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Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study.
Arterioscler Thromb Vasc Biol. 2017 08; 37(8):1570-1578.AT

Abstract

OBJECTIVE

Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a).

APPROACH AND RESULTS

A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease. OxPL carried by apoB (apolipoprotein B-100; OxPL-apoB) or apolipoprotein(a) (OxPL-apo(a)) containing lipoproteins, lipoprotein(a) levels, LPA kringle IV type 2 repeat, and rs10455872 genetic variants were measured. OxPL-apoB and OxPL-apo(a) levels correlated with lipoprotein(a) levels among cases (r=0.75 and r=0.95; both P<0.001) and controls (r=0.65 and r=0.93; both P<0.001). OxPL-apoB levels associated with risk of CAVD with odds ratios of 1.2 (95% confidence interval [CI]:1.0-1.6) for 34th to 66th percentile levels, 1.6 (95% CI, 1.2-2.1) for 67th to 90th percentile levels, 2.0 (95% CI, 1.3-3.0) for 91st to 95th percentile levels, and 3.4 (95% CI, 2.1-5.5) for levels >95th percentile, versus levels <34th percentile (trend, P<0.001). Corresponding odds ratios for OxPL-apo(a) were 1.2 (95% CI, 1.0-1.5), 1.2(95% CI, 0.9-1.6), 2.1(95% CI, 1.4-3.1), and 2.9(95% CI, 1.9-4.5; trend, P<0.001) and were similar for lipoprotein(a). LPA genotypes associated with OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels and explained 34%, 46%, and 39%, respectively, of the total variation in levels. LPA genotypes associated with risk of CAVD; a doubling in genetically determined OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels associated with odds ratio of CAVD of 1.18 (95% CI, 1.10-1.27), 1.09 (95% CI, 1.05-1.13), and 1.09 (95% CI, 1.05-1.14), respectively, comparable to the corresponding observational estimates of 1.27 (95% CI, 1.16-1.39), 1.13 (95% CI, 1.08-1.18), and 1.11 (95% CI, 1.06-1.17).

CONCLUSIONS

OxPL-apoB and OxPL-apo(a) are novel genetic and potentially causal risk factors for CAVD and may explain the association of lipoprotein(a) with CAVD.

Authors+Show Affiliations

From the Department of Clinical Biochemistry (P.R.K., B.G.N.) and the Copenhagen General Population Study (P.R.K., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Department of Medicine, University of California San Diego, La Jolla (M.-Y.H., J.L.W., S.T.); Department of Internal Medicine, School of Medicine, College of Medicine (M.-Y.H.) and Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (M.-Y.H.), Taipei Medical University, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan (M.-Y.H.); and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.). pia.roerbaek.kamstrup@regionh.dk stsimikas@ucsd.edu.From the Department of Clinical Biochemistry (P.R.K., B.G.N.) and the Copenhagen General Population Study (P.R.K., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Department of Medicine, University of California San Diego, La Jolla (M.-Y.H., J.L.W., S.T.); Department of Internal Medicine, School of Medicine, College of Medicine (M.-Y.H.) and Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (M.-Y.H.), Taipei Medical University, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan (M.-Y.H.); and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.).From the Department of Clinical Biochemistry (P.R.K., B.G.N.) and the Copenhagen General Population Study (P.R.K., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Department of Medicine, University of California San Diego, La Jolla (M.-Y.H., J.L.W., S.T.); Department of Internal Medicine, School of Medicine, College of Medicine (M.-Y.H.) and Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (M.-Y.H.), Taipei Medical University, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan (M.-Y.H.); and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.).From the Department of Clinical Biochemistry (P.R.K., B.G.N.) and the Copenhagen General Population Study (P.R.K., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Department of Medicine, University of California San Diego, La Jolla (M.-Y.H., J.L.W., S.T.); Department of Internal Medicine, School of Medicine, College of Medicine (M.-Y.H.) and Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (M.-Y.H.), Taipei Medical University, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan (M.-Y.H.); and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.). pia.roerbaek.kamstrup@regionh.dk stsimikas@ucsd.edu.From the Department of Clinical Biochemistry (P.R.K., B.G.N.) and the Copenhagen General Population Study (P.R.K., B.G.N.), Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark; Department of Medicine, University of California San Diego, La Jolla (M.-Y.H., J.L.W., S.T.); Department of Internal Medicine, School of Medicine, College of Medicine (M.-Y.H.) and Division of Cardiology, Department of Internal Medicine, Shuang Ho Hospital (M.-Y.H.), Taipei Medical University, Taiwan; Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan (M.-Y.H.); and Faculty of Health and Medical Sciences, University of Copenhagen, Denmark (B.G.N.).

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

28572160

Citation

Kamstrup, Pia R., et al. "Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: the Copenhagen General Population Study." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 37, no. 8, 2017, pp. 1570-1578.
Kamstrup PR, Hung MY, Witztum JL, et al. Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. Arterioscler Thromb Vasc Biol. 2017;37(8):1570-1578.
Kamstrup, P. R., Hung, M. Y., Witztum, J. L., Tsimikas, S., & Nordestgaard, B. G. (2017). Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 37(8), 1570-1578. https://doi.org/10.1161/ATVBAHA.116.308761
Kamstrup PR, et al. Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: the Copenhagen General Population Study. Arterioscler Thromb Vasc Biol. 2017;37(8):1570-1578. PubMed PMID: 28572160.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. AU - Kamstrup,Pia R, AU - Hung,Ming-Yow, AU - Witztum,Joseph L, AU - Tsimikas,Sotirios, AU - Nordestgaard,Børge G, Y1 - 2017/06/01/ PY - 2016/11/16/received PY - 2017/05/17/accepted PY - 2017/6/3/pubmed PY - 2017/8/9/medline PY - 2017/6/3/entrez KW - apolipoproteins B KW - case-control study KW - genotype KW - lipoprotein(a) KW - phospholipids SP - 1570 EP - 1578 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler Thromb Vasc Biol VL - 37 IS - 8 N2 - OBJECTIVE: Lipoprotein(a) is causally associated with calcific aortic valve disease (CAVD). Lipoprotein(a) carries proinflammatory and procalcific oxidized phospholipids (OxPL). We tested whether the CAVD risk is mediated by the content of OxPL on lipoprotein(a). APPROACH AND RESULTS: A case-control study was performed within the Copenhagen General Population Study (n=87 980), including 725 CAVD cases (1977-2013) and 1413 controls free of cardiovascular disease. OxPL carried by apoB (apolipoprotein B-100; OxPL-apoB) or apolipoprotein(a) (OxPL-apo(a)) containing lipoproteins, lipoprotein(a) levels, LPA kringle IV type 2 repeat, and rs10455872 genetic variants were measured. OxPL-apoB and OxPL-apo(a) levels correlated with lipoprotein(a) levels among cases (r=0.75 and r=0.95; both P<0.001) and controls (r=0.65 and r=0.93; both P<0.001). OxPL-apoB levels associated with risk of CAVD with odds ratios of 1.2 (95% confidence interval [CI]:1.0-1.6) for 34th to 66th percentile levels, 1.6 (95% CI, 1.2-2.1) for 67th to 90th percentile levels, 2.0 (95% CI, 1.3-3.0) for 91st to 95th percentile levels, and 3.4 (95% CI, 2.1-5.5) for levels >95th percentile, versus levels <34th percentile (trend, P<0.001). Corresponding odds ratios for OxPL-apo(a) were 1.2 (95% CI, 1.0-1.5), 1.2(95% CI, 0.9-1.6), 2.1(95% CI, 1.4-3.1), and 2.9(95% CI, 1.9-4.5; trend, P<0.001) and were similar for lipoprotein(a). LPA genotypes associated with OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels and explained 34%, 46%, and 39%, respectively, of the total variation in levels. LPA genotypes associated with risk of CAVD; a doubling in genetically determined OxPL-apoB, OxPL-apo(a), and lipoprotein(a) levels associated with odds ratio of CAVD of 1.18 (95% CI, 1.10-1.27), 1.09 (95% CI, 1.05-1.13), and 1.09 (95% CI, 1.05-1.14), respectively, comparable to the corresponding observational estimates of 1.27 (95% CI, 1.16-1.39), 1.13 (95% CI, 1.08-1.18), and 1.11 (95% CI, 1.06-1.17). CONCLUSIONS: OxPL-apoB and OxPL-apo(a) are novel genetic and potentially causal risk factors for CAVD and may explain the association of lipoprotein(a) with CAVD. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/28572160/Oxidized_Phospholipids_and_Risk_of_Calcific_Aortic_Valve_Disease:_The_Copenhagen_General_Population_Study_ L2 - https://www.ahajournals.org/doi/10.1161/ATVBAHA.116.308761?url_ver=Z39.88-2003&amp;rfr_id=ori:rid:crossref.org&amp;rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -