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The Association Between Serum Selenium Concentration www.nature.com/scientificreports OPEN The association between serum selenium concentration and prognosis in patients with heart failure in a Chinese population Zhiliang Zhang1,2, Chao Chang1, Yuxin Zhang2, Zhiyong Chai2, Jinbei Li3 & Chunguang Qiu1* Whether Selenium (Se) defciency relates with adverse prognosis in Chinese patients with heart failure (HF) is still unknown. This study aimed to investigate the association of serum Se level and the outcomes of patients with HF in a Chinese population. Patients with HF and serum Se examination were retrospectively included. Baseline information were collected at patient’s frst admission. The primary and secondary outcomes were all-cause mortality and rehospitalization for HF during follow-up, respectively. The study participants were divided into quartiles according to their serum Se concentrations. The Cox proportional hazard models were adopted to estimate the association of serum Se levels with observed outcomes. A total of 411 patients with HF with a mean age of 62.5 years were included. The mean serum level of Se was 68.3 ± 27.7 µg/L. There was nonsignifcant diference of baseline characterizes between the four quartile groups. In comparison with patients in the highest quartile, those with the lowest quartile (17.40–44.35 µg/L) were associated with increased risk of all- cause mortality [adjusted hazard ratios (95% CI) 2.32 (1.43–3.77); Ptrend = 0.001]. Our study suggested that a lower serum Se level was signifcantly associated with increased risk of all-cause mortality in patients with HF. Heart failure (HF) is an important disease burden worldwide with a 1–2% prevalence among global population1. Despite numerous advances in therapeutics of HF, there are still unmet needs to improve quality of life and long- term survival of those patients2. Patients with HF, especially for elderly, are commonly presented with malnutri- tion and micronutrients defciency as underdetermined reasons 3,4. Over last decade, several studies have found the associations between some trace elements defciency (e.g. Zn, Fe) and adverse clinical outcomes in patients with HF5,6. Moreover, iron supplement has been evidenced to beneft HF patients with iron deprivation regard- ing to symptoms and exercise capacity7,8. Selenium (Se) is an essential trace element for human health. Selenocysteine, the active form of Se, is incor- porated as 25 selenoproteins including glutathione peroxidase (GPx), thioredoxin reductase, selenoprotein-P, redox-regulating signaling, and thyroid hormones metabolism 9. Te soil content of selenium is varying greatly, which can afect dietary selenium intake. For example, Venezuela, Canada, the United States and Japan have high intakes of Se (> 100 μg/day)10. In contrast, China has areas both with selenium defciency and excess. Severe Se defciency has been proofed as a cause of congestive HF, a disorder known as Keshan Disease 11, and less severe Se defciency or suboptimal Se status has also been suggested associated with HF progression12. Recently, Bomer et al. using an European cohort of 2516 patients with HF reported that approximately 25% of patients with worsening HF have a serum Se < 70 µg/L, and that was associated with a poor quality of life and poor exercise capacity, as well as a worse prognosis 13. However, serum Se levels vary greatly within diferent populations. In some regions such as China, Se defciency maybe more common because of the Se-defcient soil and diet10,14. Te prevalence of Se defciency and whether it relates with adverse prognosis in Chinese patients with HF were still unknown. 1Department of Cardiology, The First Afliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, Henan, China. 2Department of Cardiology, Nanyang Central Hospital, NanYang 473000, Henan, China. 3Department of Cardiology, The Second Afliated Hospital of Zhengzhou University, Zhengzhou 450014, Henan, China. *email: [email protected] Scientifc Reports | (2021) 11:14533 | https://doi.org/10.1038/s41598-021-93873-7 1 Vol.:(0123456789) www.nature.com/scientificreports/ 1st quartile (17.4– 2nd quartile (44.35– 3rd quartile (68.05– 4th quartile (94.15– Variables Total 44.35 µg/L) (n = 104) 68.05 µg/L) (n = 102) 94.15 µg/L) (n = 103) 116.7 µg/L) (n = 102) P Age (years) 62.5 ± 15.9 60.0 ± 17.0 62.1 ± 16.5 63.8 ± 15.8 64.0 ± 14.0 0.223 Female 183 (44.5%) 45 (43.3%) 48 (47.1%) 47 (45.6%) 43 (42.2%) 0.893 BMI (kg/m2) 26.7 ± 4.7 27.6 ± 4.6 26.4 ± 4.5 25.8 ± 4.8 26.9 ± 4.7 0.596 Current smoker 82 (20.0%) 18 (17.3%) 19 (18.6%) 16 (15.5%) 29 (28.4%) 0.093 Current drinker 61 (14.8%) 15 (14.4%) 17 (16.8%) 9 (8.7%) 20 (19.6%) 0.562 Clinical features Prior history of HF 295 (71.8%) 80 (76.9%) 69 (67.6%) 71 (68.9%) 75 (73.5%) 0.426 HF duration (months) 20.4 ± 6.4 20.7 ± 6.4 20.8 ± 6.4 20.6 ± 6.1 19.5 ± 6.6 0.383 Acute/worsening chronic 100 (24.3%) 22 (21.2%) 22 (21.6%) 29 (28.2%) 27 (26.5%) 0.366 HF NT-proBNP (pg/mL) 3541 (1952–6909) 4273.0 (2287.5–8362.0) 3573.5 (1337.3–6935.8) 3361.0 (1933.0–6310.0) 2939.5 (1790.0–6616.8) 0.336 NYHA class, III-IV 335 (81.5%) 87 (83.7%) 78 (76.5%) 88 (85.4%) 82 (80.4%) 0.559 Medical history Coronary artery disease 191 (46.5%) 52 (50.0%) 51 (50.0%) 37 (35.9%) 51 (50.0%) 0.105 Myocardial infarction 87 (21.2%) 29 (27.9%) 23 (22.5%) 13 (12.6%) 22 (21.6%) 0.059 PCI 48 (11.7%) 11 (10.6%) 11 (10.8%) 11 (10.7%) 15 (14.7%) 0.751 CABG 9 (2.2%) 1 (1.0%) 2 (2.0%) 3 (2.9%) 3 (2.9%) 0.734 Dilated cardiomyopathy 53 (12.9%) 16 (15.4%) 15 (14.7%) 13 (12.6%) 9 (8.8%) 0.497 Valvular heart disease 39 (9.5%) 11 (10.6%) 10 (9.8%) 8 (7.8%) 10 (9.8%) 0.914 Congenital heart disease 4 (1.0%) 1 (1.0%) 1 (1.0%) 0 (0.0%) 2 (2.0%) 0.563 Hypertension 168 (40.9%) 36 (34.6%) 43 (42.2%) 39 (37.9%) 50 (49.0%) 0.176 Diabetes mellitus 112 (27.3%) 22 (21.2%) 33 (32.4%) 24 (23.3%) 33 (32.4%) 0.142 CKD 40 (9.7%) 9 (8.7%) 13 (12.7%) 8 (7.8%) 10 (9.8%) 0.649 Prior history of HF 295 (71.8%) 80 (76.9%) 69 (67.6%) 71 (68.9%) 75 (73.5%) 0.426 AF 121 (29.4%) 36 (34.6%) 32 (31.4%) 25 (24.3%) 28 (27.5%) 0.385 Echocardiography fndings IVST (mm) 10.0 (9.0–10.7) 10.0 (9.0–11.0) 10.0 (9.0–10.1) 10.0 (9.0–10.0) 10.0 (9.0–11.0) 0.278 PWT (mm) 10.0 (9.0–10.0) 9.0 (9.0–10.0) 9.0 (9.0–10.0) 9.0 (9.0–10.0) 9.0 (8.0–10.0) 0.592 LVDv (mL) 158.0 (107.0–211.0) 169.0 (107.5–239.0) 161.0 (101.5–206.3) 144.0 (103.0–208.0) 148.5 (113.3–207.3) 0.456 LVSv (mL) 83.0 (44.0–133.0) 101.5 (48.0–159.5) 83.0 (42.0–136.0) 68.0 (39.0–127.0) 86.5 (45.8–132.0) 0.451 LVEF (%) 48.0 (36.0–59.0) 45.5 (35.0–58.0) 46.0 (35.0–59.0) 50.0 (40.0–60.0) 50.5 (35.0–60.0) 0.305 LAD (mm) 41.0 (37.0–47.0) 43.0 (38.0–47.0) 40.0 (36.0–46.3) 39.0 (37.0–45.0) 41.0 (36.0–47.0) 0.047 Medications Beta-blocker 258 (62.8%) 64 (61.5%) 62 (60.8%) 64 (62.15) 68 (66.7%) 0.821 CCB 94 (22.9%) 17 (16.3%) 31 (30.4%) 18 (17.5%) 28 (27.5%) 0.034 Statins 189 (46.0%) 43 (41.3%) 51 (50.0%) 49 (47.6%) 46 (45.1%) 0.637 ARB 125 (30.4%) 27 (26.0%) 38 (37.3%) 27 (26.2%) 33 (32.4%) 0.234 ACE-I 146 (35.5%) 38 (36.5%) 35 (34.3%) 39 (37.9%) 34 (33.3%) 0.903 Diuretics 247 (60.1%) 62 (59.6%) 66 (64.7%) 59 (57.3%) 60 (58.8%) 0.724 Table 1. Baseline characteristics of the study population stratifed by quartile of serum Se concentration. Data are presented as mean (standard deviation), median (interquartile range), or n (%). BMI body mass index, NT-proBNP n-terminal pro brain natriuretic peptide, CKD chronic kidney disease, AF atrial fbrillation, IVST interventricular septum thickness, PWT posterior wall thickness, LVDv lef ventricular end-diastolic volume, LVSv lef ventricular end-systolic volume, LVEF lef ventricular ejection fraction, LAD lef atrial dimension, CCB calcium-channel blocker, ARB angiotensin receptor blocker, ACE-I angiotensin converting enzyme inhibitor. Terefore, this study aimed to investigate the association of serum Se level and the outcomes of patients with HF in a Chinese population. Results Patient selection and baseline characteristics. Between January 2015 and December 2018, 635 patients with confrmed HF were initial screened. Among them, 113 patients were excluded due to the absence of serum Se measurement.
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