MedicalResearch.com Interview with:
Ziyad Al-Aly, MD, FASN
Assistant Professor of Medicine
Washington University School of Medicine
Co-Director, Clinical Epidemiology Center
Associate Chief of Staff for Research and Education
Veterans Affairs Saint Louis Health Care System
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: I think the most important, and novel finding is that elevated levels of HDL-cholesterol (which is thought of as the good cholesterol) are associated with increased risk of death. Previously it was thought that high HDL (increased good cholesterol) is a good thing.
We used Big Data approach (over 16 million person-years; 1.7 million people followed for over 9 years) to evaluate the relationship between HDL-Cholesterol (the good cholesterol) and risk of death. We found that low HDL is associated with increased risk of death (which is expected and consistent with prior knowledge). The novel and unexpected finding is the observation that high HDL-Cholesterol is also associated with increased risk of death. The relationship between HDL-Cholesterol levels and risk of death is a U-shaped curve where risk is increased at both ends of the HDL-C values spectrum (at both low and high end); Too low and too high is associated with higher risk of death. The findings may explain why clinical trials aimed at increasing HDL-Cholesterol levels failed to show improvement of clinical outcomes.
This finding was not expected, and has not been reported previously in large epidemiologic studies such as Framingham Heart Study and others. The Framingham Heart study and others significantly advanced our understanding of the relationship between cholesterol parameters (including HDL-Cholesterol) and clinical outcomes. However, these studies are limited in that the number of patients in these cohorts was several thousands which is relatively small compared to what a Big Data approach (millions of patients) enables us to see. Big Data approach allows a more nuanced (a more detailed) examination of the relationship between HDL and risk of death across the full spectrum of HDL levels.
MedicalResearch.com: What should readers take away from your report?
Response: The main take away is that very high levels of HDL-Cholesterol may not lead to better clinical outcomes. “more of a good thing may be actually bad”. An important message here for researchers, and for the public at large is that examining and challenging prior knowledge with a powerful Big Data approach may yield a more nuanced and enhanced understanding.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: We need to understand why high levels of HDL-Cholesterol are associated with increased risk of death, and if this risk is mediated by inflammation or other mechanisms.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Benjamin Bowe, Yan Xie, Hong Xian, Sumitra Balasubramanian, Mohamed A. Zayed, and Ziyad Al-Aly.High Density Lipoprotein Cholesterol and the Risk of All-cause Mortality among U.S. Veterans. Clinical Journal of the American Society of Nephrology, 2016 DOI:10.2215/CJN.00730116
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