Original research 521
Low 25-OH vitamin D levels are not associated with coronary artery calcium or obstructive stenoses John S. Hoa, John J. Cannadaya, Carolyn E. Barlowb, Dale B. Reinhardta, Wendy A. Wadea and Joe R. Ellisa Background It is unclear whether low vitamin D is a significant risk factor for the presence of either calcific atherosclerosis or obstructive coronary artery stenoses. Design In this study, we measured the 25-OH vitamin D levels of 1131 consecutive individuals who underwent coronary artery calcium (CAC) scoring and coronary computed tomographic angiography at our institution. Participants and methods We looked for any association of 25-OH vitamin D levels with CAC scores. We also studied the relation of 25-OH vitamin D levels with the presence of 70% or more obstructive coronary artery stenoses, found initially by coronary computed tomographic angiography and confirmed subsequently by invasive angiography.
patients was 451 (80–1083), 338 (52–830), and 450 (100–1062), respectively. Also, no relation was noted between 25-OH vitamin D levels and the presence of severely obstructive coronary artery disease. The frequency of severe coronary artery disease in 25-OH vitamin D deficient, insufficient, and adequate patients was 3.8, 2.0, and 4.0%, respectively. Conclusion Low 25-OH vitamin D levels were not associated with CAC or severely obstructive stenoses. Coron Artery Dis 26:521–525 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Coronary Artery Disease 2015, 26:521–525 Keywords: coronary artery calcium, coronary artery stenoses, vitamin D
Results There were 132 (11.7%) 25-OH vitamin D deficient (< 20 ng/ml) and 295 (26.1%) 25-OH vitamin D insufficient (21–29 ng/ml) individuals in this study. There was no detectable association between 25-OH vitamin D levels and CAC scores. The median (interquartile range) CAC score of 25-OH vitamin D deficient, insufficient, and adequate
a
Introduction
and/or 75th or more percentile, and the presence of two or more traditional cardiovascular risk factors. Patients with atrial fibrillation, significant renal insufficiency, or a history of significant iodinated contrast allergy were excluded. In addition, we also excluded those with a history of revascularization with stents or coronary artery bypass grafting. All study participants had given written consent to be included in this study. This study was approved by the local institutional review board and was in accordance with the Declaration of Helsinki.
Recent studies suggest that vitamin D may have biological effects beyond that seen with the skeletal system. Various observational studies have linked low levels of 25-OH vitamin D with obesity [1] and diabetes [2]. Other studies have associated low levels of 25-OH vitamin D with hypertension [3]. These findings suggest possible biological mechanisms with which low 25-OH vitamin D levels could potentially increase cardiovascular risk. Studies looking for an association between low 25-OH vitamin D levels with coronary artery disease, however, have yielded conflicting results [4,5]. We thus evaluated the association, if any, of 25-OH vitamin D levels with coronary artery calcium (CAC) scores and the frequency of obstructive coronary artery stenoses, found initially by coronary computed tomographic angiography (CTA) and confirmed subsequently by invasive angiography.
Participants and methods Participants
The study population consisted of 1131 individuals who were referred to the Cooper Clinic for coronary CTA. These referrals were at the discretion of their preventive medicine physicians. Common referral indications included an equivocal exercise stress test, significant atherosclerosis defined as an Agatston CAC score more than 400 0954-6928 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Department of Cardiovascular Imaging, Cooper Clinic and bDepartment of Epidemiology and Statistics, The Cooper Institute, Dallas, Texas, USA
Correspondence to John S. Ho, MD, Cooper Clinic, 12200 Preston Rd, Dallas, TX 75230, USA Tel: + 1 972 560 2741; fax: + 1 972 560 2681; e-mail: [email protected] Received 3 February 2015 Revised 7 April 2015 Accepted 14 April 2015
Study protocol
A detailed medical history and physical examination were performed on all study participants. This evaluation included obtaining a complete medication and supplement history, performing an exercise treadmill stress test to assess for obstructive heart disease, and performing a noncontrast multidetector computed tomography scan for a CAC score. In addition, fasting blood evaluation measuring total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and glucose was carried out. Diabetes was defined as a fasting blood glucose of 126 mg/dl or more or treatment with antidiabetic medications. Hypertension was defined as a systolic blood pressure of 140 mmHg or more or a DOI: 10.1097/MCA.0000000000000261
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
522 Coronary Artery Disease 2015, Vol 26 No 6
diastolic blood pressure of 90 mmHg or more (or both) or current treatment for hypertension. Hyperlipidemia was defined as a total cholesterol of 200 mg/dl or more or concurrent treatment for such. In addition, fasting 25-OH vitamin D levels were measured concomitantly. According to a recent expert consensus [6], a deficient 25-OH vitamin D level was defined as less than 20 ng/ml, whereas an insufficient 25-OH vitamin D status was defined as 21–29 ng/ml. An adequate 25-OH vitamin D level was defined as more than 30 ng/ml. Coronary artery calcium scoring and coronary computed tomographic angiography
All study participants underwent CAC scoring initially and contrast-enhanced coronary CTA subsequently as previously described [7]. The total CAC burden was quantified using the Agatston scoring method [8]. Briefly, contrast-enhanced CTA was carried out with a 64-slice scanner system (Lightspeed VCT; GE Healthcare, Milwaukee, Wisconsin, USA). Unless clinically contraindicated, intravenous metoprolol and/or verapamil was given through an antecubital vein to achieve a target heart rate of 50–65 bpm. No rate-lowering medications were given to those with a baseline heart rate less than 60 bpm. In addition, a low-dose automatic timing bolus protocol [100 kV, 50 mA, 20 ml contrast (5 ml/s) followed by a 20-ml saline chaser (5 ml/s) using a twin injector] was used to optimize the delay time from the start of injection to the start of scanning at the level of the left main origin. Approximately 90–100 ml iodinated contrast [Visipaque (GE Healthcare) or Omnipaque (GE Healthcare)] was administered at a flow rate of 5–6 ml/s for the CTA images. Participants underwent CTA with the following scan parameters: tube voltage 100 kV, effective tube current 300–450 mA, 64 × 0.6 mm collimation, rotation time of 350 ms, and pitch 0.18–0.22. The effective tube current was selected as a function of BMI (BMI < 20 kg/m2, 300 mA; 20 ≤ BMI < 25 kg/m2, 350 mA; 25 ≤ BMI < 30 kg/ m2, 400 mA; BMI ≥ 30, 450 mA). In addition, to minimize radiation exposure, prospective, ‘step and shoot’ technology was used. Source image data sets were loaded to reconstruct both thin-slab maximum intensity projections and curved multiplanar reconstructions. Transaxial images were reconstructed at a slice width of 0.6 mm. Reconstructions were performed at 75% of the R–R interval. Both a cardiologist and a radiologist experienced with coronary CTA reviewed all scans independently, and any discrepancy was resolved after additional joint review and discussion. A semiquantitative assessment was performed on any detected coronary artery stenosis, with an estimate of stenosis severity calculated as the ratio of the minimum contrast lumen over the normal reference lumen of an unaffected distal portion. A severe stenosis was defined as a 50% or more left main or a 70% or more luminal compromise elsewhere.
Table 1
Baseline characteristics of study patients
Variables Total Age (years) Men BMI (kg/m2) Hypertension Diabetes mellitus Hyperlipidemia Current smoker Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Total cholesterol (mg/dl) High-density lipoprotein (mg/dl) Low-density lipoprotein (mg/dl) Triglycerides (mg/dl) Glucose (mg/dl) Coronary artery calcium score 25-OH vitamin D (ng/ml) Medications Antihypertensive Statin Antidiabetic Test indication Angina Chest pain, atypical Abnormal/equivocal exercise stress test Abnormal/equivocal myocardial perfusion test Hypertension Diabetes mellitus Hyperlipidemia Tobacco history BMI ≥ 30 kg/m2 Family history of heart disease Atherosclerosis
Value 1131 62.6 ± 9.6 927 (82.0) 27.9 ± 4.5 452 (40.0) 68 (6.0) 498 (44.0) 79 (7.0) 125.8 ± 14.9 78.7 ± 9.1 171.6 ± 41.6 54.1 ± 15.8 95.2 ± 36.5 111.1 ± 62.8 101.6 ± 21.0 417 (85–972) 34.8 ± 13.6 622 (55.0) 588 (52.0) 79 (7.0) 15 170 362 34 599 102 939 464 294 396 882
(1.3) (15.0) (32.0) (3.0) (53.0) (9.0) (83.0) (41.0) (26.0) (35.0) (78.0)
Data are presented as absolute number (%), mean ± SD, or median (25th to 75th percentile).
Patients with at least one severe stenosis as defined above were referred for invasive coronary angiography and possible revascularization. Cases in which the invasive coronary angiogram corroborated the CTA findings were categorized as a true positive case for severe coronary artery disease. In contrast, cases in which the invasive coronary angiogram did not corroborate the CTA findings were classified as a negative (false positive) case for severe coronary artery disease. Statistical analysis
The clinical, anthropometric, and biochemical data of the study population are reported as means ± SD, frequencies, or median values with interquartile ranges where appropriate. We compared median CAC scores across the three categories of 25-OH vitamin D levels (deficient, insufficient, and adequate). We compared descriptive characteristics and scan parameters between patients classified by obstructive stenoses category using the Wilcoxon rank-sum test, t-test, or χ2 analysis. We conducted all data analyses using SAS 9.1 statistical software (SAS Institute Inc., Cary, North Carolina, USA).
Results Table 1 depicts the baseline characteristics of the population under study. The study patients were primarily older, overweight men. There was a relatively high frequency of hypertension (40.0%) and hyperlipidemia
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Low vitamin D with coronary calcium and CAD Ho et al. 523
The indications prompting referral for coronary CTA are also listed in Table 1. The study population was largely asymptomatic, with a very low frequency of angina (< 1.0%) and a relatively low rate of atypical chest pain (15.0%). The most frequent referral indication was the presence of significant atherosclerosis (78.0%), defined as a CAC score of more than 400 and/or at least 75th percentile. Other relatively common referral indications included an abnormal/equivocal exercise treadmill stress test, an equivocal myocardial perfusion study, a family history of premature heart disease, and the presence of multiple cardiovascular risk factors. The mean ± SD 25-OH vitamin D level of the study group was normal at 34.8 ± 13.6 mg/dl. However, there was significant variation in the levels of 25-OH vitamin D seen in this study, with 132 (11.7%) cases of 25-OH vitamin D deficiency (< 20 ng/ml). In addition, there were 295 (26.1%) individuals with a borderline, insufficient 25-OH vitamin D status (21–29 ng/ml). Overall, almost 40% of the study population [427/1131 (37.8%)] exhibited either a deficient or an insufficient 25-OH vitamin D level. The overall mean ± SD calcium level was 9.4 ± 0.4 ng/dl, with no significant differences noted among the various 25-OH vitamin D categories. The prevalence of self-reported osteoporosis was 9%. Figure 1 shows the relation between 25-OH vitamin D levels and CAC scores, a validated measure of coronary atherosclerosis. There was no clinically significant relation noted between 25-OH vitamin D levels and CAC scores. The median (interquartile range) CAC score of the 132 deficient 25-OH vitamin D cases was 451 (80–1083), whereas the median (interquartile range) CAC score of the 704 adequate 25-OH vitamin D cases was 450 (100–1062). In the 295 cases of borderline 25-OH vitamin D status, the median (interquartile range) CAC score was 338 (52–830). In this study, severely obstructive coronary artery stenoses were found in 39 (3.4%) individuals. The parameters associated with the presence of these stenoses are shown in Table 2. Univariate predictors of severely obstructive coronary artery disease included being male (P = 0.04), the use of antihypertensive agents (P = 0.004),
Fig. 1
10000 Coronary artery calcim score
(44.0%), whereas there was a low prevalence of current tobacco use (7.0%) and diabetes (6.0%). Usage of antihypertensive (55%) and statin (52%) medications approximated the corresponding frequency of the appropriate cardiovascular risk factor. As would be expected from a preventative patient population, there appeared to be excellent control of these risk factors, with good blood pressure levels (mean 126/79 mmHg), lipid profiles (mean low-density lipoprotein 95 mg/dl), and glucose levels (mean 102 mg/dl) at the time of study enrollment. Nevertheless, the atherosclerosis burden of the overall study group was found to be severe, with a median (interquartile range) CAC score of 417 (85–972).
8000 6000 4000 2000 0
30 ng/ml). In those with a borderline 25-OH vitamin D level (21–29 ng/ml), the frequency of severely obstructive stenoses was actually lower than that seen with documented 25-OH vitamin D deficiency.
Discussion In this study, there was a substantial prevalence of baseline 25-OH vitamin D deficiency and insufficiency, with almost 40% exhibiting such a status. Despite this significant prevalence, 25-OH vitamin D levels were not significantly associated with either coronary atherosclerosis or the presence of severely obstructive stenoses. In a subgroup analysis focusing on those with the most severely deficient 25-OH vitamin D status, that is, in those with a 25-OH vitamin D level less than 20 ng/ml, no significant differences were found with either the CAC scores or the prevalence of severe coronary artery stenoses. These findings suggest that low 25-OH vitamin D levels may not significantly increase an individual’s overall cardiovascular risk. These results also suggest that vitamin D supplementation would not significantly lower cardiovascular risk, even in those with documented 25-OH vitamin D deficiency. In line with these results, a recent large meta-analysis of 51 trials did not reveal a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D supplementation
% With severe coronary artery stenoses ≥ 70%
Fig. 2
4.5 4 3.5 3 2.5 2 1.5 1 0.5 0
Low 25-OH vitamin D levels are not associated with coronary artery calcium or obstructive stenoses John S. Hoa, John J. Cannadaya, Carolyn E. Barlowb, Dale B. Reinhardta, Wendy A. Wadea and Joe R. Ellisa Background It is unclear whether low vitamin D is a significant risk factor for the presence of either calcific atherosclerosis or obstructive coronary artery stenoses. Design In this study, we measured the 25-OH vitamin D levels of 1131 consecutive individuals who underwent coronary artery calcium (CAC) scoring and coronary computed tomographic angiography at our institution. Participants and methods We looked for any association of 25-OH vitamin D levels with CAC scores. We also studied the relation of 25-OH vitamin D levels with the presence of 70% or more obstructive coronary artery stenoses, found initially by coronary computed tomographic angiography and confirmed subsequently by invasive angiography.
patients was 451 (80–1083), 338 (52–830), and 450 (100–1062), respectively. Also, no relation was noted between 25-OH vitamin D levels and the presence of severely obstructive coronary artery disease. The frequency of severe coronary artery disease in 25-OH vitamin D deficient, insufficient, and adequate patients was 3.8, 2.0, and 4.0%, respectively. Conclusion Low 25-OH vitamin D levels were not associated with CAC or severely obstructive stenoses. Coron Artery Dis 26:521–525 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. Coronary Artery Disease 2015, 26:521–525 Keywords: coronary artery calcium, coronary artery stenoses, vitamin D
Results There were 132 (11.7%) 25-OH vitamin D deficient (< 20 ng/ml) and 295 (26.1%) 25-OH vitamin D insufficient (21–29 ng/ml) individuals in this study. There was no detectable association between 25-OH vitamin D levels and CAC scores. The median (interquartile range) CAC score of 25-OH vitamin D deficient, insufficient, and adequate
a
Introduction
and/or 75th or more percentile, and the presence of two or more traditional cardiovascular risk factors. Patients with atrial fibrillation, significant renal insufficiency, or a history of significant iodinated contrast allergy were excluded. In addition, we also excluded those with a history of revascularization with stents or coronary artery bypass grafting. All study participants had given written consent to be included in this study. This study was approved by the local institutional review board and was in accordance with the Declaration of Helsinki.
Recent studies suggest that vitamin D may have biological effects beyond that seen with the skeletal system. Various observational studies have linked low levels of 25-OH vitamin D with obesity [1] and diabetes [2]. Other studies have associated low levels of 25-OH vitamin D with hypertension [3]. These findings suggest possible biological mechanisms with which low 25-OH vitamin D levels could potentially increase cardiovascular risk. Studies looking for an association between low 25-OH vitamin D levels with coronary artery disease, however, have yielded conflicting results [4,5]. We thus evaluated the association, if any, of 25-OH vitamin D levels with coronary artery calcium (CAC) scores and the frequency of obstructive coronary artery stenoses, found initially by coronary computed tomographic angiography (CTA) and confirmed subsequently by invasive angiography.
Participants and methods Participants
The study population consisted of 1131 individuals who were referred to the Cooper Clinic for coronary CTA. These referrals were at the discretion of their preventive medicine physicians. Common referral indications included an equivocal exercise stress test, significant atherosclerosis defined as an Agatston CAC score more than 400 0954-6928 Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Department of Cardiovascular Imaging, Cooper Clinic and bDepartment of Epidemiology and Statistics, The Cooper Institute, Dallas, Texas, USA
Correspondence to John S. Ho, MD, Cooper Clinic, 12200 Preston Rd, Dallas, TX 75230, USA Tel: + 1 972 560 2741; fax: + 1 972 560 2681; e-mail: [email protected] Received 3 February 2015 Revised 7 April 2015 Accepted 14 April 2015
Study protocol
A detailed medical history and physical examination were performed on all study participants. This evaluation included obtaining a complete medication and supplement history, performing an exercise treadmill stress test to assess for obstructive heart disease, and performing a noncontrast multidetector computed tomography scan for a CAC score. In addition, fasting blood evaluation measuring total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, and glucose was carried out. Diabetes was defined as a fasting blood glucose of 126 mg/dl or more or treatment with antidiabetic medications. Hypertension was defined as a systolic blood pressure of 140 mmHg or more or a DOI: 10.1097/MCA.0000000000000261
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
522 Coronary Artery Disease 2015, Vol 26 No 6
diastolic blood pressure of 90 mmHg or more (or both) or current treatment for hypertension. Hyperlipidemia was defined as a total cholesterol of 200 mg/dl or more or concurrent treatment for such. In addition, fasting 25-OH vitamin D levels were measured concomitantly. According to a recent expert consensus [6], a deficient 25-OH vitamin D level was defined as less than 20 ng/ml, whereas an insufficient 25-OH vitamin D status was defined as 21–29 ng/ml. An adequate 25-OH vitamin D level was defined as more than 30 ng/ml. Coronary artery calcium scoring and coronary computed tomographic angiography
All study participants underwent CAC scoring initially and contrast-enhanced coronary CTA subsequently as previously described [7]. The total CAC burden was quantified using the Agatston scoring method [8]. Briefly, contrast-enhanced CTA was carried out with a 64-slice scanner system (Lightspeed VCT; GE Healthcare, Milwaukee, Wisconsin, USA). Unless clinically contraindicated, intravenous metoprolol and/or verapamil was given through an antecubital vein to achieve a target heart rate of 50–65 bpm. No rate-lowering medications were given to those with a baseline heart rate less than 60 bpm. In addition, a low-dose automatic timing bolus protocol [100 kV, 50 mA, 20 ml contrast (5 ml/s) followed by a 20-ml saline chaser (5 ml/s) using a twin injector] was used to optimize the delay time from the start of injection to the start of scanning at the level of the left main origin. Approximately 90–100 ml iodinated contrast [Visipaque (GE Healthcare) or Omnipaque (GE Healthcare)] was administered at a flow rate of 5–6 ml/s for the CTA images. Participants underwent CTA with the following scan parameters: tube voltage 100 kV, effective tube current 300–450 mA, 64 × 0.6 mm collimation, rotation time of 350 ms, and pitch 0.18–0.22. The effective tube current was selected as a function of BMI (BMI < 20 kg/m2, 300 mA; 20 ≤ BMI < 25 kg/m2, 350 mA; 25 ≤ BMI < 30 kg/ m2, 400 mA; BMI ≥ 30, 450 mA). In addition, to minimize radiation exposure, prospective, ‘step and shoot’ technology was used. Source image data sets were loaded to reconstruct both thin-slab maximum intensity projections and curved multiplanar reconstructions. Transaxial images were reconstructed at a slice width of 0.6 mm. Reconstructions were performed at 75% of the R–R interval. Both a cardiologist and a radiologist experienced with coronary CTA reviewed all scans independently, and any discrepancy was resolved after additional joint review and discussion. A semiquantitative assessment was performed on any detected coronary artery stenosis, with an estimate of stenosis severity calculated as the ratio of the minimum contrast lumen over the normal reference lumen of an unaffected distal portion. A severe stenosis was defined as a 50% or more left main or a 70% or more luminal compromise elsewhere.
Table 1
Baseline characteristics of study patients
Variables Total Age (years) Men BMI (kg/m2) Hypertension Diabetes mellitus Hyperlipidemia Current smoker Systolic blood pressure (mmHg) Diastolic blood pressure (mmHg) Total cholesterol (mg/dl) High-density lipoprotein (mg/dl) Low-density lipoprotein (mg/dl) Triglycerides (mg/dl) Glucose (mg/dl) Coronary artery calcium score 25-OH vitamin D (ng/ml) Medications Antihypertensive Statin Antidiabetic Test indication Angina Chest pain, atypical Abnormal/equivocal exercise stress test Abnormal/equivocal myocardial perfusion test Hypertension Diabetes mellitus Hyperlipidemia Tobacco history BMI ≥ 30 kg/m2 Family history of heart disease Atherosclerosis
Value 1131 62.6 ± 9.6 927 (82.0) 27.9 ± 4.5 452 (40.0) 68 (6.0) 498 (44.0) 79 (7.0) 125.8 ± 14.9 78.7 ± 9.1 171.6 ± 41.6 54.1 ± 15.8 95.2 ± 36.5 111.1 ± 62.8 101.6 ± 21.0 417 (85–972) 34.8 ± 13.6 622 (55.0) 588 (52.0) 79 (7.0) 15 170 362 34 599 102 939 464 294 396 882
(1.3) (15.0) (32.0) (3.0) (53.0) (9.0) (83.0) (41.0) (26.0) (35.0) (78.0)
Data are presented as absolute number (%), mean ± SD, or median (25th to 75th percentile).
Patients with at least one severe stenosis as defined above were referred for invasive coronary angiography and possible revascularization. Cases in which the invasive coronary angiogram corroborated the CTA findings were categorized as a true positive case for severe coronary artery disease. In contrast, cases in which the invasive coronary angiogram did not corroborate the CTA findings were classified as a negative (false positive) case for severe coronary artery disease. Statistical analysis
The clinical, anthropometric, and biochemical data of the study population are reported as means ± SD, frequencies, or median values with interquartile ranges where appropriate. We compared median CAC scores across the three categories of 25-OH vitamin D levels (deficient, insufficient, and adequate). We compared descriptive characteristics and scan parameters between patients classified by obstructive stenoses category using the Wilcoxon rank-sum test, t-test, or χ2 analysis. We conducted all data analyses using SAS 9.1 statistical software (SAS Institute Inc., Cary, North Carolina, USA).
Results Table 1 depicts the baseline characteristics of the population under study. The study patients were primarily older, overweight men. There was a relatively high frequency of hypertension (40.0%) and hyperlipidemia
Copyright r 2015 Wolters Kluwer Health, Inc. All rights reserved.
Low vitamin D with coronary calcium and CAD Ho et al. 523
The indications prompting referral for coronary CTA are also listed in Table 1. The study population was largely asymptomatic, with a very low frequency of angina (< 1.0%) and a relatively low rate of atypical chest pain (15.0%). The most frequent referral indication was the presence of significant atherosclerosis (78.0%), defined as a CAC score of more than 400 and/or at least 75th percentile. Other relatively common referral indications included an abnormal/equivocal exercise treadmill stress test, an equivocal myocardial perfusion study, a family history of premature heart disease, and the presence of multiple cardiovascular risk factors. The mean ± SD 25-OH vitamin D level of the study group was normal at 34.8 ± 13.6 mg/dl. However, there was significant variation in the levels of 25-OH vitamin D seen in this study, with 132 (11.7%) cases of 25-OH vitamin D deficiency (< 20 ng/ml). In addition, there were 295 (26.1%) individuals with a borderline, insufficient 25-OH vitamin D status (21–29 ng/ml). Overall, almost 40% of the study population [427/1131 (37.8%)] exhibited either a deficient or an insufficient 25-OH vitamin D level. The overall mean ± SD calcium level was 9.4 ± 0.4 ng/dl, with no significant differences noted among the various 25-OH vitamin D categories. The prevalence of self-reported osteoporosis was 9%. Figure 1 shows the relation between 25-OH vitamin D levels and CAC scores, a validated measure of coronary atherosclerosis. There was no clinically significant relation noted between 25-OH vitamin D levels and CAC scores. The median (interquartile range) CAC score of the 132 deficient 25-OH vitamin D cases was 451 (80–1083), whereas the median (interquartile range) CAC score of the 704 adequate 25-OH vitamin D cases was 450 (100–1062). In the 295 cases of borderline 25-OH vitamin D status, the median (interquartile range) CAC score was 338 (52–830). In this study, severely obstructive coronary artery stenoses were found in 39 (3.4%) individuals. The parameters associated with the presence of these stenoses are shown in Table 2. Univariate predictors of severely obstructive coronary artery disease included being male (P = 0.04), the use of antihypertensive agents (P = 0.004),
Fig. 1
10000 Coronary artery calcim score
(44.0%), whereas there was a low prevalence of current tobacco use (7.0%) and diabetes (6.0%). Usage of antihypertensive (55%) and statin (52%) medications approximated the corresponding frequency of the appropriate cardiovascular risk factor. As would be expected from a preventative patient population, there appeared to be excellent control of these risk factors, with good blood pressure levels (mean 126/79 mmHg), lipid profiles (mean low-density lipoprotein 95 mg/dl), and glucose levels (mean 102 mg/dl) at the time of study enrollment. Nevertheless, the atherosclerosis burden of the overall study group was found to be severe, with a median (interquartile range) CAC score of 417 (85–972).
8000 6000 4000 2000 0
30 ng/ml). In those with a borderline 25-OH vitamin D level (21–29 ng/ml), the frequency of severely obstructive stenoses was actually lower than that seen with documented 25-OH vitamin D deficiency.
Discussion In this study, there was a substantial prevalence of baseline 25-OH vitamin D deficiency and insufficiency, with almost 40% exhibiting such a status. Despite this significant prevalence, 25-OH vitamin D levels were not significantly associated with either coronary atherosclerosis or the presence of severely obstructive stenoses. In a subgroup analysis focusing on those with the most severely deficient 25-OH vitamin D status, that is, in those with a 25-OH vitamin D level less than 20 ng/ml, no significant differences were found with either the CAC scores or the prevalence of severe coronary artery stenoses. These findings suggest that low 25-OH vitamin D levels may not significantly increase an individual’s overall cardiovascular risk. These results also suggest that vitamin D supplementation would not significantly lower cardiovascular risk, even in those with documented 25-OH vitamin D deficiency. In line with these results, a recent large meta-analysis of 51 trials did not reveal a statistically significant reduction in mortality and cardiovascular risk associated with vitamin D supplementation
% With severe coronary artery stenoses ≥ 70%
Fig. 2
4.5 4 3.5 3 2.5 2 1.5 1 0.5 0
