Impact of Vitamin D Supplementation on the Clinical Outcomes and Epigenetic Markers in Patients with Acute Coronary Syndrome

Abstract

Vitamin D has recently been found to influence the renin-angiotensin system (RAS); it can reduce the effects of renin-angiotensin system inhibitors (RASI) by decreasing plasma renin. This study examines the effect of vitamin D supplements on cardiac fibrosis markers, echocardiographic parameters, and epigenetic markers in patients with established acute coronary syndrome (ACS). It also looks at the incidence of vitamin D receptor (VDR) gene polymorphisms Apa I (rs7975232), Bsm I (rs1544410), Taq I (rs731236), and Fok I (rs2228570) and its association with the development of secondary major acute cardiovascular events (MACE) and heart failure (HF). A randomized controlled trial in which patients were divided into two groups was performed. Group 1 comprised of 125 ACS patients who received ACS standard therapy alone, while Group 2 consisted of 125 ACS patients who received ACS standard therapy plus vitamin D according to their vitamin D levels. Patients were monitored for 24 months to find subsequent MACE and HF. Vitamin D therapy for ACS patients resulted in a substantial decline in end systolic and end diastolic volumes (p = 0.0075 and 0.002, respectively), procollagen type III N-terminal peptide (PIIINP) and soluble ST2 levels (p = 0.007 and 0.001, respectively), as well as in ejection fraction and vitamin D level (p = 0.0001 and 0.008, respectively). In addition, vitamin D treatment was linked to a significant decline in the levels of noncoding RNA, such as mir361, lncRNA MEG3, and lncRNA Chaer (p = 2.9 × 10−4, 2.2 × 10−6, and 1.2 × 10−5, respectively). Furthermore, patients who suffered MACE had significantly higher levels of the Bsm I CC and Fok I GG genotypes (p = 4.8 × 10−4 and 0.003, respectively), while patients with HF had significantly higher levels of the Taq I AA genotype (p = 4.2 × 10−7). Supplementing ACS patients with vitamin D has been demonstrated to limit cardiac fibrosis and echocardiographic parameters, as well as epigenetic markers. Additionally, MACE and HF among ACS patients may be related to genetic variations among VDR gene polymorphisms.

Vitamin D and Cardiovascular Diseases: An Update

“…These results were verified by a large-scale study that compared the lowermost to uppermost baseline categories of circulating VD concentration, where the adjusted pooled relative risk for total cardiovascular incidents was 1.52 [94]. Hence, there is increasing evidence that VDD represents an innovative risk determinant regarding AMI [83].…”

“…VDR acts as a platform for overall beneficial metabolic effects by forming heterodimers with RXR and modulating VDR gene expression for improved cardiovascular health. Finally, maintaining adequate levels of VD might provide a safety shield against the development of CVD and its complications (Figure 2) [83]. In addition, an identical significance was reported among seriously ill patients, among whom a low level of VD was significantly related to the severity of disease and death [100,101].…”

“…Coronary artery disease incidence has been confirmed to relate to VDD; however, the pathophysiological systems of such a relationship have not yet been recognized [8]. The main indication for a possible relationship is the existence of VDR in the myocardium, vascular endothelial cells, and fibroblasts as well as a demonstration through epidemiological studies that the prevalence of both VDD and CAD are enhanced by activating RAAS and by increasing anti-inflammatory and decreasing proinflammatory mediators [83].…”

“…VDD occurs most commonly among acute myocardial infarction (AMI) cases, whereas preliminary studies highlight a probable relationship between VD and AMI diagnosis both in the short and long run [83]. Furthermore, VDD appears to increase due to repeated unfavorable cardiac events caused by its relationship with several affected blood vessels, cardiac remodeling, and AMI problems [84].…”

“…Numerous systems could potentially underlie the link between the risk of AMI and VD . VD reduces plasma levels of renin, which in turn results in a decrease in renin-angiotensin-aldosterone system inhibitors [83].…”