Determinants of vitamin D activation in patients with acute coronary syndromes and its correlation with inflammatory markers

Background and aim: Vitamin D deficiency is a pandemic disorder affecting over 1 billion of subjects worldwide. Calcitriol (1,25(OH)2D) represents the perpetrator of the several systemic effects of vitamin D, including the anti-inflammatory, antithrombotic and antiatherosclerotic actions, potentially preventing acute cardiovascular ischemic events. Variability in the transformation of vitamin D into 1,25(OH)2D has been suggested to modulate its cardioprotective benefits, however, the determinants of the levels of calcitriol and their impact on the cardiovascular risk have been seldom addressed and were, therefore, the aim of the present study. Methods and results: A consecutive cohort of patients undergoing coronary angiography for acute coronary syndrome (ACS) were included. The levels of 25 and 1,25(OH)2 D were assessed at admission by chemiluminescence immunoassay kit LIAISON (R) Vitamin D assay (Diasorin Inc) and LIAISON (R) XL. Hypovitaminosis D was defined as 25(OH)D < 10 ng/ml, whereas calcitriol deficiency as 1,25(OH)2D < 19.9 pg/ml. We included in our study 228 patients, divided according to median values of 1,25(OH)2D (>= 41.5 pg/ml). Lower calcitriol was associated with age (p = 0.005), diabetes (p = 0.013), renal failure (p < 0.0001), use of diuretics (p = 0.007), platelets (p = 0.019), WBC (p = 0.032), 25(0H) D (p = 0,046), higher creatinine (p = 0.011), and worse glycaemic and lipid profile. A total of 53 patients (23.2%) had hypovitaminosis D, whereas 19 (9.1%) displayed calcitriol deficiency (15.1% among patients with hypovitaminosis D and 7.1% among patients with normal Vitamin D levels, p = 0.09). The independent predictors of 1,25(OH)2D above the median were renal failure (OR[95%CI] = 0.242[0.095-0.617], p = 0.003) and level of vitamin D (OR[95%CI] = 1.057[1.018-1.098], p = 0.004). Calcitriol levels, in fact, directly related with the levels of vitamin D (r = 0.175, p = 0.035), whereas an inverse linear relationship was observed with major inflammatory and metabolic markers of cardiovascular risk (C-reactive protein: r =-0.14, p = 0.076; uric acid: r =-0.18, p = 0.014; homocysteine: r =-0.19, p = 0.007; fibrinogen: r =-0.138, p = 0.05) and LpPLA2 (r =-0.167, p = 0.037), but not for leukocytes. Conclusion: The present study shows that among ACS patients, calcitriol deficiency is frequent and can occur even among patients with adequate vitamin D levels. We identified renal failure and vitamin D levels as independent predictors of 1,25(OH)2D deficiency. Furthermore, we found a significant inverse relationship of calcitriol with inflammatory and metabolic biomarkers, suggesting a potential more relevant and accurate role of calcitriol, as compared to cholecalciferol, in the prediction of cardiovascular risk. Future trials should certainly investigate the potential role of calcitriol administration in the setting of acute coronary syndromes as much as in other inflammatory disorders, such as the SARS-CoV2 infection. (C) 2020 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.