Relation of Severe Deficiency of Vitamin D to Cardiovascular Mortality During Acute Coronary Syndromes

doi:10.1016/j.amjcard.2012.10.006

The American Journal of Cardiology

Volume 111, Issue 3, 1 February 2013, Pages 324-327

https://doi.org/10.1016/j.amjcard.2012.10.006 Get rights and content

Vitamin D deficiency is associated with risk for a first cardiovascular event in the general population, possibly because of inflammation, insulin resistance, and neurohumoral activation. However, its relation with outcomes in acute coronary syndromes has not been reported. To test the hypothesis that severe deficiency of vitamin D is independently associated with cardiovascular mortality during ACS, 206 patients admitted for unstable angina, non–ST-segment elevation myocardial infarction, or ST-segment elevation acute myocardial infarction had 25-hydroxyvitamin D serum levels measured at admission. Severe vitamin D deficiency was defined a priori as a value ≤10 ng/ml. The average concentration of vitamin D was 20 ± 8.2 ng/ml, and 10% of patients were severely deficient (95% confidence interval 6.6% to 15%). Cardiovascular mortality during hospitalization took place in 14 patients, an incidence of 6.8%. Patients with severe vitamin D deficiency had in-hospital cardiovascular mortality of 24%, significantly higher than the 4.9% observed in the remaining patients (relative risk 4.3, 95% confidence interval 1.8 to 10, p = 0.001). After adjustment for Global Registry of Acute Coronary Events (GRACE) score, Gensini angiographic score, and potential confounding variables, severe deficiency of vitamin D remained an independent predictor of in-hospital cardiovascular mortality (odds ratio 14, 95% confidence interval 1.2 to 158, p = 0.03). In conclusion, severe vitamin D deficiency is independently associated with in-hospital cardiovascular mortality in patients with acute coronary syndromes.

Section snippets

Methods

Consecutive patients with rest onset of typical chest discomfort within the previous 48 hours admitted to the coronary care units of 2 tertiary hospitals in Salvador, Brazil, from August 2007 to December 2011 were evaluated for inclusion in the Registry of Acute Coronary Syndromes (REACS). To include patients with non–ST-segment elevation ACS, ≥1 of the 3 objective criteria had to be present: electrocardiographic changes consisting of transient ST-segment depression (≥0.05 mV) or T-wave

Results

Two hundred six patients were included in the study (mean age 70 ± 13 years, 52% men, 52% African Brazilians), 93% of whom were admitted with non–ST-segment elevation ACS and the remaining with ST-segment elevation myocardial infarctions. Vitamin D concentration had a fairly normal distribution, with a mean of 19.5 ± 8.2 ng/ml, a median of 18.5 ng/ml, and an interquartile range of 13.9 to 23.3 ng/ml (Figure 1). Severe deficiency of vitamin D was present in 10% of the sample (95% confidence

Discussion

The present study demonstrates an independent association between severe deficiency of vitamin D and in-hospital cardiovascular mortality in patients with ACS. To the best of our knowledge, this is the first evidence of such an association in this clinical scenario. In the general population, a significant proportion of patients have serum deficiencies of vitamin D.3, 7 It is known that vitamin D deficiency leads to hyperparathyroidism,⁸ a condition associated with increased cardiovascular

Disclosures

The authors have no conflicts of interest to disclose.

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Vitamin D has an established role in calcium homeostasis but its deficiency is emerging also as a new risk factor for cardiovascular disease (CVD). In particular, several epidemiological and clinical studies have reported a close association between low vitamin D levels and several cardiovascular risk factors and major CVDs, such as coronary artery disease, heart failure, and cardiac arrhythmias.
In all these clinical settings, vitamin D deficiency seems to predispose to increased morbidity, mortality, and recurrent cardiovascular events. Despite this growing evidence, interventional trials with supplementation of vitamin D in patients at risk of or with established CVD are still controversial.
In this chapter, we summarize the currently available evidence on the links between vitamin D deficiency and major cardiovascular risk factors and CVD, in terms of both clinical relevance and potential therapeutic implications.
2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines
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The “2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the Management of Patients With Chronic Coronary Disease” provides an update to and consolidates new evidence since the “2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease” and the corresponding “2014 ACC/AHA/AATS/PCNA/SCAI/STS Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease.”
A comprehensive literature search was conducted from September 2021 to May 2022. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.
This guideline provides an evidenced-based and patient-centered approach to management of patients with chronic coronary disease, considering social determinants of health and incorporating the principles of shared decision-making and team-based care. Relevant topics include general approaches to treatment decisions, guideline-directed management and therapy to reduce symptoms and future cardiovascular events, decision-making pertaining to revascularization in patients with chronic coronary disease, recommendations for management in special populations, patient follow-up and monitoring, evidence gaps, and areas in need of future research. Where applicable, and based on availability of cost-effectiveness data, cost–value recommendations are also provided for clinicians. Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.
Circulating 25-hydroxy-vitamin D and the risk of cardiovascular diseases. Systematic review and meta-analysis of prospective cohort studies
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There is no previous meta-analysis examining the association between 25(OH)D and recurrent CVD events from a clinical perspective. In line with the current findings, the prospective cohort studies (N = 5 [55–59]) that have been included in our meta-analysis reported that the risk of recurrent CVD events was higher for the deficient (<12 ng/ml) compared to the non-deficient (≥20 ng/ml) 25(OH)D categories. The definition of vitamin D deficiency is quite debatable.
Circulating vitamin D is linked with the risk of cardiovascular disease (CVD). A meta-analysis has yet to explicitly explore correlation between vitamin D and the risk of CVD incidence and recurrent CVD. This meta-analysis examines the association between 25-hydroxy-vitamin D (25(OH)D) and the risk of CVD incidence (fatal, non-fatal, fatal and non-fatal combined events) and the risk of recurrent CVD (fatal, recurrent, and fatal and recurrent combined events). PROSPERO registration-CRD42021251483.
A total of 79 studies (46 713 CVD cases in 1 397 831 participants) were included in the meta-analysis, of which 61 studies examined the risk of CVD incidence events, and 18 studies examined risk of recurrent CVD events. The risk of CVD incidence events (RR = 1.34, 95% CI: 1.26–1.43, p < 0.001) and recurrent CVD events (RR = 1.86, 95% CI: 1.46–2.36, p < 0.001) was higher in the lowest than the highest category of circulating 25(OH)D. Dose–response analysis reported a linear association for every 10 ng/ml increment of 25(OH)D and non-fatal CVD incidence events (RR = 0.94; 95% CI = 0.89–0.98, p = 0.005), lower fatal recurrent CVD events (RR = 0.45; 95% CI = 0.32–0.62, p < 0.001) and lower combined recurrent CVD events (RR = 0.80; 95% CI = 0.65–0.97, p = 0.023). A non-linear association was observed between higher 25(OH)D and lower fatal CVD incidence events (P-nonlinear<0.001), lower combined CVD incidence events (P-nonlinear = 0.001), and lower non-fatal recurrent CVD events (P-nonlinear = 0.044).
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Vitamin D deficiency is associated with impaired reperfusion in STEMI patients undergoing primary percutaneous coronary intervention
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Vitamin D displays a broad spectrum of cardioprotective effects, preventing oxidative stress, inflammation and thrombosis and improving endothelial function.
Previous studies have associated vitamin D deficiency with more extended and severe coronary artery disease (CAD) and worse outcome, and especially among patients with ST-segment elevation myocardial infarction (STEMI). However, few data have been reported on the association of vitamin D levels with the angiographic findings and epicardial reperfusion in STEMI patients undergoing primary percutaneous coronary intervention (pPCI), that was therefore the aim of the present study.
A consecutive cohort of patients admitted for STEMI and treated with pPCI were included. The levels of 25(OH)D were assessed at admission by chemiluminescence immunoassay kit LIAISON® Vitamin D assay (Diasorin Inc). Hypovitaminosis D was defined for 25(OH)D < 10 ng/ml.
We included in our study 450 patients, divided according to tertiles values of 25(OH)D. Lower vitamin D was associated to a higher use of diuretics (p = 0.02), higher levels of white blood cells and glycemia (p < 0.001), lower prevalence of lesions on bifurcations (p = 0.03) and smaller diameter of the target coronary vessel (p = 0.03). Procedural characteristics and pre-procedural TIMI flow were not different according to vitamin D levels, but for a higher rate of impaired epicardial reperfusion (12.8% vs 8.1% vs 5.3%, p = 0.03, adjusted OR[95%CI] = 2.6[1.05–6.6], p = 0.04 for I vs III tertile), requiring higher use of adenosine (p = 0.006) and glycoprotein IIbIIIa inhibitors (p = 0.01).
The present study shows that among patients with STEMI undergoing pPCI, lower levels of vitamin D are independently associated with impaired reperfusion, Future dedicated studies will shed light on the prognostic implications of hypovitaminosis D in these patients and the potential therapeutic perspectives.
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The results of studies overall support an inverse association between vitamin D levels and the risk of incident coronary events. In a sample of 206 patients admitted to hospital for unstable angina, low vitamin D levels were a prognostic factor for in-hospital CV mortality [63]. In the Danish CopD study, increased risk of acute myocardial infarction was observed in patients with both very low (12.5 nmol/L) or very high (125 nmol/L) 25OHVitD levels compared with the reference category of 70 nmol/L (HR 2.1 95% CI: 1.7–2.7; HR 1.6, 95% CI: 1.2–2.0 respectively) [52].
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Coronary artery diseaseRelation of Severe Deficiency of Vitamin D to Cardiovascular Mortality During Acute Coronary Syndromes

Section snippets

Methods

Results

Discussion

Disclosures

Am J Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

J Am Coll Cardiol

Prog Biophys Mol Biol

Am J Cardiol

Coronary artery disease
Relation of Severe Deficiency of Vitamin D to Cardiovascular Mortality During Acute Coronary Syndromes