Carotid Atherosclerosis Predicted by Cholesterol-Overloaded HDL Particles Interview with:
Dong Zhao MD.PhD Deputy Director & Professor andDong Zhao MD.PhD
Deputy Director & Professor and
Dr. Que Qi, MD.PhD Assistant Professor Beijing Institute of Heart,Lung & Blood Vessel Diseases Capital Medical University Beijing Anzhen HospitalDr. Que Qi, MD.PhD Assistant Professor
Beijing Institute of Heart,Lung & Blood Vessel Diseases
Capital Medical University Beijing Anzhen Hospital

Medical Research: What is the background for this study? What are the main findings?

Dr. Dong Zhao: Lower serum HDL-C level used to be considered as a key risk factor of atherosclerotic cardiovascular diseases. This knowledge was based on very consistent findings from researcher of basic science and observational studies of epidemiology. HDL-C has been also introduced as “good cholesterol” to the public. However, this well accepted knowledge was challenged when two large RCTs demonstrated that increased serum HDL-C by CETP inhibitor (ILLUMINATE and dal-OUTCOMES) failed to show benefits on reducing the risk of atherosclerotic cardiovascular disease. Therefore, many researchers questioned whether serum HDL-C can fully represent the capacity of cholesterol reverse transport of HDL particle, an underpinning of the anti-atherogenic function of HDL. And HDL particle number was considered to be better than HDL-C as a proper parameter to assess the function of HDL. In fact, RCTs that increased serum HDL-C substantially by CETP inhibitor had little effect on HDL particle number, thus resulting in increased cholesterol-overloaded HDL particle. Previous experimental studies observed that cholesterol-overloaded HDL particle exerted a negative impact on cholesterol reverse transport. However, it remains unclear whether cholesterol-overloaded HDL is involved in the development of atherosclerosis in humans. In our study, we measured HDL particle number using nuclear magnetic resonance spectroscopy, and calculated the ratio of HDL-C to HDL particles number to estimate the cholesterol content per HDL particle (HDL-C/P ratio). We found that cholesterol-overloaded HDL particles, indicated by high HDL-C/P ratio, are independently associated with the progression of carotid atherosclerosis in asymptomatic individuals from a community-based cohort study of the Chinese Multi-provincial Cohort Study-Beijing Project.

Medical Research: What should clinicians and patients take away from your report?

Dr. Dong Zhao: Our findings suggested that cholesterol-overload HDL particles may predict of atherosclerotic risk despite high HDL-C levels and might explain why high plasma HDL-C levels have failed to avoid ischemic events in some clinical trials. Furthermore, it is strongly advised that consideration of the combination of cholesterol content and HDL particle number, rather than either parameter alone, may help direct future efforts to reduce atherogenesis by lowering the cholesterol content of HDL particles.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Dong Zhao: We hope that our findings will motivate investigators to explore the mechanisms of cholesterol-overloaded HDL in increasing atherosclerotic risk. One possible reason is that cholesterol-overloaded HDL particle exerted a negative impact on the efflux potential of cholesterol from extra-hepatic cells. This possible explanation is supported by the findings from previously published studies. For future research, it would be of interest to identify other possible reasons that may include the hepatic selective uptake of cholesterol, anti-inflammatory and anti-oxidative effects of HDL. Moreover, we will need cardiovascular outcome studies of interventions that unequivocally lower cholesterol-overloaded HDL particle and improve aspects of HDL function to test this hypothesis.


Cholesterol-Overloaded HDL Particles Are Independently Associated With Progression of Carotid Atherosclerosis in a Cardiovascular Disease-Free Population: A Community-Based Cohort Study

Yue Qi, MD, PhD,Jie Fan, MD,Jing Liu, MD, PhD,Wei Wang, MD,Miao Wang, MD,Jiayi Sun, MD,Jun Liu, MD,Wuxiang Xie, PhD,Fan Zhao, PhD,Yan Li, MD,Dong Zhao, MD, PhD,

Department of Epidemiology, Beijing An Zhen Hospital, Capital Medical University, The Key Laboratory of Remodeling-Related Cardiovascular Diseases, Ministry of Education, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, China


Interview with Dong Zhao MD.PhD (2015). Carotid Atherosclerosis Predicted by Cholesterol-Overloaded HDL Particles