PHILADELPHIA — New research is adding to a growing body of evidence showing the effects that genetics, cholesterol and other lipids in the blood have on coronary heart disease (CHD). Previous research has shown elevated levels of low-density lipoprotein cholesterol (LDLc, commonly known as “bad” cholesterol) are known to cause heart disease, but the effects of other lipids such as high-density lipoprotein cholesterol (HDLc, or “good” cholesterol) and triglycerides (TG) have been less clear. In a new study, published online in the European Heart Journal, an international team led by researchers at the Perelman School of Medicine at the University of Pennsylvania and the Children’s Hospital of Philadelphia, used a novel genetics approach integrated with cardiovascular outcomes and lipid data taken from blood samples from study participants to target specific lipids in the blood. The approach allowed the team to rule out other behavioral or environmental factors that may contribute to heart disease. The results are lending support to existing evidence showing that levels of TG are likely associated with risk of heart disease, while elevated levels of HDLc alone do not provide protection against CHD.
“These results contribute to our current understanding of which blood lipids cause heart disease and which ones don’t,” said Michael Holmes, MD, PhD, research assistant professor of Surgery in the division of Transplant at Penn Medicine. “Knowing that LDLc and TG contribute to an increased CHD risk allows health care providers to better offer individualized treatment plans with drugs that specifically target those lipids.”
Results of the new study were gathered using a recently developed tool called Mendelian randomization (MR), which identifies genes responsible for particular diseases and analyzes genetic variations, while ruling out other behavioral or environmental variables that can be difficult to adjust for in study design. Using genetic risk scores, researchers analyzed genetic data from 62,199 participants in 12 previous studies. More than 12,000 of the participants were found to have experienced an event related to coronary heart disease (CHD).
After analyzing the genetic data, the results of the new study not only confirm that higher levels of LDLc are more likely to cause heart disease, but also show that high levels of TG also cause a higher risk of heart disease, a finding that has previously only been speculated upon. At the same time, there was little evidence to suggest that higher levels of HDLc provided protective effects against heart disease.
While the findings provide an important contribution to existing knowledge on blood lipid traits and risk of CHD, the authors suggest further studies using emerging technologies in the genomics arena are needed to precisely understand the role specific lipids and genetic predispositions play in a patient’s risk of CHD.
“It’s still not clear exactly what role HDLc plays in a patient’s risk of heart disease, or to what extent” said senior author Brendan Keating, PhD, research assistant professor of Pediatrics and Surgery at Penn Medicine and lead clinical data analyst in the Center for Applied Genomics at The Children’s Hospital of Philadelphia. “This requires further testing with new methods like Mendelian randomizing that can account for behavioral or environmental factors and focus specifically on the effects of those cholesterol subtypes.”
Funding for the study came was provided by multiple sources, including the National Institutes of Health (grants N01-HC-65226, HL36310 and NHLBI33014), the UK Medical Research Council and the British Heart Foundation.
For more information on the study design and results, please see the full press release.
Penn Medicine is one of the world's leading academic medical centers, dedicated to the related missions of medical education, biomedical research, and excellence in patient care. Penn Medicine consists of the Raymond and Ruth Perelman School of Medicine at the University of Pennsylvania (founded in 1765 as the nation's first medical school) and the University of Pennsylvania Health System, which together form a $4.9 billion enterprise.
The Perelman School of Medicine has been ranked among the top five medical schools in the United States for the past 17 years, according to U.S. News & World Report's survey of research-oriented medical schools. The School is consistently among the nation's top recipients of funding from the National Institutes of Health, with $409 million awarded in the 2014 fiscal year.
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