LPA Gene Variants Linked To Cardiac Events Despite Statins

MedicalResearch.com Interview with:

Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203

Dr. Wei-Qi Wei

Wei-Qi Wei, MD, PhD
Assistant Professor
Department of Biomedical Informatics
Vanderbilt University
Nashville, TN 37203

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events.

Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant.

We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway. 

MedicalResearch.com: What should readers take away from your report?

Response: Lipoprotein(a), or Lp(a), has been shown to be an important risk factor for cardiovascular disease. The LPA gene encodes Lp(a). This study shows that variants in LPA add risk of cardiovascular disease independent of statin treatment. Thus, future strategies targeting Lp(a) might be helpful in lowering the residual cardiovascular risk of patients already treated with statins. 

MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: I would like to see the replication of this finding of  the residual risk associated with Lp(a) in large clinical trials. In addition, it will be important to further explore the potential effects of lowering plasma Lp(a) in populations followed in clinical trials.

MedicalResearch.com: Is there anything else you would like to add? 

Response: The study demonstrates the power of genetic-linked longitudinal electronic health records (EHRs) to find links between genetic variation and disease. As the data accumulated within large projects like the NIH’s All of Us Research Program, we should be able to discover more useful information to improve healthcare in a personalized way. 


LPA Variants are Associated with Residual Cardiovascular Risk in Patients Receiving Statins

Wei-Qi Wei, Xiaohui Li, Qiping Feng, Michiaki Kubo, Iftikhar J. Kullo, Peggy L. Peissig, Elizabeth W. Karlson, Gail P. Jarvik, Ming Ta Michael Lee, Ning Shang, Eric A. Larson, Todd Edwards, Christian Shaffer, Jonathan D. Mosley, Shiro Maeda, Momoko Horikoshi, Marylyn Ritchie, Marc S. Williams, Eric B. Larson, David R. Crosslin, Sarah T. Bland, Jennifer A. Pacheco, Laura J. Rasmussen-Torvik, David Cronkite, George Hripcsak, Nancy J. Cox, Russell A. Wilke, C. Michael Stein, Jerome I. Rotter, Yukihide Momozawa, Dan M. Roden, Ronald M. Krauss, Joshua C. Denny
Circulation. 2018;CIRCULATIONAHA.117.031356
Originally published April 27, 2018

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Last Updated on May 18, 2018 by Marie Benz MD FAAD