Efficacy of Long-term Selenium Supplementation in the Treatment of Chronic Keshan Disease with Congestive Heart Failure

Abstract

Few effective treatments for chronic Keshan disease have been available till now. The efficacy of long-term selenium supplementation in the treatment of chronic Keshan disease with congestive heart failure is inconclusive. This study aimed to determine whether selenium supplementation is associated with a decreased risk of cardiac death in chronic Keshan disease with congestive heart failure by ten years of follow-up. A retrospective long-term follow-up analysis was performed on a monitored cohort consisting of 302 chronic Keshan disease patients with a mean age of 40.8±11.4 years. Of the 302 chronic Keshan disease patients, 170 (56.3%) were given selenium supplementation until the end point of follow-up. Cox proportional hazards regression models were used to identify the independent predictors of cardiac events. Our results showed that during the follow-up, there were 101 deaths of patients with chronic Keshan disease in the selenium supplementation group (101/170, 59.4%) and 98 in non-selenium supplementation group (98/132, 74.2%). Multivariate analyses suggested that selenium supplementation was associated with a decreased risk of cardiac death (HR 0.39, 95% CI 0.28–0.53) after adjustment for baseline age, sex, cigarette smoking, family history of Keshan disease, body mass index (BMI), heart rate, electrocardiogram (ECG) abnormalities, blood pressure, initial cardiothoracic ratio, left ventricular ejection fractions (LVEF) and whole-blood selenium concentration. Our ten-year follow-up analysis indicated that selenium supplementation, specifically combined with the use of angiotensin-converting enzyme inhibitor and beta blocker therapy, improved the survival of patients with chronic Keshan disease with congestive heart failure. BMI, selenium deficiency, male, combined ECG abnormalities, LVEF, and fast heart rate increased the risk of cardiac events.

Keywords

Keshan disease / selenium supplementation / follow-up

References

[1] GeK, XueA, BaiJ, et al.. Keshan disease — an endemic cardiomyopathy in China. Virchows Arch A Pathol Anat Histopathol, 1983, 401(1): 1-15

[2] TanJ, HuangY. Selenium in geo-ecosystem and its relation to endemic diseases in china. Water Air Soil Pollut, 1991, 57–58(1): 59-68

[3] KakehashiY. Why did Keshan disease occur? The relationship between White muscle disease, Shinshu cardiomyopathy and Keshan disease. Chin J Endemiol (Chinese), 2000, 19(3): 150-152

[4] LiGS, WangF, KangD, et al.. Keshan disease: an endemic cardiomyopathy in China. Hum Pathol, 1985, 16(6): 602-609

[5] WangS, LvY, WangY, et al.. Network Analysis of Se- and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease. Biological Trace Element Res, 2018, 183(1): 40-48

[6] Institute of Keshan Disease of the Chinese Center for Endemic Disease Control.. Criteria for Diagnosis of Keshan Disease (GB17021—1997), 1997General Administration of Quality Supervision, Inspection and Quarantine of the People’s Republic of China

[7] YangJ, TongW, WuC, et al.. Selenium level surveillance for the year 2007 of Keshan disease in endemic areas and analysis on surveillance results between 2003 and 2007. Biol Trace Elem Res, 2010, 138(1–3): 53-59

[8] FengLI, CaiW, OuyangB, et al.. Investigation on Keshan Disease in Sichuan Province in 2006. J Prev Med Inf (Chinese), 2007, 23(6): 680-682

[9] LiQ, LiuM, HouJ, et al.. The prevalence of Keshan disease in China. Intern J Cardiol, 2013, 168(2): 1121-1126

[10] ZhuY, WeiJ, KangY, et al.. Long-term efficiency of captopril on patients with chronic Keshan disease. Chin J Endemiol (Chinese), 2007, 26(2): 206-208

[11] WangLN, NiuXL. Preliminary implementation and effect of clinical pathways for chronic Keshan disease in endemic areas. Chin J Endemiol (Chinese), 2013, 32(5): 500-503

[12] ZhouQ, XuDY. Efficacy of metoprolol and captopril on chronic Keshan disease. J Prevent Med Inform (Chinese), 2013, 29(12): 1090-1093

[13] YuWH. A study of nutritional and bio-geochemical factors in the occurrence and development of Keshan disease. Jpn Circul J, 1982, 46(11): 1201-1207

[14] XuGL, WangSC, GuBQ, et al.. Further Investigation on the Role of Selenium Deficiency in the Aetiology and Pathogenesis of Keshan Disease. Biomed Environ Sci, 1997, 10(2–3): 316-326

[15] ChengYY, QianPC. The effect of selenium-fortified table salt in the prevention of Keshan disease on a population of 1.05 million. Biomed Environ Sci, 1990, 3(4): 422-428

[16] The State Technology Supervision Bureauthe Ministry of Health of the People’s Republic of China.. Delimitation and classification of Keshan disease areas (GB17020-1997), 1998National standards of the People’s Republic of China, Standards Press of China

[17] KlapcińskaB, PoprzęckiS, DanchA. Blood selenium concentration of residents of Upper Silesia: relation to age and gender. Pol J Environ Stud, 2006, 15(5): 753

[18] GaoX, LiuZ, WangT, et al.. A randomized trial of the effects of increased antioxidant capacity through selenium supplement on the prognosis of chronic Keshan disease. Chin J Endemiol (Chinese), 2016, 35(8): 577-581

[19] ZhouH, WangT, LiQ, et al.. Prevention of Keshan Disease by Selenium Supplementation: a Systematic Review and Meta-analysis. Biol Trace Elem Res, 2018, 186(1): 98-105

[20] LiuH, YuF, ShaoW, et al.. Associations between Selenium Content in Hair and Kashin-Beck Disease/Keshan Disease in Children in Northwestern China: a Prospective Cohort Study. Biol Trace Elem Res, 2018, 184(1): 16-23

[21] LiC, NiuX, LeiC. Circulating adhesion molecules in patients with Keshan disease and their relationship with Coxsackie B virus infection. J Huazhong Univ Sci Technol Med Sci, 2009, 29(2): 173-176

[22] LinNF, TangJ, BianJM. Geochemical Environment and Health Problems in China. Environ Geochem Health, 2004, 26(1): 81-88

[23] ZhouHH, WangT. Advance research on etiology of Keshan disease. Chin J Endemiol (Chinese), 2015, 34(6): 466-468

[24] YangGQ. The relationship between selenium and etiology of Keshan disease. Sheng Li Ke Xue Jin Zhan (Chinese), 1983, 14(4): 313-317

[25] WangSQ, NiuXL, LiuZW, et al.. Selenium deficiency is associated with endoplasmic reticulum stress in a rat model of cardiac malfunction. Biol Trace Elem Res, 2013, 156(1–3): 196-201

[26] LiuW, YaoH, ZhaoW, et al.. Selenoprotein W was Correlated with the Protective Effect of Selenium on Chicken Myocardial Cells from Oxidative Damage. Biol Trace Elem Res, 2016, 171(2): 419-426

[27] RemmeWJ, RieggerG, HildebrandtP, et al.. The benefits of early combination treatment of carvedilol and an ACE-inhibitor in mild heart failure and left ventricular systolic dysfunction. The carvedilol and ACE-inhibitor remodelling mild heart failure evaluation trial (CARMEN). Cardiovasc Drugs Ther, 2004, 18(1): 57-66

[28] SliwaK, NortonGR, KoneN, et al.. Impact of initiating carvedilol before angiotensin-converting enzyme inhibitor therapy on cardiac function in newly diagnosed heart failure. J Am Coll Cardiol, 2004, 44(9): 1825-1830

[29] WillenheimerR, van VeldhausenDJ, SilkeB, et al.. CIBIS III Investigators. Effect on survival and hospitalization of initiating treatment for chronic heart failure with bisoprolol followed by enalapril, as compared with the opposite sequence: results of the randomized Cardiac Insufficiency Bisoprolol Study (CIBIS) III. Circulation, 2005, 112(16): 2426-2435

[30] KomajdaM, LapuertaP, HermansN, et al.. Adherence to guidelines is a predictor of outcome in chronic heart failure: the MAHLER survey. Eur Heart J, 2005, 26(16): 1653-1659