Elevated lipoprotein(a) in mitral and aortic valve calcification and disease: The Copenhagen General Population Study

Abstract

Background and aims: We tested the hypotheses (i) that elevated lipoprotein(a) is causally associated with both mitral and aortic valve calcification and disease, and (ii) that aortic valve calcification mediates the effect of elevated lipoprotein(a) on aortic valve stenosis. Methods: From the Copenhagen General Population study, we included 12,006 individuals who underwent cardiac computed tomography to measure mitral and aortic valve calcification and 85,884 to examine risk of heart valve disease. Participants had information on plasma lipoprotein(a) and genetic instruments associated with plasma lipoprotein(a) to investigate potential causality. Results: At age 70-79 years, 29% and 54% had mitral and aortic valve calcification, respectively. For 10-fold higher lipoprotein(a) levels, multifactorially adjusted odds ratios for mitral and aortic valve calcification were 1.26 (95% confidence interval: 1.13-1.41) and 1.62 (1.48-1.77). For mitral and aortic valve stenosis, corresponding hazard ratios were 0.93 (95%CI:0.40-2.15, 19 events) and 1.54 (1.38-1.71, 1158 events), respectively. For ≤23 versus ≥36 kringle IV type 2 number of repeats, the age and sex adjusted odds ratios for mitral and aortic valve calcification were 1.53 (1.18-1.99) and 2.23 (1.81-2.76). For carriers versus non-carriers of LPA rs10455872, odds ratios for mitral and aortic valve calcification were 1.33 (1.13-1.57) and 1.86 (1.64-2.13). For aortic valve stenosis, 31% (95%CI:16%-76%) of the effect of lipoprotein(a) was mediated through calcification. Conclusions: Elevated lipoprotein(a) was genetically and observationally associated with mitral and aortic valve calcification and aortic valve stenosis. Aortic valve calcification mediated 31% of the effect of elevated lipoprotein(a) on aortic valve stenosis.

Are we seeing the light at the end of the tunnel for high lipoprotein(a)? Lipoprotein(a)

“…Additionally, Lp(a) levels >90 mg/dL is associated with a 3-fold increase in the risk of aortic-valve calcification (48). The Copenhagen General Population Study also presented that elevated Lp(a) is not only associated with the calcification of the aortic valve but also of the mitral valve (OR 1.53) (49). The risk of aortic involvement with high Lp(a) levels is especially important in patients with FH who already have smaller aortic valve areas and increased inflammatory markers, therefore susceptible to accelerated valvular dysfunction even within the normal range of Lp(a) levels (50).…”

Gefährliches Zusammenspiel: erhöhtes Lipoprotein(a) bei fortgeschrittener Niereninsuffizienz

“…So wächst das Risiko für das Auftreten von kardiovaskulären Ereignissen mit steigenden Plasmakonzentration von Lp(a) linear an 5 . Darüber hinaus steht das Risiko für die Entwicklung und die Progression von kalzifizierenden Aortenklappenstenosen in Beziehung zu einer erhöhten Lp(a)-Konzentration im Blut 6 , 7 . Der Einfluss von Lp(a) auf das kardiovaskuläre Risiko ist in der kürzlich erschienenen Konsensuserklärung der European Society of Cardiology (ESC) 3 , 8 sehr übersichtlich zusammengefasst.…”

Coronary artery- and aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms

“…In MPNs a 256-slice CT-scanner (Phillips iCT 256), with 2.5 mm slice thickness was used. In the CGPS cardiac CT was performed using a 320-multidetector CT scanner (Aquilion One, Toshiba Medical Systems, Japan) and for the non-contrast analyses the images were reconstructed in 3.0 mm slice thickness [23,24].…”