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Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: a Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011–2016

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Abstract

We aimed to explore the overall association between trace elements and cardiovascular disease (CVD) and its types in humans. A total of 5101 participants’ blood samples from the 2011–2016 National Health and Nutrition Examination Survey were included. Biochemical data were collected from laboratory tests conducted at mobile screening centers. After assessing linearity, weighted logistic regression estimated the association between trace elements and various CVD types. Weighted quantile sum (WQS) regression and quantile-based g-computation (Qgcomp) evaluated the overall relationship between biological trace elements and CVD types. After fully adjusting for confounding factors, the odds ratios of overall CVD morbidity corresponding to the second, third, and fourth quartiles of higher selenium (Se) concentration were 0.711 (95% CI, 0.529–0.956, p = 0.024), 0.734 (95% CI, 0.546–0.987, p = 0.041), and 0.738 (95% CI, 0.554–0.983, p = 0.038), respectively. Moreover, an increase in the concentration of copper (Cu) was associated with an increased risk of stroke (95% CI, 1.012–1.094, p = 0.01), heart failure (95% CI, 1.001–1.095, p = 0.046), and heart attack (95% CI, 1.001–1.083, p = 0.046). As the concentration of trace elements in the body increased, there was a significant positive association between Cu and CVD prevalence. On the other hand, Se and zinc were negatively associated with CVD prevalence. A nonlinear relationship between Se and CVD was found, and an appropriate Se intake may reduce the risk of CVD. Cu levels positively correlated with CVD risk. However, prospective cohort studies are warranted to confirm the causal effects of the micronutrients on CVD and its types.

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Data Availability

The dataset supporting the conclusions of this article is available from the National Health and Nutrition Examination Survey (NHANES) database at https://www.cdc.gov/nchs/nhanes/index.htm.

Abbreviations

CAD :

coronary artery disease

CHD :

coronary heart disease

CI :

confidence interval

CRP :

C-reactive protein

Cu :

copper

CVDs :

cardiovascular diseases

FBG :

fasting blood glucose

GPX1 :

glutathione peroxidase 1

HDL-C :

high-density lipoprotein cholesterol

ICP-DRC-MS :

inductively coupled plasma dynamic reaction cell mass spectrometry

LDL-C :

low-density lipoprotein cholesterol

MI :

myocardial infarction

Mn :

manganese

NAFLD :

non-alcoholic fatty liver disease

NHANES :

National Health and Nutrition Examination Survey

ORs :

odds ratios

Qgcomp :

quantile-based g-computation

SBP :

systolic blood pressure

Se :

selenium

WQS :

weighted quantile sum

Zn :

zinc

References

  1. Benjamin EJ, Muntner P, Alonso A et al (2019) Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation 139:e56–e528. https://doi.org/10.1161/cir.0000000000000659

    Article  PubMed  Google Scholar 

  2. Jaarsma T, Hill L, Bayes-Genis A et al (2019) Self-care of heart failure patients: practical management recommendations from the Heart Failure Association of the European Society of Cardiology. Eur J Heart Fail 23:157–174. https://doi.org/10.1002/ejhf.2008

    Article  Google Scholar 

  3. Fuchs FD, Whelton PK (2020) High blood pressure and cardiovascular disease. Hypertension 75:285–292. https://doi.org/10.1161/hypertensionaha.119.14240

    Article  CAS  PubMed  Google Scholar 

  4. Osuchowska-Grochowska I, Blicharska E, Gogacz M, Nogalska A, Winkler I, Szopa A, Ekiert H, Tymczyna-Borowicz B, Rahnama-Hezavah M, Grochowski C (2021) Brief review of endometriosis and the role of trace elements. Int J Mol Sci 22:11098. https://doi.org/10.3390/ijms222011098

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Mertz W (1981) The essential trace elements. Science 213:1332–1338. https://doi.org/10.1126/science.7022654

    Article  CAS  PubMed  Google Scholar 

  6. Zoroddu MA, Aaseth J, Crisponi G, Medici S, Peana M, Nurchi VM (2019) The essential metals for humans: a brief overview. J Inorg Biochem 195:120–129. https://doi.org/10.1016/j.jinorgbio.2019.03.013

    Article  CAS  PubMed  Google Scholar 

  7. Eshak ES, Iso H, Yamagishi K, Maruyama K, Umesawa M, Tamakoshi A (2018) Associations between copper and zinc intakes from diet and mortality from cardiovascular disease in a large population-based prospective cohort study. J Nutr Biochem 56:126–132. https://doi.org/10.1016/j.jnutbio.2018.02.008

    Article  CAS  PubMed  Google Scholar 

  8. Momen-Heravi M, Barahimi E, Razzaghi R, Bahmani F, Gilasi HR, Asemi Z (2017) The effects of zinc supplementation on wound healing and metabolic status in patients with diabetic foot ulcer: a randomized, double-blind, placebo-controlled trial. Wound Repair Regen 25:512–520. https://doi.org/10.1111/wrr.12537

    Article  PubMed  Google Scholar 

  9. Olechnowicz J, Tinkov A, Skalny A, Suliburska J (2018) Zinc status is associated with inflammation, oxidative stress, lipid, and glucose metabolism. J Physiol Sci 68:19–31. https://doi.org/10.1007/s12576-017-0571-7

    Article  CAS  PubMed  Google Scholar 

  10. Dias PCS, Sena-Evangelista KCM, Paiva M, Ferreira DQC, Ururahy MAG, Rezende AA, Abdalla DSP (2014) Pedrosa LFC (2014) The beneficial effects of rosuvastatin are independent of zinc supplementation in patients with atherosclerosis. J Trace Elem Med Biol 28:194–199. https://doi.org/10.1016/j.jtemb.2014.01.003

    Article  CAS  PubMed  Google Scholar 

  11. Seet RC, Lee CY, Lim EC, Quek AM, Huang H, Huang SH, Looi WF, Long LH, Halliwell B (2011) Oral zinc supplementation does not improve oxidative stress or vascular function in patients with type 2 diabetes with normal zinc levels. Atherosclerosis 219:231–239. https://doi.org/10.1016/j.atherosclerosis.2011.07.097

    Article  CAS  PubMed  Google Scholar 

  12. Palaniswamy S, Piltonen T, Koiranen M, Mazej D, Järvelin MR, Abass K, Rautio A, Sebert S (2019) The association between blood copper concentration and biomarkers related to cardiovascular disease risk-analysis of 206 individuals in the Northern Finland Birth Cohort 1966. J Trace Elem Med Biol 51:12–18. https://doi.org/10.1016/j.jtemb.2018.09.003

    Article  CAS  PubMed  Google Scholar 

  13. Roshanravan N, Koche Ghazi MK, Ghaffari S, Naemi M, Alamdari NM, Shabestari AN, Mosharkesh E, Soleimanzadeh H, Sadeghi MT, Alipour S, Bastani S, Tarighat-Esfanjani A (2022) Sodium selenite and Se-enriched yeast supplementation in atherosclerotic patients: effects on the expression of pyroptosis-related genes and oxidative stress status. Nutr Metab Cardiovasc Dis 32:1528–1537. https://doi.org/10.1016/j.numecd.2022.02.014

    Article  CAS  PubMed  Google Scholar 

  14. Laclaustra M, Navas-Acien A, Stranges S, Ordovas JM, Guallar E (2009) Serum selenium concentrations and hypertension in the US Population. Circ: Cardiovasc Qual. Outcomes 2:369–376. https://doi.org/10.1161/circoutcomes.108.831552

    Article  PubMed  Google Scholar 

  15. Ma Y, Hu Q, Yang D, Zhao Y, Bai J, Mubarik S, Yu C (2022) Combined exposure to multiple metals on serum uric acid in NHANES under three statistical models. Chemosphere 301:134416. https://doi.org/10.1016/j.chemosphere.2022.134416

    Article  CAS  PubMed  Google Scholar 

  16. Sanders AP, Mazzella MJ, Malin AJ, Hair GM, Busgang SA, Saland JM, Curtin P (2019) Combined exposure to lead, cadmium, mercury, and arsenic and kidney health in adolescents age 12-19 in NHANES 2009-2014. Environ Int 131:104993. https://doi.org/10.1016/j.envint.2019.104993

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kim K, Argos M, Persky VW, Freels S, Sargis RM, Turyk ME (2022) Associations of exposure to metal and metal mixtures with thyroid hormones: results from the NHANES 2007-2012. Environ Res 212:113413. https://doi.org/10.1016/j.envres.2022.113413

    Article  CAS  PubMed  Google Scholar 

  18. Ferreira RLU, Sena-Evangelista KCM, de Azevedo EP, Pinheiro FI, Cobucci RN, Pedrosa LFC (2021) Selenium in human health and gut microflora: bioavailability of selenocompounds and relationship with diseases. Front Nutr 8:685317. https://doi.org/10.3389/fnut.2021.685317

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D, Bao GW, Singh T, Cardozo LJ (2010) Zinc decreases C-reactive protein, lipid peroxidation, and inflammatory cytokines in elderly subjects: a potential implication of zinc as an atheroprotective agent. Am J Clin Nutr 91:1634–1641. https://doi.org/10.3945/ajcn.2009.28836

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Knez M, Glibetic M (2021) Zinc as a biomarker of cardiovascular health. Front Nutr 8:686078. https://doi.org/10.3389/fnut.2021.686078

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Stone J, Doube A, Dudson D, Wallace J Inadequate calcium, folic acid, vitamin E, zinc, and selenium intake in rheumatoid arthritis patients: results of a dietary survey. Semin Arthritis Rheu 27:180–185. https://doi.org/10.1016/s0049-0172(97)80018-2

  22. Barrett CW, Singh K, Motley AK et al (2013) Dietary selenium deficiency exacerbates DSS-induced epithelial injury and AOM/DSS-induced tumorigenesis. PLoS One 8:e67845. https://doi.org/10.1371/journal.pone.0067845

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hambidge M (2000) Human zinc deficiency. J Nutr 130:1344s–1349s. https://doi.org/10.1093/jn/130.5.1344S

    Article  CAS  PubMed  Google Scholar 

  24. Naseri K, Saadati S, Ghaemi F, Ashtary-Larky D, Asbaghi O, Sadeghi A, Afrisham R, de Courten B (2023) The effects of probiotic and synbiotic supplementation on inflammation, oxidative stress, and circulating adiponectin and leptin concentration in subjects with prediabetes and type 2 diabetes mellitus: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials. Eur J Nutr 62:543–561. https://doi.org/10.1007/s00394-022-03012-9

    Article  CAS  PubMed  Google Scholar 

  25. Kodavanti UP, Schladweiler MC, Gilmour PS (2008) The role of particulate matter-associated zinc in cardiac injury in rats. Environ Health Perspect 116:13–20. https://doi.org/10.1289/ehp.10379

    Article  CAS  PubMed  Google Scholar 

  26. Ling SC, Luo Z, Chen GH, Zhang DG, Liu X (2018) Waterborne Zn influenced Zn uptake and lipid metabolism in two intestinal regions of juvenile goby Synechogobius hasta. Ecotoxicol Environ Saf 148:578–584. https://doi.org/10.1016/j.ecoenv.2017.10.064

    Article  CAS  PubMed  Google Scholar 

  27. Choi S, Liu X, Pan Z (2018) Zinc deficiency and cellular oxidative stress: prognostic implications in cardiovascular diseases. Acta Pharmacol Sin 39:1120–1132. https://doi.org/10.1038/aps.2018.25

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chowdhury R, Ramond A, O'Keeffe LM et al (2018) Environmental toxic metal contaminants and risk of cardiovascular disease: systematic review and meta-analysis. Br Med J (Clin Res Ed) 362:k3310. https://doi.org/10.1136/bmj.k3310

    Article  Google Scholar 

  29. Domingo-Relloso A, Grau-Perez M, Briongos-Figuero L et al (2019) The association of urine metals and metal mixtures with cardiovascular incidence in an adult population from Spain: the Hortega Follow-Up Study. Int J Epidemiol 48:1839–1849. https://doi.org/10.1093/ije/dyz061

    Article  PubMed  PubMed Central  Google Scholar 

  30. Beckers-Trapp ME, Lanoue L, Keen CL, Rucker RB, Uriu-Adams JY (2006) Abnormal development and increased 3-nitrotyrosine in copper-deficient mouse embryos. Free Radic Biol Med 40:35–44. https://doi.org/10.1016/j.freeradbiomed.2005.08.020

    Article  CAS  PubMed  Google Scholar 

  31. Srinivasan S, Avadhani NG (2012) Cytochrome c oxidase dysfunction in oxidative stress. Free Radic Biol Med 53:1252–1263. https://doi.org/10.1016/j.freeradbiomed.2012.07.021

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Heinecke JW, Rosen H, Chait A (1984) Iron and copper promote modification of low density lipoprotein by human arterial smooth muscle cells in culture. J Clin Investig 74(5):1890–1894. https://doi.org/10.1172/jci111609

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Constantinescu-Aruxandei D, Frîncu RM, Capră L, Oancea F (2018) Selenium analysis and speciation in dietary supplements based on next-generation selenium ingredients. Nutrients 10:1466. https://doi.org/10.3390/nu10101466

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rayman MP (2012) Selenium and human health. Lancet 379:1256–1268. https://doi.org/10.1016/s0140-6736(11)61452-9

    Article  CAS  PubMed  Google Scholar 

  35. Shimada BK, Alfulaij N, Seale LA (2021) The impact of selenium deficiency on cardiovascular function. Int J Mol Sci 22:10713. https://doi.org/10.3390/ijms221910713

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Yoshida T, Watanabe M, Engelman DT, Engelman RM, Schley JA, Maulik N, Ho YS, Oberley TD, Das DK (1996) Transgenic mice overexpressing glutathione peroxidase are resistant to myocardial ischemia reperfusion injury. J Mol Cell Cardiol 28:1759–1767. https://doi.org/10.1006/jmcc.1996.0165

    Article  CAS  PubMed  Google Scholar 

  37. Verma S, Hoffmann FW, Kumar M, Huang Z, Roe K, Nguyen-Wu E, Hashimoto AS, Hoffmann PR (2011) Selenoprotein K knockout mice exhibit deficient calcium flux in immune cells and impaired immune responses. J Immunol 186:2127–2137. https://doi.org/10.4049/jimmunol.1002878

    Article  CAS  PubMed  Google Scholar 

  38. Gao C, Hsu FC, Dimitrov LM, Okut H, Chen YI, Taylor KD, Rotter JI, Langefeld CD, Bowden DW, Palmer ND (2017) A genome-wide linkage and association analysis of imputed insertions and deletions with cardiometabolic phenotypes in Mexican Americans: the Insulin Resistance Atherosclerosis Family Study. Genet Epidemiol 41:353–362. https://doi.org/10.1002/gepi.22042

    Article  PubMed  PubMed Central  Google Scholar 

  39. Frączek-Jucha M, Kabat M, Szlósarczyk B, Czubek U, Nessler J, Gackowski A (2019) Selenium deficiency and the dynamics of changes of thyroid profile in patients with acute myocardial infarction and chronic heart failure. Kardiol Pol 77:674–682. https://doi.org/10.33963/kp.14822

    Article  PubMed  Google Scholar 

  40. Guo Y, Yu P, Zhu J, Yang S, Yu J, Deng Y, Li N, Liu Z (2019) High maternal selenium levels are associated with increased risk of congenital heart defects in the offspring. Prenat Diagn 39:1107–1114. https://doi.org/10.1002/pd.5551

    Article  CAS  PubMed  Google Scholar 

  41. Jyothsna S, Manjula G, Suthari S, Nageswara Rao AS (2020) Qualitative elemental analysis of selected potential anti-asthmatic medicinal plant taxa using EDXRF technique. Heliyon 6:e03260. https://doi.org/10.1016/j.heliyon.2020.e03260

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Shao JJ, Yao HD, Zhang ZW, Li S, Xu SW (2012) The disruption of mitochondrial metabolism and ion homeostasis in chicken hearts exposed to manganese. Toxicol Lett 214:99–108. https://doi.org/10.1016/j.toxlet.2012.08.011

    Article  CAS  PubMed  Google Scholar 

  43. Jiang Y, Zheng W (2005) Cardiovascular toxicities upon manganese exposure. Cardiovasc Toxicol 5:345–354. https://doi.org/10.1385/ct:5:4:345

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The authors thank the patients and investigators who participated in NHANES for providing the data. The authors are also thankful to Jiajin Chen of the Department of Biostatistics, School of Public Health at Nanjing Medical University, for providing statistical guidance.

Funding

This work was supported by the National Natural Science Foundation of China (Grant number 81970339 to XL Li) and the National High Technology Research and Development Programme of China (Grant number 2017YFC1700505 to XL Li).

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Author notes

  1. Qixin Guo, Jingshan Cai, and Qiang Qu contributed equally.

Authors and Affiliations

  1. Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Guangzhou Road 300, Nanjing, 210029, China

    Qixin Guo, Qiang Qu, Iokfai Cheang, Jinjin Shi & Xinli Li

  2. Department of Cardiology, Suzhou University Clinical Testing Center, Affiliated First People’s Hospital, Suzhou, China

    Jingshan Cai

  3. Department of Cardiology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine of Nanjing Medical University, Xuzhou, Jiangsu, China

    Hui Pang

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  1. Qixin Guo
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Contributions

XL and HP contributed to the conception and design of the study. QG, QQ, and JC performed the statistical analysis. QG wrote the first draft of the manuscript. IC and JJ wrote sections of the manuscript. All authors contributed to the manuscript revisions and read and approved the submitted version.

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Correspondence to Hui Pang or Xinli Li.

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The National Centre for Health Statistics’ Research Ethics Review Board approved the study protocols.

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Guo, Q., Cai, J., Qu, Q. et al. Association of Blood Trace Elements Levels with Cardiovascular Disease in US Adults: a Cross-Sectional Study from the National Health and Nutrition Examination Survey 2011–2016. Biol Trace Elem Res 202, 3037–3050 (2024). https://doi.org/10.1007/s12011-023-03913-8

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