层随机抽样方法入选的25～64岁男女两性共7023人进行随访,对随访期间发生的急性心血管病事件和死亡进行登记,排除非高血压性左心室肥厚的211人后,应用Cox比例风险模型对高血压伴左心室肥厚与急性心血管病事件和死亡的关系进行分析.结果 (1)基线7023人中有高血压2240例,高血压人群中左心室肥厚的患病率为11.8%,男性为16.1%,女性为7.5%.(2)与血压正常且无左心室肥厚者比较,高血压合并左心室肥厚者发生急性冠心病、急性脑卒中、总心血管病事件和总死亡的相对危险(RR)分别为4.92(95% CI:2.25,10.74)、4.24(95% CI: 2.58,6.97)、4.06(95% CI:2.60,6.34)和3.26(95% CI:1.99,5.34).(3)与有高血压但无左心室肥厚者比较,高血压合并左心室肥厚者发生急性冠心病、急性脑卒中、总心血管病事件和总死亡的RR分别为1.47(95% CI:0.71,3.05)、1.79(95% CI:1.14,2.80)、1.65(95% CI:1.19,2.28)和1.70(95% CI:1.08,2.69).(4)急性冠心病、急性脑卒中、总心血管病事件和总死亡归因于高血压左心室肥厚的危险百分比(PARP)分别为13.0%、11.0%、10.4%和7.9%,其中男件急性脑卒中归因于高血压左心室肥厚的PARP为15.5%;女性急性冠心病归因于高血压左心室肥厚的PARP为21.7%.结论 高血压左心窒肥厚是急性心血管病发病和死亡的独市的预测指标.