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Objective: To examine the role of cardiovascular disease (CVD) as a mediator in the pathway between rheumatoid arthritis (RA) and Alzheimer's disease and related dementias (ADRD)., Methods: This retrospective population-based study included patients over 50 years of age with incident RA, who met the 1987 ACR criteria in 1980-2014. This cohort was matched 1:1 on age, sex and index year to comparators without RA. Information on CVD events was manually extracted from electronic health records. The relationships between RA, CVD and ADRD were examined using Cox proportional hazard models. Time dependent mediation analysis was used to examine the role of CVD as a mediator between RA and ADRD., Results: 1754 individuals were included (877 persons with RA and 877 comparators without RA). During follow-up, 105 patients with RA and 102 individuals without RA developed ADRD; 444 patients with RA and 375 individuals without RA developed CVD. There was a non-significant association between RA and ADRD both without (aHR 1.27, 95 % CI 0.96, 1.69) and with (aHR 1.27, 95 % CI 0.95,1.68) CVD as a time dependent mediator. The mediation effect of any CVD on ADRD risk was not significant (p = 0.84). We found a significant interaction between RA and CVD on the risk of ADRD (aHR 1.95, 95 % CI 1.11, 3.42; p = 0.021)., Conclusions: The risk of ADRD in RA appears to be increased mainly in the presence of CVD. CVD was not a significant mediator on the risk of ADRD in RA. There was a significant synergistic effect of RA and CVD on ADRD risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The objective is to examine utilisation of cardiovascular preventive services in patients with rheumatoid arthritis (RA), compared with a non-RA population, and to examine cardiovascular disease (CVD) screening rates among RA patients without diabetes mellitus (DM), hypertension or hyperlipidaemia to non-RA patients with one of these diagnoses., Methods: All ≥18-year-old patients with an RA diagnosis living in one of eight Minnesota counties on 1 January 2015 were included and matched (1:1) by sex, age and county to non-RA comparators. Rates of screening for CVD risk factors, including DM (ie, glucose), hypertension (ie, blood pressure) and hyperlipidaemia (ie, lipids), were compared between groups using Cox models., Results: The study included 1614 patients with RA and 1599 non-RA comparators. DM screening was more common among patients with RA (HR: 1.10, 95% CI: 1.01 to 1.19), as was hypertension screening (HR: 1.37, 95% CI: 1.24 to 1.52). Hyperlipidaemia screening in RA was similar to comparators (HR: 0.99, 95% CI: 0.89 to 1.10). Conversely, patients with RA and no CVD risk factors had a lower probability of undergoing diabetes (HR: 0.67, 95% CI: 0.57 to 0.78) and hyperlipidaemia screening (HR: 0.65, 95% CI: 0.54 to 0.79) than non-RA patients with only one CVD risk factor diagnosis. Hypertension screening was similar between both groups., Conclusions: RA patients undergo CVD preventive screening at rates at least comparable to the general population. However, patients with RA as their sole CVD risk factor were less likely to undergo screenings, despite an equivalent-to-higher risk as the traditional CVD risk factors. These findings demonstrate opportunities for improvement of RA patient care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Cardiovascular disease (CVD) risk is increased in most inflammatory rheumatic diseases (IRDs), reiterating the role of inflammation in the initiation and progression of atherosclerosis. An inverse association of CVD risk with body weight and lipid levels has been described in IRDs. Coronary artery calcium scores, plaque burden and characteristics, and carotid plaques on ultrasound optimize CVD risk estimate in IRDs. Biomarkers of cardiac injury, autoantibodies, lipid biomarkers, and cytokines also improve risk assessment in IRDs. Machine learning and deep learning algorithms for phenotype and image analysis hold promise to improve CVD risk stratification in IRDs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Growing evidence suggests that patients with rheumatoid arthritis (RA) have increased risk for dementia. We assessed risk factors for incident dementia in an inception cohort of patients with RA., Methods: This retrospective population-based cohort study included residents of 8 counties in Minnesota who were ≥ 50 years of age when they met 1987 American College of Rheumatology criteria for incident RA between 1980 and 2014 and were followed until death/migration or December 31, 2019. Patients with dementia before RA incidence were excluded. Incident dementia was defined as 2 relevant International Classification of Diseases, 9th or 10th revision codes at least 30 days apart. Data on sociodemographics, disease characteristics, cardiovascular/cerebrovascular disease (CVD) risk factors, and comorbidities were abstracted from medical records., Results: The study included 886 patients with RA (mean age 65.1 yrs, 65.2% female). During the follow-up period (median 8.5 yrs), 103 patients developed dementia. After adjusting for age, sex, and calendar year of RA incidence, older age at RA incidence (HR 1.14 per 1 year increase, 95% CI 1.12-1.17), rheumatoid nodules (HR 1.76, 95% CI 1.05-2.95), hypertension (HR 1.84, 95% CI 1.19-2.85), presence of large joint swelling (HR 2.03, 95% CI 1.14-3.60), any CVD (HR 2.25, 95% CI 1.38-3.66), particularly ischemic stroke (HR 3.16, 95% CI 1.84-5.43) and heart failure (HR 1.82, 95% CI 1.10-3.00), anxiety (HR 1.86, 95% CI 1.16-2.97), and depression (HR 2.63, 95% CI 1.76-3.93) were associated with increased risk of dementia. After adjusting for CVD risk factors and any CVD, all covariates listed above were still significantly associated with risk of dementia., Conclusion: Apart from age, hypertension, depression, and anxiety, all of which are universally recognized risk factors for dementia, clinically active RA and presence of CVD were associated with an elevated risk of dementia incidence among patients with RA., (Copyright © 2023 by the Journal of Rheumatology.)

Aims: To assess differences in estimated cardiovascular disease (CVD) risk among rheumatoid arthritis (RA) patients from different world regions and to evaluate the management and goal attainment of lipids and blood pressure (BP)., Methods and Results: The survey of CVD risk factors in patients with RA was conducted in 14 503 patients from 19 countries during 2014-19. The treatment goal for BP was <140/90 mmHg. CVD risk prediction and lipid goals were according to the 2016 European guidelines. Overall, 21% had a very high estimated risk of CVD, ranging from 5% in Mexico, 15% in Asia, 19% in Northern Europe, to 31% in Central and Eastern Europe and 30% in North America. Of the 52% with indication for lipid-lowering treatment (LLT), 44% were using LLT. The lipid goal attainment was 45% and 18% in the high and very high risk groups, respectively. Use of statins in monotherapy was 24%, while 1% used statins in combination with other LLT. Sixty-two per cent had hypertension and approximately half of these patients were at BP goal. The majority of the patients used antihypertensive treatment in monotherapy (24%), while 10% and 5% as a two- or three-drug combination., Conclusion: We revealed considerable geographical differences in estimated CVD risk and preventive treatment. Low goal attainment for LLT was observed, and only half the patients obtained BP goal. Despite a high focus on the increased CVD risk in RA patients over the last decade, there is still substantial potential for improvement in CVD preventive measures., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: To compare cardiovascular disease (CVD) rates in rheumatoid arthritis (RA) beneficiaries of the Social Security Disability Insurance (SSDI) with commercially insured RA patients., Method: We created three cohorts of RA patients aged < 65 years for SSDI and three for Marketscan using claims data from 2006 to 2016. The cohort definitions were as follows: (1) cohort 1: ≥ 2 diagnosis codes for RA occurring 7-365 days apart with ≥ 1 diagnosis code from a rheumatologist; (2) cohort 2: ≥ 1 diagnosis code for RA from a rheumatologist and a disease-modifying antirheumatic drugs (DMARDS); and (3) cohort 3: cohort 2, plus initiation of a new biologic/tofacitinib. We used Cox regression to determine the CVD risk comparing SSDI vs. Marketscan. Models were sequentially adjusted for age and sex (model 1); model 1 + diabetes, smoking, and high CVD risk (model 2); and model 2 + dual eligible (Medicare and Medicaid), subsidy, and state buy in (model 3)., Results: There were 380,336 RA patients, mean age 53.3 (SD 8.1) years, 21-24% male. Prevalence of comorbidities was higher in SSDI vs. Marketscan. SSDI RA patients in cohort 2 (model 3) had higher CVD risk (HR 1.23 (1.14-1.33). In cohort 3 (model 3), CVD risk was not statistically significantly different between SSDI and Marketscan (HR 0.89 (0.69-1.15)., Conclusion: RA patient beneficiaries of the SSDI had higher risk for CVD events than those employed. The differences in CVD events between SSDI and Marketscan were partially attributable to differences in CVD risk factors., (© 2022. The Author(s).)

Objective: Both erectile dysfunction (ED) and rheumatoid arthritis (RA) are associated with increased cardiovascular (CV) risk. It is unknown if these diagnoses are associated or if their combination confers additional CV risk. We aimed to define the incidence of ED in RA, and to determine if ED correlates with increased CV risk in RA., Methods: Medical information concerning RA, ED, and CV diagnoses for men with RA (n = 260) diagnosed in Olmsted County, Minnesota, and age-matched male comparators was extracted from a comprehensive medical record system., Results: ED incidence was similar between the RA cohort and comparators (HR 0.80, 95% CI 0.55-1.16). In men with RA, ED diagnosis was associated with a trend toward an increase in peripheral arterial disease (HR 2.22, 95% CI 0.98-5.03) and a significantly decreased rate of myocardial infarction (HR 0.26, 95% CI 0.07-0.90), heart failure (HR 0.49, 95% CI 0.25-0.94), and death (HR 0.56; 95% CI 0.36-0.87). In men with RA and ED, phosphodiesterase-5 inhibitor use was associated with a decreased risk of death (HR 0.35, 95% CI 0.16-0.79), with a trending decreased risk of some CV diagnoses., Conclusion: Incidence of ED was not statistically increased in RA. Although patients with both RA and ED had a similar overall CV risk to those with RA alone, men with both RA and ED had decreased risk of heart failure, myocardial infarction, and death, as well as an increased risk of peripheral arterial disease. Further studies are needed to clarify these associations and their implications for pathogenesis and therapeutics., (Copyright © 2021 by the Journal of Rheumatology.)

Objective: To assess trends in incidence of cardiovascular disease (CVD) and mortality following incident CVD events in patients with rheumatoid arthritis (RA) onset in 1980-2009 vs non-RA subjects., Methods: We studied Olmsted County, Minnesota residents with incident RA (aged > 18 yrs, 1987 American College of Rheumatology criteria met in 1980-2009) and non-RA subjects from the same source population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2016. Incident CVD events included myocardial infarction and stroke. Patients with CVD before RA incidence/index date were excluded. Cox models were used to compare incident CVD events by decade, adjusting for age, sex, and CVD risk factors., Results: The study included 905 patients with RA and 904 non-RA subjects. Cumulative incidence of any CVD event was lower in patients with incident RA in the 2000s vs the 1980s. The HR for any incident CVD in the 2000s vs 1980s was 0.53 (95% CI 0.31-0.93). The strength of association attenuated after adjustment for anti-rheumatic medication use (HR 0.64, 95% CI 0.34-1.22). Patients with RA in the 2000s had no excess in CVD over non-RA subjects (HR 0.71, 95% CI 0.42-1.19). Risk of death after a CVD event was somewhat lower in patients with RA after the 1980s with an HR of 0.54 (95% CI 0.33-0.90) in the 1990s vs 1980s and 0.68 (95% CI 0.33-1.41) in the 2000s vs 1980s., Conclusion: The incidence of major CVD events in RA has declined in recent decades. The gap in CVD occurrence between patients with RA and the general population is closing. Mortality after CVD events in RA may be improving., (© 2021 The Journal of Rheumatology.)

Background: Rheumatoid arthritis (RA) patients have increased risk for cardiovascular disease (CVD). Accurate CVD risk prediction could improve care for RA patients. Our goal is to develop and validate a biomarker-based model for predicting CVD risk in RA patients., Methods: Medicare claims data were linked to multi-biomarker disease activity (MBDA) test results to create an RA patient cohort with age ≥ 40 years that was split 2:1 for training and internal validation. Clinical and RA-related variables, MBDA score, and its 12 biomarkers were evaluated as predictors of a composite CVD outcome: myocardial infarction (MI), stroke, or fatal CVD within 3 years. Model building used Cox proportional hazard regression with backward elimination. The final MBDA-based CVD risk score was internally validated and compared to four clinical CVD risk prediction models., Results: 30,751 RA patients (904 CVD events) were analyzed. Covariates in the final MBDA-based CVD risk score were age, diabetes, hypertension, tobacco use, history of CVD (excluding MI/stroke), MBDA score, leptin, MMP-3 and TNF-R1. In internal validation, the MBDA-based CVD risk score was a strong predictor of 3-year risk for a CVD event, with hazard ratio (95% CI) of 2.89 (2.46-3.41). The predicted 3-year CVD risk was low for 9.4% of patients, borderline for 10.2%, intermediate for 52.2%, and high for 28.2%. Model fit was good, with mean predicted versus observed 3-year CVD risks of 4.5% versus 4.4%. The MBDA-based CVD risk score significantly improved risk discrimination by the likelihood ratio test, compared to four clinical models. The risk score also improved prediction, reclassifying 42% of patients versus the simplest clinical model (age + sex), with a net reclassification index (NRI) (95% CI) of 0.19 (0.10-0.27); and 28% of patients versus the most comprehensive clinical model (age + sex + diabetes + hypertension + tobacco use + history of CVD + CRP), with an NRI of 0.07 (0.001-0.13). C-index was 0.715 versus 0.661 to 0.696 for the four clinical models., Conclusion: A prognostic score has been developed to predict 3-year CVD risk for RA patients by using clinical data, three serum biomarkers and the MBDA score. In internal validation, it had good accuracy and outperformed clinical models with and without CRP. The MBDA-based CVD risk prediction score may improve RA patient care by offering a risk stratification tool that incorporates the effect of RA inflammation.

Objectives: Smoking is a major risk factor for the development of both cardiovascular disease (CVD) and RA and may cause attenuated responses to anti-rheumatic treatments. Our aim was to compare disease activity, CVD risk factors and CVD event rates across smoking status in RA patients., Methods: Disease characteristics, CVD risk factors and relevant medications were recorded in RA patients without prior CVD from 10 countries (Norway, UK, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico). Information on CVD events was collected. Adjusted analysis of variance, logistic regression and Cox models were applied to compare RA disease activity (DAS28), CVD risk factors and event rates across categories of smoking status., Results: Of the 3311 RA patients (1012 former, 887 current and 1412 never smokers), 235 experienced CVD events during a median follow-up of 3.5 years (interquartile range 2.5-6.1). At enrolment, current smokers were more likely to have moderate or high disease activity compared with former and never smokers (P < 0.001 for both). There was a gradient of worsening CVD risk factor profiles (lipoproteins and blood pressure) from never to former to current smokers. Furthermore, former and never smokers had significantly lower CVD event rates compared with current smokers [hazard ratio 0.70 (95% CI 0.51, 0.95), P = 0.02 and 0.48 (0.34, 0.69), P < 0.001, respectively]. The CVD event rates for former and never smokers were comparable., Conclusion: Smoking cessation in patients with RA was associated with lower disease activity and improved lipid profiles and was a predictor of reduced rates of CVD events., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics., Methods: RA patients aged 30-70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up., Results: A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R 2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15-32% of patients. C-statistics ranged 0.68-0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results., Conclusions: The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.

Objective: To assess the cardiovascular disease (CVD) and venous thromboembolism (VTE) risks among patients with newly diagnosed antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV)., Patients and Methods: A population-based incident AAV cohort of 58 patients diagnosed between 1996 and 2015 in Olmsted County, MN, was identified by medical record review. For each patient, 3 age- and sex-matched non-AAV comparators were randomly selected from the same population and assigned an index date corresponding to the AAV incidence date. Medical records of cases and comparators were reviewed for CVD events, which included cardiac events (coronary artery disease, heart failure, and atrial fibrillation), cerebrovascular accidents (CVA), peripheral vascular disease (PVD), and VTE, which included deep vein thrombosis (DVT) and pulmonary embolism (PE)., Results: Baseline total cholesterol, high-density lipoprotein, and current smoking rate were lower in AAV than in comparators (P=.03, P=.01, and P=.04, respectively), whereas other CVD risk factors and Framingham risk score were not significantly different between the 2 groups. The CVD events developed in 13 patients and 17 comparators, corresponding to a more than 3-fold increased risk (hazard ratio [HR], 3.15; 95% CI, 1.51-6.57). By subtypes, risks were increased for cardiac events (HR, 2.96; 95% CI, 1.42-6.15) and CVA (HR, 8.16; 95% CI, 2.45-27.15), but not for PVD. The HR for VTE was 3.26 (95% CI, 0.84-12.60), significantly increased for DVT (HR, 6.25; 95% CI, 1.16-33.60), but not for PE (HR, 1.33; 95% CI, 0.23-7.54)., Conclusion: Despite a similar prevalence of CVD risk factors at baseline, the risk of CVD is more than 3-fold higher and for CVA 8-fold higher in patients with incident AAV than in matched comparator subjects., (Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.)

Objectives: Patients with rheumatoid arthritis (RA) have an excess risk of cardiovascular disease (CVD). We aimed to assess the impact of CVD risk factors, including potential sex differences, and RA-specific variables on CVD outcome in a large, international cohort of patients with RA., Methods: In 13 rheumatology centres, data on CVD risk factors and RA characteristics were collected at baseline. CVD outcomes (myocardial infarction, angina, revascularisation, stroke, peripheral vascular disease and CVD death) were collected using standardised definitions., Results: 5638 patients with RA and no prior CVD were included (mean age: 55.3 (SD: 14.0) years, 76% women). During mean follow-up of 5.8 (SD: 4.4) years, 148 men and 241 women developed a CVD event (10-year cumulative incidence 20.9% and 11.1%, respectively). Men had a higher burden of CVD risk factors, including increased blood pressure, higher total cholesterol and smoking prevalence than women (all p<0.001). Among the traditional CVD risk factors, smoking and hypertension had the highest population attributable risk (PAR) overall and among both sexes, followed by total cholesterol. The PAR for Disease Activity Score and for seropositivity were comparable in magnitude to the PAR for lipids. A total of 70% of CVD events were attributable to all CVD risk factors and RA characteristics combined (separately 49% CVD risk factors and 30% RA characteristics)., Conclusions: In a large, international cohort of patients with RA, 30% of CVD events were attributable to RA characteristics. This finding indicates that RA characteristics play an important role in efforts to reduce CVD risk among patients with RA., Competing Interests: Competing interests: CSC reports grants from National Institute of Arthritis and Musculoskeletal and Skin Disease of the National Institutes of Health during the conduct of the study. AGS has received speaker honoraria and/or consulting fee from Merck/Schering-Plough, Abbott, BMS, UCB, Pfizer/Wyeth, Eli Lilly and Hoffmann-La Roche. TKK reports grants and personal fees from AbbVie, BMS, Biogen, Boehringer Ingelheim, Celgene, Celltrion, Eli Lilly, Hospira/Pfizer, Merck-Serono, MSD, Mundipharma, Novartis, Oktal, Orion Pharma, Roche, Sandoz and UCB. SR, EI, GDK, PLCMvR, SEG, ELM, KD, AS, EA, SW-J, LI, GK, PHD, LT, HE-G, CH, VPR, ICY, PPS, EZ, MAG-G, AC, MvdL, HEV and IM: none declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objectives: The prevalence of atherosclerotic risk factors and disease in Takayasu's arteritis (TAK) has not been well defined. We aimed to assess the frequency of cardiovascular (CV) risk factors and the incidence of CV events (CVEs) in patients with TAK from two ethnically different populations., Methods: Patients with TAK followed at Mayo Clinic, Rochester, MN, USA and Marmara University, Istanbul, Turkey were included in this retrospective study. Patients with TAK were compared with age-, sex- and calendar year-matched controls from the same geographical region without TAK. The 2008 Framingham 10-year general CV risk score (FRS) was used for the evaluation of CV risk at the time of TAK incidence/index date., Results: In total, 191 patients with TAK and 191 non-TAK controls were included. Hypertension and the prevalence of lipid-lowering treatments were significantly more frequent in TAK. Prior to the incidence/index date, occurrence of CVE was significantly higher in TAK. The FRS was significantly higher in TAK compared with non-TAK at incidence/index date. The cumulative incidence of CVE was 15.4% at 10 years in TAK vs 5.8% in non-TAK; the risk of CVE was increased among patients with TAK (hazard ratio = 4.36; 95% CI: 1.25, 15.13)., Conclusion: CV risk factors are more common in patients with TAK, particularly hypertension. The FRS is higher in patients with TAK at the time of diagnosis. The cumulative incidence of CVE was also significantly higher during follow-up in TAK. Our results suggest that patients with TAK should undergo careful assessment of CV risk factors, and an aggressive risk modification approach is warranted., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Chronic inflammation is an independent risk factor for cardiovascular disease (CVD), but most risk calculators, including the Framingham risk score (FRS) and the American College of Cardiology (ACC)/American Heart Association (AHA) risk score do not account for it. These calculators underestimate cardiovascular risk in patients with rheumatoid arthritis and systemic lupus erythematosus. To date, how these scores perform in the estimation of CVD risk in patients with sarcoidosis has not been assessed. In this study, the FRS and the ACC/AHA risk score were calculated for a previously identified cohort of patients with incident cases of sarcoidosis in Olmsted County, Minnesota, United States, from 1989 to 2013 as well as their gender- and age-matched comparators. The standardized incidence ratio (SIR) was estimated as the ratio of the predicted and observed numbers of CVD events. All CVD events were identified by diagnosis codes and were verified by individual medical record reviews. The predicted number of CVD events among 188 cases by FRS was 11.8 and the observed number of CVD events was 34, which corresponded to an SIR of 2.88 (95% confidence interval 2.06 to 4.04). FRS underestimated the risk of CVD events in patients with sarcoidosis by gender, age and severity of sarcoidosis. The predicted number of CVD events among cases by ACC/AHA risk score was 4.6 and the observed number of CVD events was 19, corresponding to an SIR of 4.11 (95% confidence interval 2.62 to 6.44). In conclusion, the FRS and the ACC/AHA risk score underestimate the risk of CVD in patients with sarcoidosis., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Objectives: Cardiovascular disease (CVD) risk calculators developed for the general population do not accurately predict CVD events in patients with RA. We sought to externally validate risk calculators recommended for use in patients with RA including the EULAR 1.5 multiplier, the Expanded Cardiovascular Risk Prediction Score for RA (ERS-RA) and QRISK2., Methods: Seven RA cohorts from UK, Norway, Netherlands, USA, South Africa, Canada and Mexico were combined. Data on baseline CVD risk factors, RA characteristics and CVD outcomes (including myocardial infarction, ischaemic stroke and cardiovascular death) were collected using standardized definitions. Performance of QRISK2, EULAR multiplier and ERS-RA was compared with other risk calculators [American College of Cardiology/American Heart Association (ACC/AHA), Framingham Adult Treatment Panel III Framingham risk score-Adult Treatment Panel (FRS-ATP) and Reynolds Risk Score] using c-statistics and net reclassification index., Results: Among 1796 RA patients without prior CVD [mean ( s . d .) age: 54.0 (14.0) years, 74% female], 100 developed CVD events during a mean follow-up of 6.9 years (12430 person-years). Estimated CVD risk by ERS-RA [mean ( s . d .) 8.8% (9.8%)] was comparable to FRS-ATP [mean ( s . d .) 9.1% (8.3%)] and Reynolds [mean ( s . d .) 9.2% (12.2%)], but lower than ACC/AHA [mean ( s . d .) 9.8% (12.1%)]. QRISK2 substantially overestimated risk [mean ( s . d .) 15.5% (13.9%)]. Discrimination was not improved for ERS-RA (c-statistic = 0.69), QRISK2 or EULAR multiplier applied to ACC/AHA compared with ACC/AHA (c-statistic = 0.72 for all) or for FRS-ATP (c-statistic = 0.75). The net reclassification index for ERS-RA was low (-0.8% vs ACC/AHA and 2.3% vs FRS-ATP)., Conclusion: The QRISK2, EULAR multiplier and ERS-RA algorithms did not predict CVD risk more accurately in patients with RA than CVD risk calculators developed for the general population., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com)

Objective: To assess trends in cardiovascular (CV) mortality in patients with incident rheumatoid arthritis (RA) in 2000-07 versus the previous decades, compared with non-RA subjects., Methods: The study population consisted of Olmsted County, Minnesota, USA residents with incident RA (age ≥ 18 yrs, 1987 American College of Rheumatology criteria was met in 1980-2007) and non-RA subjects from the same underlying population with similar age, sex, and calendar year of index. All subjects were followed until death, migration, or December 31, 2014. Followup was truncated for comparability. Aalen-Johansen methods were used to estimate CV mortality rates, adjusting for competing risk of other causes. Cox proportional hazards models were used to compare CV mortality by decade., Results: The study included 813 patients with RA and 813 non-RA subjects (mean age 55.9 yrs; 68% women for both groups). Patients with incident RA in 2000-07 had markedly lower 10-year overall CV mortality (2.7%, 95% CI 0.6-4.9%) and coronary heart disease (CHD) mortality (1.1%, 95% CI 0.0-2.7%) than patients diagnosed in 1990-99 (7.1%, 95% CI 3.9-10.1% and 4.5%, 95% CI 1.9-7.1%, respectively; HR for overall CV death: 0.43, 95% CI 0.19-0.94; CHD death: HR 0.21, 95% CI 0.05-0.95). This improvement in CV mortality persisted after accounting for CV risk factors. Ten-year overall CV mortality and CHD mortality in 2000-07 RA incidence cohort was similar to non-RA subjects (p = 0.95 and p = 0.79, respectively)., Conclusion: Our findings suggest significantly improved overall CV mortality, particularly CHD mortality, in patients with RA in recent years. Further studies are needed to examine the reasons for this improvement.

Objective: Women and men with rheumatoid arthritis (RA) have an increased risk for fragility fractures and cardiovascular disease (CVD), each of which has been reported to contribute to excess morbidity and mortality in these patients. Fragility fractures share similar risk factors for CVD but may occur at relatively younger ages in patients with RA. We aimed to determine whether a fragility fracture predicts the development of CVD in women and men with RA., Methods: We studied a population-based cohort with incident RA from 1955 to 2007 and compared it with age- and sex-matched non-RA subjects. We identified fragility fractures and CVD events following the RA incidence/index date, along with relevant risk factors. We used Cox models to examine the association between fractures and the development of CVD, in which fractures and CVD risk factors were modeled as time-dependent covariates., Results: There were 1171 subjects (822 women; 349 men) in each of the RA and non-RA cohorts. Over followup, there were 406 and 346 fragility fractures and 286 and 225 CVD events, respectively. The overall CVD risk was increased significantly for RA subjects following a fragility fracture (HR 1.81, 95% CI 1.38-2.37) but not for non-RA subjects (HR 1.18, 95% CI 0.85-1.63). Results were similar for women and men with RA., Conclusion: Fragility fractures in both women and men with RA are associated with an increased risk for CVD events and should raise an alert to clinicians to target these individuals for further screening and preventive strategies for CVD.

This study aimed to determine the relationship between noninvasive measures of arterial health and both estimated 10-year cardiovascular risk and measures of disease activity over time in established rheumatoid arthritis. Fifty rheumatoid arthritis patients underwent noninvasive arterial health testing (brachial artery reactivity, aortic augmentation index [AIx], pulse wave velocity, carotid artery intima-media thickness, and carotid artery plaque presence) and assessment of clinical disease activity (tender or swollen joint counts, Clinical Disease Activity Index [CDAI], and Health Assessment Questionnaire II [HAQ-II]). Clinical measures during 3 years before the study visit were averaged. Arterial health testing was compared with the American Heart Association/American College of Cardiology (AHA/ACC) Pooled Cohort Equation. Spearman methods identified correlations between disease activity measures, cardiac biomarkers, and arterial health parameters. Among the patients (mean age, 57.5 years), disease activity was moderate (mean [SD] CDAI, 16.9 [15.3]). At the study visit, corrected aortic augmentation index correlated with CDAI (r = 0.37, P = .009) and HAQ-II (r = 0.33, P = .02). AIx correlated with time-averaged tender joint count (r = 0.37, P = .008), CDAI (r = 0.36, P = .01), HAQ-II (r = 0.36, P = .01), swollen joint count (r = 0.36, P = .10), patient global assessment (r = 0.33, P = .02), physician global assessment (r = 0.35, P = .01), and pain score (r = 0.38, P = .007). The AHA/ACC low-risk group (<5% 10-year risk) had highest prevalence of carotid plaques. Arterial health testing may identify increased risk of cardiovascular disease compared with risk obtained through AHA/ACC Pooled Cohort Equation. Measures of arterial stiffness correlate with the burden of disease activity over time.

Objective: Cardiovascular disease (CVD) risk calculators designed for use in the general population do not accurately predict the risk of CVD among patients with rheumatoid arthritis (RA), who are at increased risk of CVD. The process of developing risk prediction models involves numerous issues. Our goal was to develop a CVD risk calculator for patients with RA., Methods: Thirteen cohorts of patients with RA originating from 10 different countries (UK, Norway, Netherlands, USA, Sweden, Greece, South Africa, Spain, Canada and Mexico) were combined. CVD risk factors and RA characteristics at baseline, in addition to information on CVD outcomes were collected. Cox models were used to develop a CVD risk calculator, considering traditional CVD risk factors and RA characteristics. Model performance was assessed using measures of discrimination and calibration with 10-fold cross-validation., Results: A total of 5638 RA patients without prior CVD were included (mean age: 55 [SD: 14] years, 76% female). During a mean follow-up of 5.8 years (30139 person years), 389 patients developed a CVD event. Event rates varied between cohorts, necessitating inclusion of high and low risk strata in the models. The multivariable analyses revealed 2 risk prediction models including either a disease activity score including a 28 joint count and erythrocyte sedimentation rate (DAS28ESR) or a health assessment questionnaire (HAQ) along with age, sex, presence of hypertension, current smoking and ratio of total cholesterol to high-density lipoprotein cholesterol. Unfortunately, performance of these models was similar to general population CVD risk calculators., Conclusion: Efforts to develop a specific CVD risk calculator for patients with RA yielded 2 potential models including RA disease characteristics, but neither demonstrated improved performance compared to risk calculators designed for use in the general population. Challenges encountered and lessons learned are discussed in detail.

A higher incidence of cardiovascular disease (CVD) has been observed in several chronic inflammatory diseases. However, data on sarcoidosis are limited.In this study, 345 patients with incident sarcoidosis in Olmsted County (Minnesota, USA) during 1976-2013 were identified based on comprehensive medical record review. 345 sex- and age-matched comparators were also identified from the same underlying population. Medical records were individually reviewed for CVD, including coronary artery disease, congestive heart failure, atrial fibrillation, cerebrovascular accident, transient ischaemic attack, peripheral arterial disease and abdominal aortic aneurysm. Cox proportional hazards models with adjustment for age, sex, calendar year and cardiovascular risk factors were used to compare the rate of development of CVD between cases and comparators.The prevalence of CVD before the index date was not significantly different between the two groups. Adjusting for age, sex and calendar year, the risk of incident CVD after the index date was significantly elevated among patients with sarcoidosis with an adjusted hazard ratio of 1.57 (95% CI 1.15-2.16). Adjustment for cardiovascular risk factors yielded an adjusted hazard ratio of 1.65 (95% CI 1.08-2.53). Significantly increased risk was also observed for several types of CVD, including coronary artery disease, congestive heart failure, atrial fibrillation and cerebrovascular accident.Increased incidence of CVD among patients with sarcoidosis was demonstrated in this population-based cohort, even after controlling for baseline traditional atherosclerotic risk factors., (Copyright ©ERS 2017.)

Objective: To examine the role of rheumatoid arthritis (RA) flare, remission and RA severity burden in cardiovascular disease (CVD)., Methods: In a population-based cohort of patients with RA without CVD (age ≥30 years; 1987 American College of Rheumatology criteria met in 1988-2007), we performed medical record review at each clinical visit to estimate flare/remission status. The previously validated RA medical Records-Based Index of Severity (RARBIS) and Claims-Based Index of RA Severity (CIRAS) were applied. Age- and sex-matched non-RA subjects without CVD comprised the comparison cohort. Cox models were used to assess the association of RA activity/severity with CVD, adjusting for age, sex, calendar year of RA, CVD risk factors and antirheumatic medications., Results: Study included 525 patients with RA and 524 non-RA subjects. There was a significant increase in CVD risk in RA per time spent in each acute flare versus remission (HR 1.07 per 6-week flare, 95% CI 1.01 to 1.15). The CVD risk for patients with RA in remission was similar to the non-RA subjects (HR 0.90, 95% CI 0.51 to 1.59). Increased cumulative moving average of daily RARBIS (HR 1.16, 95% CI 1.03 to 1.30) and CIRAS (HR 1.38, 95% CI 1.12 to 1.70) was associated with CVD. CVD risk was higher in patients with RA who spent more time in medium (HR 1.08, 95% CI 0.98 to 1.20) and high CIRAS tertiles (HR 1.18, 95% CI 1.06 to 1.31) versus lower tertile., Conclusions: Our findings show substantial detrimental role of exposure to RA flare and cumulative burden of RA disease severity in CVD risk in RA, suggesting important cardiovascular benefits associated with tight inflammation control and improved flare management in patients with RA., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Objective: To determine trends in the incidence and clinical presentation of ankylosing spondylitis (AS), the incidence of cardiovascular disease (CVD), and cardiovascular (CV) risk factors among patients with AS and compare the observed incidence of CVD with that predicted by the Framingham Risk Score (FRS)., Methods: A population-based inception cohort of residents of Olmsted County, Minnesota age ≥18 years who fulfilled Modified New York Criteria for AS in 1980-2009 was assembled. Clinical features at presentation were recorded. Age- and sex-adjusted incidence rates and survival were estimated. Incident CVD and CV risk factors were identified. The 10-year CVD risk was calculated using the FRS. Standardized incidence ratios (ratios of observed CVD in AS to that predicted by the FRS) were calculated., Results: Eighty-six patients were diagnosed with AS over the study period with an age- and sex-adjusted incidence of 3.1 per 100,000 (95% confidence interval [95% CI] 2.5-3.8). The mean age at diagnosis was 35 years (range 19-69 years). Inflammatory back pain, seen in 90% of patients, was the most common presenting manifestation. The 10-year mean ± SD cumulative incidence of CVD was 15.8% ± 6.1%, three times higher than the predicted events based on the FRS (standardized incidence ratio 3.01, 95% CI 1.35-6.69; P = 0.007). Overall survival was similar to the general population., Conclusion: AS occurs in approximately 3 persons per 100,000 per year. Clinical features, extraarticular manifestations, and interval from symptom onset to diagnosis have remained constant in this population over the study period. The CVD risk in these patients is higher than expected and underestimated by the FRS., (© 2015, American College of Rheumatology.)

Objective: To assess the occurrence of acute coronary syndrome (ACS) in patients with giant cell arteritis (GCA) compared to subjects without GCA., Methods: We retrospectively reviewed a population-based incidence cohort of Olmsted County, Minnesota residents with GCA diagnosed in 1950-2009. We compared this cohort with a cohort of patients without GCA of similar age, sex, and calendar year from the same population., Results: The study included 245 patients with GCA and 245 non-GCA subjects. The mean ± SD Framingham cardiovascular risk score was 30% ± 19% in GCA patients and 34% ± 23% in non-GCA subjects (P = 0.096) at the incidence/index date. Diabetes mellitus was significantly less common in GCA patients than non-GCA subjects at the index date. The mean high-density lipoprotein was higher and triglycerides were lower, with fewer patients taking lipid-lowering medications in the GCA cohort compared to the non-GCA cohort at the index date. During followup, no difference between the 2 cohorts was noted in the overall rate of ACS events (hazard ratio 0.74, 95% confidence interval 0.44-1.26). Overall thrombosis in myocardial infarction scores were similar in both cohorts. Revascularization procedures were done less frequently in GCA than in non-GCA subjects (19% versus 50%; P = 0.015). Post-ACS hospital length of stays and complications were similar in both cohorts., Conclusion: Multiple cardiovascular risk factors are less atherogenic at incidence of GCA. There is no overall increased risk of ACS in patients with GCA., (Copyright © 2015 by the American College of Rheumatology.)

Objective: To examine longterm visit-to-visit blood pressure (BP) variability in patients with rheumatoid arthritis (RA) versus non-RA subjects and to assess its effect on cardiovascular (CV) events and mortality in RA., Methods: Clinic BP measures were collected in a population-based incident cohort of patients with RA (1987 American College of Rheumatology criteria met between January 1, 1995, and January 1, 2008) and non-RA subjects. BP variability was defined as within-subject SD in systolic and diastolic BP., Results: The study included 442 patients with RA (mean age 55.5 yrs, 70% females) and 424 non-RA subjects (mean age 55.7 yrs, 69% females). Patients with RA had higher visit-to-visit variability in systolic BP (13.8 ± 4.7 mm Hg) than did non-RA subjects (13.0 ± 5.2 mm Hg, p = 0.004). Systolic BP variability declined after the index date in RA (p < 0.001) but not in the non-RA cohort (p = 0.73), adjusting for age, sex, and calendar year of RA. During the mean followup of 7.1 years, 33 CV events and 57 deaths occurred in the RA cohort. Visit-to-visit systolic BP variability was associated with increased risk of CV events (HR per 1 mm Hg increase in BP variability 1.12, 95% CI 1.01-1.25). Diastolic BP variability was associated with all-cause mortality in RA (HR 1.14, 95% CI 1.03-1.27), adjusting for systolic and diastolic BP, body mass index, smoking, diabetes, dyslipidemia, and use of antihypertensives., Conclusion: Patients with RA had higher visit-to-visit systolic BP variability than did non-RA subjects. There was a significant decline in systolic BP variability after RA incidence. Higher visit-to-visit BP variability was associated with adverse CV outcomes and all-cause mortality in RA.

Objective: Early menopause is associated with an increased risk for developing rheumatoid arthritis (RA). The risk for cardiovascular disease (CVD) in women increases following menopause. Because RA is associated with an increased risk of CVD, this study was undertaken to determine whether early menopause affects the risk of developing CVD in women with RA., Methods: A population-based inception cohort of 600 women with RA who fulfilled 1987 American College of Rheumatology criteria for RA between 1955 and 2007 and were age ≥ 45 years at diagnosis was assembled and followed. Age at menopause and duration of hormone replacement therapy, along with occurrence of CVD, was ascertained by review of medical records. Cox proportional hazard models compared women who underwent early menopause (natural or artificial menopause at age ≤ 45 yrs) to those within the cohort who did not undergo early menopause., Results: Of 600 women, 79 experienced early menopause. Women who underwent early menopause were at significantly higher risk for developing CVD when compared to women who did not (HR 1.56; 95% CI 1.08-2.26)., Conclusion: The risk of CVD in women with RA was higher in those who experienced early menopause, and like other known risk factors should increase clinician concern for development of CVD in these patients.

Background: Rheumatic disease and heart disease share common underpinnings involving inflammation. The high levels of inflammation that characterize rheumatic diseases provide a "natural experiment" to help elucidate the mechanisms by which inflammation accelerates heart disease. Rheumatoid arthritis (RA) is the most common of the rheumatic diseases and has the best studied relationships with heart disease., Methods: A review of current literature on heart disease and RA was conducted., Results: Patients with RA have an increased risk of developing heart disease that is not fully explained by traditional cardiovascular risk factors. Therapies used to treat RA may also affect the development of heart disease; by suppressing inflammation, they may also reduce the risk of heart disease. However, their other effects, as in the case of steroids, may increase heart disease risk., Conclusions: Investigations of the innate and adaptive immune responses occurring in RA may delineate novel mechanisms in the pathogenesis of heart disease and help identify novel therapeutic targets for the prevention and treatment of heart disease., (© 2013 Mosby, Inc. All rights reserved.)

Objective: To determine whether the impact of aging on cardiovascular disease (CVD) risk in patients with rheumatoid arthritis (RA) differs from that in the general population (as estimated by the Framingham Risk Score [FRS])., Methods: A population-based inception cohort of Olmsted County, Minnesota residents ages≥30 years who fulfilled the American College of Rheumatology 1987 criteria for RA in 1988-2008 was assembled and followed up until death, migration, or July 1, 2012. Data on CVD events were collected by medical records review. The 10-year FRS for CVD was calculated. Cox models adjusted for FRS were used to examine the influence of age on CVD risk., Results: The study included 563 patients with RA without prior CVD (mean age 55 years, 72% women, and 69% seropositive [i.e., rheumatoid factor and/or anti-citrullinated protein antibody positive]). During a mean followup of 8.2 years, 98 patients developed CVD (74 seropositive and 24 seronegative), but the FRS predicted only 59.7 events (35.4 seropositive and 24.3 seronegative). The gap between observed and predicted CVD risk increased exponentially across age, and the effect of age on CVD risk in seropositive RA was nearly double its effect in the general population, with additional log(age) coefficients of 2.91 for women (P=0.002) and 2.06 for men (P=0.027)., Conclusion: Our findings indicate that age exerts an exponentially increasing effect on CVD risk in seropositive RA, but no increased effect among seronegative patients. The causes of accelerated aging in patients with seropositive RA deserve further investigation., (Copyright © 2013 by the American College of Rheumatology.)

Objective: Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease and mortality. Lipid-lowering therapy is reportedly underused in patients with RA. Longitudinal cohort studies comparing use of lipid-lowering medications in patients with RA versus the general population are lacking., Methods: Cardiovascular risk factors, lipid measures, and use of lipid-lowering agents were assessed in a population-based inception cohort of patients with RA and a cohort of non-RA subjects followed from January 1, 1988, to December 31, 2008. The National Cholesterol Education Program (NCEP) Adult Treatment Panel III (ATPIII) guidelines were assessed at the time of each lipid measure throughout followup. Time from meeting guidelines to initiation of lipid-lowering agents was assessed using Kaplan-Meier methods., Results: The study population included 412 RA and 438 non-RA patients with ≥ 1 lipid measure during followup and no prior use of lipid-lowering agents. Rates of lipid testing were lower among patients with RA compared to non-RA subjects. Among patients who met NCEP ATPIII criteria for lipid-lowering therapy (n = 106 RA; n = 120 non-RA), only 27% of RA and 26% of non-RA subjects initiated lipid-lowering agents within 2 years of meeting the guidelines for initiation., Conclusion: There was substantial undertreatment in both the RA and the non-RA cohorts who met NCEP ATPIII criteria for initiation of lipid-lowering agents. Patients with RA did not have as frequent lipid testing as individuals in the general population.

Background: Emerging evidence suggests that severe psoriasis is associated with increased risk of cardiovascular disease. The goal of this study was to examine the risk and predictors of clinical cardiovascular events in psoriasis., Methods: We performed a historical cohort and a nested case-cohort study using the population-based resources in Olmsted County, Minnesota. The study population included a population-based incidence cohort of patients with psoriasis first diagnosed between January 1, 1970, and January 1, 2000, and 2678 age- and sex-matched non-psoriasis subjects. Cardiovascular events, including hospitalized myocardial infarction, coronary revascularization procedures, stroke, heart failure, and cardiovascular death., Results: Psoriasis was associated with an increased risk of myocardial infarction based on diagnostic codes (hazard ratio 1.26; 95% confidence intervals: 1.01, 1.58) but not when the analyses were restricted to validated myocardial infarction (hazard ratio 1.18; 95% confidence intervals: 0.80, 1.74). Psoriasis was not associated with an increased risk of heart failure or cardiovascular death. Traditional cardiovascular risk factors were significantly associated with cardiovascular risk in psoriasis. Each 1% increase in Framingham risk score at psoriasis incidence corresponded with a 5-10% increase in risk of cardiovascular events., Conclusion: In this large incidence cohort of patients with psoriasis representing the full disease severity spectrum, psoriasis was not associated with an increased cardiovascular risk., (© 2013 The International Society of Dermatology.)

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., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To determine the frequency of hypothyroidism in patients with rheumatoid arthritis (RA), and to elucidate the association of hypothyroidism and development of cardiovascular disease (CVD) in these patients., Methods: A retrospective medical record review was performed using all incident cases of adult-onset RA from Olmsted County, MN, USA, that fulfilled criteria for RA in the years 1988-2007. Patients with and without thyroid disease were followed longitudinally for the development of CVD., Results: A cohort of 650 patients with RA and an age and sex-matched comparison cohort of 650 patients without RA was assembled (both cohorts mean age 55.8 yrs; 69% were women). There was no significant difference between cohorts in the presence of hypothyroid disease or subclinical hypothyroidism at time of RA diagnosis. No significant difference was found in the cumulative incidence of hypothyroid disease between the 2 cohorts. Hypothyroid disease was found to be significantly associated with CVD in patients with RA (hazard ratio 2.0; 95% CI 1.1, 3.6). This difference remained significant and unchanged after adjustment for traditional CV risk factors (HR 2.0; 95% CI 1.1, 3.6)., Conclusion: No significant difference was found in either incidence or prevalence of hypothyroidism between patients with and those without RA. Hypothyroid disease was significantly associated with CVD in patients with RA, even after adjustment for other traditional CV risk factors.

Purpose of Review: To highlight recent evidence regarding the contribution of traditional and nontraditional [e.g. inflammatory markers, rheumatoid arthritis (RA) features] risk factors toward the excess cardiovascular risk in RA., Recent Findings: The impact of traditional risk factors on the development of cardiovascular disease in persons with RA is an area of active research. Some are more prevalent among people with RA (e.g. smoking); others appear to have paradoxical relationships (e.g. body mass index), and findings remain inconsistent with others (e.g. dyslipidemia). Collectively the data suggest that cardiovascular risk factors behave differently in RA. Thus, risk scores developed for the general population based on traditional cardiovascular risk factors alone are unlikely to accurately estimate cardiovascular risk in RA, highlighting the need for RA-specific risk prediction tools.Nontraditional risk factors, in particular RA disease activity/severity measures, including inflammatory markers, disease activity scores, seropositivity, physical disability, destructive changes on joint radiographs, extra-articular manifestations, and corticosteroid use, have repeatedly shown significant associations with increased cardiovascular risk. Medications used to treat RA may also affect cardiovascular risk. A recent meta-analysis suggests that all nonsteroidal anti-inflammatory drugs confer some cardiovascular risk. The cardiovascular risks/benefits associated with use of disease-modifying antirheumatic drugs and/or biologics remain controversial, as does the role of statins in RA., Summary: Cardiovascular disease remains a major problem for people with RA. Future work should focus on further delineating the underlying biological mechanisms involved, developing and evaluating risk assessment tools and biomarkers, as well as prevention/treatment strategies specific to the RA population.

Objective: To examine the impact of systemic inflammation and serum lipids on cardiovascular disease (CVD) in rheumatoid arthritis (RA)., Methods: In a population-based RA incident cohort (1987 American College of Rheumatology criteria first met between 1988 and 2007), details were collected of serum lipid measures, erythrocyte sedimentation rates (ESRs), C-reactive protein (CRP) measures and cardiovascular events, including ischaemic heart disease and heart failure. Cox models were used to examine the association of lipids and inflammation with the risk of CVD and mortality, adjusting for age, sex and year of RA incidence., Results: The study included 651 patients with RA (mean age 55.8 years, 69% female); 67% were rheumatoid factor positive. ESR was associated with the risk of CVD (HR=1.2 per 10 mm/h increase, 95% CI 1.1 to 1.3). Similar findings, although not statistically significant, were seen with CRP (p=0.07). A significant non-linear association for total cholesterol (TCh) with risk of CVD was found, with 3.3-fold increased risk for TCh <4 mmol/l (95% CI 1.5 to 7.2) and no increased risk of CVD for TCh ≥4 mmol/l (p=0.57). Low low-density lipoprotein cholesterol (LDL <2 mmol/l) was associated with marginally increased risk of CVD (p=0.10); there was no increased risk for LDL ≥2 mmol/l (p=0.76)., Conclusion: Inflammatory measures (particularly, ESR) are significantly associated with the risk of CVD in RA. Lipids may have paradoxical associations with the risk of CVD in RA, whereby lower TCh and LDL levels are associated with increased cardiovascular risk.

Objective: to examine whether patients with rheumatoid arthritis (RA) with no overt cardiovascular disease (CVD) have a higher prevalence of metabolic syndrome (MetS) than subjects without RA or CVD. We also examined whether RA disease characteristics are associated with the presence of MetS in RA patients without CVD., Methods: subjects from a population-based cohort of patients who fulfilled 1987 American College of Rheumatology criteria for RA between January 1, 1980, and December 31, 2007, were compared to non-RA subjects from the same population. All subjects with any history of CVD were excluded. Waist circumference, body mass index (BMI), and blood pressure were measured during the study visit. Data on CVD, lipids, and glucose measures were ascertained from medical records. MetS was defined using NCEP/ATP III criteria. Differences between the 2 cohorts were examined using logistic regression models adjusted for age and sex., Results: the study included 232 RA subjects without CVD and 1241 non-RA subjects without CVD. RA patients were significantly more likely to have increased waist circumference and elevated blood pressure than non-RA subjects, even though BMI was similar in both groups. Significantly more RA patients were classified as having MetS. In RA patients, MetS was associated with Health Assessment Questionnaire Disability Index, large-joint swelling, and uric acid levels, but not with C-reactive protein or RA therapies., Conclusion: among subjects with no history of CVD, patients with RA are more likely to have MetS than non-RA subjects. MetS in patients with RA was associated with some measures of disease activity.

Objective: Inflammation and autoimmunity are associated with increased cardiovascular (CV) risk in patients with rheumatoid arthritis. This association may also be present in those without rheumatic diseases. Our purpose was to determine whether rheumatoid factor (RF), antinuclear antibody (ANA), and cyclic citrullinated peptide antibody (CCP) positivity are associated with increased risk of CV events and overall mortality in those with and without rheumatic diseases., Methods: We performed a population-based cohort study of all subjects who had a RF and/or ANA test performed between January 1, 1990, and January 1, 2000, and/or CCP test performed between September 1, 2003, and January 1, 2005, with followup until April 1, 2007. Outcomes were ascertained using diagnostic indices from complete medical records, including CV events [myocardial infarction (MI), heart failure (HF), and peripheral vascular disease (PVD)] and mortality. Cox models were used to analyze the data., Results: There were 6783 subjects with RF, 7852 with ANA, and 299 with CCP testing. Of these, 10.4%, 23.9%, and 14.7% were positive for RF, ANA, and CCP, respectively. Adjusting for age, sex, calendar year, comorbidity, and rheumatic disease, RF and ANA positivity were significant predictors of CV events [hazard ratio (HR) 1.24 and 1.26] and death (HR 1.43 and 1.18). Adjusting for age, CCP positivity was associated with CV events, but this association was not statistically significant (HR 3.1; 95% CI 0.8, 12.3)., Conclusion: RF and ANA positivity are significant predictors of CV events and mortality in both those with and those without rheumatic diseases. These results support the role of immune dysregulation in the etiology of CV disease.

Introduction: Idiopathic aortitis is a rare condition characterized by giant cell or lymphoplasmacytic inflammation of the aorta. The purpose of this study was to describe risk factors for the development of idiopathic aortitis., Methods: We conducted a case control study of 50 patients who were age-matched with two control subjects with non-inflammatory ascending aortic aneurysms. We examined whether the prevalences of gender, hypertension, hyperlipidemia, diabetes mellitus, smoking, family history of any aortic aneurysms, and elevated inflammatory markers differed between cases and controls., Results: The mean age of cases was 71.6 +/- 8.9 years and that of controls was 71.1 +/- 8.9 years. We found female gender (odds ratio [OR] 2.41, 95% confidence interval [CI] 1.20 to 4.85; P = 0.014) and active smoking (OR 3.37, 95% CI 1.12 to 10.08; P = 0.03) to be associated with idiopathic aortitis. The association with smoking persisted after adjustment for gender (OR 3.24, 95% CI 1.05 to 9.96; P = 0.04). There was a trend toward lower prevalence of diabetes mellitus in cases (OR 0.39, 95% CI 0.11 to 1.43; P = 0.16) but no difference in prevalences of other risk factors. The median pre-operative erythrocyte sedimentation rate (ESR) was 20 mm/hour in cases (n = 13) and 9 mm/hour in controls (n = 22). The median pre-operative C-reactive protein (CRP) levels were 12 mg/L in cases (n = 8) and 3 mg/L in controls (n = 6) (normal: <8 mg/L). A higher proportion of cases versus controls had elevations in ESR (38% versus 9%; P = 0.075) and CRP (62% versus 0%; P = 0.031)., Conclusions: Gender and smoking may interact in complex mechanisms with immune and proteolytic pathways in older, less distensible thoracic aortas. Elevated acute-phase reactants as a marker of systemic inflammation may be present in some patients.

Objective: To estimate the 10-year absolute risk of cardiovascular (CV) events in newly diagnosed rheumatoid arthritis (RA) patients and the potential contribution of CV risk factors to absolute risk assessment., Methods: A population-based incidence cohort of RA patients (defined according to the American College of Rheumatology 1987 criteria) was assembled and compared with an age- and sex-matched non-RA cohort. Data were collected on CV risk factors and CV events. Cox regression models were used to estimate the 10-year risk of a combined CV end point, adjusting for CV risk factors. Subjects were classified into 5 risk categories based on their 10-year absolute risk., Results: The absolute CV risk in RA patients was similar to that in non-RA subjects who were 5-10 years older. The absolute risk varied substantially according to the presence of CV risk factors. The 10-year absolute CV risk among 60-69-year-old RA patients with no risk factors was 16.8%, but rose to 60.4% if risk factors such as smoking, hypertension, dyslipidemia, diabetes, and obesity were present. Among RA patients with a low body mass index, in addition to the above risk factors, the 10-year absolute CV risk rose to 86.2%., Conclusion: More than half of the newly diagnosed RA patients who were 50-59 years of age and all of those >60 years of age had a >10% risk of CV disease within 10 years of their RA incidence and should be targeted for specific CV risk reduction strategies tailored to their personal risk profiles.

Objective: To examine the effect of glucocorticoid use on the risk of various cardiovascular diseases in patients with polymyalgia rheumatica (PMR)., Methods: We assembled a population-based incidence cohort of 364 patients with PMR first diagnosed between January 1, 1970 and December 31, 1999. Inclusion criteria were age > or = 50 years, bilateral aching and morning stiffness involving at least 2 areas (neck, shoulders, hips, or proximal aspects of the thighs), and erythrocyte sedimentation rate (ESR) > or = 40 mm/hour. In patients who fulfilled the first 2 criteria but had a normal ESR, a rapid response to low-dose glucocorticoids served as the third criterion. Patients were followed up until death or December 31, 2004. Cox models with time-dependent covariates were used to examine the association between glucocorticoid exposure and risk of myocardial infarction, heart failure, peripheral vascular disease, and cerebrovascular disease., Results: A total of 364 PMR patients (mean age 73 years, 67% women) were followed for a median of 7.6 years. During the disease course, 310 (85%) patients received glucocorticoids. After adjusting for age, calendar year, and ESR, patients who received glucocorticoids did not have a significantly higher risk for myocardial infarction, heart failure, peripheral vascular disease, or cerebrovascular disease (hazard ratio [95% confidence interval] 0.58 [0.29-1.18], 0.85 [0.45-1.54], 0.58 [0.24-1.40], and 0.65 [0.33-1.26], respectively) compared with those who did not receive glucocorticoids. In fact, a trend for a protective effect was seen. No significant association was observed between cumulative glucocorticoid dose and any of the outcomes (P = 0.39)., Conclusion: In patients with PMR, treatment with glucocorticoids is not associated with an increased risk of cardiovascular diseases.

Objective: To determine the relationship between glucocorticoid exposure and cardiovascular (CV) events in patients with rheumatoid arthritis (RA)., Methods: A total of 603 adult residents of Rochester, Minnesota with incident RA between 1955 and 1995 were followed up through their medical records for a median of 13 years (total of 9,066 person-years). Glucocorticoid exposure was defined 3 ways: tertiles of cumulative exposure; recent use (< or =3 months) versus past use (>3 months); and average daily dosage (< or =7.5 mg/day or >7.5 mg/day). CV events, including myocardial infarction, heart failure, and death from CV causes, were defined according to validated criteria. Cox regression models were adjusted for demographic features, CV risk factors, and RA characteristics., Results: Rheumatoid factor (RF)-negative patients with exposure to glucocorticoids were not at increased risk of CV events, irrespective of the glucocorticoid dosage or timing of use, as compared with the reference group of RF-negative patients who had never been exposed to glucocorticoids. In contrast, RF-positive patients were at increased risk of CV events, particularly with higher cumulative exposure, higher average daily dosage, and recent use of glucocorticoids. RF-positive patients with high cumulative exposure to glucocorticoids had a 3-fold increased risk of CV events (hazard ratio 3.06 [95% confidence interval 1.81-5.18]), whereas RF-negative patients with high cumulative exposure were not at increased risk (hazard ratio 0.85 [95% confidence interval 0.39-1.87])., Conclusion: RF-positive but not RF-negative patients were at increased risk of CV events following exposure to glucocorticoids. These findings suggest that glucocorticoids interact with RF status to modulate the occurrence of CV events in patients with RA. The mechanisms underlying this interaction are unknown and should be the subject of further research.

Objective: To determine whether systemic inflammation confers any additional risk for cardiovascular death among patients with rheumatoid arthritis (RA), after adjusting for traditional cardiovascular risk factors and comorbidities., Methods: Using the population-based data resources of the Rochester Epidemiology Project, we assembled an incidence cohort of all Rochester, Minnesota residents ages >or=18 years who first fulfilled the American College of Rheumatology 1987 criteria for RA between January 1, 1955 and January 1, 1995. All subjects were followed up longitudinally through their complete (inpatient, outpatient) medical records, beginning at age 18 years and continuing until death, migration, or January 1, 2001. Detailed information on the occurrence of various cardiovascular risk factors (personal history of coronary heart disease [CHD], congestive heart failure, smoking, hypertension, dyslipidemia, body mass index [BMI], diabetes mellitus, menopausal status) as well as indicators of systemic inflammation and RA disease severity (rheumatoid factor [RF] seropositivity, erythrocyte sedimentation rate [ESR], joint swelling, radiographic changes, RA nodules, RA complications, RA treatments, disease duration) and comorbidities were collected on all subjects. Causes of death were ascertained from death certificates and medical records. Cox regression models were used to estimate the independent predictors of cardiovascular death., Results: This inception cohort comprised a total of 603 RA patients whose mean age was 58 years, of whom 73% were women. During a mean followup of 15 years, 354 patients died and cardiovascular disease was the primary cause of death in 176 patients. Personal history of CHD, smoking, hypertension, low BMI, and diabetes mellitus, as well as comorbidities, including peripheral vascular disease, cerebrovascular disease, chronic pulmonary disease, dementia, ulcers, malignancies, renal disease, liver disease, and history of alcoholism, were all significant risk factors for cardiovascular death (P < 0.01 for each). Multivariable Cox regression analyses, controlled for cardiovascular risk factors and comorbidities, revealed that the risk of cardiovascular death was significantly higher among RA patients with at least 3 ESR values of >or=60 mm/hour (hazard ratio [HR] 2.03, 95% confidence interval [95% CI] 1.45-2.83), RA vasculitis (HR 2.41, 95% CI 1.00-5.81), and RA lung disease (HR 2.32, 95% CI 1.11-4.84)., Conclusion: These results indicate that markers of systemic inflammation confer a statistically significant additional risk for cardiovascular death among patients with RA, even after controlling for traditional cardiovascular risk factors and comorbidities.

Objective: Various etiologic mechanisms have been implicated in the observed increase in cardiovascular mortality in rheumatoid arthritis (RA). Body mass index (BMI) is associated with cardiovascular mortality in the general population. This study compared the effect of BMI on cardiovascular mortality in a population-based cohort of subjects with RA with that in a cohort of individuals without RA from the same population., Methods: The RA cohort comprised all members of an incidence cohort of Rochester, Minnesota residents ages > or =18 years who were first diagnosed with RA (by the American College of Rheumatology 1987 criteria) from 1955 through 1994. An age- and sex-matched comparison cohort of subjects without RA was assembled. Both cohorts were followed up longitudinally through their complete (inpatient, outpatient) medical records beginning at age 18 years and continuing until death, migration, or January 1, 2001, and the details of weight and height changes during this period were recorded. High BMI was defined as a BMI >30 kg/m(2) and low BMI as <20 kg/m(2). Cox regression models were used to estimate the effect of BMI on cardiovascular mortality after accounting for traditional cardiac risk factors and malignancies., Results: RA subjects with low BMI at incidence had a significantly higher risk of cardiovascular death (hazard ratio [HR] 3.34, 95% confidence interval [95% CI] 2.23-4.99) compared with non-RA subjects with normal BMI, after adjusting for age, sex, personal cardiac history, smoking status, and presence of diabetes, hypertension, and malignancies. RA subjects with normal BMI at incidence who experienced low BMI during followup also had a higher risk of cardiovascular death (HR 2.09, 95% CI 1.50-2.92) when compared with non-RA subjects who maintained normal BMI throughout followup., Conclusion: Among patients with RA, low BMI is associated with a significantly increased risk of cardiovascular death.

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) and tumor necrosis factor inhibitors (TNFi) are the most common therapies used in AS, however, the associated long-term cardiovascular risk is unclear. We performed a systematic review and meta-analysis on the association of therapies used for ankylosing spondylitis (AS) such as NSAIDs and TNFi on cardiovascular events (CVE) in AS. Methods: A comprehensive search was performed from database inception to May 29, 2020 to include controlled studies of AS treated with NSAIDs, oral small molecules, or biologics reporting CVE. Study-specific risk ratios (RR) were pooled using a random effects model. Results: Nine non-randomized studies from 1570 studies screened fulfilled inclusion criteria. Among NSAID users as a whole versus no NSAIDs, no increased risk of CVE (composite outcome) was observed; however, the risk of cerebrovascular accident was significantly lower (RR 0.58, 95% CI 0.37–0.93, I2 = 66%). Cox-2 inhibitor use was associated with reduced risk of all CVE (RR 0.48, 95% CI 0.33–0.70, I2 = 0%). Non-selective NSAIDs were not associated with any increased/decreased risk of any CVE. Meta-analysis of three studies of MI did not show a significant association with TNFi (RR 0.88, 95% CI 0.57–1.35, I2 = 76%). Conclusions: In this meta-analysis of non-randomized studies, NSAID users as a whole and users of non-selective NSAIDs did not seem to have a higher risk of any CVE. Limited data suggest a lower risk of composite CVE outcome with Cox-2 inhibitors, unlike the increased risk reported in the general population. No significant association between TNFi and MI was observed. The certainty in evidence was very low due to all studies being observational. More studies are needed to study the association between TNFi use and CVE in general to evaluate a possible protective role in AS. [ABSTRACT FROM AUTHOR]

Objective. To evaluate whether hyperuricemia is a risk factor for cardiovascular disease (CVD) in patients with rheumatoid arthritis (RA). Methods. A population-based inception cohort of patients diagnosed between 1980 and 2007 with adult-onset RA was assembled. Acomparison cohort of age- and sex-matched subjectswithout RA (non-RA) was also assembled. All clinically obtained uric acid values were collected. CVD and noncardiac vascular events were recorded for each patient. Cox proportional hazards models were used to assess the impact of hyperuricemia on development of CVD, mortality, and noncardiac vascular disease. Results. In patients without RA, hyperuricemia was associated with heart failure (HR: 1.95; 95% CI: 1.13-3.39) and CVD (HR: 1.59; 95% CI: 0.99-2.55). In patients with RA, hyperuricemia was not significantly associated with CVD but was significantly associated with peripheral arterial events (HR: 2.52; 95% CI: 1.17-5.42).Hyperuricemia appeared to be more strongly associated with mortality among RA patients (HR: 1.96; 95% CI: 1.45-2.65) than among the non-RA subjects (HR: 1.57; 95% CI: 1.09-2.24). Conclusion. In patients with RA, hyperuricemia was a significant predictor of peripheral arterial events and mortality but not of CVD. [ABSTRACT FROM AUTHOR]

In this article, the authors provide a brief overview of the spectrum of cardiovascular disease (CVD) in rheumatoid arthritis (RA). The authors focus on the role of traditional cardiovascular risk factors in the development of CVD in this population. They address whether RA patients are more or less likely to experience individual cardiovascular risk factors, their association with CVD, and their contribution to cardiovascular risk prediction in RA patients.