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Lipoprotein(a)-activated autoimmunity: possible link between restless legs syndrome and mortality risk?

  • Altan Onat, Emeritus Professor, Department of Cardiology, Cerrahpa?a Medical Faculty, Istanbul Universityalt_onat@yahoo.com.tr
  • Altan Onat, Department of Cardiology, Cerrahpa?a Medical Faculty, Istanbul University, Istanbul
Submitted July 24, 2013

In a study of older nondiabetic men, Li et al. reported that those with restless legs syndrome (RLS) at baseline had nearly 40% increased risk of death compared to men without RLS. [1] The authors emphasized that the elevated mortality risk was not associated with the usual known risk factors but rather with respiratory, endocrine, nutritional/metabolic and immunological disorders. Excess plasma lipoprotein[Lp](a) is a recognized risk factor for cardiovascular disease and this has been shown in aortic valve stenosis. [2] We demonstrated that Lp(a), which forms a complex with an autoimmune component, may significantly contribute to chronic disease while being assayed late in life as (misleadingly) reduced. [3] Beyond type-2 diabetes and coronary disease, chronic kidney disease [4] and rheumatoid arthritis are potential outcomes related to such autoimmune activation. Data have also shown that several serum proteins (such as Lp(a), creatinine [4]) may be subjected to damage in an environment of enhanced pro-inflammatory state inducing autoimmune activation. [3] Antibodies directed against oxidized epitopes of Lp(a) interacting with beta2- glycoprotein-I have been shown. [5] RLS may be yet another manifestation of the fundamental process of enhanced proinflammatory state and autoimmune activation leading to chronic diseases and mortality.

1. Li Y, Wang W, Winkelman JW, et al. Prospective study of restless legs syndrome and mortality in men. Neurology 2013; 81:52-59.

2. Thanassoulis G, Campbell CY, Owens DS, et al. for the CHARGE Extracoronary Calcium Working Group. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med 2013; 368:503-512.

3. Onat A, Can G. Enhanced pro-inflammatory state and autoimmune activation: a breakthrough to understanding chronic diseases. Curr Pharmaceut Design 2013 Apr 2 [Epub].

4. Onat A, Can G, Ademoğlu E, Çelik E, Karagöz A, Örnek E. Coronary disease risk curve of serum creatinine is linear in Turkish men, U-shaped in women. J Investig Med 2013; 61:27-33.

5. Lopez LR, Bruckner TR, Hurley BL, et al. Determination of oxidized low- density lipoprotein (ox-LDL) versus oxLDL/beta2-GPI complexes for the assessment of autoimmune-mediated atherosclerosis

For disclosures, please contact the Editorial office at journal@neurology.org.

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