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The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and Without Rheumatoid Arthritis.

ABSTRACT: To determine, using data from a real-world setting, the overall and sex-specific risk of cardiovascular (CV) events in patients with rheumatoid arthritis (RA), with or without comorbid hyperlipidemia, relative to those in a non-RA cohort.This retrospective cohort study using claims data from a US commercial health plan (2005-2011) included patients with RA and a matched non-RA cohort. Cox proportional hazards regression model determined the hazard ratio (HR) for CV events (myocardial infarction, stroke, revascularization procedures), using the presence of RA and hyperlipidemia as the independent variables, controlling for other covariates (age, sex, diabetes, and hypertension).The incidence of CV events per 1000 person-years was 10.19 for the RA cohort and 6.41 for the non-RA cohort (crude rate ratio [RR] =1.59). Within the RA cohort, incidence was 15.54 for patients with hyperlipidemia and 7.05 for patients without hyperlipidemia (crude RR=2.21); in the non-RA cohort, incidence was 10.55 and 3.82 for those with and without hyperlipidemia, respectively (crude RR=2.76). After controlling for covariates, the HR of CV events among RA patients was 1.68 (95% CI: 1.50, 1.87) relative to non-RA patients. After multivariable adjustment, hyperlipidemia conferred a significant risk of CV events in both RA and non-RA patients; the interaction between RA and hyperlipidemia was not significant (p=0.13).This real-world analysis demonstrates that patients with RA have an increased risk of CV events. Similar to a non-RA cohort, CV event rates were incrementally higher for those patients with hyperlipidemia.Cardiovascular disease is an increasingly visible topic of concern in the rheumatoid arthritis community. However, there are only limited data that informs both the absolute and relative rates of CVD events, and the contribution of various risk factors such as hyperlipidemia, compared to non-RA populationsThe 'lipid paradox' hypothesis in RA suggests that elevated LDL cholesterol has a negligible effect on CVD risk in RA, unlikely in the general population where it is a well-accepted CVD risk factorThe incidence of CVD events in RA patients was 10/1000 patient years, a 1.6 fold greater risk compared to non-RA patientsThe contribution of hyperlipidemia to CVD risk was associated with comparable or greater absolute increases in the rate of CV events compared to non RA patients, a finding that does not support the lipid paradox.

SUBMITTER: Nadkarni A

PROVIDER: S-EPMC4727537 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

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Project description:Cardiovascular disease (CVD) is the leading cause of death in rheumatoid arthritis (RA) patients. This study is the first to report the association of hydroxychloroquine (an antirheumatic medication that has been associated with decreased risk of diabetes, a less atherogenic lipid profile, and antithrombotic properties) with CVD in RA. A retrospective incident RA cohort from January 1, 2001, to October 31, 2013, excluding patients with CVD prior to RA diagnosis, was constructed. Patients were categorized as hydroxychloroquine users versus nonusers and were allowed to contribute time to either group according to hydroxychloroquine exposure. The primary outcome was adjudicated incident CVD defined as a composite of coronary artery disease, stroke, transient ischemic attack, sudden cardiac death, and peripheral artery disease with arterial revascularization procedure. The secondary outcome was a composite of incident coronary artery disease, stroke, and transient ischemic attack. Cox time-varying regression models were used to estimate the association between hydroxychloroquine exposure and development of CVD, after adjusting for propensity score and relevant confounders, including demographics, CVD-related comorbidities, RA severity, and activity indicators and medications. We included 1266 RA patients, 547 hydroxychloroquine users, and 719 nonusers. During the observation period, 102 CVD events occurred, 3 in hydroxychloroquine users and 99 in nonusers. The fully adjusted Cox model showed a hazard ratio of 0.28 (95% CI 0.12-0.63, P=0.002) for incident CVD and 0.30 (95% CI 0.13-0.68, P=0.004) for incident composite coronary artery disease, stroke, and transient ischemic attack for hydroxychloroquine users versus nonusers, respectively. In this hypothesis-generating study, hydroxychloroquine use was associated with a 72% decrease in the risk of incident CVD in RA patients. If these preliminary results are confirmed in larger studies, our findings may be used as a rationale for a randomized study of hydroxychloroquine use for primary prevention of CVD in RA or nonrheumatic high-risk patients.

Project description:Lower levels of low-density lipoprotein (LDL) cholesterol may be associated with increased cardiovascular (CV) risk in rheumatoid arthritis (RA). This study was undertaken to determine whether the complex relationship between levels of LDL and high-density lipoprotein (HDL) cholesterol and CV risk is different in RA patients as compared to non-RA controls.Using data from a US health insurance plan (2003-2012), we conducted a cohort study that included patients with RA and non-RA control subjects matched with regard to age, sex, and index date. The nonlinearity of associations between lipid levels and incidence of major adverse CV events (MACE) was tested. We used multivariable Cox proportional hazards regression models to examine for an interaction between lipid levels and RA status in relation to the risk of MACE, after adjustment for CV risk factors.In total, 16,085 RA patients and 48,499 non-RA controls were studied. The mean age was 52.6 years and 78.6% were women. The relationship between LDL cholesterol levels and incidence of MACE was nonlinear and similar between RA patients and non-RA controls (P for interaction?=?0.72). No significant increase in CV risk was observed between the lowest quintile of LDL cholesterol levels (?91.0 mg/dl) and the second, third, or fourth quintiles, whereas the highest quintile (>190.0 mg/dl) conveyed a 40% increase in risk of MACE (hazard ratio [HR] 1.40, 95% confidence interval [95% CI] 1.17-1.68). The relationship between HDL cholesterol levels and incidence of MACE was also nonlinear and similar between RA patients and non-RA controls (P for interaction?=?0.39). Compared to the lowest quintile of HDL cholesterol levels, each successive quintile was associated with a reduced risk of MACE (HR 0.45, 95% CI 0.48-0.72 for lowest quintile [?43.0 mg/dl] versus highest quintile [>71.0 mg/dl]).The complex relationship between LDL cholesterol levels, HDL cholesterol levels, and risk of MACE was nonlinear in RA patients and also not statistically significantly different from that in an age- and sex-matched non-RA cohort.

Project description:ObjectivesTo investigate factors associated with major adverse cardiovascular events (MACEs) in patients with rheumatoid arthritis (RA).MethodsWe conducted a nationwide, population-based, case-control study using Taiwan's National Health Insurance Research Database for 2003-2013. From 2004 to 2012, we identified 108,319 newly diagnosed RA patients without previous MACEs, of whom 7,580 patients (7.0%) developed MACEs during follow-up. From these incident RA patients, we included 5,994 MACE cases and 1:4 matched 23,976 non-MACE controls for analysis. The associations of MACEs with comorbidities and use of anti-rheumatic medications within 1 year before the index date were examined using conditional logistic regression analyses.ResultsUsing multivariable conditional logistic regression analysis, the risk of MACE in RA patients was associated with use of golimumab [odd's ratio (OR), 0.09; 95% confidence interval (CI), 0.01-0.67], abatacept (OR, 0.13; 95% CI, 0.02-0.93), hydroxychloroquine (OR, 0.90; 95% CI, 0.82-0.99), methotrexate (OR, 0.72; 95% CI, 0.64-0.81), cyclosporin (OR, 1.43; 95% CI, 1.07-1.91), nonsteroidal anti-inflammation drugs (NSAIDs) (OR, 1.36; 95% CI, 1.27-1.46), antiplatelet agent (OR, 2.47; 95% CI, 2.31-2.63), hypertension (without anti-hypertensive agents: OR, 1.04; 95% CI, 0.96-1.12; with anti-hypertensive agents: OR, 1.47; 95% CI, 1.36-1.59), diabetes (OR, 1.27; 95% CI, 1.18-1.37), hyperlipidemia without lipid-lowering agents (OR, 1.09; 95% CI, 1.01-1.17), ischemic heart disease (OR, 1.20; 95% CI, 1.10-1.31), and chronic obstructive pulmonary disease (COPD) (OR, 1.12; 95% CI, 1.03-1.23) in the parsimonious model. The risk of MACE in RA patients also increased markedly in participants younger than 65 years with some comorbidities.ConclusionsThis population-based case-control study revealed that the use of golimumab, abatacept, hydroxychloroquine, and methotrexate were associated with a decreased risk of MACE development in newly diagnosed RA patients, while the use of cyclosporin, NSAIDs, and antiplatelet agents, and comorbidities, including hypertension, diabetes, hyperlipidemia without lipid-lowering agent therapy, ischemic heart disease, and COPD, were associated with an increased risk of MACE development in RA patients.

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The Risk for Cardiovascular Events Associated with Hyperlipdemia among Patients with and Without Rheumatoid Arthritis.

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