Association of hyperlipidaemia, inflammation and serological status and coronary heart disease among patients with rheumatoid arthritis: data from the National Veterans Health Administration

Abstract

ObjectiveTo examine the association of serum lipids, inflammation and seropositivity on coronary heart disease (CHD) and stroke in patients with rheumatoid arthritis (RA).MethodsThe incidence of hospitalised myocardial infarction (MI) or stroke was calculated in a cohort of patients with RA receiving care within the national Veterans Health Administration from 1998 to 2011. Cox proportional hazard models were used to examine the association between these outcomes and low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) as time-varying variables, divided into quintiles.ResultsThere were 37 568 patients with RA in the cohort with mean age of 63 years (SD 12.1); 90% were men. There was a no clear association between LDL-C and CHD/stroke. Compared with lower HDL-C (<34 mg/dL), higher HDL-C (≥54 mg/dL) was inversely associated with MI (hazard ratio (HR)=0.68, 95% CI 0.55 to 0.85) and stroke (HR=0.69, 95% CI 0.50 to 0.96). Higher CRP >2.17 mg/dL (vs CRP <0.26 mg/dL) was associated with increased risk (HR=2.43, 95% CI 1.77 to 3.33) for MI and 2.02 (95% CI 1.32 to 3.08) for stroke. ESR >47 mm/h compared with <8 mm/h had an HR 1.87 (95% CI 1.39 to 2.52) for MI and 2.00 (95% CI 1.26 to 3.18) for stroke. The association between MI was significant for RA seropositivity (HR=1.23, 95% CI 1.03 to 1.48).ConclusionsIn this predominantly older male RA cohort, there was no clear association between LDL-C and CHD, whereas higher HDL-C was inversely associated with MI and stroke. CRP and ESR were similarly associated with increase MI risk and stroke, reflecting the prominent role of inflammation in CHD risk in RA.

Increased cardiovascular risk in rheumatoid arthritis: mechanisms and implications

“…These observations were further corroborated in the Nijmegen early rheumatoid arthritis cohort, in which a 1 unit increase in time averaged DAS28, but not disease duration, was associated with a 33% higher risk of cardiovascular disease 16. Likewise, higher C reactive protein (CRP) and erythrocyte sedimentation rates (ESR) were associated with a significantly increased risk of cardiovascular disease in two large US studies and a Spanish rheumatoid arthritis cohort 171819. A population based cohort study of incident rheumatoid arthritis showed that each six week flare was associated with a 7% increase in risk of cardiovascular disease, whereas patients in remission had a risk similar to that of non-rheumatoid arthritis controls 20…”

“…Epidemiologic studies have reported varying results specific to autoantibody associations with cardiovascular disease. Anti-cyclic citrullinated peptide (CCP; a commercial ACPA measure) and rheumatoid factor positivity have been linked to increased risk of ischemic heart disease and incident CHF 175152. In separate nested case-control and cohort studies, however, seropositivity was not associated with risk of ACS or with cardiovascular disease related morbidity or mortality 1453.…”

“…For example, rheumatoid arthritis patients with moderate LDL cholesterol concentrations (70-130 mg/dL) have been observed to have the lowest risk of myocardial infarction, with low and high LDL concentrations corresponding to increased risk 18. Lower total cholesterol and LDL were associated with increased cardiovascular events in a separate rheumatoid arthritis cohort 69; and in a study of US Veterans with rheumatoid factor, LDL was not associated with either myocardial infarction or stroke 17. These findings have prompted the description of a “lipid paradox” in rheumatoid arthritis,69 which is not a universal finding as higher LDL concentrations have portended higher risk of cardiovascular disease in at least one large claims based study 70.…”

“…These findings have prompted the description of a “lipid paradox” in rheumatoid arthritis,69 which is not a universal finding as higher LDL concentrations have portended higher risk of cardiovascular disease in at least one large claims based study 70. In contrast to reports for total cholesterol and LDL, associations between HDL and cardiovascular events have been relatively consistent and similar to the general population, with higher HDL concentrations yielding lower cardiovascular risk 171870…”

Tumor Necrosis Factor-Alpha and Inflammation-Mediated Cardiac Injury

“…Although, it is not clear what causes age-associated chronic inflammation, both experimental and clinical evidence accumulated within the past decade, linking the chronic inflammation to the development and progression of chronic heart failure. Indeed, inflammation has been identified as a cardiovascular risk factor; therefore, treatments to lessen the inflammation and inflammation-associated cardiac damage could have significant health and fiscal impact [6][7][8][9]. Herein we review the participation of TNF-α, the "master regulator" of the immune response, as key components of the immunemediated inflammation and injury in acute and chronic heart conditions and will also explore the delicate balance between the protective roles of TNF-α and its damaging functions during the development and progression of heart disease.…”