Influence of Abdominal Obesity on the Relationship of Low-Density Lipoprotein Cholesterol with Atherosclerosis and Cardiovascular Risk in Rheumatoid Arthritis

Abstract

Methods. Coronary artery calcium, number of coronary plaques, and extensive ( 5 plaques) or obstructive (>50% stenosis) disease was evaluated with computed tomography angiography in 150 patients at baseline and 101 patients 6.9±0.4 years later. Cardiovascular events were recorded. Oxidized LDL was measured with monoclonal antibody E06. Serum cholesterol loading capacity on macrophages was measured as intracellular cholesterol content with a fluorometric assay. Results. Abdominal obesity was not associated with per-patient number of coronary plaques or coronary artery calcium score at baseline. Low LDLc positively associated with number of plaques (b 2.13 [95% confidence interval 1.03 to 3.22]), likelihood of extensive or obstructive plaque (odds ratio 6.58, 95% confidence interval [1.63 to 26.46]), and log-transformed CAC (b 1.90 [0.89 to 2.91]) exclusively in nonobese patients (p-for-interaction <0.001, 0.061, and 0.001 respectively). Low LDLc associated with increased likelihood of >median oxidized LDL and higher ratio of cholesterol loading capacity to LDLc in nonobese patients (p-for-interaction 0.041 and 0.001 respectively). Abdominal obesity negatively associated with likelihood of plaque stenosis progression (odds ratio 0.19 [0.07 to 0.54]). Low LDLc associated with greater likelihood of per-segment plaque formation (OR 4.68 [2.26 to 9.66]) and increased stenotic severity (odds ratio 5.35 [1.62 to 17.67]) only in nonobese patients (p-for-interaction 0.002 and 0.040 respectively). Abdominal obesity was not linked to cardiovascular risk (Hazard Ratio 1.57, 95% confidence interval [0.66-3.73]). Low LDLc associated with higher cardiovascular risk in nonobese (Hazard Ratio 7.94 [1.52 to 41.36]) but not obese patients (p-for-interaction=0.017). Conclusion. Abdominal obesity was not linked to plaque progression or cardiovascular risk in RA. Only in nonobese patients, low LDLc associated with higher atherosclerosis burden, plaque progression and cardiovascular risk. This may reflect higher oxidation and macrophage cholesterol loading capacity of LDL when LDLc is <70mg/dl.