Background Leptin and particularly adiponectin are likely involved in the pathophysiology of rheumatoid arthritis (RA) and therefore potential new therapeutic targets. In the general population, leptin enhances and adiponectin reduces cardiovascular metabolic risk. Hence, adiponectin inhibition would be expected to result in increased cardiovascular disease risk1. However, whereas the presence of autoimmunity can impact on adipokine-cardiovascular risk relationships, it is unknown whether RA changes the influence of adipokines on cardiovascular metabolic risk.
Objectives We determined whether RA impacts on the relationships of circulating leptin and adiponectin concentrations with cardiovascular risk factors and atherosclerosis.
Methods We evaluated circulating adipokine concentrations by solid-phase sandwich enzyme-linked immunosorbant assays, metabolic risk factors and ultrasound determined carotid intima-media (cIMT) in 277 black Africans from a developing population; 119 had RA. Associations will determined in comprehensively adjusted mixed regression models.
Results RA impacted on the relationships of adiponectin concentrations with lipid concentrations and blood pressure, independent of confounders including adiposity (interaction P <0.05). This translated into an association of adiponectin concentrations with more favorable lipid variables including HDL cholesterol (partial R=0.335, P=0.0005), non-HDL cholesterol (partial R=-0.263, P=0.007) and triglyceride (partial R=-0.271, P=0.005) concentrations and total cholesterol-HDL cholesterol (partial R=-0.363, P=0.0002) and triglycerides-HDL cholesterol (partial R=-0.347, P=0.0003) ratios and, higher systolic (partial R=0.331, P=0.0006), diastolic (partial R=0.280, P=0.0004) and mean blood pressure (partial R=0.329, P=0.0007) in patients with RA. No independent associations between adiponectin concentrations and cardiovascular metabolic risk factors were observed in non-RA subjects. Leptin concentrations were not associated with metabolic risk after adjustment for adiposity in either RA or non-RA subjects. The cIMT did not differ by RA status and adipokine concentrations were unrelated to atherosclerosis.
Conclusions This study suggests that upon adiponectin inhibition, cardiovascular risk factors and especially lipid profiles would require close monitoring. Nevertheless, neither adiponectin nor leptin inhibition are expected to alter overall cardiovascular risk and disease and should therefore be safe in RA.
Frommer KW et al. Ann Rheum Dis 2012; 71: 1724-32.
Acknowledgements This study was supported by a South African Medical Research Council grant and the National Research Foundation.
Disclosure of Interest None Declared