Lipoprotein(a), Oxidized Phospholipids, and Aortic Valve Microcalcification Assessed by 18F-Sodium Fluoride Positron Emission Tomography and Computed Tomography

被引：45

作者：

Despres, Audrey-Anne ^{[1
,2
]}

Perrot, Nicolas ^{[1
,2
]}

Poulin, Anthony ^{[1
]}

Tastet, Lionel ^{[1
,2
]}

Shen, Mylene ^{[1
,2
]}

Chen, Hao Yu ^{[3
]}

Bourgeois, Raphaelle ^{[1
,2
]}

Trottier, Mikael ^{[1
]}

Tessier, Michel ^{[1
]}

Guimond, Jean ^{[1
]}

Nadeau, Maxime ^{[1
]}

Engert, James C. ^{[3
]}

Theriault, Sebastien ^{[1
,4
]}

Bosse, Yohan ^{[1
,5
]}

Witztum, Joseph L. ^{[6
]}

Couture, Patrick ^{[2
,7
]}

Mathieu, Patrick ^{[1
,8
]}

Dweck, Marc R. ^{[9
]}

Tsimikas, Sotirios ^{[10
]}

Thanassoulis, George ^{[3
]}

Pibarot, Philippe ^{[1
,2
]}

Clavel, Marie-Annick ^{[1
,2
]}

Arsenault, Benoit J. ^{[1
,2
]}

机构：

[1] Inst Univ Cardiol & Pneumol Quebec, Ctr Rech, Y-3106,Pavil Marguerite DYouville, Quebec City, PQ G1V 4G5, Canada

[2] Univ Laval, Dept Med, Fac Med, Quebec City, PQ, Canada

[3] McGill Univ, Hlth Res Ctr, Montreal, PQ, Canada

[4] Univ Laval, Dept Mol Biol Med Biochem & Pathol, Fac Med, Quebec City, PQ, Canada

[5] Univ Laval, Dept Mol Med, Fac Med, Quebec City, PQ, Canada

[6] Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA

[7] CHU Quebec, Ctr Rech, Quebec City, PQ, Canada

[8] Univ Laval, Dept Surg, Fac Med, Quebec City, PQ, Canada

[9] Univ Edinburgh, Ctr Cardiovasc Sci, Edinburgh, Midlothian, Scotland

[10] Univ Calif San Diego, Sulpizio Cardiovasc Ctr, Div Cardiovasc Dis, La Jolla, CA 92093 USA

来源：

CJC OPEN | 2019年 / 1卷 / 03期

基金：

加拿大健康研究院;

关键词：

D O I：

10.1016/j.cjco.2019.03.004

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Lipoprotein(a) (Lp[a]) is the preferential lipoprotein carrier of oxidized phospholipids (OxPLs) and a well-established genetic risk factor for calcific aortic valve stenosis (CAVS). Whether Lp(a) predicts aortic valve microcalcification in individuals without CAVS is unknown. Our objective was to estimate the prevalence of elevated Lp(a) and OxPL levels in patients with CAVS and to determine if individuals with elevated Lp(a) but without CAVS have higher aortic valve microcalcification. Methods: We recruited 214 patients with CAVS from Montreal and 174 patients with CAVS and 108 controls from Qu?ebec City, Canada. In a second group of individuals with high (>= 75 nmol/L, n = 27) or low (<75 nmol/L, n = 28) Lp(a) levels, 18F-sodium fluoride positron emission tomography/computed tomography was performed to determine the difference in mean tissue-to-background ratio (TBR) of the aortic valve. Results: Patients with CAVS had 62.0% higher Lp(a) (median = 28.7, interquartile range [8.2-116.6] vs 10.9 [3.6-28.8] nmol/L, P < 0.0001), 50% higher OxPL-apolipoprotein-B (2.2 [1.3-6.0] vs 1.1 [0.7-2.6] nmol/L, P < 0.0001), and 69.9% higher OxPL-apolipoprotein(a) (7.3 [1.8-28.4] vs 2.2 [0.8-8.4] nmol/L, P < 0.0001) levels compared with individuals without CAVS (all P < 0.0001). Individuals without CAVS but elevated Lp(a) had 40% higher mean TBR compared with individuals with low Lp(a) levels (mean TBR = 1.25 +/- 0.23 vs 1.15 +/- 0.11, P = 0.02). Conclusions: Elevated Lp(a) and OxPL levels are associated with prevalent CAVS in patients studied in an echocardiography laboratory setting. In individuals with elevated Lp(a), evidence of aortic valve microcalcification by 18F-sodium fluoride positron emission tomography/computed tomography is present before the development of clinically manifested CAVS.

引用

页码：131 / 140

页数：10

共 25 条

[1]

Rajamannan N.M., Evans F.J., Aikawa E., Et al., Calcific aortic valve disease: not simply a degenerative process: a review and agenda for research from the National Heart and Lung and Blood Institute Aortic Stenosis Working Group. Executive summary: Calcific aortic valve disease-2011 update, Circulation, 124, pp. 1783-1791, (2011)

[2]

Thanassoulis G., Campbell C.Y., Owens D.S., Et al., Genetic associations with valvular calcification and aortic stenosis, N Engl J Med, 368, pp. 503-512, (2013)

[3]

Arsenault B.J., Boekholdt S.M., Dube M.P., Et al., Lipoprotein(a) levels, genotype, and incident aortic valve stenosis: a prospective Mendelian randomization study and replication in a case-control cohort, Circ Cardiovasc Genet, 7, pp. 304-310, (2014)

[4]

Chen H.Y., Dufresne L., Burr H., Et al., Association of LPA variants with aortic stenosis: a large-scale study using diagnostic and procedural codes from electronic health records, JAMA Cardiol, 3, pp. 18-23, (2018)

[5]

Bouchareb R., Mahmut A., Nsaibia M.J., Et al., Autotaxin derived from lipoprotein(a) and valve interstitial cells promotes inflammation and mineralization of the aortic valve, Circulation, 132, pp. 677-690, (2015)

[6]

Torzewski M., Ravandi A., Yeang C., Et al., Lipoprotein(a)-associated molecules are prominent components in plasma and valve leaflets in calcific aortic valve stenosis, JACC Basic Transl Sci, 2, pp. 229-240, (2017)

[7]

Nsaibia M.J., Boulanger M.C., Bouchareb R., Et al., OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-κB pathway, Cardiovasc Res, 113, pp. 1351-1363, (2017)

[8]

Que X., Hung M.-Y., Yeang C., Et al., Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice, Nature, 558, (2018)

[9]

Nsaibia M.J., Mahmut A., Boulanger M.C., Et al., Autotaxin interacts with lipoprotein(a) and oxidized phospholipids in predicting the risk of calcific aortic valve stenosis in patients with coronary artery disease, J Intern Med, 280, pp. 509-517, (2016)

[10]

Kamstrup R.P., Hung L.M.-Y., Witztum G.J., Tsimikas G.S., Nordestgaard G.B., Oxidized phospholipids and risk of calcific aortic valve disease: the Copenhagen General Population Study, Arterioscler Thromb Vasc Biol, 37, (2017)

← 1 2 3 →