This article is more than 5 years old. Information may no longer be current.
Role of HDL in predicting, preventing CVD questionable
Click Here to Manage Email Alerts
AHA Scientific Sessions 2011
ORLANDO, Fla. — Using HDL as both a target for treatment and a predictor for CVD has received a great deal of attention, several speakers said here. Questions remain, however, about its potential place for use in clinical practice.
One important issue discussed by Frank Sacks, MD, of the Harvard School of Public Health in Boston, was the “HDL paradox.” Basic science has identified the predictive functions of HDL and epidemiological studies firmly characterize HDL as a “powerful risk factor,” he said. Even so, several trials indicate that lowering HDL with various medications did not significantly reduce risk for CVD.
Unanswered questions
Questions persist about whether HDL is beneficial or harmful. Alan M. Fogelman, MD, of the David Geffen School of Medicine at University of California, Los Angeles, said, the answer is complicated by the complex nature of HDL. For example, HDL is able to change in the setting of inflammation, converting from anti-inflammatory to pro-inflammatory depending on a patient’s state. Because inflammation may play a role in the development of atherosclerosis, this mutability could affect a patient’s risk for CHD, Fogelman explained. Nevertheless, he noted that only “multiple clinical trials will answer the question of whether HDL is ‘good’ or ‘bad.’”
Considering HDL cholesterol might be even more difficult in patients with diabetes, as low HDL may not only be a consequence but a cause of the disease as well, according to Arnold von Eckardstein, MD, of the University of Zurich, Switzerland. Data from the PROCAM study, for instance, show that participants in the lowest tertile for HDL had a twofold higher risk for developing diabetes compared with those in higher HDL tertiles, he said. Additionally, other trials suggest that HDL can protect beta cells and that dysfunctional HDL metabolism may contribute to the development of type 2 diabetes. Consequently, von Eckardstein said, HDL may be an appropriate therapeutic target for preventing both diabetes and CVD.
In terms of treatment, many researchers have focused their efforts on developing cholesteryl ester transfer protein (CETP) inhibitors, such as torcetrapib (Pfizer), to raise HDL. Although the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial associated torcetrapib with significant toxicity, which halted its development, researchers determined the adverse events were unrelated to CETP inhibition, according to H. Bryan Brewer, Jr., MD, of Washington Cardiovascular Associates and MedStar Research Institute. Now, studies are suggesting that second-generation CETP inhibitors, including anacetrapib (Merck) and dalcetrapib (Hoffman-La Roche), are safe and effective for lowering LDL and raising HDL, Brewer said.
Moving forward
Recently, the concept of raising HDL to lower CVD risk has taken several hits, Daniel J. Rader, MD, of the University of Pennsylvania, said. For example, some genetic studies show that certain variants that raise HDL do not seem to protect against CHD. Similarly, trials indicating no connection between reduced risk for CVD and interventions for raising HDL also serve to debunk this simple “HDL hypothesis.”
Nevertheless, Rader pointed out that HDL still plays a role in reverse cholesterol transport and cholesterol efflux, both of which contribute to prevention of CHD. Instead of discarding HDL altogether, maybe a shift in focus is needed, he said.
“There are quite a few novel approaches to explore, such as targeting and regulating macrophage cholesterol efflux pathways and conducting a genome-wide association study to look for variants relating to HDL,” Rader said. “It is time to abandon the HDL hypothesis and time to move toward an HDL efflux hypothesis that promotes cholesterol efflux and macrophage reverse cholesterol transport to reduce CV events.” – by Melissa Foster
For more information:
- Braun L. HDL-based therapy: The new frontier in atheroprevention. Presented at: American Heart Association Scientific Sessions 2011; Nov. 12-16, 2011; Orlando, Fla.
Disclosure: Dr. Brewer has received honoraria from or has been a speaker, consultant or advisory board member for Abbott, Lilly, Merck, Roche and Sanofi-Aventis. Dr. Fogelman has received grant support from HL-30568, and is an officer and has ownership interest in Bruin Pharma. Dr. Rader has ownership interest in VascularStrategies and Aegerion and has been a consultant, speaker or advisory board member for AstraZeneca, Eli Lilly, Merck, Novartis, Pfizer, Roche and Sanofi-Aventis. Dr. Sacks has received grant support from R3i Foundation, has been an expert witness for Abbott and a consultant or advisory board member for Amgen, Eli Lilly, Merck and Roche. Dr. von Eckardstein reports no relevant financial disclosures.
 |
Follow CardiologyToday.com on Twitter. |