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Cholesterol and CVD risk: beyond quality and density, time to look at typology and number

Cholesterol is a steroid precursor used by the body to keep cells functioning properly and make hormones. But when low-density lipoprotein (LDL) cholesterol levels are too high, cholesterol can accumulate inside blood vessels, forming deposits called plaques. These plaques can eventually lead to blood vessel blockages that cause heart attacks or strokes. HDL cholesterol helps remove cholesterol from blood vessels. According to the CDCs, heart disease is the leading cause of death in the United States. More than 12% of adults. have high total cholesterol levels, and more than 18% have what’s currently considered low levels of HDL cholesterol. For decades, high-density lipoprotein (HDL) cholesterol has been dubbed “good cholesterol” because of its role in moving fats and other cholesterol molecules out of artery walls. People with higher HDL cholesterol levels tend to have lower rates of cardiovascular disease, studies have shown. But recent studies have come to mixed conclusions about the association between HDL cholesterol levels and CVD risk, indicating that also high HDL may pose a threat to blood vessels.

Now, UT Southwestern scientists have analyzed data on more than 15,000 people to better understand the association between HDL cholesterol, heart attacks, and strokes in diverse populations. They found that the number of HDL particles, a little-used measurement of HDL, is a more reliable predictor of heart attack and stroke risk than the standard HDL cholesterol metric. Moreover, they found that among black people, neither HDL measurement was significantly associated with heart attack. For the new research, Anand Rohatgi, MD, Associate Professor, Department of Internal Medicine, explained: “Previous studies have looked at HDL levels in the population as a whole. But we know that sometimes biology differs by gender and race, so we thought it was important to separately tease apart what’s happening in those populations, as well as how HDL is associated with stroke, which has been understudied.” Rohatgi and his colleagues pooled together information on people who had participated in four large, nationwide studies called DHS, MESA, ARCS and PREVED.

In all, the studies included 15,784 people followed over an average of 8 to 12 years. Of the participants, 54 percent were male, 22 percent were black, and their average age was 56 years. By combining all these large existing cohorts, scientists had enough numbers to look at these populations that had been understudied in the past. In addition, the data included two different measurements of HDL: HDL-P levels tally how many particles of HDL are circulating in the blood. HDL-C levels, the standard test, instead quantify how much total HDL cholesterol is inside those particles. Since the number of HDL particles may vary with regards to how much cholesterol they contain, the two measurements can be quite different and are only moderately correlated. In the study, people with the highest HDL-P levels, above 37 mmol/L, had a 37% lower risk of heart attack and a 34% lower risk of stroke than those who had the lowest HDL-P levels. In women, this association was stronger – those with the highest HDL-P levels had a 49% reduction in heart attacks and 46% reduction in stroke.

While HDL-C predicted heart attack risk in the overall pool of people as well as in women, it was not associated with stroke. When the researchers homed in on black participants, the results were different – neither HDL-C nor HDL-P was linked to a black person’s risk of heart attack. Dr. Katvina Singh, first author of the research, commented: “If you’re white, low HDL cholesterol is still a powerful predictor of heart attack and stroke risk, and that has not changed. But if you’re not white, it’s not that straightforward. These risk markers are really relevant in everyday primary care and cardiology. Doctors use cholesterol levels to make decisions like whether a patient goes on medication or not”. The team is planning future studies on the functionality of HDL particles among black people, how HDL-P may be used clinically, and whether HDL-P might be associated with specific subtypes of strokes. According to researchers, a better understanding of how HDL can help predict disease, and how that association varies among populations, is vital to lowering rates of cardiovascular disease.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Thakkar H et al. Lipids Health Dis. 2020 Apr 15; 19(1):75. 

Riggs KA, Joshi PH et al. J Clin Med. 2019 Dec; 8(12):2137. 

Abdullah SM et al. Circulation 2018; 138(21):2315-2325.

Singh K, Rohatgi A. J Thorac Dis. 2018 Jan; 10(1):109-112. 

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di un brevetto sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of a patent concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica, salute e benessere sui siti web salutesicilia.com e medicomunicare.it