High-density lipoproteins (HDL) comprise particles of different size, density and composition and their vasoprotective functions may differ.
In the cardiovascular field, both HDL cholesterol (HDL-C) concentration and HDL particle size are independently associated with cardiovascular risk. In particular, large HDL particles appear to be protective in coronary artery disease. HDL particle (HDL-P) number has been proposed as improved inverse predictor of CVD compared to plasma HDL-C.
HDL-Cholesterol (HDL-C) has been repeatedly inversely related to cardiovascular risk in all epidemiological studies. However, pharmacological trials aimed at increasing HDL-C have failed to demonstrate a beneficial effect on clinical outcomes. Also, some genetic variants associated to increased HDL-C have not been found associated to a decreased cardiovascular risk but those HDL randomization studies are questionable because they disregarded the complexity of lipoprotein metabolism by excluding from their analyses important genes that not exclusively regulate HDL-C levels but also those of other lipoproteins. This has led to the concept that a single measurement of HDL-C does not necessarily reflect the functional properties of HDL particles and their effects against atherosclerosis. Indeed, HDL particles are heterogeneous in size and biochemical composition, and HDL subpopulations might have different functional properties. Numerous recent studies have shown that the atheroprotective properties of HDL are supported by small and medium-sized HDL particles, which were inversely related to cardiovascular risk in various clinical settings.
Larger and smaller HDL particles have been reported to relate differently to lipid transport, as well as to anti-inflammatory and antioxidative functions.
A note on postmenopausal women and HDL-C/Particles:
Elevated HDL-C may not always be cardioprotective in postmenopausal women. The cardioprotective capacity of large HDL-P may adversely compromise close to menopause supporting the importance of assessing how the menopause transition might impact HDL quality and related cardiovascular disease risk later in life.
References:
Parra ES, Panzoldo NB, Zago VH, Scherrer DZ, Alexandre F, Bakkarat J, Nunes VS, Nakandakare ER, Quintão EC, Nadruz W Jr, de Faria EC, Sposito AC. HDL size is more accurate than HDL cholesterol to predict carotid subclinical atherosclerosis in individuals classified as low cardiovascular risk. PLoS One. 2014 Dec 3;9(12):e114212. doi: 10.1371/journal.pone.0114212. PMID: 25470778; PMCID: PMC4254940.
Groenen AG, Bazioti V, van Zeventer IA, Chen L, Groot HE, Balder JW, Zhernakova A, van der Harst P, Rimbert A, Kuivenhoven JA, Fu J, Westerterp M. Large HDL particles negatively associate with leukocyte counts independent of cholesterol efflux capacity: A cross sectional study in the population-based LifeLines DEEP cohort. Atherosclerosis. 2022 Feb;343:20-27. doi: 10.1016/j.atherosclerosis.2022.01.008. Epub 2022 Jan 18. PMID: 35091264.
Singh K, Chandra A, Sperry T, Joshi PH, Khera A, Virani SS, Ballantyne CM, Otvos JD, Dullaart RPF, Gruppen EG, Connelly MA, Ayers CR, Rohatgi A. Associations Between High-Density Lipoprotein Particles and Ischemic Events by Vascular Domain, Sex, and Ethnicity: A Pooled Cohort Analysis. Circulation. 2020 Aug 18;142(7):657-669. doi: 10.1161/CIRCULATIONAHA.120.045713. Epub 2020 Jun 18. PMID: 32804568; PMCID: PMC7425196.
Duparc, T., Ruidavets, JB., Genoux, A. et al. Serum level of HDL particles are independently associated with long-term prognosis in patients with coronary artery disease: The GENES study. Sci Rep 10, 8138 (2020). https://doi.org/10.1038/s41598-020-65100-2
Sokooti S, Flores-Guerrero JL, Kieneker LM, Heerspink HJL, Connelly MA, Bakker SJL, Dullaart RPF. HDL Particle Subspecies and Their Association With Incident Type 2 Diabetes: The PREVEND Study. J Clin Endocrinol Metab. 2021 May 13;106(6):1761-1772. doi: 10.1210/clinem/dgab075. PMID: 33567068; PMCID: PMC8118359.
Drew BG, Rye KA, Duffy SJ, Barter P, Kingwell BA. The emerging role of HDL in glucose metabolism. Nat Rev Endocrinol. 2012;8(4):237-245.
El Khoudary SR, Ceponiene I, Samargandy S, Stein JH, Li D, Tattersall MC, Budoff MJ. HDL (High-Density Lipoprotein) Metrics and Atherosclerotic Risk in Women. Arterioscler Thromb Vasc Biol. 2018 Sep;38(9):2236-2244. doi: 10.1161/ATVBAHA.118.311017. PMID: 30026268; PMCID: PMC6202150.
Jin, Q., Lau, E.S.H., Luk, A.O. et al. High-density lipoprotein subclasses and cardiovascular disease and mortality in type 2 diabetes: analysis from the Hong Kong Diabetes Biobank. Cardiovasc Diabetol 21, 293 (2022). https://doi.org/10.1186/s12933-022-01726-y
Arnold von Eckardstein, The encounter of elevated high-density lipoprotein cholesterol and high blood pressure lowers life expectancy, European Journal of Preventive Cardiology, 2023;, zwad108, https://doi.org/10.1093/eurjpc/zwad108
Tambalis K, Panagiotakos DB, Kavouras SA, Sidossis LS. Responses of blood lipids to aerobic, resistance, and combined aerobic with resistance exercise training: a systematic review of current evidence. Angiology. 2009 Oct-Nov;60(5):614-32. doi: 10.1177/0003319708324927. Epub 2008 Oct 30. PMID: 18974201.
Gao F, Ren Y-J, Shen X-Y, Bian Y-F, Xiao C-S, Li H. Correlation between the high density lipoprotein and its subtypes in coronary heart disease. Cell Physiol Biochem Int J Exp Cell Physiol Biochem Pharmacol. 2016;38(5):1906–14.
Li J-J, Zhang Y, Li S, Cui C-J, Zhu C-G, Guo Y-L, et al. Large HDL subfraction but not HDL-C is closely linked with risk factors, coronary severity and outcomes in a cohort of nontreated patients with stable coronary artery disease: a prospective observational study. Medicine (Baltimore). 2016;95(4):e2600.
In the cardiovascular field, both HDL cholesterol (HDL-C) concentration and HDL particle size are independently associated with cardiovascular risk. In particular, large HDL particles appear to be protective in coronary artery disease. HDL particle (HDL-P) number has been proposed as improved inverse predictor of CVD compared to plasma HDL-C.
Here are five tips to increase large HDL particles:
Engage in aerobic exercise: Regular aerobic exercise, such as running or high-intensity workouts, has been associated with higher HDL levels. Aim for moderate to high-intensity exercises for at least 20 minutes per session. Increasing the duration of exercise has been shown to further boost HDL levels.
Replace unhealthy fats with healthy ones: Incorporate healthy fats into your diet while reducing unhealthy fats. Opt for sources like nuts, all-natural nut butters, seeds, avocado, and fatty fish such as salmon, trout, or sardines. Monounsaturated fats found in foods like avocados, nuts, and plant-based oils can specifically help increase HDL levels.
Quit smoking: Smoking negatively impacts HDL levels. Studies have shown that HDL levels significantly increase after smoking cessation. Seek support from organizations like Smokefree.gov, which provide resources and tips to help quit smoking.
Achieve and maintain a healthy weight: Losing excess weight can improve HDL levels. Start by tracking your food intake and maintaining a food journal. This simple practice can increase weight loss progress. Participants who kept a food journal as part of a nutrition intervention program lost more weight compared to those who didn't keep a record.
Reduce sugar intake and improve carbohydrate quality: High consumption of simple sugars and starches can lead to unfavorable lipid profiles, including low HDL levels. Opt for low-carbohydrate diets or focus on carbohydrate quality by choosing whole grains over refined grains. Limit sugar intake according to the American Heart Association guidelines: 6 teaspoons (or 24 grams) per day for women and less than 9 teaspoons (or 36 grams) per day for men.
Remember to consult with a healthcare professional or registered dietitian for personalized advice and guidance based on your specific health needs.
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