Searching for a common mechanism for placenta mediated pregnancy complications and cardiovascular disease: role of Lipoprotein (a)

Objective: To investigate Lipoprotein (a) [Lp(a)], a well-know cardiovascular risk factor, in women with history of placenta mediated pregnancy complications (PMPC) compared with healthy uneventful pregnancy women (HW), and the role of LPA functional polymorphisms in modulating both Lp(a) levels and PMPC risk. Design: Retrospective, observational study . Setting: Gender Medicine Clinic, Centre for Atherothrombotic Disease, University Hospital. Patients: 360 women with history of PMPC [154 preeclampsia (PE), 121 stillbirth (SB), 85 small for gestational age (SGA)] and in 270 HW. Intervention(s): None Main Outcome Measure(s): Lp(a) levels measurement and LPA +93C>T and +121G>A polymorphisms genotyping. Results: In PMPCs we observed higher Lp(a) levels than those found in HW (p=0.03), and an association with PMPC risk [OR= 1.93 (1.20-3.09)], also after adjustment for age, familial history of cardiovascular disease, and traditional risk factors. By analyzing Lp(a) concentrations according to each pregnancy complication, we observed significantly higher Lp(a) levels in women with history of SB and PE, conferring a 2.5-fold and a 2-fold increased risk, respectively; no association with SGA was observed. Lp(a) concentrations progressively and significantly increased as LPA unfavorable allelic burden increased; unfavorable allelic burden influenced SB and PE risk. Conclusions: We evidenced, for the first time, an association between high Lp(a) concentrations and history of SB, and we confirmed the role of Lp(a) in PE risk; this well-known atherothrombotic marker might represent one of the possible mechanisms shared by PMPC and cardiovascular disease.