Nutr Res Pract.  2022 Dec;16(6):745-754. 10.4162/nrp.2022.16.6.745.

Serum 25-hydroxyvitamin D₃ is associated with homocysteine more than with apolipoprotein B

• Kim NK
• Jung MA
• Choi Bh
• Joo NS

• KMID: 2536508
• DOI: http://doi.org/10.4162/nrp.2022.16.6.745

Abstract

BACKGROUND/OBJECTIVES
The incidence of cardiovascular diseases (CVDs) has increased worldwide. Although a low serum vitamin D level is known to be associated with the risk of CVD, the mechanism is not well understood yet. The aim of this study was to determine the relationship of serum 25-hydroxyvitamin D₃ (25[OH]D) with homocysteine and apolipoprotein B (ApoB).
SUBJECTS/METHODS
Of 777 subjects recruited from one health promotion center for routine heath exam from January 2010 to December 2016, 518 subjects were included in this study. Serum 25(OH)D, serum homocysteine, and other metabolic parameters including ApoB were analyzed. Simple and partial correlations were carried out after adjustments. Simple linear regression analysis was used for precise correlation of parameters. Multivariate regression analysis was done to know which factor (serum homocysteine or ApoB) was more related to serum 25(OH)D after adjustments. Finally, logarithms of homocysteine concentrations according to tertiles of serum 25(OH)D were compared.
RESULTS
After sex and age adjustments, serum 25(OH)D showed negative correlations with serum homocysteine (r’ = −0.114) and ApoB (r’ = −0.098). In simple linear regression analysis, serum 25(OH)D showed a significant negative correlation with ApoB (P = 0.035). However, in multivariate regression analysis, serum 25(OH)D was significantly associated with serum homocysteine after adjustments (P = 0.022). In addition, serum homocysteine concentration was significantly high in the lowest 25(OH)D group (P = 0.046).
CONCLUSION
Serum 25(OH)D concentration showed a stronger negative association with serum homocysteine than with ApoB.

Keyword

Homocysteine; apolipoprotein B; 25-hydroxyvitamin D₃; cardiovascular diseases

Reference

1. Roth GA, Mensah GA, Johnson CO, Addolorato G, Ammirati E, Baddour LM, Barengo NC, Beaton AZ, Benjamin EJ, Benziger CP, et al. Global burden of cardiovascular diseases and risk factors, 1990–2019: update from the GBD 2019 study. J Am Coll Cardiol. 2020; 76:2982–3021. PMID: 33309175.

2. Shin JI, Oh J, Kim HC, Choi D, Yoon YS. Current state of cardiovascular research in Korea. Circ Res. 2019; 125:1141–1145. PMID: 31804914.

3. Tousoulis D, Psarros C, Demosthenous M, Patel R, Antoniades C, Stefanadis C. Innate and adaptive inflammation as a therapeutic target in vascular disease: the emerging role of statins. J Am Coll Cardiol. 2014; 63:2491–2502. PMID: 24613322.

4. Young KA, Snell-Bergeon JK, Naik RG, Hokanson JE, Tarullo D, Gottlieb PA, Garg SK, Rewers M. Vitamin D deficiency and coronary artery calcification in subjects with type 1 diabetes. Diabetes Care. 2011; 34:454–458. PMID: 20978098.

5. Lavie CJ, Lee JH, Milani RV. Vitamin D and cardiovascular disease will it live up to its hype? J Am Coll Cardiol. 2011; 58:1547–1556. PMID: 21958881.

6. Lee JH, O’Keefe JH, Bell D, Hensrud DD, Holick MF. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2008; 52:1949–1956. PMID: 19055985.

7. Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015; 14:6. PMID: 25577237.

8. Joo NS, Jung S, Kim YN, Choi BH. Cut-off value of serum homocysteine in relation to increase of coronary artery calcification. J Investig Med. 2021; 69:345–350.

9. Sniderman AD, Thanassoulis G, Glavinovic T, Navar AM, Pencina M, Catapano A, Ference BA. Apolipoprotein B particles and cardiovascular disease: a narrative review. JAMA Cardiol. 2019; 4:1287–1295. PMID: 31642874.

10. Chan DC, Watts GF. Apolipoproteins as markers and managers of coronary risk. QJM. 2006; 99:277–287. PMID: 16504986.

11. Melguizo-Rodríguez L, Costela-Ruiz VJ, García-Recio E, De Luna-Bertos E, Ruiz C, Illescas-Montes R. Role of vitamin D in the metabolic syndrome. Nutrients. 2021; 13:830. PMID: 33802330.

12. Chung JY, Hong SH. Vitamin D status and its association with cardiometabolic risk factors in Korean adults based on a 2008–2010 Korean National Health and Nutrition Examination Survey. Nutr Res Pract. 2013; 7:495–502. PMID: 24353836.

13. Lee SJ, Lee EY, Lee JH, Kim JE, Kim KJ, Rhee Y, Kim HC, Youm Y, Kim CO. Associations of serum 25-hydroxyvitamin D with metabolic syndrome and its components in elderly men and women: the Korean Urban Rural Elderly cohort study. BMC Geriatr. 2019; 19:102. PMID: 30975093.

14. Manson JE, Cook NR, Lee IM, Christen W, Bassuk SS, Mora S, Gibson H, Gordon D, Copeland T, D’Agostino D, et al. Vitamin D supplements and prevention of cancer and cardiovascular disease. N Engl J Med. 2019; 380:33–44. PMID: 30415629.

15. Jani R, Mhaskar K, Tsiampalis T, Kassaw NA, González MÁM, Panagiotakos DB. Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies. Nutr Metab Cardiovasc Dis. 2021; 31:3282–3304. PMID: 34656382.

16. Han D, Ó Hartaigh B, Gransar H, Yoon JH, Kim KJ, Kim MK, Choi SY, Sung J, Chang HJ. Incremental benefit of coronary artery calcium score above traditional risk factors for all-cause mortality in asymptomatic Korean adults. Circ J. 2015; 79:2445–2451. PMID: 26356835.

17. Rai V, Agrawal DK. Role of vitamin D in cardiovascular diseases. Endocrinol Metab Clin North Am. 2017; 46:1039–1059. PMID: 29080634.

18. Kim SH, Oh JE, Song DW, Cho CY, Hong SH, Cho YJ, Yoo BW, Shin KS, Joe H, Shin HS, et al. The factors associated with Vitamin D deficiency in community dwelling elderly in Korea. Nutr Res Pract. 2018; 12:387–395. PMID: 30323906.

19. Park S, Lee BK. Vitamin D deficiency is an independent risk factor for cardiovascular disease in Koreans aged ≥ 50 years: results from the Korean National Health and Nutrition Examination Survey. Nutr Res Pract. 2012; 6:162–168. PMID: 22586506.

20. Cholesterol Treatment Trialists’ (CTT) Collaboration. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010; 376:1670–1681. PMID: 21067804.

21. Barter PJ, Ballantyne CM, Carmena R, Castro Cabezas M, Chapman MJ, Couture P, de Graaf J, Durrington PN, Faergeman O, Frohlich J, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med. 2006; 259:247–258. PMID: 16476102.

22. Sniderman AD, Williams K, Contois JH, Monroe HM, McQueen MJ, de Graaf J, Furberg CD. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011; 4:337–345. PMID: 21487090.

23. Thanassoulis G, Williams K, Ye K, Brook R, Couture P, Lawler PR, de Graaf J, Furberg CD, Sniderman A. Relations of change in plasma levels of LDL-C, non-HDL-C and ApoB with risk reduction from statin therapy: a meta-analysis of randomized trials. J Am Heart Assoc. 2014; 3:e000759. PMID: 24732920.

24. Borén J, Williams KJ. The central role of arterial retention of cholesterol-rich apolipoprotein-B-containing lipoproteins in the pathogenesis of atherosclerosis: a triumph of simplicity. Curr Opin Lipidol. 2016; 27:473–483. PMID: 27472409.

25. Langlois MR, Chapman MJ, Cobbaert C, Mora S, Remaley AT, Ros E, Watts GF, Borén J, Baum H, Bruckert E, et al. Quantifying atherogenic lipoproteins: current and future challenges in the era of personalized medicine and very low concentrations of LDL cholesterol. A consensus statement from EAS and EFLM. Clin Chem. 2018; 64:1006–1033. PMID: 29760220.

26. Karhapää P, Pihlajamäki J, Pörsti I, Kastarinen M, Mustonen J, Niemelä O, Kuusisto J. Diverse associations of 25-hydroxyvitamin D and 1,25-dihydroxy-vitamin D with dyslipidaemias. J Intern Med. 2010; 268:604–610. PMID: 20831628.

27. Sun X, Cao ZB, Tanisawa K, Ito T, Oshima S, Ishimi Y, Tabata I, Higuchi M. Associations between the serum 25(OH)D concentration and lipid profiles in Japanese men. J Atheroscler Thromb. 2015; 22:355–362. PMID: 25346256.

28. Li S, He Y, Lin S, Hao L, Ye Y, Lv L, Sun Z, Fan H, Shi Z, Li J, et al. Increase of circulating cholesterol in vitamin D deficiency is linked to reduced vitamin D receptor activity via the Insig-2/SREBP-2 pathway. Mol Nutr Food Res. 2016; 60:798–809. PMID: 26694996.

29. Schaffer A, Verdoia M, Cassetti E, Marino P, Suryapranata H, De Luca G. Novara Atherosclerosis Study Group (NAS). Relationship between homocysteine and coronary artery disease. Results from a large prospective cohort study. Thromb Res. 2014; 134:288–293. PMID: 24928335.

30. Wald DS, Law M, Morris JK. Homocysteine and cardiovascular disease: evidence on causality from a meta-analysis. BMJ. 2002; 325:1202–1206. PMID: 12446535.

31. Faraci FM, Lentz SR. Hyperhomocysteinemia, oxidative stress, and cerebral vascular dysfunction. Stroke. 2004; 35:345–347. PMID: 14757874.

32. Esse R, Barroso M, Tavares de Almeida I, Castro R. The contribution of homocysteine metabolism disruption to endothelial dysfunction: state-of-the-art. Int J Mol Sci. 2019; 20:867. PMID: 30781581.

33. Li WF, Zhang DD, Xia JT, Wen SF, Guo J, Li ZC. The association between B vitamins supplementation and adverse cardiovascular events: a meta-analysis. Int J Clin Exp Med. 2014; 7:1923–1930. PMID: 25232372.

34. Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017; 8:CD006612. PMID: 28816346.

35. Al-Bayyari N, Al-Zeidaneen S, Hailat R, Hamadneh J. Vitamin D₃ prevents cardiovascular diseases by lowering serum total homocysteine concentrations in overweight reproductive women: A randomized, placebo-controlled clinical trial. Nutr Res. 2018; 59:65–71. PMID: 30442234.

36. Mao X, Xing X, Xu R, Gong Q, He Y, Li S, Wang H, Liu C, Ding X, Na R, et al. Folic acid and vitamins D and B12 correlate with homocysteine in Chinese patients with type-2 diabetes mellitus, hypertension, or cardiovascular disease. Medicine (Baltimore). 2016; 95:e2652. PMID: 26871790.

37. Verdoia M, Nardin M, Gioscia R, Saghir Afifeh AM, Viglione F, Negro F, Marcolongo M, De Luca G. Novara Atherosclerosis Study Group (NAS). Association between vitamin D deficiency and serum Homocysteine levels and its relationship with coronary artery disease. J Thromb Thrombolysis. 2021; 52:523–531. PMID: 33538987.

38. Amer M, Qayyum R. The relationship between 25-hydroxyvitamin D and homocysteine in asymptomatic adults. J Clin Endocrinol Metab. 2014; 99:633–638. PMID: 24276459.

39. Glueck CJ, Jetty V, Rothschild M, Duhon G, Shah P, Prince M, Lee K, Goldenberg M, Kumar A, Goldenberg N, et al. Associations between serum 25-hydroxyvitamin D and lipids, lipoprotein cholesterols, and homocysteine. N Am J Med Sci. 2016; 8:284–290. PMID: 27583236.

40. Kriebitzsch C, Verlinden L, Eelen G, van Schoor NM, Swart K, Lips P, Meyer MB, Pike JW, Boonen S, Carlberg C, et al. 1,25-dihydroxyvitamin D₃ influences cellular homocysteine levels in murine preosteoblastic MC3T3-E1 cells by direct regulation of cystathionine β-synthase. J Bone Miner Res. 2011; 26:2991–3000. PMID: 21898591.

41. Jung SJ, Hwangbo Y, Jung JH, Kim J, Kim H, Jeong KH, Lee DW, Cho SH, Kim HW. Recent trends in serum vitamin D levels among Korean population: Korea National Health and Nutrition Examination Survey 2008~2014. Korean J Clin Geriatr. 2018; 19:55–62.