The primary goal of this study was to investigate the association between vitamin D serum levels and hs-CRP, as a prognostic factor for post-PCI complications. The main findings of this research were as follows: 1. higher levels of post-PCI and pre-post hs-CRP difference are significantly related to lower levels of vitamin D 2. No significant differences in pre-PCI and post-PCI hs-CRP, and pre-post PCI hs-CRP difference were found between women and men 3. In terms of vitamin D status, most of vitamin D deficient patients were male.
A review of 41 observational studies demonstrated various prevalence of vitamin D deficiency in adults ranging from 44% to 96% with the mean 25(OH)D level in the range of 11-20 ng/ml.(1) Several studies have also reported the widespread prevalence of vitamin D deficiency even in sunny regions. An analysis on 12,346 patients in Abu-Dhabi, a sun-rich country, demonstrated about 83% suboptimal vitamin D level in the investigated population.(11) Another study performed on 547 patients in Qatar, another sunny country, revealed 91% vitamin D deficiency (25(OH) D level < 30 ng/ml) among studied population.(12)
In most studies, female gender was identified as a predictor for hypovitaminosis D.(1, 13) A meta-analysis of 48 investigations demonstrated a more prevalence of vitamin D deficiency in women (45% in male Vs 60% in female) among Iranian population.(14) In contrast, one study showed higher prevalence of vitamin D deficiency in obese Norwegian males compared to females.(15) Similarly, our results showed a statistically significant relation between vitamin D levels and gender (P˂0.05). In other words, the majority of vitamin D deficient patients were male. In comparison to females, males who are vitamin D deficient could be at a higher risk for diseases such as diabetes mellitus, dyslipidemia, and coronary artery disease. Also, they might have a lower left ventricle ejection fraction.(12) It is believed that Matrix metalloproteinase (MMP) may be involved in the vitamin D deficiency pathophysiology. In addition, Framingham heart study mentioned that males with elevated plasma levels of MMP-9 may have a higher risk of cardiac wall thickness and large end-diastolic left ventricular size.(16) Taking all these facts into consideration, it is conceivable that males with vitamin D deficiency might be more prone to cardiovascular complications. In addition, our results revealed that vitamin D deficient cases have significantly higher weight than patients with vitamin D levels above 20 ng/dl that is consistent with the result of studies reporting higher frequency of vitamin D deficiency in overweight and obese children and adolescents.(17)
Several mechanisms have been described for the relation between vitamin D deficiency and increment in the risk for cardiovascular diseases (CVD). Low levels of vitamin D are believed to contribute to a rise in blood pressure. The pathophysiology suggested for this indirect association, is a multifold enhancement in renin expression and plasma angiotensin II in vitamin D receptor null (VDR-null) subjects. As a result, hypertension, cardiac hypertrophy, and increased water and sodium retention may occur in vitamin D deficient subjects. This hypothesis was confirmed by injecting 1,25(OH)2D to mice, followed by a suppression in renin-angiotensin system (RAS).(18) As reported in several studies, RAS has a pivotal role in cardiovascular system functions. Unregulated RAS may develop pathologic conditions including atherosclerosis, hypertension, and insulin resistance.(19)
Another explanation for the relationship between vitamin D deficiency and cardiac diseases would be the observed role of vitamin D in improving glycemic control and insulin sensitivity as demonstrated in a recent meta-analysis.(14) Overall, vitamin D deficiency is associated with multiple components of metabolic syndrome, including insulin resistance, abdominal obesity, hypertension, and even dyslipidemia.(19) As shown in our study, vitamin D deficient patients are more frequently overweight than vitamin D insufficient/sufficient ones. A study on 105 women undergoing elective coronary angiography, reported a significant negative linear correlation between 25(OH)D categories and burden of coronary artery disease (CAD). It also indicated an inverse association between vitamin D level and left circumflex (LCx) and right coronary artery (RCA) stenosis degree.(20) Even though higher degree of left anterior descending (LAD) and RCA coronary stenosis was found in vitamin D deficient patients; this difference was neither statistically nor clinically significant between groups in our study.
High hs-CRP levels have been regarded as an independent risk factor for CVDs. In addition, higher hs-CRP may increase early complications of coronary procedures such as PCI, including MI, coronary dissection, and perforation.(9, 21) Increased hs-CRP can also augment the risk of late cardiac complications, in patients undergoing coronary angioplasty, even up to 3 years after the procedure.(22) Hence, there is a concern for short term or long term cardiac complications in patients with high hs-CRP who have undergone PCI. Therefore, it is assumed that addition of agents capable of decreasing this inflammatory biomarker, to the standard drug regimen before PCI may be effective in the prevention of post-PCI complications.(23)
There are several reports demonstrating the relationship between vitamin D and inflammation. Vitamin D deficiency has been also reported to be associated with cardiovascular inflammation(24) and vascular endothelial dysfunction.(20) It has been stated that vitamin D may reduce smooth muscle cell proliferation and pro-inflammatory cytokines secretion such as tumor necrosis factor-α (TNF-α), increase anti-inflammatory cytokines such as interleukin-10 (IL-10), and impair macrophage maturation.(24) Macrophages and dendritic cells convert vitamin D to its active form, 1, 25(OH)2D that suppresses the production of inflammatory factors, namely interferon-γ (IFN-γ), interleukin-5 (IL-5), and interleukin 2 (IL-2). It is noteworthy that interleukin 6 (IL-6) synthesis, which stimulates CRP production, is inhibited by vitamin D.(25) As a result, vitamin D deficiency is theoretically expected to be associated with elevated levels of hs-CRP.
The goal of our research was to evaluate the association between serum vitamin D status and hs-CRP levels as a proposed pathway for the adverse effect of vitamin D deficiency on PCI outcome. In this study, a statistically significant inverse relationship was observed between baseline vitamin D level and post-PCI hs-CRP level. In a clinical trial, vitamin D was administered at the dose of 300 000 IU orally 12 hours before PCI. The mean difference in hs‐CRP was reported to be significantly lower in the vitamin D group compared to controls. Although no clear effect of vitamin D in the prevention of cardiac injury was observed in this study, a significant lower mean difference in CK‐MB was reported between 8 and 24 hours in vitamin D groups. (26) Reports of this trial in addition to ours substantiate our hypothesis about the negative impact of vitamin D deficiency on PCI outcome through masking its anti-inflammatory effect, with emphasis on hs-CRP, in these patients.
The limitation of this study was the impossibility of following the subjects up after PCI. In order to obtain more reliable clinical results, future studies should address the association between vitamin D deficiency and short-term and long-term cardiovascular complications following PCI.