Cholesterol-overloaded high-density lipoproteins particles (HDL-P) may be associated with increased progression of carotid atherosclerosis, according to a study published Jan. 26 in the Journal of the American College of Cardiology. Although other observational studies have suggested that high-density lipoprotein cholesterol (HDL-C) can inversely predict atherosclerotic cardiovascular diseases (ASCVDs), the 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults do not recommend raising HDL-C for the prevention of ASCVD. 

Led by Yue Qi, MD, PhD, the study examined the ratio of HDL-C to HDL-P in participants taken from the Chinese Multi-provincial Cohort Study-Beijing Project. At baseline, there were 930 participants, ages 51 to 67, with complete data from two previous examinations who did not already have cardiovascular disease. Researchers found that the prevalence of carotid plaque was 20 percent at baseline, with the mean HDL-C level and HDL-P number at 1.40 mmol/l and 30.3 µmol/l, respectively.

The results of the study showed that “very high levels of cholesterol-overloaded HDL-P are independently associated with the increased risk of carotid atherosclerosis.” After the five year follow-up period, 53 percent of participants developed new-onset plaque, while 49 percent of participants with no baseline plaque had incidence of new-onset plaque. Further, researchers found that participants who had both the highest HDL-C and the lowest HDL-P numbers were at higher risk for plaque progression than those with both the highest HDL-C and HDL-P numbers.

The authors of the study state that the results “suggest that HDL-C indicates the cargo of HDL particles, and may... reflect the potential for reverse cholesterol transport if the undesirable effects of cholesterol-overloaded HDL-P can be removed.” They conclude that cholesterol-overloaded HDL-P may be a strong indicator of carotid atherosclerosis risk, making an individual with a high HDL-P number more likely to develop atherosclerosis. 

In an accompanying editorial comment, Alan T. Remaley, MD, PhD, notes that “although the results of this study are quite promising and could be readily implemented with existing routine clinical laboratory assays, it is, of course, important to replicate these results in larger studies with longer observational periods. A more careful assessment will also have to be made to show that HDL-C/HDL-P ratio provides additional independent predictive information over other currently used cardiovascular biomarkers, particularly for those subjects at intermediate cardiovascular disease risk, a population on which the test is most likely to be first used. Finally, it will eventually be important to demonstrate, not only an association with atherosclerosis progression, but that the HDL-C/HDL-P ratio is predictive of future cardiovascular disease based on clinical events, such as myocardial infarction, revascularization, and stroke."

Keywords: Arteriosclerosis, Atherosclerosis, Biomarkers, Cardiovascular Diseases, Carotid Artery Diseases, Cholesterol, Cholesterol, HDL, Cohort Studies, Follow-Up Studies, Incidence, Lipoproteins, Lipoproteins, HDL, Myocardial Infarction, Prevalence, Qi, Research Personnel, Risk Factors, Stroke, United States

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