Vitamin D Deficiency Treatment Outcomes on Inflammation, Endothelial Function and Ventricular Retrieval After Non ST-Segment Elevation Myocardial Infarction: A Randomized Placebo Controlled Clinical Trial (NAVID Study)

The leading cause of death in the world is due to cardiovascular events, which originate from coronary artery stenosis therefore it affects myocardial blood flow and finally may cause infarction. ST-Segment elevation is an indicator of infarction (STEMI) in electrocardiography (ECG) besides cardiac enzymes like troponin; however, there is another type of infarction without elevation, which called non ST-Segment Elevation myocardial infarction (NSTEMI).

The most established method of treating this condition is percutaneous coronary intervention (PCI) and balloon angiography although in some cases coronary artery bypass grafting surgery is more beneficial. Atherosclerosis is the most debatable hypothesis in coronary stenosis. Scientists think body inflammation is one of the main etiologies. There are many factors affect this inflammatory process, which Vitamin D is one of them. Vitamin D deficiency has been linked to various inflammatory diseases. However, the mechanism by which vitamin D reduces inflammation remains poorly understood. Vitamin D Inhibits Monocyte/Macrophages Pro-inflammatory Cytokine Production by Targeting mitogen-activated protein kinase (MAPK) Phosphatase-1 and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway therefore decrease production of IL-6 and tumor necrosis factor-alpha (TNFα) and increasing interleukin (IL) 10 and transforming growth factor beta (TGFβ) from human monocytes. Chronic inflammatory diseases that are vitamin D deficient (20 ng/ml) may benefit from oral supplementation of vitamin D to get their serum vitamin D level>30 ng/ml.

Galectin-3 is emerging fibrotic biomarkers that is thought to be causally involved in the development of heart failure. Galectin-3 is a beta-galactoside binding lectin that is produced by macrophages during myocardial stress and activates fibroblasts. Besides its roles in inflammation and in cellular adhesion, galectin-3 plays an important role in cardiac fibrosis. Furthermore, galectin-3 has an established role as a modulator in tumor progression. Galectin-3 is released in the circulation, and can be measured reliably and has been shown to independently predict outcomes in heart failure patients and in the general population. However, galectin-3 is not cardiac specific, but is expressed in several fibrotic and inflammatory diseases.

Vitamin D is one of the fat-soluble micronutrients, which sunlight is the principle key to make this vitamin in our body. Vitamin D deficiency is pandemic around the world with 30-50% prevalence in adult population and several evidences advocated its association with immune-based disease like asthma, multiple sclerosis (MS), Type 2 diabetes and many cancers. Additionally, there are some study suggesting patients who suffered from myocardial infarction have lower serum vitamin D level. It has been revealed Vitamin D deficiency has numerous major drawbacks on cardiovascular system. Its deficiency benefits atherosclerosis progression and may cause endothelial inflammation and dysfunction in coronary artery. Endothelial malfunction with lipid sedimentation beneath the intima layer attract leukocytes and make foam cells. Therefore it leads to produce active agents and make smooth muscle cells to proliferate and lead the lumen to be narrower, which consequently decrease oxygenated blood flow and causes ischemia and infarction. Monocyte chemoattractant protein 1 (MCP-1) and n-terminal fragment of pro-brain natriuretic peptide (NT-pro-BNP) are two newly discovered molecules associated independently with coronary calcification level. MCP-1 has a role in representing the relationship between acute myocardial infarction and inflammation.

Renin-Angiotensin-Aldosterone system has a principle role in blood pressure maintenance. It has been shown this vitamin can regulate this system too.