Role of lipoprotein (a) and LPA KIV2 repeat polymorphism in bicuspid aortic valve stenosis and calcification: a proof of concept study
- 89 Downloads
Hemodynamic valvular impairment is a frequent determinant of the natural history of bicuspid aortic valve (BAV). The role of elevated Lp(a) levels and LPA Kringle IV type 2 (KIV-2) size polymorphism in influencing aortic valve calcification and stenosis development in patients with tricuspid aortic valve was recognized. In this study, we investigate the association between Lp(a) and LPA KIV-2 repeat number, and the presence of calcification and stenosis in BAV patients. Sixty-nine patients [79.7% males; median age 45(30–53) yrs], consecutively referred to Center for Cardiovascular Diagnosis or Referral Center for Marfan syndrome or related disorders, AOU Careggi, from June to November 2014, were investigated. For each patient, clinical (ECG and echocardiography) and laboratory [Lp(a) (Immunoturbidimetric assay) and LPA KIV-2 repeat number (real-time PCR)] evaluation were performed. Patients were compared with 69 control subjects. No significant association between Lp(a) circulating levels and LPA KIV-2 repeat number and BAV was evidenced. Among BAV patients, significantly higher Lp(a) levels according to calcification degree were found [no calcifications:78(42–159) mg/L, mild/moderate: 134(69–189) mg/L; severe: 560(286–1511) mg/L, p = 0.008]. Conversely, lower LPA KIV-2 repeat numbers in subjects with more severe calcification degree were observed. Furthermore, higher Lp(a) levels in patients with aortic stenosis [214(67–501) mg/L vs 104(56–169) mg/L, p = 0.043] were also found. In conclusion, present data suggest the potential role for Lp(a) as a possible risk marker useful to stratify, among BAV patients, those with a higher chance to develop valvular calcifications and aortic stenosis.
KeywordsLipoprotein (a) Kringle IV type 2 Bicuspid aortic valve Calcification Stenosis
This research was supported by departmental funds (ex-60%) for scientific research 2016 and 2017 to Prof. Betti Giusti.
Compliance with ethical standards
Conflict of interest
The authors declare that there is no conflict of interest.
Statement of human rights
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.
Written informed consent was obtained from all individual participants included in the study.
- 8.Rajamannan NM, Evans FJ, Aikawa E, Grande-Allen KJ, Demer LL, Heistad DD, Simmons CA, Masters KS, Mathieu P, O’Brien KD, Schoen FJ, Towler DA, Yoganathan AP, Otto CM (2011) 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 diseased 2011 update. Circulation 124:1783–1791CrossRefGoogle Scholar
- 10.Blaser MC, Wei K, Adams RLE, Zhou YQ, Caruso LL, Mirzaei Z, Lam AY, Tam RKK, Zhang H, Heximer SP, Henkelman RM, Simmons CA (2018) Deficiency of natriuretic peptide receptor 2 promotes bicuspid aortic valves, aortic valve disease, left ventricular dysfunction, and ascending aortic dilatations in mice. Circ Res 122:405–416CrossRefGoogle Scholar
- 11.Bozbas H, Yildirir A, Atar I, Pirat B, Eroglu S, Aydinalp A, Ozin B, Muderrisoglu H (2007) Effects of serum levels of novel atherosclerotic risk factors on aortic valve calcification. J Heart Valve Dis 16:387–393Google Scholar
- 13.Bouchareb R, Mahmut A, Nsaibia MJ, Boulanger MC, Dahou A, Lépine JL, Laflamme MH, Hadji F, Couture C, Trahan S, Pagé S, Bossé Y, Pibarot P, Scipione CA, Romagnuolo R, Koschinsky ML, Arsenault BJ, Marette A, Mathieu P (2015) Autotaxin derived from lipoprotein(a) and valve interstitial cells promotes inflammation and mineralization of the aortic valve. Circulation 132:677–690CrossRefGoogle Scholar
- 24.Gotoh T, Kuroda T, Yamasawa M, Nishinaga M, Mitsuhashi T, Seino Y, Nagoh N, Kayaba K, Yamada S, Matsuo H, Hosoe M, Itoh Y, Kawai T, Igarashi M, Shimada K (1995) Correlation between lipoprotein(a) and aortic valve sclerosis assessed by echocardiography (the JMS Cardiac Echo and Cohort Study). Am J Cardiol 76:928–932CrossRefGoogle Scholar
- 26.Capoulade R, Chan KL, Yeang C, Mathieu P, Bossé Y, Dumesnil JG, Tam JW, Teo KK, Mahmut A, Yang X, Witztum JL, Arsenault BJ, Després JP, Pibarot P, Tsimikas S (2015) Oxidized phospholipids, lipoprotein(a), and progression of calcific aortic valve stenosis. J Am Coll Cardiol 66:1236–1246CrossRefGoogle Scholar
- 27.Cao J, Steffen BT, Budoff M, Post WS, Thanassoulis G, Kestenbaum B, McConnell JP, Warnick R, Guan W, Tsai MY (2016) Lipoprotein(a) levels are associated with subclinical calcific aortic valve disease in white and black individuals: the multi-ethnic study of atherosclerosis. Arterioscler Thromb Vasc Biol 36:1003–1009CrossRefGoogle Scholar
- 30.Watts GF, Chan DC, Somaratne R, Wasserman SM, Scott R, Marcovina SM, Barrett PHR (2018) Controlled study of the effect of proprotein convertase subtilisin-kexin type 9 inhibition with evolocumab on lipoprotein(a) particle kinetics. Eur Heart J. https://doi.org/10.1093/eurheartj/ehy122 [Epub ahead of print] Google Scholar