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Serum α-chlorofatty acid as a biomarker for baseline subclinical cardiovascular disease in systemic lupus erythematosus

Objective

α-chlorofatty acid (α-ClFA) is one product of myeloperoxidase activity in vivo during atherogenesis [1]. Our study investigates whether serum α-ClFA may be a biomarker for subclinical cardiovascular disease (CVD) in patients with systemic lupus erythematosus (SLE).

Methods

One hundred and eighty-five women with SLE and 186 controls participated in this ancillary study of the Study of Lupus Vascular and Bone Long-term Endpoints (SOLVABLE). Data collection included demographic information, CVD and SLE risk factors, and baseline laboratory assessments. α-ClFA was measured in stored serum by liquid chromatography-electrospray ionization mass spectrometry with selected reaction monitoring detections. Each sample was run in triplicate. Coronary artery calcium (CAC) and aorta calcium (AC) were measured by electron beam computed tomography or multi-detector computed tomography. Calcium scores were calculated using the Agatston method. Outcome measures were the presence of higher risk CAC or AC scores (CAC >10 or AC >100) versus lower risk scores (CAC ≤10 or AC ≤100) [2]. Significant associations were identified with descriptive characteristics, univariate, and multivariate analyses.

Results

Cases had higher baseline levels of α-ClFA than controls (42.2 ± 19.2 fmol/μl vs. 34.5 ± 10.9 fmol/μl, P = 0.014). Cases with lower risk CAC and AC scores had statistically higher levels of α-ClFA compared with controls, while cases and controls with higher risk CAC and AC scores had similar α-ClFA levels (Table 1). In multivariate analyses, SLE had the strongest independent association with higher risk CAC scores, followed by dyslipidemia and age (Table 2). SLE also had the strongest association with higher risk AC scores, followed by history of tobacco use, age, and C-reactive protein level (Table 3). α-ClFA was not independently associated with higher risk CAC or AC scores.

Table 1 Baseline serum α-ClFA levels (fmol/μl) in cases and controls by higher risk versus lower risk CAC and AC scores
Table 2 Multivariate analysis for higher risk CAC scores
Table 3 Multivariate analysis for higher risk AC scores

Conclusion

SLE had the strongest independent association with the presence of higher risk subclinical CVD, while serum α-ClFA levels were not independently associated at baseline.

References

  1. Ford DA: Lipid oxidation by hypochlorous acid: chlorinated lipids in atherosclerosis and myocardial ischemia. Clin Lipidol. 2010, 5: 835-852. 10.2217/clp.10.68.

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  2. Budoff MJ, McClelland RL, Nasir K, Greenland R, Kronmal RA, Kondos GT, Shea S, Lima JAC, Blumenthal RS: Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J. 2009, 158: 554-561. 10.1016/j.ahj.2009.08.007.

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Acknowledgements

This research was supported by R21-HL098907, UL1-RR025741, K24-AR02318, P60-AR30692, P60-AR48098, M01-RR00048, and T32-AR07611 through the National Institutes of Health and the Mary Kirkland Center for Lupus Research and Rheuminations, Inc.

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DA Ford and R Ramsey-Goldman contributed equally to this work.

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Mahieu, M., Guild, C., Albert, C. et al. Serum α-chlorofatty acid as a biomarker for baseline subclinical cardiovascular disease in systemic lupus erythematosus. Arthritis Res Ther 14 (Suppl 3), A22 (2012). https://doi.org/10.1186/ar3956

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