Vitamin D deficiency and its impact on outcomes in myocardial infarction patients: a prospective observational study

Document Type : original articles

Authors

1 Department of Cardiology, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

2 Department of Orthopedics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Epidemiology and Biostatistics, School of Medicine, Urmia University of Medical Sciences, Urmia, Iran

4 Seyed al-Shohada Cardiology Hospital, Department of Cardiology, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Objectives: Vitamin D deficiency has been linked to cardiovascular diseases, but its impact on outcomes in myocardial infarction (MI) patients remains unclear. This study investigated the relationship between serum vitamin D levels and short-term and medium-term outcomes in patients with myocardial infarction. Ischemic heart diseases (IHD) are the most common cause of death in the world. Identifying risk factors and predictors can play a critical role in identifying high-risk people in screenings, identifying high-risk patients during admission to the hospital, and adjusting these risk factors in patients to improve prognosis.
 
Methods: This prospective observational study was conducted on 212 patients diagnosed with myocardial infarction at Seyed al-Shohada Hospital in Urmia, Iran. Having been admitted, the patients had their serum vitamin D levels measured using the same blood sample for routine tests. Levels of vitamin D were categorized as normal (>30 ng/ml), insufficient (21-29 ng/ml), or deficient (<20 ng/ml). The patient's files provided the demographic, clinical, and biomedical information, echocardiography, and angiography data. The patients were followed for at least six months post-MI, with a maximum follow-up of 11 months.  Follow-up occurred through monthly phone calls and outpatient clinic visits as needed. Primary outcomes included in-hospital complications (such as death, significant bleeding, acute pulmonary edema, cardiogenic shock, and arrhythmias), cardiac readmissions, and mortality. Logistic regression and Cox regression analyses were used to examine the connection between outcome variables and vitamin D levels, adjusting for potential confounders including age, gender, blood pressure, diabetes, blood lipids, creatinine, disease severity (SYNTAX score*), and left ventricular ejection fraction. The mean serum level of vitamin D in patients on admission was 33. 62 ng/dL. The average number of hospitalization days was 4.8 days, and the rate of re-hospitalization was 26.6% in the six-month follow-up and 30.3% in the 9-month follow-up. The hospital mortality rate was equal to 1.4%, and the mortality rate at the end of the follow-up period was equal to 8.3%. The most common complication during hospitalization among the patients was ventricular tachycardia. However, in follow-up, re-hospitalization due to previous issues was the most common complication.
 
Results: The mean serum vitamin D level was 33. 62 ng/ml,with 52.8% of patients having insufficient or deficient levels. The most common in-hospital complication was ventricular tachycardia (11.5%). Vitamin D deficiency was not significantly associated with in-hospital complications. However, during the follow-up period, vitamin D deficiency was significantly related to increased risk of readmission to hospital (HR: 6.984, 95% CI: 3.500-13.936, p<0.001). The 6-month readmission rate was 26.6%, increasing to 30.3% at 9 months. Vitamin D deficiency was also associated with increased cardiac mortality (HR: 12.936, 95% CI: 1.494-112.016, p=0.020) during follow-up. The 9-month mortality rate was 8.3%. Other factors contributing to cardiac mortality included disease severity (SYNTAX score) and female gender.
 
Conclusions: While vitamin D deficiency did not impact short-term complications, it was associated with increased risk of hospitalreadmission and mortality in MI patients during medium-term follow-up. These findings suggest that vitamin D status can significantly impact long-term outcomes for MI patients.

Keywords


1.Organization WHO. Cardiovascular diseases (CVDs) 2023 [updated 2023. Available from:https://www.who.int/news-room/factsheets/detail/cardiovascular-diseases-(cvds).
2.Mithal A, Wahl DA, Bonjour JP, et al. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int. 2009;20(11):1807-20.
3.Loscalzo J, Fauci AS, Kasper DL, et al. Harrison's Principles of Internal Medicine. CiNii Research. 2022.
4.Lee JH, O'Keefe JH, Bell D, et al. Vitamin D deficiency an important, common, and easily treatable cardiovascular risk factor? J Am Coll Cardiol. 2008;52(24):1949-56.
5.Tabrizi R, Moosazadeh M, Akbari M, et al. High Prevalence of Vitamin D Deficiency among Iranian Population: A Systematic Review and Meta-Analysis. Iran J Med Sci. 2018;43(2):125-139.
6.Borges AC, Feres T, Vianna LM, et al. Recovery of impaired K+ channels in mesenteric arteries from spontaneously hypertensive rats by prolonged treatment with cholecalciferol. Br J Pharmacol. 1999;127(3):772-8.
7.Borges AC, Feres T, Vianna LM, et al. Effect of cholecalciferol treatment on the relaxant responses of spontaneously hypertensive rat arteries to acetylcholine. Hypertension. 1999;34(4 Pt 2):897-901.
8.Ohsawa M, Koyama T, Yamamoto K, et al. 1alpha, 25-dihydroxyvitamin D(3) and its potent synthetic analogs downregulate tissue factor and upregulate thrombomodulin expression in monocytic cells, counteracting the effects of tumor necrosis factor and oxidized LDL. Circulation. 2000;102(23):2867-72.
9.Li YC, Qiao G, Uskokovic M, et al. Vitamin D: a negative endocrine regulator of the renin-angiotensin system and blood pressure. J Steroid Biochem Mol Biol. 2004;89-90(1-5):387-92.
10.Simpson RU, Hershey SH, Nibbelink KA. Characterization of heart size and blood pressure in the vitamin D receptor knockout mouse. J Steroid Biochem Mol Biol. 2007;103(3-5):521-4.
11.Xiang W, Kong J, Chen S, et al. Cardiac hypertrophy in vitamin D receptor knockout mice: role of the systemic and cardiac renin-angiotensin systems. Am J Physiol Endocrinol Metab. 2005;288(1):E125-32.
12.Pittas AG, Lau J, Hu FB, et al. The role of vitamin D and calcium in type 2 diabetes. A systematic review and meta-analysis. J Clin Endocrinol Metab. 2007;92(6):2017-29.
13.Pittas AG, Chung M, Trikalinos T, et al. Systematic review: Vitamin D and cardiometabolic outcomes. Ann Intern Med. 2010;152(5):307-14.
14.Holick MF. Vitamin D deficiency. N Engl J Med. 2007;357(3):266-81.
15.Saleh FN, Schirmer H, Sundsfjord J, et al. Parathyroid hormone and left ventricular hypertrophy. Eur Heart J. 2003;24(22):2054-60.
16.Nainby-Luxmoore JC, Langford HG, Nelson NC, et al. A case-comparison study of hypertension and hyperparathyroidism. J Clin Endocrinol Metab. 1982;55(2):303-6.
17.González EA, Sachdeva A, Oliver DA, et al. Vitamin D insufficiency and deficiency in chronic kidney disease. A single center observational study. Am J Nephrol.2004;24 (5):503-10.
18.Milazzo V, De Metrio M, Cosentino N, et al. Vitamin D and acute myocardial infarction. World J Cardiol. 2017;9(1):14-20.
19.Aleksova A, Belfiore R, Carriere C, et al. Vitamin D Deficiency in Patients with Acute Myocardial Infarction: An Italian Single-Center Study. Int J Vitam Nutr Res. 2015;85(1-2):23-30.
20.Lee JH, Gadi R, Spertus JA, et al. Prevalence of vitamin D deficiency in patients with acute myocardial infarction. Am J Cardiol. 2011;107(11):1636-8.
21.Brøndum-Jacobsen P, Benn M, Jensen GB, et al. 25-hydroxyvitamin d levels and risk of ischemic heart disease, myocardial infarction, and early death: population-based study and meta-analyses of 18 and 17studies. Arterioscler Thromb Vasc Biol. 2012;32(11):2794-802.
22.Gotsman I, Shauer A, Zwas DR, et al. Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. Eur J Heart Fail. 2012;14(4):357-66.
23.Zittermann A, Schleithoff SS, Koerfer R. Vitamin D and vascular calcification. Curr Opin Lipidol. 2007;18(1):41-6.
24.Scragg R, Stewart AW, Waayer D, et al. Effect of Monthly High-Dose Vitamin D Supplementation on Cardiovascular Disease in the Vitamin D Assessment Study : A Randomized Clinical Trial. JAMA cardiol. 2017;2(6):608-616.
25.Zittermann A, Ernst JB, Prokop S, et al. Effect of vitamin D on all-cause mortality in heart failure (EVITA): a 3-year randomized clinical trial with 4000 IU vitamin D daily. Eur Heart J. 2017;38(29):2279-2286.
26. Hsia J, Heiss G, Ren H, et al. Calcium/Vitamin D Supplementation and Cardiovascular Events. Circulation. 2007; 115(7):846-54.
27.Bairey Merz CN, Shaw LJ, Reis SE, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease. J Am Coll Cardiol. 2006;47(3S):S21-S9.
28.Shaw LJ, Bairey Merz CN, Pepine CJ, et al. Insights from the NHLBI-Sponsored Women’s Ischemia Syndrome Evaluation (WISE) Study: Part I: gender differences in traditional and novel risk factors, symptom evaluation, and gender-optimized diagnostic strategies. J Am Coll Cardiol. 2006;47(3S):S4-S20.
29.Yusuf S, Reddy S, Ôunpuu S, et al. Global burden of cardiovascular diseases: part I: general considerations, the epidemiologic transition, risk factors, and impact of urbanization. Circulation. 2001;104(22):2746-53.
30.Khan MA, Hashim MJ, Mustafa H, et al. Global epidemiology of ischemic heart disease: Results from the global burden of disease study. Cureus. 2020;12(7) :e9349.
31.Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of obesity and risk of coronary heart disease in women. N Engl J Med. 1990;322(13):882-9.
32.Whitlock G, Lewington S, Sherliker P, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083-96.
33.Nordestgaard BG, Palmer TM, Benn M, et al.The effect of elevated body mass index on ischemic heart disease risk: causal estimates from a Mendelian randomisation approach. PLoS Med.2012;9(5):e1001212.
34.Bambra C, Eikemo TA. Welfare state regimes, unemployment and health: a comparative study of the relationship between unemployment and self-reported health in 23 European countries.  JEpidemiol Community Health. 2009;63 (2):92-8.
35.Aleksova A, Beltrami AP, Belfiore R, et al. U-shaped relationship between vitamin D levels and long-term outcome in large cohort of survivors of acute myocardial infarction. Int J Cardiol. 2016;223:962-966.
36.De Metrio M, Milazzo V, Rubino M, et al. Vitamin D plasma levels and in-hospital and 1-year outcomes in acute coronary syndromes: a prospective study. Medicine(Baltimore). 2015;94(19):e857.
37.Correia LC, Sodré F, Garcia G, et al. Relation of severe deficiency of vitamin D to cardiovascular mortality during acute coronary syndromes. Am J Cardiol. 2013;111(3):324-7.
38.Reinehr T, de Sousa G, Alexy U, et al. Vitamin D status and parathyroid hormone in obese children before and after weight loss. Eur J Endocrinol. 2007;157(2):225-32.
39.Carlin AM, Rao DS, Meslemani AM, et al. Prevalence of vitamin D depletion among morbidly obese patients seeking gastric bypass surgery.Surg Obes Relat Dis.2006;2(2):98-103