Abstract
BackgroundIn rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are also reduced with increased inflammation and disease activity in RA patients. Here we sought to identify which measure(s) of inflammation, disease activity and cardiometabolic risk contribute most to the RA-associated lipoprotein profile.MethodsNMR lipoprotein measurements were obtained for individuals with RA (n = 50) and age-, gender-, and body mass index (BMI)-matched controls (n = 39). Groups were compared using 39 matched pairs with 11 additional subjects used in RA only analyses. Among RA patients, relationships were determined for lipoprotein parameters with measures of disease activity, disability, pain, inflammation, body composition, insulin sensitivity and exercise. Percentage of time spent in basal activity (<1 metabolic equivalent) and exercise (≥3 metabolic equivalents) were objectively-determined.ResultsSubjects with RA had fewer total and small LDL-P as well as larger LDL and HDL size (P < 0.05). Among RA patients, pain and disability were associated with fewer small HDL-P (P < 0.05), while interleukin (IL)-6, IL-18, and TNF-α were associated with LDL size (P < 0.05). BMI, waist circumference, abdominal visceral adiposity and insulin resistance were associated with more total and small LDL-P, fewer large HDL-P, and a reduction in HDL size (P < 0.05). Most similar to the RA lipoprotein profile, more basal activity (minimal physical activity) and less exercise time were associated with fewer small LDL-P and total and small HDL-P (P < 0.05).ConclusionsThe RA-associated lipoprotein profile is associated with a lack of physical activity.As this was a cross-sectional investigation and not an intervention and was performed from 2008–13, this study was not registered in clinicaltrials.gov.
Highlights
In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C)
We hypothesized that the changes observed in the “lipid paradox” are less related to metabolic syndrome risk factors and more related to lack of physical activity as a result of increased disease activity, pain and inflammation. To test this hypothesis we looked at the associations between nuclear magnetic resonance spectroscopy (NMR) lipoprotein parameters and various measures of disease activity, inflammation, body composition, insulin sensitivity and physical activity
Lipoprotein profile in subjects with RA While triglycerides and HDL-C did not differ between RA and controls, both total cholesterol and Low density lipoprotein (LDL)-C were lower in persons with RA (Table 1; P < 0.05 for both)
Summary
In rheumatoid arthritis (RA), cardiovascular risk is associated with paradoxical reductions in total cholesterol, low density lipoprotein-cholesterol (LDL-C), and high density lipoprotein-cholesterol (HDL-C). Concentrations of small LDL (LDL-P) and HDL (HDL-P) particles are reduced with increased inflammation and disease activity in RA patients. Patients with rheumatoid arthritis (RA), a chronic inflammatory disease, have a 2- to 3-fold increased risk of cardiovascular disease (CVD) [1,2,3,4] This has been attributed to disease-associated chronic inflammation, physical inactivity, increased adiposity, insulin resistance, and altered lipid profiles [5, 6]. Despite the increased CVD risk, RA patients often present with reduced total cholesterol, low density lipoprotein cholesterol (LDL-C) and high. After anti-inflammatory therapy, total cholesterol, LDL-C, HDL-C, HDL-P levels increase [13] Such increases have been attributed to reduced inflammation and cholesterol ester catabolism leading to an increase in lipoprotein cholesteryl ester levels [13]. While increased cholesterol levels are often associated with increased CVD risk, in the context of chronic inflammatory disease increased circulating cholesterol may be a reflection of the reduced inflammation and an accompanied reduction in CVD risk [13, 14]
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