Current Knowledge of the Impact of Vitamin D in Coronary Artery Disease
Abstract
1. Introduction
1.1. Coronary Artery Disease (CAD)
1.2. Mechanisms of CAD Development
1.3. Current Treatment of CAD
1.4. Vitamin D
1.5. The Effect of Vitamin D Supplementation on the Ca2+ Metabolism
1.6. Effect of Vitamin D on Cardiac Physiology
2. Results
2.1. Vitamin D and Hypertension
2.2. Vitamin D and Atherosclerosis
2.3. Vitamin D and Vascular Reactivity
2.4. Vitamin D and Myocardial Infarction
2.5. Randomized Controlled Trials
3. Discussion
4. Materials and Methods
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
Abbreviations
AMI | Acute myocardial infarction |
AVC | Aortic valve calcification |
BMI | Body mass index |
CAC | Coronary artery calcification |
CAD | Coronary artery disease |
CRP | C-reactive protein |
CVD | Cardiovascular disease |
DAG | Diacylglycerols |
ER | Endoplasmic reticulum |
FGF-23 | Fibroblast growth factor 23 |
FGFR | fibroblast growth factor receptor |
HDL | High-density lipoproteins |
LDL | Low-density lipoprotein |
MACE | Major cardiovascular events |
NO | Nitric oxide |
POAF | Postoperative atrial fibrillation |
PTH | Parathyroid hormone |
RCT | Randomized controlled trial |
ROS | Reactive oxygen species |
TG | Triglycerides |
TRPC | Transient receptor potential channel |
VDR | Vitamin D receptor |
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Study, Identifier | Design | Intervention | Results |
---|---|---|---|
Vitamin D supplementation and major cardiovascular events: D-health randomized controlled trial [44,45,46] ACTRN12613000743763 | Phase 3, randomized, double blinded, placebo-controlled trial n = 21,315 (60–84 years old) follow-up: 5 years endpoint: major cardiovascular event (Myocardial infarction, stroke or coronary revascularization) | One monthly dose of 60,000 IU vitamin D vs. soya oil placebo data | The rate of major cardiovascular events was lower in vitamin D group than in placebo group (HR = 0.91, 95% CI: 0.81–1.01) The rate of major cardiovascular events was even lower in patients taking cardiovascular drugs (HR = 0.84, 95% CI: 0.74–0.97, p = 0.12) The hazard ratio was lower when looking at incidents of myocardial infarction (HR = 0.81, 95% CI = 0.67–0.98) and coronary revascularization (HR = 0.89, 95% CI: 0.78–1.01) However, all differences were not statistically significant |
Calcifediol supplementation in adults on hemodialysis: a randomized controlled trial [47] NCT01457001 | Phase 3, multicenter, randomized controlled trial n = 284 (≥18 years) follow-up period = 24 months Endpoint: composite of nonfatal myocardial infarction, nonfatal stroke and death | 40 µg calcifediol 3 times a week vs. no additional treatment | Calcifediol did not have effect on cardiovascular death (HR: 1.06, 95% CI: 0.41–2.74) or nonfatal myocardial infarction (HR: 0.20, 95% CI: 0.02–1.67) The intervention did not show an effect on the composite of nonfatal myocardial infarction, nonfatal stroke, and death (HR = 1.03 95% CI: 0.63–1.67) |
The International Polycap Study 3 (TIPS-3) [48] NCT01646437 | Phase 3, double-blind, placebo-controlled, randomized trial n = 5670 (men aged ≥ 50 years and women aged ≥ 55 years) Mean follow-up: 4.6 years Endpoint: fracture and composite of CV death, myocardial infarction stroke, cancer, fracture or fall | One monthly dose of 60,000 IU of vitamin D3 vs. placebo | High dose vitamin D did not reduce non-skeletal outcomes (HR = 1.13, 95% CI: 0.93–1.37, p = 0.22) More people in the vitamin D group died (HR = 1.29, 95% CI: 1.03–1.61, p = 0.03) |
Impact of Vitamin D supplementation on the Clinical Outcomes and Epigenetic Markers in Patients with Acute Coronary Syndrome [49] Trial registration not given | Randomized controlled trial n = 250 Follow up: 2 years Endpoints: cardiac fibrosis markers, echocardiographic parameters, epigenetic markers | Intervention arm: Vitamin D based on serum vitamin D level at baseline. The intervention was: 50,000 IU/week for 8 weeks followed by 10,000 IU/week for 4 months if serum vitamin D was 12 ng/mL and 10,000 IU/week for 6 months if serum vitamin D was above 12 ng/mL | The intervention lowered ejection fraction (p = 1.1 × 10−4), end systolic volume (p = 0.0075), and end diastolic volume (p = 0.002) There was a decrease in cardiac fibrosis markers There were fewer events of MACE (p = 0.043) Taq I (rs731236) was a predictor of heart failure, Bsm I (rs1544410) was a predictor of MACE, Fok I (rs2228570) protected against MACE |
The Aortic Valve DECalcification Trial (AVADEC) [50] NCT03243890 | Randomized, controlled, double blinded trial n = 304 (men, 65–75 years old) Follow-up time: 2 years Endpoint: absolute change in CAC score and changes in plaque volume | Menaquinone-7 720 µg/day including the recommended daily dose of vitamin D (25 µg/day) vs. placebo | There was no overall reduction in mean CAC progression (mean difference = 51 AU, p = 0.089) Participants with CAC scores ≥400 AU had a smaller progression in CAC (380 AU vs. 288 AU, p = 0.047) Participants with statin use also had a smaller progression in CAC (p = 0.048) |
Can Vitamin D Reduce Heart Muscle Damage After Bypass Surgery? [51] NCT04323852 | Phase 4, double blind, randomized, placebo-controlled trial n = 70 (≥18 years) follow-up: 30 days Endpoint: caspases 2, 3 and 7 activity, IL-10 serum level, IGF-I serum levels and pro-BNP | 3 doses of vitamin D (50,000 U) a day for 3 days before surgery vs. placebo | Lower average number of caspases 2 and 3 in the vitamin D group (p = 0.006) Increased levels of IL-10 in the vitamin D group before surgery (p = 0.001). It remained elevated after surgery compared to the intervention group (p < 0.001) No difference in pro-BNP |
Effect of preoperative Vitamin D on postoperative atrial fibrillation incidence after coronary artery bypass graft [52] IRCT20230506058103N1 | Phase 3, randomized controlled clinical trial n = 246 follow-up = 5 days Endpoints: POAF up to 5 days after surgery, duration of hospitalization, duration of intubation | Starting 3 days before the surgery, patients receive 50,000 units of vitamin D three times a day vs. placebo | There was no significant difference in the duration of the hospital stay (p = 0.975) or intubation period (p = 0.886) Decrease in POAF incidence in the intervention group (p = 0.003) |
Vitamin D and Omega-3 Trial (VITAL) [53] NCT01169259 | Phase 3, double-blind, placebo-controlled trial n = 15,917 (men ≥ 50 years and women ≥ 55 years) Endpoint: major cardiovascular events, invasive cancer | Daily doses of: 2000 IU vitamin D3 + 840 mg of marine omega-3 fatty acids vs. 2000 IU vitamin D3 + fish oil placebo vs. vitamin D placebo + 840 mg of marine omega-3 fatty acids vs. vitamin D placebo + fish oil placebo | There was no significant difference in major cardiovascular events between the intervention and control group There was no significant interaction between eGFR, vitamin D, and major cardiovascular events |
DO-HEALTH/Vitamin D3—Omega3—Home Exercise—Healthy Ageing and Longevity Trial (DO-HEALTH)) [54,55] NCT01745263 | Phase 3, double-blind, randomized placebo-controlled trial n (biomarkers) = 2157 n (MACE) = 2089 age ≥ 70 years Endpoint: lipid and CVD biomarkers, incident hypertension, and major cardiovascular events. Follow-up: 3 years | 2000 IU/d of vitamin D3, 1 g/d of omega-3s, and a strength-training exercise program vs. vitamin D3 and omega-3s vs. vitamin D3 and vs. vitamin D3 alone vs. omega-3s and exercise vs. omega-3s alone vs. exercise alone vs. placebo | Vitamin D3 did not change the lipid profile significantly Vitamin D3 supplements showed no effect on MACE (HR = 1.37, 95% CI: 0.88–2.14), there were also no effects on hypertension (HR = 1.05, 95% CI: 0.76–1.44) |
The effect of vitamin D deficiency treatment on lipid profile in ischemic heart diseases: a double blinded randomized clinical trial [56] IRCT20200905048622N1 | Phase 3, double-blind, randomized controlled trial n = 44 (40–65 years) Follow-up time: 5 weeks Endpoints: serum levels of TGs, LDL-C, HDL-C, TC and CRP | 50,000 IU vitamin D3 weekly up to 2 months vs. placebo | A significant increase in HDL (p = 0.048) and a significant decrease in TG (p = 0.008) in the intervention group No correlation between vitamin D and CRP levels |
Vitamin D supplementation modulates platelet-mediated inflammation in subjects with type 2 diabetes: A randomized double-blind, placebo-controlled trial [57] CTRI/2019/01/016921 | Randomized, double-blind, placebo-controlled trial n = 59 (25–65 years) follow-up = 12 months endpoint: platelet activation, platelet-immune-cell aggregation, immune profile, vitamin D metabolite levels | Vitamin D 60,000 IU/week for 3 months followed by 60,000/month for 9 months | No improvement of glycemic control or a difference in immune cells between the groups Platelet activation was reduced, and platelet-immune cell aggregates were altered (p < 0.05) Reduced levels of cytokines such as IL-18, TNF-alpha, IFN-gamma, etc. Reduction in intracellular reactive oxygen species |
Simultaneous use of chromium picolinate and vitamin D reconstruction or prevention of endothelial dysfunction in patients with type 2 diabetes by examining the pattern of changes in metabolic markers of oxidative stress, inflammation, and endothelial dysfunction [58] IRCT2017052034038N1 | Phase 3, randomized, single-blind, placebo-controlled trial n = 92 (25–60 years) Follow-up time: 4 months Endpoints: Hct, MDA, total antioxidant capacity, total thiol groups, vascular cell adhesion molecule-1, plasminogen activator inhibitor-1 | 6 months of: 400 mg of chromium picolinate daily vs. 50,000 IU vitamin D per week vs. combination of 50,000 IU per week vitamin D and 400 mg of chromium picolinate per day vs. placebo | Vitamin D3 significantly reduced homocysteine Vitamin D3 significantly changed the mean concentration of MDA Vitamin D3 significantly decreased the expression of PAI-1 |
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Jespersen, F.E.; Grimm, D.; Krüger, M.; Wehland, M. Current Knowledge of the Impact of Vitamin D in Coronary Artery Disease. Int. J. Mol. Sci. 2025, 26, 5002. https://doi.org/10.3390/ijms26115002
Jespersen FE, Grimm D, Krüger M, Wehland M. Current Knowledge of the Impact of Vitamin D in Coronary Artery Disease. International Journal of Molecular Sciences. 2025; 26(11):5002. https://doi.org/10.3390/ijms26115002
Chicago/Turabian StyleJespersen, Freja Esager, Daniela Grimm, Marcus Krüger, and Markus Wehland. 2025. "Current Knowledge of the Impact of Vitamin D in Coronary Artery Disease" International Journal of Molecular Sciences 26, no. 11: 5002. https://doi.org/10.3390/ijms26115002
APA StyleJespersen, F. E., Grimm, D., Krüger, M., & Wehland, M. (2025). Current Knowledge of the Impact of Vitamin D in Coronary Artery Disease. International Journal of Molecular Sciences, 26(11), 5002. https://doi.org/10.3390/ijms26115002