Elevated Lp(a) is linked to mitral annular calcification but not regurgitation, propensity-matched study of 66,292 pairs (J Clin Lipidol 2026)

Original title: Lipoprotein(a) is associated with mitral annular calcification but not mitral regurgitation: A propensity-matched study of 66,292 pairs

J Clin Lipidol · 1 April 2026 · 7

Eldawud D, Fahim M, Rattan K, Alwahadneh O, Khouri P, Salciccioli L

Retrospective TriNetX cohort of over 130,000 adults with Lp(a) measured, propensity-matched 1:1 (66,292 pairs) comparing Lp(a) above 50 mg/dL to below 50 mg/dL across 54 variables, testing associations with mitral valve disease using aortic stenosis as a positive control. Elevated Lp(a) was significantly associated with mitral annular calcification (MAC, the primary outcome; HR 1.330, 95% CI 1.172-1.509) and, as expected, with aortic stenosis (HR 1.313, 95% CI 1.175-1.466). No significant associations were found for mitral regurgitation (HR 1.006, 95% CI 0.940-1.077), mitral stenosis (HR 1.178, 95% CI 0.875-1.587), or mitral valve prolapse (HR 1.035, 95% CI 0.863-1.241). The authors conclude elevated Lp(a) is independently associated with mitral annular calcification specifically, not with mitral regurgitation, stenosis or prolapse, warranting prospective studies of causality.

Original abstract

Background: Lipoprotein(a) [Lp(a)] is a genetically determined cardiovascular risk factor increasingly linked to calcific valvular disease. Although its role in aortic stenosis is well established, the association between Lp(a) and mitral valve pathology, particularly mitral annular calcification (MAC), mitral stenosis (MS), and mitral regurgitation (MR), remains uncertain.

Objective: To evaluate the association between elevated Lp(a) levels and mitral valve disease in a large, real-world cohort.

Methods: We conducted a retrospective observational analysis using the TriNetX research network, including over 130,000 adults with available Lp(a) measurements. Patients with Lp(a) >50 mg/dL were propensity score matched 1:1 to those with Lp(a) <50 mg/dL across 54 demographic, clinical, and treatment variables. Valvular outcomes were defined using administrative codes. Kaplan-Meier survival estimates and log-rank tests were calculated in the matched cohorts. The primary outcome was MAC, with MR, MS, and mitral valve prolapse (MVP) as secondary outcomes. AS served as a positive control.

Results: Each matched cohort included 66,292 patients. Elevated Lp(a) was significantly associated with the primary outcome of MAC (hazard ratio [HR] 1.330, 95% CI 1.172-1.509, P < .001). The positive control outcome of AS(Aortic stenosis) was also significant (HR 1.313, 95% CI 1.175-1.466, P < .001). No significant associations were observed for the secondary outcomes of MR (HR 1.006, 95% CI 0.940-1.077, P = .856), MS (HR 1.178, 95% CI 0.875-1.587, P = .280), or MVP (HR 1.035, 95% CI 0.863-1.241, P = .710).

Conclusion: In this large multicenter propensity-matched cohort, elevated Lp(a) was independently associated with MAC but not with MS, MR, or mitral valve prolapse. These findings support a potential role of Lp(a) in mitral annular calcification and highlight the need for prospective studies to clarify causality and clinical implications.

Summary written by lp-a.org from the published abstract; figures as published. Page updated 17 August 2026. Methods.