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Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study.
Circ Cardiovasc Genet. 2014 Oct; 7(5):650-8.CC

Abstract

BACKGROUND

Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis.

METHODS AND RESULTS

Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol.

CONCLUSIONS

Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease.

Authors+Show Affiliations

From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.).From the Department of Clinical Biochemistry (E.M.O., S.A., B.G.N.), The Copenhagen General Population Study (E.M.O., S.A., B.G.N.), Herlev Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark (S.A., B.G.N.); The Copenhagen City Heart Study, Frederiksberg Hospital, Frederiksberg, Denmark (B.G.N.); and School of Medicine and Pharmacology, University of Western Australia, Perth, Western Australia, Australia (E.M.O.). Boerge.Nordestgaard@regionh.dk.

Pub Type(s)

Journal Article
Observational Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25065375

Citation

Ooi, Esther M., et al. "Elevated Remnant Cholesterol in 25-hydroxyvitamin D Deficiency in the General Population: Mendelian Randomization Study." Circulation. Cardiovascular Genetics, vol. 7, no. 5, 2014, pp. 650-8.
Ooi EM, Afzal S, Nordestgaard BG. Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study. Circ Cardiovasc Genet. 2014;7(5):650-8.
Ooi, E. M., Afzal, S., & Nordestgaard, B. G. (2014). Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study. Circulation. Cardiovascular Genetics, 7(5), 650-8. https://doi.org/10.1161/CIRCGENETICS.113.000416
Ooi EM, Afzal S, Nordestgaard BG. Elevated Remnant Cholesterol in 25-hydroxyvitamin D Deficiency in the General Population: Mendelian Randomization Study. Circ Cardiovasc Genet. 2014;7(5):650-8. PubMed PMID: 25065375.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Elevated remnant cholesterol in 25-hydroxyvitamin D deficiency in the general population: Mendelian randomization study. AU - Ooi,Esther M, AU - Afzal,Shoaib, AU - Nordestgaard,Børge G, Y1 - 2014/07/27/ PY - 2014/7/29/entrez PY - 2014/7/30/pubmed PY - 2015/7/18/medline KW - Mendelian randomization analysis risk factors KW - genetics KW - vitamin D SP - 650 EP - 8 JF - Circulation. Cardiovascular genetics JO - Circ Cardiovasc Genet VL - 7 IS - 5 N2 - BACKGROUND: Low plasma 25-hydroxyvitamin D [25(OH)D] levels are associated with high cardiovascular risk. This may be because that low 25(OH)D levels are associated with high levels of atherogenic lipoproteins, but whether these 2 risk factors are genetically associated is unknown. We tested this hypothesis. METHODS AND RESULTS: Using a Mendelian randomization approach, potential genetic associations between plasma levels of atherogenic lipoproteins and 25(OH)D were examined in ≤85,868 white, Danish individuals in whom we genotyped for variants affecting plasma levels of 25(OH)D, nonfasting remnant cholesterol, low-density lipoprotein-cholesterol, and high-density lipoprotein-cholesterol. Lipoprotein levels were measured in all and 25(OH)D levels in 31,435. A doubling in nonfasting remnant cholesterol levels was observationally and genetically associated with -6.0%(95% confidence interval [CI], -6.5% to -5.5%) and -8.9% (95% CI, -15% to -2.3%) lower plasma 25(OH)D levels. For low-density lipoprotein-cholesterol levels, corresponding values were -4.6% (95% CI, -5.4% to -3.7%) observationally and -11% (95% CI, -29% to +6.9%) genetically. In contrast, a halving in high-density lipoprotein-cholesterol levels was observationally associated with -1.5% (95% CI, -2.2% to -0.7%) lower but genetically associated with +20% (95% CI, +7.4% to +34%) higher plasma 25(OH)D levels. Plasma levels of lipoprotein(a) and 25(OH)D did not associate. Finally, low 25(OH)D levels did not associate genetically with levels of remnant and low-density lipoprotein-cholesterol. CONCLUSIONS: Genetically elevated nonfasting remnant cholesterol is associated with low 25(OH)D levels, whereas genetically reduced high-density lipoprotein-cholesterol is not associated with low 25(OH)D levels. These findings suggest that low 25(OH)D levels observationally is simply a marker for elevated atherogenic lipoproteins and question a role for vitamin D supplementation in the prevention of cardiovascular disease. SN - 1942-3268 UR - https://www.unboundmedicine.com/medline/citation/25065375/Elevated_remnant_cholesterol_in_25_hydroxyvitamin_D_deficiency_in_the_general_population:_Mendelian_randomization_study_ L2 - https://www.ahajournals.org/doi/10.1161/CIRCGENETICS.113.000416?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -