Circulating vitamin D levels are associated with the presence and severity of coronary artery disease but not peripheral arterial disease in patients undergoing coronary angiography

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Highlights

  • What is already known about this subject?

  • An association exists between low vitamin D levels and risk of cardiovascular disease.

  • What does this study add?

  • Low vitamin D levels predict the extent of angiographic coronary artery disease.

  • How might this impact on clinical practice. While we await the results of large prospective studies aimed to show whether vitamin D supplementation reduces cardiovascular events this study suggests that in patients with low vitamin d levels who are at increased risk for the development of coronary artery disease vitamin d supplementation should be considered. Furthermore further studies need to be performed to determine the potential mechanism by which low vitamin D may lead to the development of atherosclerotic disease.

Abstract

Background and aims

To investigate the association between vitamin D levels, angiographic severity of coronary artery disease, arterial stiffness and degree of peripheral arterial disease (PAD) as assessed by ankle brachial index (ABI).

Methods and results

375 patients undergoing coronary angiography from November 2012 to September 2013 were recruited. Serum 25-hydroxyvitamin D (25OHD) levels were measured as were ABI and pulse wave velocity (PWV). Based on the findings of the coronary angiogram, patients were divided into subgroups: Absent, Single, Double and Triple Vessel Disease (as defined by >50% stenosis in each major coronary artery) 0.275 patients not taking vitamin D supplements were included in the analysis. Mean age was 66.0 ± 11.2 (mean ± SD) years. Levels of 25(OH)D were significantly lower in patients with CAD when compared to patients without CAD (57.0 ± 1.73 versus 70.1 ± 2.46 nmol/L; p < 0.01). One way ANOVA revealed triple vessel disease patients had significantly lower 25(OH)D levels when compared to single vessel disease patients (50.6 ± 2.84 nmol/L versus 61.3 ± 3.16 p < 0.01) and trended to be lower when compared to double vessel disease patients (50.6 ± 2.84 versus 59.0 ± 2.99 nmol/L; p = 0.07). Stepwise regression revealed that age, gender (male), hypertension, hyperlipidemia and 25(OH)D were significant predictors of CAD (p < 0.05). Vitamin D was the most significant predictor for CAD (p < 0.001) There was no correlation between 25(OH)D levels, ABI and PWV.

Conclusion

Among patients presenting for coronary angiography, low serum 25-hydroxyvitamin D levels are associated with the presence and extent of angiographic CAD but not arterial stiffness or PAD.

Introduction

Worldwide, cardiovascular disease (CVD) is the most common cause of morbidity and remains the number one cause of death despite improved understanding of CVDs and effective therapies which have resulted in improved outcomes in these patients [1]. To further reduce CV events, novel risk factors need to be identified. Recent observational and prospective studies have shown an association between vitamin D deficiency and hypertension, diabetes mellitus, metabolic syndrome, coronary and peripheral arterial disease (PAD), and heart failure [2], [3]. Vitamin D, a secosteroid molecule, is known traditionally to play a role in calcium homeostasis and bone metabolism. Interestingly, vitamin D has been shown to exert a wider range of biological activities. These include reduction in blood pressure through down regulation of the renin–angiotensin system (RAS) [4], enhancement in insulin secretion and insulin sensitivity [5] protection against angiogenesis [6] and regulation of cellular differentiation and proliferation through locally-formed calcitriol in tissues [7].

Globally, vitamin D deficiency is a re-emerging public health problem, being found in approximately 30%–50% of the general population [8], [9]. There have been conflicting data published concerning the relationship between vitamin D and the extent of atherosclerotic disease. Some studies suggest a relationship exists while others have shown no such relationship [10], [11]. Furthermore, there is limited literature regarding what if any association exists between vitamin D status and peripheral arterial disease and arterial stiffness. In the current study, we investigated the relationship between serum 25-hydroxyvitamin D levels, extent of coronary artery disease as assessed by coronary angiography and the presence of peripheral arterial disease measured with ankle brachial index (ABI) and arterial stiffness.

Section snippets

Study population

375 patients undergoing coronary angiography at the Alfred Hospital Cardiac Catheterisation Laboratory between the period of November 2012 to September 2013 were prospectively recruited. Relevant current diagnoses, co-morbidities and current medication list were identified from inpatient and outpatient medical files.

The inclusion criteria included patients undergoing a coronary angiogram, patients who consented to additional vitamin D, calcium and phosphate blood tests within 3 months of the

Results

There were a total of 375 patients recruited mean age was 66.0 ± 11.2 (mean ± SD). Baseline characteristics and co-morbidities are shown in Table 1 and current cardiac medications in Table 2. Hypertension and hyperlipidemia were common co-morbidities amongst study patients. Diabetes was a less common co-morbidity (25.8%). 273 patients had normal renal function, 81 patients had stage 3 CKD (eGFR of 30–60 mL/min) and 6 patients had stage 4 CKD (eGFR <30 mL/min).

The majority of patients, as

Discussion

The key finding of this study was that serum 25 OHD levels were negatively associated with the presence and extent of angiographic CAD. Stepwise regression revealed that age, gender, hypertension, hyperlipidemia and 25(OH)D were appropriate models for CAD prediction, whilst DM was an appropriate predictor for PAD. However, 25(OH)D was not significantly associated with arterial stiffness or PAD. To our knowledge, this is the first study assessing the relationship of serum 25(OH)D level with

Conclusion

The current study suggests that serum 25(OH)D levels are inversely associated with coronary lesion severity established by coronary angiography, but not with arterial stiffness or PAD. While mechanistic studies have shown potential mechanisms by which vitamin D supplementation may be cardioprotective, further studies are required to determine whether vitamin D interventions prevent the development and progression of CVD and ultimately reduce clinical end points such as myocardial infarction and

Funding

This works was supported by an National Health and Medical Research (NHMRC) program grant. Grant number 1036352.

Competing interests

The authors have no conflicts of interest to disclose.

Acknowledgements

The authors would like to thank Vivian Mak, Jan Jennings and Liz Jenkins for their help with the study. Dr Dart and Shaw are supported by an National Health and Medical Research (NHMRC Australia) program grant and Dr Wark is supported by an NHMRC project grant.

References (21)

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