Association of cardiovascular disease and traditional cardiovascular risk factors with the incidence of dementia among patients with rheumatoid arthritis

ObjectiveTo determine the incidence of dementia in patients with rheumatoid arthritis (RA) 65 years and older, and compare the incidence of dementia in patients with RA with prevalent cardiovascular (CV) disease (CVD), CV risk factors but no prevalent CVD and neither (referent group).MethodsWe analyzed claims data from the Center for Medicare & Medicaid Services (CMS) from 2006–2014. Eligibility criteria included continuous medical and pharmacy coverage for ≥ 12 months (baseline period 2006), > 2 RA diagnoses by a rheumatologist and at least 1 medication for RA. CVD and CV risk factors were identified using codes from the Chronic Condition Data Warehouse. Incident dementia was defined by 1 inpatient or 2 outpatient claims, or one dementia specific medication. Age-adjusted incident rates were calculated within each age strata. Univariate and multivariate Cox proportional hazard models were used to calculate Hazard Ratios (HR) and 95% confidence intervals.ResultsAmong 56,567 patients with RA, 11,789 (20.1%) incident cases of dementia were included in the main analysis. Age adjusted incident rates were high among all groups and increased with age. After adjustment for age, sex, comorbidities and baseline CV and RA medications, patients with CVD and CV risk factors between 65 and 74 years had an increased risk for incident dementia compared to those without CVD and without CV risk factors (HR 1.18 (95% CI 1.04–1.33) and HR 1.03 (95% CI 1.00–1.11), respectively). We observed a trend towards increased risk in patients between 75 and 84 years with CVD at baseline.ConclusionPatients with RA with both CVD and CV risk factors alone are at an increased risk for dementia compared to those with neither CVD nor CV risk factors; however, this risk is attenuated with increasing age. The impact of RA treatment and CV primary prevention strategies in the prevention of dementia in patients with RA warrants further studies.     

Vascular disease in rheumatoid arthritis: From subclinical lesions to cardiovascular risk

Rheumatoid arthritis (RA) is one of the most prevalent and complex inflammatory diseases affecting primarily the joints, but also associating several extra-articular features. The vascular disease in RA encompasses a large spectrum of lesions, from rheumatoid vasculitis to atherosclerotic lesions. During the last years the importance of the vascular disease related to atherosclerosis in terms of cardiovascular morbidity and global mortality became evident in RA. The inflammatory hypothesis of atherosclerosis in RA implies that mediators originating from the inflamed synovial tissue or from the liver may have systemic vascular consequences, leading to endothelial dysfunction and structural abnormalities of the vessels. Hence, the global management of patients with RA must include the improvement of cardiovascular risk in parallel with the management of joint disease.     

Therapy Insight: managing cardiovascular risk in patients with rheumatoid arthritis

Chronic low-grade inflammation was recognized during the past decade as an important risk factor for the development of atherosclerosis and, more recently, for the development of heart failure. Patients with rheumatoid arthritis (RA) are at increased risk of morbidity and mortality from ischemic cardiovascular events and heart failure. Epidemiologic and clinical studies indicate that RA is an independent risk factor for cardiovascular disease, which suggests that chronic exposure to high levels of inflammatory mediators contributes to this enhanced risk. The relative contribution of conventional risk factors to the acceleration of cardiovascular disease does not seem to be increased in patients with RA compared with control populations. Nonetheless, some preclinical laboratory measures of risk factors (e.g. insulin sensitivity) are adversely modulated in the context of the highly inflammatory rheumatoid microenvironment. Discerning the net effect of RA therapies on cardiovascular disease is also challenging because, theoretically, their biologic effects could either promote or attenuate atherosclerosis and ventricular dysfunction; however, available data suggest a beneficial effect on cardiovascular morbidity and mortality in patients with RA. This review provides an overview of the potential influence of RA and its treatment on the development and progression of cardiovascular disease, and outlines some preliminary recommendations for prevention and management of this complication in patients with RA.     

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.     

The effect of etanercept on traditional metabolic risk factors for cardiovascular disease in patients with rheumatoid arthritis

Clinical Rheumatology - Patients with rheumatoid arthritis (RA) are at an increased risk of cardiovascular disease (CVD). Treatment with tumor necrosis factor inhibitors improves both joint...     

Atherosclerotic cardiovascular disease in rheumatoid arthritis

The past 3 years have seen a remarkable growth in the inter-est of cardiovascular disease in rheumatoid arthritis. There have been studies published documenting an increased inci-dence and prevalence of cardiovascular conditions in patients with rheumatoid arthritis compared with individuals without rheumatoid arthritis. There has also been interest in the occurrence of cardiovascular risk factors in rheumatoid arthritis and in the role of antirheumatic therapy, including cyclooxygenase-2 selective nonsteroidal anti-inflammatory drugs, methotrexate, corticosteroids, and tumor necrosis fac-tor inhibitors. A number of studies using noninvasive means to detect atherosclerosis have shown that patients with rheu-matoid arthritis may be prone to atherosclerosis. This infor-mation should be important to physicians who provide care to patients with rheumatoid arthritis, given the difficulty of recognizing cardiovascular signs and symptoms among patients with the disease.     

The best cardiovascular risk calculator to predict carotid plaques in rheumatoid arthritis patients

Clinical Rheumatology - Atherosclerotic cardiovascular disease (ASCVD) is the leading cause of death in patients with rheumatoid arthritis (RA). Chronic inflammation and traditional risk factors...     

The comparison of cardiovascular disease risk prediction scores and evaluation of subclinical atherosclerosis in rheumatoid arthritis: a cross-sectional study

Clinical Rheumatology - Primary objectives estimated prevalence of traditional cardiovascular disease (CVD) risk factors and compared different CVD risk prediction algorithms in an Indian...     

Prevalence of cardiovascular disease and major risk factors in patients with rheumatoid arthritis: a multinational cross-sectional study

Clinical Rheumatology - To compare the prevalence of cardiovascular disease (CVD) and major CVD risk factors among rheumatoid arthritis (RA) patients enrolled in a large US and multinational...     

Apolipoprotein B–containing lipoprotein subclasses as risk factors for cardiovascular disease in patients with rheumatoid arthritis

Objective

The purpose of this study was to explore whether nontraditional risk factors, such as apolipoprotein C‐III (Apo C‐III) and its corresponding Apo B lipoprotein (Lp) subclasses, contribute to the risk of cardiovascular disease in rheumatoid arthritis (RA) patients.

Methods

Apolipoprotein and lipoproteins were measured in 152 RA patients by immunoturbidimetric procedures, electroimmunoassay, and immunoprecipitation. Patients had a coronary artery calcium (CAC) score assessed at baseline and at year 3. Differences in the CAC scores between baseline and year 3 were calculated and dichotomized at 0, where patients with a difference score >0 were denoted as progressors and the rest were denoted as nonprogressors. Differences between means were tested with a 2‐sided independent Student's t‐test with Satterthwaite's adjustment. Proportion differences were tested with a chi‐square test. Multiple logistic regression was performed to assess the relationship between apolipoprotein and lipoprotein levels and the dichotomized CAC score.

Results

Progressors accounted for almost 60% of the cohort. Progressors had significantly higher levels of triglycerides, very low‐density lipoprotein (VLDL) cholesterol, total cholesterol/high‐density lipoprotein (HDL), triglycerides/HDL, Apo B, LpA‐II:B:C:D:E, LpB:C, Apo B/Apo A‐I, Apo C‐III, and Apo C‐III–heparin precipitate than the nonprogressors. After adjusting for age, sex, statin use (yes/no), and hypertension (yes/no), significant risk factors of progressors were total cholesterol, triglycerides, VLDL cholesterol, LDL cholesterol, Apo B, LpB:C, Apo C‐III, and Apo B/Apo A‐I.

Conclusion

Apo C‐III–containing Apo B lipoprotein subclasses were found to be significantly elevated in progressors compared to nonprogressors. Many of these same lipoproteins were found to be associated with an increase in CAC scores among progressors. These lipoproteins may be considered new risk factors for progression of atherosclerosis in RA patients.