Lipoprotein(a) and Oxidized Phospholipids Promote Valve Calcification in Patients With Aortic Stenosis
| Autor: | Zheng, Kang H, Tsimikas, Sotirios, Pawade, Tania, Kroon, Jeffrey, Jenkins, William SA, Doris, Mhairi K, White, Audrey C, Timmers, Nyanza KLM, Hjortnaes, Jesper, Rogers, Maximillian A, Aikawa, Elena, Arsenault, Benoit J, Witztum, Joseph L, Newby, David E, Koschinsky, Marlys L, Fayad, Zahi A, Stroes, Erik SG, Boekholdt, S Matthijs, Dweck, Marc R |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Hyperlipidemias aortic valve stenosis Cardiorespiratory Medicine and Haematology Cardiovascular Risk Assessment Cohort Studies Sex Factors lipoprotein(a) 80 and over Humans Prospective Studies Tomography Phospholipids Proportional Hazards Models Aged Doppler Age Factors Calcinosis Aortic Valve Stenosis Middle Aged Prognosis Survival Analysis X-Ray Computed calcific aortic valve disease Heart Disease Cardiovascular System & Hematology Echocardiography Aortic Valve Positron-Emission Tomography Apolipoprotein B-100 Disease Progression Public Health and Health Services Biomedical Imaging Female oxidized phospholipids Biomarkers valvular interstitial cells Lipoprotein(a) |
| Zdroj: | Journal of the American College of Cardiology, vol 73, iss 17 |
| Popis: | BackgroundLipoprotein(a) [Lp(a)], a major carrier of oxidized phospholipids (OxPL), is associated with an increased incidence of aortic stenosis (AS). However, it remains unclear whether elevated Lp(a) and OxPL drive disease progression and are therefore targets for therapeutic intervention.ObjectivesThis study investigated whether Lp(a) and OxPL on apolipoprotein B-100 (OxPL-apoB) levels are associated with disease activity, disease progression, and clinical events in AS patients, along with the mechanisms underlying any associations.MethodsThis study combined 2 prospective cohorts and measured Lp(a) and OxPL-apoB levels in patients with AS (Vmax >2.0m/s), who underwent baseline 18F-sodium fluoride (18F-NaF) positron emission tomography (PET), repeat computed tomography calcium scoring, and repeat echocardiography. Invitro studies investigated the effects of Lp(a) and OxPL on valvular interstitial cells.ResultsOverall, 145 patients were studied (68% men; age 70.3 ± 9.9 years). On baseline positron emission tomography, patients in the top Lp(a) tertile had increased valve calcification activity compared with those in lower tertiles (n=79; 18F-NaF tissue-to-background ratio of the most diseased segment: 2.16 vs. 1.97; p=0.043). During follow-up, patients in the top Lp(a) tertile had increased progression of valvular computed tomography calcium score (n=51; 309 AU/year [interquartile range: 142 to 483 AU/year] vs. 93 AU/year [interquartile range: 56 to 296 AU/year; p=0.015), faster hemodynamic progression on echocardiography (n=129; 0.23 ± 0.20m/s/year vs. 0.14 ± 0.20m/s/year] p=0.019), and increased risk for aortic valve replacement and death (n=145; hazard ratio: 1.87; 95% CI: 1.13 to 3.08; p=0.014), compared with lower tertiles. Similar results were noted with OxPL-apoB. Invitro, Lp(a) induced osteogenic differentiation of valvular interstitial cells, mediated by OxPL and inhibited with the E06 monoclonal antibody againstOxPL.ConclusionsIn patients with AS, Lp(a) and OxPL drive valve calcification and disease progression. These findings suggest lowering Lp(a) or inactivating OxPL may slow AS progression and provide a rationale for clinical trials to test this hypothesis. |
| Databáze: | OpenAIRE |
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