Prognostic impact of Vitamin D deficiency in patients with coronary artery disease undergoing percutaneous coronary intervention.

BACKGROUND: Whether Vitamin D deficiency represents an independent predictor of mortality and major cardiovascular events or rather the mirror of a more advanced clinical condition with increased comorbidities is still debated. We aimed at assessing the impact of vitamin D levels on the long-term outcomes among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention. METHODS: Consecutive patients from a single centre were included. Vitamin D levels were measured at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Severe deficiency was defined for 25(OH)D < 10 ng/ml. The primary study endpoint was overall mortality. Secondary endpoints were cardiovascular mortality, recurrent acute coronary syndrome or major cardiovascular events (a composite of death, recurrent MI and target vessel revascularization) at the longest available follow-up. RESULTS: We included a total of 705 patients, that were divided according to vitamin D tertiles (<12.7; 12.7-21.59; ≥21.6 ng/ml). Lower levels of Vitamin D were associated with renal failure (p=0.03), more severe coronary disease (p=0.001), diabetes mellitus and previous CABG (p<0.001), lower ejection fraction (p=0.02), acute presentation (p=0.04), use of statins (p=0.02), diuretics, nitrates and clopidogrel (p<0.001) and RASI (p=0.008). An inverse association was documented with BMI, glycemia, total cholesterol (p<0.001), creatinine and WBC (p=0.001). At a median follow-up of 996.5 [377-1552] days, 3.8% of the patients died. Vitamin D deficiency was significantly associated with overall mortality (7.6% vs 2.9% vs 0.4%, adjusted HR[95%CI]=3.6[1.43-8.9], p=0.006), MACE (adjusted HR[95%CI]=1.32[1.07-1.63], p=0.01) and the composite of death and MI (adjusted HR[95%CI]=1.3[1.03-1.65], p=0.03). A similarly increased risk was confirmed for all major higher-risk subsets of patients, with no significant interaction according to age, gender, diabetes mellitus or chronic kidney disease. CONCLUSION: Among patients undergoing percutaneous coronary interventions, lower levels of vitamin D are associated with an over 3-fold increased risk of mortality and major cardiovascular events. Future larger studies are certainly warranted in order to define the prognostic implications of cholecalciferol supplementation among high-risk patients with established coronary artery disease.

Cholecalciferol levels, inflammation and leukocytes parameters: Results from a large single-centre cohort of patients.

BACKGROUND: Vitamin D deficiency represents a pandemic health problem with a broad spectrum of clinical implications. Several studies have involved lower levels of vitamin D with inflammatory disorders including cardiovascular, autoimmune and infectious disease. Indeed, the pathophysiological mechanisms are still poorly ascertained. We aimed at evaluating the impact of cholecalciferol (25(OH)D) levels on the biomarkers of acute-phase response and inflammation in a large cohort of patients with cardiovascular disease. METHODS: Consecutive patients undergoing coronary angiography were included. Main clinical features and chemistry parameters were assessed at admission. 25(OH)D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc, Stillwater, US). Hypovitaminosis D was defined for 25(OH)D < 10 ng/ml. RESULTS: A total of 3974 patients were included, of whom 29.4% had hypovitaminosis D. 25(OH)D deficiency was associated to age, female gender, diabetes mellitus, renal failure, previous percutaneous coronary intervention and smoke, acute presentation, severe coronary disease, higher glycemia and cholesterol and lower hemoglobin and ejection fraction (p < 0.001), higher platelet count (p = 0.004) and BMI (p = 0.05). 25(OH)D significantly directly related with white blood cells count and the different components of leukocytes formula, Neutrophils-to-Lymphocytes Ratio, Monocytes-to-Lymphocytes Ratio and C-reactive protein, but not with lymphocytes levels. In fact, hypovitaminosis D predicted levels above the median for both Neutrophils-to-Lymphocytes Ratio (≥2.56; 57.3% vs. 47.6%; p < 0.001; adjusted OR[95%CI] = 1.28[1.07-1.52; p = 0.007) and Monocytes -to-Lymphocytes Ratio (≥0.33; 59.1% vs. 49.8%; p < 0.001; adjusted OR[95%CI] = 1.3[1.1-1.54; p = 0.002), results were confirmed in major subgroups of patients. CONCLUSION: The present study demonstrates that, among patients with cardiovascular disease, 25(OH)D deficiency is associated with a higher metabolic and clinical risk profile and with an elevation of cellular and humoral inflammatory parameters. Future dedicated studies should be, therefore, advocated in order to define whether 25(OH)D supplementation can modulate the mediators of the acute phase response and therefore potentially offer clinical and prognostic advantages on a broad spectrum of inflammatory disease.

Vitamin D levels condition the outcome benefits of renin-angiotensin system inhibitors (RASI) among patients undergoing percutaneous coronary intervention.

BACKGROUND: Vitamin D deficiency is estimated as the most common medical condition worldwide, with severe implications on survival and on several inflammatory, immune-mediated and thrombotic disorders, and especially for cardiovascular disease. Recent studies have suggested that vitamin D could directly regulate the Renin-Angiotensin System (RAS) activity, therefore potentially interfering with the pharmacological effects of RAS Inhibitors (RASI), an issue that has seldom been explored. Therefore, the aim of the present study was to evaluate the prognostic impact of the use of RASI according to vitamin D levels among patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). METHODS: Consecutive patients undergoing PCI were included. Main clinical features and chemistry parameters were assessed at admission. Vitamin D levels were measured by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Severe deficiency was defined for 25(OH)D < 10 ng/mL. The primary study endpoint was defined as the occurrence of major cardiovascular events (MACE, a composite of death, recurrent Myocardial Infarction (MI) and target vessel revascularization) at the longest available follow-up. RESULTS: We included a total of 705 patients, that were divided according to vitamin D tertiles (< 12.7 ng/mL; 12.7-21.59 ng/mL; ≥21.6 ng/mL) and use of RASI. RASI therapy was significantly associated to arterial hypertension, creatinine, lower 25(OH)D, use of statins, diuretics, ASA and ticagrelor across vitamin D tertiles. At a median follow-up of 996 [377-1552] days, MACE occurred in 174 (24.7 %) patients. Severe hypovitaminosis D was significantly associated with a higher rate of MACE (HR[95 %CI] = 0.75[0.62-0.91], p = 0.004). The use of RASI significantly lowered the rate of MACE in patients with lower vitamin D (I tertile: 41.3 % vs 25.9 %, adjusted HR[95 %CI] = 0.43[0.26-0.73], p = 0.002); whilst a non-significant effect was observed for II and III tertiles values (18.6 %vs 29.5 %, adjusted HR[95 %CI] = 1.16[0.57-2.34], p = 0.69, and 21.2 % vs 12.6 %, adjusted HR[95 %CI] = 1.1[0.46-2.62], p = 0.83) (p int = 0.04). A similar prognostic interaction for RASI and vitamin D was observed for cardiovascular mortality and MI (p int = 0.03). CONCLUSION: Among patients undergoing PCI, the use of RASI was associated with lower risk of MACE only among patients with lower levels of vitamin D. Future larger studies are certainly warranted in order to define the prognostic implications of vitamin D supplementation on the RAS system modulation, especially among patients treated with RASI.

Vitamin D levels and platelet reactivity in diabetic patients receiving dual antiplatelet therapy.

BACKGROUND: Hypovitaminosis D represents an emerging cardiovascular risk factor, and especially among higher-risk subsets of patients, such as in those with diabetes mellitus. The anti-inflammatory and anti-thrombotic properties of vitamin D, in fact, could be even more beneficial among diabetics, where platelet hyperreactivity and suboptimal response to antiplatelet drugs has been associated with poorer outcomes. However, no study has so far evaluated the impact of vitamin D levels on platelet reactivity and high-on treatment platelet reactivity (HRPR) among diabetic patients receiving dial antiplatelet therapy (DAPT). METHODS: Our population is represented by a consecutive cohort ofdiabetic patients treated with DAPT (ASA + clopidogrel or ticagrelor or dose-adjusted prasugrel) for an acute coronary syndrome or elective PCI, undergoing platelet reactivity assessment at 30-90 days post-discharge. Aggregation was assessed by multiple-electrode aggregometry. HRPR was defined for values above the lower limit of normality (in non-treated patients). RESULTS: We included 440 patients, that were divided according to quartiles values of vitamin D (< 9.4; 9.4-15.59; 15.6-21.64; ≥ 21.65 ng/ml). Among them, 31 were excluded as chronically treated with vitamin D supplementation. Lower vitamin D quartiles were associated with more advanced age (p = 0.01), female gender (p = 0.04), renal failure (p = 0.005), history of previous MI (p = 0.01), CABG and use of diuretics (p = 0.003), severe coronary disease (p = 0.002), but lower ejection fraction (p = 0.001), treatment with statins (p = 0.04) and new ADP-antagonists (p = 0.002). Vitamin D levels related with higher HbA1c (p = 0.001), cholesterol (p = 0.02) and creatinine (p = 0.004) and lower hemoglobin (p = 0.004). The prevalence of HRPR with ASA was low and not related to vitamin D quartiles (3.4% vs 2.7% vs 1.8% vs 2.1%, p = 0.44; adjusted OR[95%CI] = 1.16[0.60-2.26], p = 0.67). The prevalence of HRPR for ADP antagonists was associated to hypovitaminosis D (40.2% vs 29.1% vs 29.4% vs 25.5%, p = 0.03; (adjusted OR[95%CI] = 1.76[1.04-2.98], p = 0.036for I vs II-IV quartile). The impact of vitamin D quartiles, was significant only in patients on new ADP antagonists (n = 225, of whom 81 on prasugrel 5 mg; p = 0.03; adjusted OR[95%CI] = 3.12[1.34-7.49], p = 0.009) but not with clopidogrel (p = 0.85, adjusted OR[95%CI] = 1.05[0.49-2.24], p = 0.89). CONCLUSIONS: Among diabetic patients receiving dual antiplatelet therapy for an acute coronary syndrome or elective percutaneous coronary intervention, severe vitamin D deficiency is associated with a higher ADP-mediated platelet reactivity and rate of HRPR, and especially for new ADP-antagonists over clopidogrel.