Background:
The pathophysiology of lipoprotein (a) [Lp(a)] remains obscure. We conducted a phenome wide analysis study (PheWAS) to identify pleiotropic effects of LPA variants.
Methods:
Among 51,843 European-ancestry participants (age 58±16 years, 54% female) of the electronic MEdical Records and Genomics (eMERGE) network we assessed whether
LPA
variants exhibited pleiotropic affects through an electronic health record-based PheWAS. We adjusted significant associations by presence of atherosclerotic cardiovascular disease (ASCVD; defined as a composite of coronary heart disease, cerebrovascular disease, and peripheral artery disease) to determine whether those associations were independent of ASCVD.
Results:
In PheWAS analysis, we tested 864 phecodes with 36 independent
LPA
variants. We identified 21 significant associations with non-ASCVD phenotypes including heart failure, aortic valve stenosis, and chronic kidney disease of which 14 were replicated across independent cohorts. The strength of associations between the
LPA
variant rs10455872 and both heart failure and aortic valve stenosis related phecodes were significantly attenuated after adjustment for ASCVD. However, the association with chronic kidney disease phecode remained independent following adjustment for ASCVD without any attenuation in the estimated odds ratio (Table).
Conclusions:
LPA
genetic variants were associated with aortic valve stenosis, heart failure and chronic kidney disease. The observed association of
LPA
variant rs10455872 with aortic stenosis and heart failure appear to be partially mediated by ASCVD, while the association with chronic kidney disease appears to be independent of ASCVD. Additional studies are needed to elucidate potential mechanisms by which Lp(a) may contribute to the pathogenesis of non-ASCVD disease phenotypes.
Successful Treatment of Congestive Heart Failure Due to Severe Aortic Valve Stenosis With Low Dose Tolvaptan in Elderly Patients
