Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery
Eur Heart J (2013) doi: 10.1093/eurheartj/ehs468 First published online: January 12, 2013
Armin Zittermann 1,*; Joachim Kuhn 2; Jens Dreier 2; Cornelius Knabbe 2; Jan F. Gummert 1; Jochen Börgermann 1
1 Clinic for Thoracic and Cardiovascular Surgery, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstrasse 11, Bad Oeynhausen, Germany
2 Institute for Laboratory and Transfusion Medicine, Heart and Diabetes Center North Rhine-Westphalia, Ruhr University Bochum, Georgstrasse 11, Bad Oeynhausen, Germany
↵*Corresponding author. Tel: +49 5731 97 1912, Fax: +49 5731 97 2020, Email: firstname.lastname@example.org
Aims A significant proportion of cardiac surgical patients develop critical post-operative complications. We aimed to investigate the association of pre-operative 25-hydroxyvitamin D (25(OH)D) levels with major cardiac and cerebrovascular events (MACCE) in cardiac surgical patients.
Methods and results From January 2010 to August 2011, we consecutively measured circulating 25(OH)D in 4418 operated patients.
Of the study cohort, 38.0% had deficient 25(OH)D values (<30 nmol/L) and additional 32.3% had insufficient values (30–49.9 nmol/L), whereas only 3.1% had values >100 nmol/L.
The incidence of MACCE was 11.5%. In multivariable-adjusted logistic regression models, the odds ratio of MACCE at deficient, inadequate, and high 25(OH)D levels was 2.23 [95% confidence interval (CI): 1.31–3.79], 1.73 (95% CI: 1.01–2.96) and 2.34 (95% CI: 1.12–4.89), respectively, compared with 25(OH)D levels of 75–100 nmol/L.
A U-shaped association with circulating 25(OH)D was also present for duration of mechanical ventilatory support and intensive care unit stay.
Multivariable-adjusted 6- and 12-month mortality were higher in patients with deficient 25(OH)D levels compared with patients with 25(OH)D levels of 75–100 nmol/L.
Conclusion Deficient 25(OH)D levels are prevalent in cardiac surgical patients in Central Europe and are independently associated with the risk of MACCE. Further research should clarify the potential of vitamin D supplements in reducing cardiovascular risk in vitamin D-deficient patients and also the mechanisms leading to adverse effects on the cardiovascular system in the small group of patients with 25(OH)D levels >100 nmol/L.
Trial registration information: Clinicaltrials.gov identifier number: NCT01552382
- Look at death rate for 1 year after heart surgery (4418 patients)
|Vitamin D Level|
|% with this amount|
of vitamin D
|Death Rate compared |
to 20-40 ng
|< 12 ng||38%||2.23|
Hypothesis 1: Took supplements because not healthy
Most people who have vitamin D levels > 40 ng have been taking supplements.
Many people take supplements because they are not feeling healthy.
Thus those who died more often after the heart surgery might have been those who had poor health prior to the surgery.
Hypothesis 2: Vitamin D levels dropped a lot after surgery
Serum levels of Vitamin D are known to drop dramatically after surgery/trauma.
Individuals with the higher vitamin D levels prior to surgery may have dropped much more than those with lower levels.
The post-surgery dramatic drop from high level, if not compensated for with increased sunshine, UVB, or supplements, may have put those with high levels of vitamin D at risk.
Hypothesis 3: Vitamin A blocked the benefits of vitamin D in the blood
Vitamin A may thwart the ability of vitamin D to reduce risk of osteoporosis – June 2010
Vitamin D protects against lung cancer unless there is excess vitamin A – July 2012
Hypothesis 4: Vitamin D increased or decreased the benefit of the drugs being taken
- Search of all U-Shaped and Mortality 277 hits as of Dec 2013
- Mortality increased with highest levels of vitamin D – article and 4 letters Aug 2012
- 50 percent more elderly deaths when vitamin D under 18 ng or over 40 ng – Aug 2010
- Is 50 ng of vitamin D too high, just right, or not enough has a section on U-Shaped responses
- Is High Dose Vitamin D Harmful – Dec 2012
- Vitamin D and Pancreatic Cancer Risk - No U-Shaped Curve - Mar 2012
- Frailty and vitamin D – U shaped curve – Dec 2010
- Is too much vitamin D bad – possible causes and cures
CLICK HERE for references with authors
- Prognostic impact of previous percutaneous coronary interventions on coronary artery bypass graft surgery: a multicenter analysis. J Thorac Cardiovasc Surg 2009;137:840-845. Abstract/FREE Full Text
- Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass surgery: systematic review with meta-analyses and trial sequential analyses. Eur Heart J 2008;29:2601-2616. Abstract/FREE Full Text
- Independent association of low serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D levels with all-cause and cardiovascular mortality. Arch Intern Med 2008;168:1340-1349. CrossRefMedlineWeb of Science
- Low vitamin D levels predict stroke in patients referred to coronary angiography. Stroke 2008;39:2611-2613. Abstract/FREE Full Text
- Association of vitamin D deficiency with heart failure and sudden cardiac death in a large cross-sectional study of patients referred for coronary angiography. J Clin Endocrinol Metab 2008;93:3927-3935. Abstract/FREE Full Text
- Vitamin D deficiency is associated with sudden cardiac death, combined cardiovascular events, and mortality in haemodialysis patients. Eur Heart J 2010;31:2253-2261. Abstract/FREE Full Text
- Vitamin D deficiency is a predictor of reduced survival in patients with heart failure; vitamin D supplementation improves outcome. Eur J Heart Fail 2012;14:357-366. Abstract/FREE Full Text
- Nonrandomized comparison of coronary artery bypass surgery and percutaneous coronary intervention for the treatment of unprotected left main coronary artery disease in octogenarians. Circulation 2008;118:2374-2381. Abstract/FREE Full Text
- 25-Hydroxyvitamin D and risk of myocardial infarction in men: a prospective study. Arch Intern Med 2008;168:1174-1180. CrossRefMedlineWeb of Science
- 25-Hydroxyvitamin D levels and the risk of mortality in the general population. Arch Intern Med 2008;168:1629-1637. CrossRefMedlineWeb of Science
- High doses of vitamin D to reduce exacerbations in chronic obstructive pulmonary disease: a randomized trial. Ann Intern Med 2012;156:105-114. Medline
- Vitamin D status and mortality risk in chronic kidney disease: a meta-analysis of prospective studies. Am J Kid Dis 2011;58:374-382. MedlineWeb of Science
- IOF Committee of Scientific Advisors (CSA) Nutrition Working Group. Global vitamin D status and determinants of hypovitaminosis D. Osteoporos Int 2009;20:1807-1820. CrossRefMedlineWeb of Science
- HELENA Study Group. Vitamin D status among adolescents in Europe: the Healthy Lifestyle in Europe by Nutrition in Adolescence study. Br J Nutr 2012;107:755-764. CrossRefMedline
- The estimated benefits of vitamin D for Germany. Mol Nutr Food Res 2010;54:1164-1171. Medline
- A Reverse J-Shaped Association of All-Cause Mortality with Serum 25-Hydroxyvitamin D in General Practice, the CopD Study. J Clin Endocrinol Metab 2012;97:2644-2652. Abstract/FREE Full Text
- Low 25-hydroxyvitamin D is associated with increased mortality in female nursing home residents. J Clin Endocrinol Metab 2012;97:E653-E657. Abstract/FREE Full Text
- State-of-the-art vitamin D assays: a comparison of automated immunoassays with liquid chromatography-tandem mass spectrometry methods. Clin Chem 2012;58:531-542. Abstract/FREE Full Text
- IOM (Institute of Medicine). Dietary Reference Intakes for Calcium and Vitamin D. Washington, DC: The National Academies Press; 2011. . Plasma vitamin D and mortality in older men: a community-based prospective cohort study. Am J Clin Nutr 2010;92:841-848. Abstract/FREE Full Text
- Estimation of optimal serum concentrations of 25-hydroxyvitamin D for multiple health outcomes. Am J Clin Nutr 2006;84:18-28. Abstract/FREE Full Text
- Vitamin D deficiency and mortality risk in the general population: a meta-analysis of prospective cohort studies. Am J Clin Nutr 2012;95:91-100. Abstract/FREE Full Text
- Vitamin D, cardiovascular disease and mortality. Clin Endocrinol 2011;75:575-584. CrossRefMedline
- Increasing requests for vitamin D measurement: costly, confusing, and without credibility. Lancet 2012;379:95-96. CrossRefMedlineWeb of Science
- Vitamin D deficiency in critically ill patients. N Engl J Med 2009;360:1912-1914. CrossRefMedline
- Low serum 25-hydroxyvitamin D at critical care initiation is associated with increased mortality. Crit Care Med 2012;40:63-72. CrossRefMedlineWeb of Science
- Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials. BMJ 2009;339:b3692. Abstract/FREE Full Text
- A pooled analysis of vitamin D dose requirements for fracture prevention. N Engl J Med 2012;367:40-49. CrossRefMedline
- Vitamin D supplementation and total mortality: a meta-analysis of randomized controlled trials. Arch Intern Med 2007;167:1730-1737. CrossRefMedline
- Vitamin D supplementation for prevention of mortality in adults. Cochrane Database Syst Rev 2011;7:CD007470. Medline
- Effect of vitamin D supplementation on muscle strength: a systematic review and meta-analysis. Osteoporos Int 2011;22:859-871. Medline
- Circulating 25-hydroxy-vitamin D and risk of cardiovascular disease: a meta-analysis of prospective studies. Circ Cardiovasc Qual Outcomes 2012;5:819-829. Abstract/FREE Full Text
- Seasonal variations in vitamin D status and calcium absorption do not influence bone turnover in young women. Eur J Clin Nutr 1998;52:501-506. CrossRefMedlineWeb of Science
- Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. Abstract/FREE Full Text
- Calcium supplementation and vitamin D: a trigger for adverse cardiovascular events? Future Cardiol 2011;7:725-727. CrossRefMedline
- Observations in vitamin D and dihydrotachysterol poisoning. Dtsch Med Wochenschr 1975;100:415-416. 419–423. [article in German]. CrossRefMedline
- Pharmacokinetics of vitamin D toxicity. Am J Clin Nutr 2008;88:582S-586S. Abstract/FREE Full Text
- Cautious interpretation of the reverse J-shaped association between circulating 25-hydroxyvitamin D and total mortality is necessary. J Clin Endocrinol Metab 2012. [Letter to the Editor] Published online 14 June. Search Google Scholar
- Vitamin D in preventive medicine – are we ignoring the evidence? Br J Nutr 2003;89:552-572. CrossRefMedlineWeb of Science
- APOE ɛ4 is associated with higher vitamin D levels in targeted replacement mice and humans. FASEB J 2011;25:3262-3270. Abstract/FREE Full Text
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