The relationship between vitamin D deficiency and hypertensive organ damage

Abstract

Aim: In this study, we aimed to examine the relationship between vitamin D level and target organ damage (TOD) in primary hypertension patients by eliminating the effects of hypertension duration and antihypertensive treatments. Material and Method: The study included 144 patients with primary hypertension. Vitamin D levels were classified as sufficiency (VDS), deficiency (VDD), and severe deficiency (VDSD). In case of more than one TOD indicator (microalbuminuria or proteinuria, left ventricular mass index and carotid intima-media thickness), it was considered as multi organ involvement (OI). In the multiple regression model, besides the traditional risk factors, the effects of hypertension duration and anti-hypertensive treatments were adjusted. Results: The rates of VDS and VDD were lower in TOD (+) compared to TOD (-) (14.1% vs 51.5%, 32.1% vs 42.4%; p<0.001), while VDSD ratio was higher (53.8% vs 6.1%, p<0.001). VDSD ratio was higher in hypertensive patients with single-OI compared to TOD (-), while its was higher in patients with multi-OI compared to single-IO. In the multivariable regression model; showed that 1 ng/mL decrease in the Vitamin D increased the probability of TOD by 1.22 folds [vs TOD (-)], probability of single organ involvement by 1.19 folds [vs TOD (-)], and probability of multi-IO by 1.11 folds (vs single-IO). Conclusion: In hypertensive patients, a decrease in vitamin D levels is associated with an increase in TOD indicators. The risk of developing TOD and multi-IO is higher in vitamin D deficiency. Vitamin D supplements may be beneficial in hypertensive organ damage, regardless of disease duration and anti-hypertensive treatments.

Keywords

• Atherosclerosis
• hypertension
• vitamin D
• target organ damage

References

1. Jeong HY, Park KM, Lee MJ, Yang DH, Kim SH, Lee SY. Vitamin D and hypertension. Electrolyte Blood Press 2017; 15: 1-11.
2. Mehta V, Agarwal S. Does Vitamin D Deficiency Lead to Hypertension? Cureus 2017; 9: e1038.
3. Ulu SM, Ulasli A, Yaman F, Yaman G, Ozkececi G, Yuksel S. The relationship between vitamin D and PTH levels and cardiovascular risk in the elderly hypertensives. Clin Exp Hypertens 2014; 36: 52-7.
4. Lawler PR, Hiremath P, Cheng S. Cardiac target organ damage in hypertension: insights from epidemiology. Curr Hypertens Rep 2014; 16: 446.
5. Andersen LB, Przybyl L, Haase N, et al. Vitamin D depletion aggravates hypertension and target-organ damage. J Am Heart Assoc 2015; 4: e001417.
6. Kim DH, Meza CA, Clarke H, Kim JS, Hickner RC. Vitamin D and endothelial function. Nutrients 2020; 12: 575.
7. Manrique C, Lastra G, Gardner M, Sowers JR. The renin angiotensin aldosterone system in hypertension: roles of insulin resistance and oxidative stress. Med Clin North Am 2009; 93: 569-82.
8. Kuloglu O, Gur M, Seker T, et al. Serum 25-hydroxyvitamin D level is associated with arterial stiffness, left ventricle hypertrophy, and inflammation in newly diagnosed hypertension. J Investig Med 2013; 61: 989-94.

9. Yilmaz F, Sozel H. Relationship between 25-hydroxyvitamin D and microalbuminuria in patients with newly diagnosed essential hypertension. Clin Exp Hypertens 2021; 43: 217-22.
10. Lupoli R, Vaccaro A, Ambrosino P, Poggio P, Amato M, Di Minno MN. Impact of Vitamin D deficiency on subclinical carotid atherosclerosis: a pooled analysis of cohort studies. J Clin Endocrinol Metab 2017; 102: 2146-53.
11. Karki A, Vaidhya S, Kunwar D, Kunwar R. Vitamin D Deficiency among Patients Presenting to Outpatient Department of Medicine of a Tertiary Care Centre: A Descriptive Cross-sectional Study. JNMA J Nepal Med Assoc 2022; 60: 465-8.
12. Meehan M, Penckofer S. The Role of Vitamin D in the Aging Adult. J Aging Gerontol 2014; 2: 60-71.
13. Williams B, Mancia G, Spiering W, et al. 2018 ESC/ESH Guidelines for the management of arterial hypertension. Eur Heart J 2018; 39: 3021-104.
14. Perrone-Filardi P, Coca A, Galderisi M, et al. Noninvasive cardiovascular imaging for evaluating subclinical target organ damage in hypertensive patients: a consensus article from the European Association of Cardiovascular Imaging, the European Society of Cardiology Council on Hypertension and the European Society of Hypertension. J Hypertens 2017; 35: 1727-41.
15. Holick MF, Binkley NC, Bischoff-Ferrari HA, et al. Evaluation, treatment, and prevention of vitamin D deficiency: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab 2011; 96: 1911-30.
16. Devereux RB, Alonso DR, Lutas EM, et al. Echocardiographic assessment of left ventricular hypertrophy: comparison to necropsy findings. Am J Cardiol 1986; 57: 450-8.
17. Touboul PJ, Hennerici MG, Meairs S, et al. Mannheim carotid intima-media thickness consensus (2004-2006). An update on behalf of the Advisory Board of the 3rd and 4th Watching the Risk Symposium, 13th and 15th European Stroke Conferences, Mannheim, Germany, 2004, and Brussels, Belgium, 2006. Cerebrovasc Dis 2007; 23: 75-80.
18. Liu Y, Shi L, Lin Y, et al. Relationship between serum 25-hydroxyvitamin D and target organ damage in children with essential hypertension. J Hum Hypertens 2022; 36: 604-9.
19. Vimaleswaran KS, Cavadino A, Berry DJ, et al. Association of vitamin D status with arterial blood pressure and hypertension risk: a mendelian randomisation study. Lancet Diabetes Endocrinol 2014; 2: 719-29.
20. McMullan CJ, Borgi L, Curhan GC, Fisher N, Forman JP. The effect of vitamin D on renin-angiotensin system activation and blood pressure: a randomized control trial. J Hypertens 2017; 35: 822-9.
21. Vaidya A, Williams JS. The relationship between vitamin D and the renin-angiotensin system in the pathophysiology of hypertension, kidney disease, and diabetes. Metabolism 2012; 61: 450-8.
22. Forman JP, Williams JS, Fisher ND. Plasma 25-hydroxyvitamin D and regulation of the renin-angiotensin system in humans. Hypertension 2010; 55: 1283-8.
23. Ke L, Mason RS, Kariuki M, Mpofu E, Brock KE. Vitamin D status and hypertension: a review. Integr Blood Press Control 2015; 8: 13-35.
24. Fisher SB, Perrier ND. Primary hyperparathyroidism and hypertension. Gland Surg 2020; 9: 142-9.
25. Yildiz M, Oktay AA, Stewart MH, Milani RV, Ventura HO, Lavie CJ. Left ventricular hypertrophy and hypertension. Prog Cardiovasc Dis 2020; 63: 10-21.
26. Tomek J, Bub G. Hypertension-induced remodelling: on the interactions of cardiac risk factors. J Physiol 2017; 595: 4027-36.
27. Seker T, Gur M, Ucar H, et al. Lower serum 25-hydroxyvitamin D level is associated with impaired myocardial performance and left ventricle hypertrophy in newly diagnosed hypertensive patients. Anatol J Cardiol 2015; 15: 744-50.
28. Carrelli AL, Walker MD, Lowe H, et al. Vitamin D deficiency is associated with subclinical carotid atherosclerosis: the Northern Manhattan study. Stroke 2011; 42: 2240-5.
29. Fallo F, Catena C, Camozzi V, et al. Low serum 25-hydroxyvitamin D levels are associated with left ventricular hypertrophy in essential hypertension. Nutr Metab Cardiovasc Dis 2012; 22: 871-6.
30. Budzyn M, Gryszczynka B, Boruczkowski M, et al. The potential role of circulating endothelial cells and endothelial progenitor cells in the prediction of left ventricular hypertrophy in hypertensive patients. Front Physiol 2019; 10: 1005.
31. Poulikakos D, Ross L, Recio-Mayoral A, et al. Left ventricular hypertrophy and endothelial dysfunction in chronic kidney disease. Eur Heart J Cardiovasc Imaging 2014; 15: 56-61.
32. Mule G, Castiglia A, Cusumano C, et al. Subclinical kidney damage in hypertensive patients: A renal window opened on the cardiovascular system. focus on microalbuminuria. Adv Exp Med Biol 2017; 956: 279-306.
33. Sevencan NO, Ozkan AE. Associations between neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, albuminuria and uric acid and the estimated glomerular filtration rate in hypertensive patients with chronic kidney disease stages 1-3. Arch Med Sci 2019; 15: 1232-9.
34. Wang H, Hu Y, Geng Y, et al. The relationship between neutrophil to lymphocyte ratio and artery stiffness in subtypes of hypertension. J Clin Hypertens (Greenwich) 2017; 19: 780-5.
35. Machado Cda S, Venancio VP, Aissa AF, et al. Vitamin D3 deficiency increases DNA damage and the oxidative burst of neutrophils in a hypertensive rat model. Mutat Res Genet Toxicol Environ Mutagen 2016; 798-799: 19-26.
36. Gallagher JC. Vitamin D and aging. Endocrinol Metab Clin North Am 2013; 42: 319-32.
37. Legarth C, Grimm D, Wehland M, Bauer J, Kruger M. The impact of Vitamin D in the treatment of essential hypertension. Int J Mol Sci 2018; 19: 455.
38. Sheikh V, Mozaianimonfared A, Gharakhani M, Poorolajal J, Ph D. Effect of vitamin D supplementation versus placebo on essential hypertension in patients with vitamin D deficiency: a double-blind randomized clinical trial. J Clin Hypertens (Greenwich) 2020; 22: 1867-73.