Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
REVIEWS   (Open Access)

Emerging Lipid-Lowering Therapies: A Comprehensive Review of Novel Agents Targeting Hyperlipidemia

Subasini Uthirapathy 1*

+ Author Affiliations

Journal of Angiotherapy 8(10) 1-15 https://doi.org/10.25163/angiotherapy.8109920

Submitted: 17 July 2024  Revised: 29 September 2024  Published: 02 October 2024 

Abstract

Background: Hyperlipidemia is a major risk factor for cardiovascular diseases, often necessitating long-term pharmacological intervention to manage cholesterol and triglyceride levels. Traditional treatments, such as statins and niacin, have been effective but are often associated with adverse effects and limited efficacy in certain populations. The development of novel lipid-lowering therapies, targeting specific mechanisms of lipid metabolism, offers new potential for personalized treatment approaches. Methods: This review examines a range of emerging pharmacological therapies for hyperlipidemia, including PCSK9 inhibitors, CETP inhibitors, ACL inhibitors, MTP inhibitors, APOC3 inhibitors, ANGPTL inhibitors, and antisense oligonucleotides (ASOs). Each class of drugs was evaluated for its mechanism of action, efficacy in clinical trials, and associated side effects. Relevant clinical studies were analyzed to compare their efficacy in reducing LDL cholesterol, raising HDL cholesterol, and improving overall cardiovascular outcomes. Results and Discussion: PCSK9 inhibitors (Alirocumab and Evolocumab) demonstrated a significant 60% reduction in LDL cholesterol levels and improved cardiovascular outcomes when combined with statins. CETP inhibitors, such as Dalcetrapib, increased HDL cholesterol by 31% without affecting LDL cholesterol levels, while Bempedoic acid, an ACL inhibitor, proved effective in lowering cholesterol and glucose levels, especially in statin-intolerant patients. APOC3 inhibitors (Volanesorsen, Olezarsen) successfully reduced triglyceride levels by inhibiting lipoprotein lipase activity. ASO drugs (Mipomersen, Inclisiran) provided gene-targeted therapy for primary hypercholesterolemia, offering a novel therapeutic avenue. ANGPTL inhibitors impacted triglyceride metabolism, and icosapent ethyl significantly reduced cardiovascular risk in statin-treated individuals. These novel therapies have demonstrated significant reductions in LDL and triglyceride levels while improving HDL cholesterol and reducing cardiovascular risks.

Keywords: Hyperlipidemia, PCSK9 inhibitors, CETP inhibitors, Antisense oligonucleotides, Lipid metabolism

References

Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, et al. 2003. Mutations in PCSK 9 cause autosomal dominant hypercholesterolemia. Nat Genet, 34, 154-156.

Altmann, S. W., Davis, H. R., Zhu, L. J. Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption. Science., 2004; 303(5661): 1201–1204. Am Fam Physician. 2011;84(5):551-558.

American Heart Association/American Stroke Association. TIA (Transient Ischemic Attack). Accessed October 6, 2016.

Arnold, M.A., Swanson, B.J., Crowder, C.D., Frankel, W.L., Lam-Himlin, D., Singhi, A.D., Stanich, P.P., Arnold, C.A. Colesevelam and colestipol: novel medication resins in the gastrointestinal tract. Am. J. Surg. Pathol.; 2014; 38(11):1530-7.

Arshad H, Iftikhar A, Waqar K and Fatima Y., (2019) Correlation between Body Mass Index and Lipid Profile in patients with Type 2 Diabetes attending a tertiary care hospital in Peshawar, Pak J Med Sci. May-Jun; 35 (3): 591–597.

Aslesh, T.; Yokota, T. 2020.  Development of Antisense Oligonucleotide Gapmers for the Treatment of Dyslipidemia and Lipo-dystrophy, Methods Mol. Biol, 2176, 69–85.

Aygun, S.; Tokgozoglu, L. 2022. Comparison of Current International Guidelines for the Management of Dyslipidemia. J. Clin. Med, 11, 7249.

Balakumar P, Babbar L. Preconditioning the hyperlipidemic myocardium: fact or fantasy? Cell Signal. 2012;24(3):589–95.

Basatemur, G. L. et al. Vascular smooth muscle cells in atherosclerosis. Nat. Rev. Cardiol. 16, 727–744 (2019).

Bathum L, Depont Christensen R, Engers Pedersen L, Lyngsie Pedersen P, Larsen J, Nexøe J. Association of lipoprotein levels with mortality in subjects aged 50+ without previous diabetes or cardiovascular disease: a population-based register study. Scand J Prim Health Care2013; 31:172-80.

Bei, Y., Zhou, Q., Sun, Q. & Xiao, J. (2015). Exercise as a platform for pharmacotherapy development in cardiac diseases. Current pharmaceutical design, 21, 4409-4416.

Belay, B., Belamarich, P. F., Tom-Revzon, C. The use of statins in pediatrics: knowledge base, limitations, and future directions. Pediatrics.,2006; 119(2): 370–380.

Bellosta, S., Paoletti, R., Corsini, A. Atherosclerosis: Evolving vascular biology and clinical implications, safety of statins: focus on clinical pharmacokinetics and drug interactions. Circulation.,2004; (109): 50-57.

Berthou, L., Duverger, N., Emmanuel, F., Langoue¨t, S., Auwerx, J., Guillouzo, A., Fruchart, J-C., Rubin, E., Dene`fle, P., Staels, B., Branellec, D. Opposite regulation of human versus mouse apolipoprotein A-I by fibrates in human apo A-I transgenic mice.J. Clin. Invest., 1996; 97(11): 2408 –2416.

Binder CJ, Chang MK, Shaw PX et al. Innate and acquired immunity in atherogenesis. Nat Med 2002; 8: 1218–26.

Black, D.D “Development and Physiological Regulation of Intestinal Lipid Absorption. I. Development of intestinal lipid absorption: Cellular events in chylomicron assembly and secretion,” American Journal of Physiology, vol. 293, no. 3, pp. G519–G524, 2007.

Borghi, C.; Fogacci, F.; Agnoletti, D.; Cicero, A.F.G. 2022. Hypertension and Dyslipidemia Combined Therapeutic Approaches. High Blood Press. Cardiovasc. Prev, 29, 221–230.

Bornfeldt, K. E., Linton, M. F., Fisher, E. A. & Guyton, J. R. JCL roundtable: lipids and inflammation in atherosclerosis. J. Clin. Lipido. 15, 3–17 (2021).

Brites, F.; Martin, M.; Guillas, I.; Kontush, A. Antioxidative activity of high-density lipoprotein (HDL): Mechanistic insights into potential clinical benefit. BBA Clin. 2017, 8, 66–77.

Calcaterra, I.; Lupoli, R.; Di Minno, A.; Di Minno, M.N.D. 2022. Volanesorsen to treat severe hypertriglyceridaemia: A pooled analy-sis of randomized controlled trials. Eur. J. Clin. Investig, 52, e13841

Carlson, L.A. Nicotinic acid: the broad-spectrum lipid drug. A 50th anniversary review.J. Intern. Med.,2005;258(2):94-114.

Caslake, M., Packard, C., Gaw, E., Murray, E., Griffin, B., Vallance, B., Shepherd, J. Fenofibrate and LDL metabolic heterogeneity in hypercholesterolemia. Arterioscler.Thromb. Vasc. Biol., 1993; (13): 702–711.

Chen YQ, Zhao SP, Ye HJ. Efficacy and safety of coenzyme A versus fenofibrate in patients with hyperlipidemia: a multicenter, double-blind, double-mimic, randomized clinical trial. Curr Med Res Opin. 2020 Jun;36(6):941-945.

Chen, R.; Lin, S.; Chen, X. The promising novel therapies for familial hypercholesterolemia. J. Clin. Lab. Anal. 2022, 36, e24552.

Cosman F, de Beur SJ, LeBoff M, Lewiecki E, Tanner B, Randall S, et al. Clinician’s guide to prevention and treatment of osteoporosis. Osteoporosis International. 2014;25(10):2359-81.

Dalen JE, Alpert JS, Goldberg RJ, Weinstein RS. The epidemic of the 20(th) centuries: coronary heart disease. Am J Med. 2014 Sep;127(9):807-12. 

Denke, M., Pearson, T., McBride, P. Ezetimibe added to ongoing statin therapy improves LDL-C goal attainment and lipid profile in patients with diabetes or metabolic syndrome. Diab. Vasc. Dis. Res., 2006; 3(2): 93–102.

Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, Thompson A, Butter-worth AS, Sarwar N, Wormser D et al.  Lipid-related markers and cardiovascular disease prediction. JAMA 2012; 307, 2499–2506.

Ding, W.Y.; Protty, M.B.; Davies, I.G.; Lip, G.Y. Relationship between lipoproteins, thrombosis, and atrial fibrillation. Cardiovasc. Res. 2021, 118, 716–731.

Eiland, L. S., Luttrell, P. L. Use of statins for dyslipidemia in the pediatric population.J. Pediatr. Pharmacol. Therap.,2010; 15(3): 160–172.

Ettehad D, Emdin CA, Kiran A, et al., (2016) Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta- analysis. Lancet; 387: 957–967.

Feingold, K.R.; Grunfeld, C. Introduction to Lipids and Lipoproteins; MDText.com, Inc.: South Dartmouth, MA, USA, 2015.

Fenk S, Fischer M, Strack C, Schmitz G, Loew T, Lahmann C, Baessler A. Successful weight reduction improves left ventricular diastolic function and physical performance in severe obesity. Int Heart J. 2015;56(2):196–202.

Ference BA, Ginsberg HN, Graham I, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J2017; 38:2459-72.

Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, Kahn J, Afonso L, Williams, KA, Flack JM. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: A Mendelian randomization analysis. J. Am. Coll. Cardiol. 2012; 60, 2631–2639.

Fisher, E.A. The degradation of apolipoprotein B100: Multiple opportunities to regulate VLDL triglyceride production by different proteolytic pathways. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids 2012, 1821, 778–781.

Frostegard J, Ulfgren AK, Nyberg P et al. Cytokine expression in advanced human atherosclerotic plaques: dominance of pro-inflammatory (Th1) and macrophage-stimulating cytokines. Atherosclerosis 1999; 145: 33–43.

Fruchart, J-C., Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E. Mechanism of action of fibrates on lipid and lipoprotein metabolism. Circulation,1998; 98(19): 2088-2093

Funatsu, T. et al. Prolonged inhibition of cholesterol synthesis by atorvastatin inhibits apo B-100 and triglyceride secretion from HepG2 cells Atherosclerosis (2001).

Ghanwat, G. H. & Sontakke, A. V. (2018). Effect of Vitamin C Supplementation on Anthropometric Measurements, Lipid Profile and Atherogenic Indices in Obese and Non-Obese Individuals. Journal of Clinical & Diagnostic Research, 12.

Ginsberg, H.N.; Packard, C.J.; Chapman, M.J.; Borén, J.; Aguilar-Salinas, C.A.; Averna, M.; Catapano, A.L. Triglyceride-rich lipoproteins and their remnants: Metabolic insights, role in atherosclerotic cardiovascular disease, and emerging therapeutic strategies—A consensus statement from the European Atherosclerosis Society. Eur. Heart J. 2021, 42, 4791–4806.

Giugliano RP, and Sabatine MS. 2015. Are PCSK 9 inhibitors the next breakthrough in the cardiovascular field? J Am Coll Cardiol, 65,2638-2651.

Goldberg, A. S., Hegele, R. A. 2012.  Cholesteryl ester transfer protein inhibitors for dyslipidemia: focus on dalcetrapib. Druges. Devel. Ther., 6, 251–259.

Goldstein, J.L and Brown, M.S “A century of cholesterol and coronaries: from plaques to genes to statins,” Cell, vol. 161, no. 1, pp. 161–172, 2015.

Hansson GK, Libby P, Schonbeck U, Yan ZQ. Innate and adaptive immunity in the pathogenesis of atherosclerosis. Circ Res 2002; 91: 281–91.

Hussain, M., Rava, P., Walsh, M., Rana, M., Jahangir Iqbal, J. 2012. Multiple functions of microsomal triglyceride transfer protein. Nutr. Metab., (9),14-30.

Ignarro, L.J.; Balestrieri, M.L.; Napoli, C. 2007.  Nutrition, physical activity, and cardiovascular disease: An update. Cardiovasc. Res,73, 326–340.

Ilatovskaya, D. V., Halade, G. V. & DeLeon-Pennell, K. Y. Adaptive immunity-driven inflammation and cardiovascular disease. Am. J. Physiol. Heart Circ. Physiol. 317, H1254–H1257 (2019).

Jaipersad, A. S., Lip, G. Y., Silverman, S. & Shantsila, E. The role of monocytes in angiogenesis and atherosclerosis. J. Am. Coll. Cardiol. 63, 1–11 (2014).

Jamal A, Phillips E, Gentzke AS, Homa DM, Babb SD, King BA, Neff LJ. Current Cigarette Smoking Among Adults - United States, 2016. MMWR Morb Mortal Wkly Rep. 2018 Jan 19;67(2):53-59. 

Jayaraman, S.; Pérez, A.; Miñambres, I.; Sánchez-Quesada, J.L.; Gursky, O. Heparin binding triggers human VLDL remodeling by circulating lipoprotein lipase: Relevance to VLDL functionality in health and disease. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids 2022, 1867, 159064.

Jayaraman, S.; Pérez, A.; Miñambres, I.; Sánchez-Quesada, J.L.; Gursky, O. Heparin binding triggers human VLDL remodeling by circulating lipoprotein lipase: Relevance to VLDL functionality in health and disease. Biochim. Biophys. Acta (BBA)-Mol. Cell Biol. Lipids 2022, 1867, 159064.

Jiang, Z. G, Liu, Y, Hussain, M.M, Atkinson, D, and McKnight, C.J.  “Reconstituting initial events during the assembly of apolipoprotein B-containing lipoproteins in a cell-free system,” Journal of Molecular Biology, vol. 383, no. 5, pp. 1181–1194, 2008.

Jung JY, Choi Y, Suh CH, Yoon D, Kim HA. Effect of fenofibrate on uric acid level in patients with gout. Sci Rep. 2018, 13;8(1):16767.

Kadam N, Chiplonkar S, Khadilkar A, Divate U, Khadilkar V. Low bone mass in urban Indian women above 40 years of age: prevalence and risk factors. Gynecological Endocrinology. 2010;26(12):909-17.

Kayikçioglu M, Shahbazova S, Ibrahimov F, Can LH. Cumulative non-HDL-cholesterol burden in patients with hypertriglyceridemia receiving long-term fibrate therapy: Real life data from a lipid clinic cohort. Turk Kardiyol Dern Ars. 2020 Jun;48(4):359-367.

Kersten, S. 2021.  Role and mechanism of the action of angiopoietin-like protein ANGPTL4 in plasma lipid metabolism. J. Lipid Res, 62, 100150.

Kim, K.; Ginsberg, H.N.; Choi, S.H. 2022.  New, Novel Lipid-Lowering Agents for Reducing Cardiovascular Risk: Beyond Statins. Diabetes Metab. J, 46, 517–532.

Kishor, S., Kathiravan, M., Somani, R., Shishoo, C.H. The biology and chemistry of hyperlipidemia. Bioorg. Med. Chem.,2007; 15(14): 4674-4699.

Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. Int J Cardiol. 2013 Oct 15;168(6):5126-34. 

Kosmas, C.E.; Bousvarou, M.D.; Sourlas, A.; Papakonstantinou, E.J.; Peña Genao, E.; Echavarria Uceta, R.; Guzman, E. 2022.  Angiopoietin- Like Protein 3 (ANGPTL3) Inhibitors in the Management of Refractory Hypercholesterolemia. Clin. Pharmacol, 14, 49–59.

Kundu, D., Saikia, M. & Paul, T. (2017). Study of the Correlation between Total Lipid Profile and Glycosylated Hemoglobin Among the Indigenous Population of Guwahati.Int. J. Life. Sci. Scienti. Res, 3, 1175-1180.

L. Goldstein and M. S. Brown, “A century of cholesterol and coronaries: from plaques to genes to statins,” Cell, vol. 161, no. 1, pp. 161–172, 2015.

Lamb, Y.N. 2021. Inclisiran: First Approval. Drugs 2021, 81, 389–395, Erratum in Drugs, 81, 1129.

Langsted, A.; Nordestgaard, B.G. 2019. Antisense Oligonucleotides Targeting Lipoprotein(a). Curr. Atheroscler. Rep, 21, 30.

Li, J. J., Wang, H., Tino, J. A., Robl, J. A., Herpin, T. F., Lawrence, R. M., Biller, S. et al. 2007.  2-hydroxy-Narylbenzenesulfonamides as ATP-citrate lyase inhibitors, Bioorg. Med. Chem. Lett., 17(11),3208–3211.

Llaverías, G., Laguna, J. C., Alegret, M. 2003. Pharmacology of the ACAT inhibitor avasimibe (CI-1011). Cardiovasc. Drug Rev, 21(1), 33-50.

Lloyd-Jones DM, et al., (2017) Focused Update of the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol.2017 Oct 3; 70 (14): 1785-1822.

López-Farré, A. J., Sacristán, D., Zamorano- León, J. J., San-Martín, N.,Macaya, C. 2008.  Inhibition of acyl-CoA cholesterol acyltransferase by F12511 (Eflucimibe): Could it be a new antiatherosclerotic therapeutic? Cardiovasc. Ther, 26(1), 65– 74.

Lucas, J.-M. & Kozlowski, K. F. (2019). The Underutilization of Lifestyle Modifications in Primary Care Medicine. Exercise Medicine, 3, 3.

Ma, Y, Wang, W, Zhang, J, et al., “Hyperlipidemia and atherosclerotic lesion development in Ldlr-deficient mice on a long-term high-fat diet,” PloS One, vol. 7, no. 4, article e35835, 2012.

Ma, Z., Chu, C.-H., Cheng, D. 2009.  A novel direct homogeneous assay for ATP citrate lyase.J. Lipid Res., 50(10), 2131-2135.

Magnin, D. R.,Biller, S. A.,Wetterau, J., Robl, J. A., Dickson, J. K. Jr.,Taunk, P. et al.  2003.  Microsomal triglyceride transfer protein inhibitors: discovery and synthesis of alkyl phosphonates as potent MTP inhibitors and cholesterol lowering agents.Bioorg. Med. Chem. Lett., 13(7), 1337-1340.

Mahley, R. W., Bersot, T. P. Drug therapy for hypercholesterolemia and dyslipidemia, In: Hardman, J.G.; Limbird, L. E. and Gilman, A. G., Goodman & Gilman’s, The Pharmacological Basis of Therapeutics. 10thedn, New York: McGraw Hill, 2001; pp971–1002.

Mansbach, C.M and Gorelick, F “Development and physiological regulation of intestinal lipid absorption. II. Dietary lipid absorption, complex lipid synthesis, and the intracellular packaging and secretion of chylomicrons,” American Journal of Physiology, vol. 293, no. 4, pp. G645–G650, 2007.

Markham, A. 2015.  Alirocumab: First Global Approval. Drugs, 75, 1699–1705.

Marrs, J.C.; Anderson, S.L. 2020. Bempedoic acid for the treatment of dyslipidemia. Drugs Context, 9, 6-5.

Marston, N.A.; Giugliano, R.P.; Melloni, G.E.; Park, J.G.; Morrill, V.; Blazing, M.A.; Ference, B.; Stein, E.; Stroes, E.S.; Braunwald, E.; et al. Association of Apolipoprotein B–Containing Lipoproteins and Risk of Myocardial Infarction in Individuals With and Without Atherosclerosis: Distinguishing Between Particle Concentration, Type, and Content. JAMA Cardiol. 2021, 7, 250–256.

Martin, G., Schoonjans, K., Lefebvre, A., Staels, B., Auwerx, J. Coordinate regulation of the expression of the fatty acid transporter protein (FATP) and acyl CoA synthetase (ACS) genes by PPARα and PPARγ activators. J.Biol. Chem., 1997;272:28210–28217.

Mauricio, D., Castelblanco, E. & Alonso, N. Cholesterol and Inflammation in atherosclerosis: an immune-metabolic hypothesis. Nutrients 12, 2444 (2020).

McCrindle, B.W., et al. Efficacy and safety of atorvastatin in children and adolescents with familial hypercholesterolemia or severe hyperlipidemia: a multicenter, randomized, placebo-controlled trial J Pediatr (2003).

McKeage K, Keating GM. Fenofibrate: a review of its use in dyslipidaemia. Drugs. 2011 Oct 01;71(14):1917-46.

Miller, Y. I. et al. Oxidation-specific epitopes are danger-associated molecular patterns recognized by pattern recognition receptors of innate immunity. Circ. Res. 108, 235–248 (2011).

Mills, E. J., Wu, P., Chong, G., Ghement, I.,Singh, S.,Akl. E. A., Eyawo, O., Guyatt, G., Berwanger, O., Briel, M. Efficacy and safety of statin treatment for cardiovascular disease: a network meta-analysis of 170,255 patients from 76 randomized trials.QJM.,2011; 104(2):109-124.

Nakajima, K.; Tokita, Y.; Tanaka, A.; Takahashi, S. The VLDL receptor plays a key role in the metabolism of postprandial remnant lipoproteins. Clin. Chim. Acta 2019, 495, 382–393.

Nutescu, E. A., Shapiro, N. L. Ezetimibe: a selective cholesterol absorption inhibitor. Pharmacotherapy., 2003; 23(11): 1463-74.

Page MM, Watts GF. 2015. Evolocumab in the treatment of dyslipidemia; pre-clinical and clinical pharmacology. Expert Opin Drug Metab.Toxicol, 11, 1505-1515.

Pathak RK, Mahajan R, Lau DH, Sanders P. The implications of obesity for cardiac arrhythmia mechanisms and management. Can J Cardiol. 2015;31(2):203–10.

Patnode CD, Evans CV, Senger CA, Redmond N, Lin JS. (2019). Behavioral Counseling to Promote a Healthful Diet and Physical Activity for Cardiovascular Disease Prevention in Adults Without Known Cardiovascular Disease Risk Factors: Updated Systematic Review for the U.S. Preventive Services Task Force.

Pattis, P., Wiedermann, C. J. Ezetimibe-associated immune thrombocytopenia.Ann. Pharmacother., 2008; 42(3): 430-433.

Pedro-Botet, J, Millán Núñez-Cortés, J. J. Chillarón, J. A. Flores-le Roux, and J. Rius, “Severity of statin-induced adverse effects on muscle and associated conditions: data from the DAMA study,” Expert Opinion on Drug Safety, 15(12), pp. 1583–1587, 2016.

Porta M, Last JM. A dictionary of public health [Internet]. Vol. 1. Oxford University Press; 2018

Psaty BM, Anderson M, Kronmal RA, et al. The association between lipid levels and the risks of incident myocardial infarction, stroke, and total mortality: the Cardiovascular Health Study. J Am GeriatrSoc2004; 52:1639-47.

Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: Current perspectives ondiagnosis and treatment. Atherosclerosis 2012; 223, 262–268.

Reid RD, McDonnell LA, Riley DL, Mark AE, Mosca L, Beaton L, et al. Effect of an intervention to improve the cardiovascular health of family members of patients with coronary artery disease: a randomized trial. CMAJ. 2014;186(1):23–30.

Rinaldi, C.; Wood, M.J.A. 2018.  Antisense oligonucleotides: The next frontier for treatment of neurological disorders. Nat. Rev. Neu-rol, 14, 9–21.

Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. 2015. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med, 372, 1489-1499.

Rodríguez-Mortera, R.; Caccavello, R.; Garay-Sevilla, M.E.; Gugliucci, A. Higher ANGPTL3, apoC-III, and apoB48 dyslipidemia, and lower lipoprotein lipase concentrations are associated with dysfunctional visceral fat in adolescents with obesity. Clin. Chim. Acta 2020, 508, 61–68.

Roth GA, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, et al. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736–88.

Roy, P., Orecchioni, M. & Ley, K. How the immune system shapes atherosclerosis: roles of innate and adaptive immunity. Nat. Rev. Immunol. (2021).

Russell, D. W. The enzymes, regulation, and genetics of bile acid synthesis, Annu. Rev. Bioch.,2003; (72): 137–174.

S. Cham, H. J. Koslik, and B. A. Golomb, “Mood, personality, and behavior changes during treatment with statins: a case series,” Drug Safety - Case Reports, vol. 3, no. 1, p. 1, 2016.

Safeer, R. S., Lacivita, C.L. Choosing drug therapy for patients with hyperlipidemia.Am. Fam. Physician., 2000; 61(11): 3371-82.

Said MA, Verweij N, van der Harst P. Associations of combined genetic and lifestyle risks with incident cardiovascular disease and diabetes in the UK biobank study. JAMA Cardiol. 2018;3(8):693. This is the largest study to date to investigate the interaction between combined lifestyle and genetic risk factors on CAD–702.

Santos RD, Gidding SS, Hegele RA, Cuchel MA, Barter PJ, Watts GF, Baum SJ, Catapano AL, Chapman MJ, Defesche JC. et al. Defining severe familial hypercholesterolaemia and the implications for clinical management: A consensus statement from the International Atherosclerosis Society Severe Familial Hypercholesterolemia Panel. Lancet Diabetes Endocrinol. 2016; 4, 850–861.

Sharma, M., Tiwari, M., Chandra, R. Bis [3-(4′-substituted phenyl) prop-2-ene] disulfides as a new class of antihyperlipidemic compounds. Bioorg. Med. Chem. Lett., 2004; 14(21); 5347-5350.

Shattat G. F. A Review Article on Hyperlipidemia: Types, Treatments and New Drug Targets. Biomed Pharmacol J 2014;7(2).

Shinkai, H. 2012. Cholesteryl ester transfer-protein modulator and inhibitors and their potential for the treatment of cardiovascular diseases.Vasc. Health risk Manag., (8), 323- 33.

Singh, R. J., Kohli, K., Gupta, A. K., & Gupta, S. (2018). Hyperlipidemia: Treatment Modality and Busting Myths of Dietary Approach. World Journal of Pharmaceutical ResearchSJIF Volume 7, Issue 16, 395-406.

Smith LC, Pownall HJ, Gotto AM Jr. The plasma lipoproteins: structure and metabolism. Annu Rev Biochem. 1978; 47:751–757. 

Sniderman, A.D.; Thanassoulis, G.; Glavinovic, T.; Navar, A.M.; Pencina, M.; Catapano, A.; Ference, B.A. Apolipoprotein B particles and cardiovascular disease: A narrative review. JAMA Cardiol. 2019, 4, 1287–1295.

Soehnlein, O. & Libby, P. Targeting inflammation in atherosclerosis - from experimental insights to the clinic. Nat. Rev. Drug Discov. 20, 589–610 (2021).

Sözen T, Özisik L, Basaran NÇ. An overview and management of osteoporosis. European journal of rheumatology. 2017;4(1):46.

Spagnuolo, C.M.; Hegele, R.A. 2023.  Recent advances in treating hypertriglyceridemia in patients at high risk of cardiovascular disease with apolipoprotein C-III inhibitors. Expert Opin. Pharmacother, 24, 1013–1020.

Sudhakaran S, Bottiglieri T, Tecson KM, Kluger AY, McCullough PA. Alteration of lipid metabolism in chronic kidney disease, the role of novel antihyperlipidemic agents, and future directions. Rev Cardiovasc Med. 2018;19(3):77–88.

Surma, S.; Romanczyk, M.; Filipiak, K.J. 2023.  Angiopoietin-like proteins inhibitors: New horizons in the treatment of atherogenic dyslipidemia and familial hypercholesterolemia. Cardiol. J, 30, 131–142.

Tabas, I. Macrophage death and defective inflammation resolution in atherosclerosis. Nat. Rev. Immunol. 10, 36–46 (2010).

Thygesen K, Alpert JS, Jaffe AS, et al.: Third universal definition of myocardial infarction. Circulation. 2012;126(16):2020–35. 10.1161/CIR.0b013e31826e1058.

Tiwari, S.; Siddiqi, S.A. Intracellular trafficking and secretion of VLDL. Arterioscler. Thromb. Vasc. Biol. 2012, 32, 1079–1086.

Tong, W, Paradise, E. Kim, E, et al., “Clinical investigations of SLx-4090 in combination with metformin in type 2 diabetes,” Diabetes Care, 2010, ADA abstracts.

Tsao CW, Aday AW, Almarzooq ZI, Beaton AZ, Bittencourt MS, Boehme AK, et al. heart disease and Stroke Statistics—2023 Update: A Report from the American Heart Association. Circulation. 2023;147: e93–e621.

Vodnala D, Rubenfire M, Brook RD. Secondary causes of dyslipidemia. Am. J. Cardiol. 2012; 110, 823–825.

Weber C, Badimon L, Mach F, van der Vorst EPC. (2017) Therapeutic strategies for atherosclerosis and atherothrombosis: past, present and future. Thromb Haemost;117: 1258–1264.

Whitmarsh T, Otake Y, Uemura K, Takao M, Sugano N, Sato Y. A crosssectional study on the age-related cortical and trabecular bone changes at the femoral head in elderly female hip fracture patients. Scientific reports.2019;9(1):1-8.

Wick G, Perschinka H, Millonig G. Atherosclerosis as an autoimmune disease: an update. Trends Imanol 2001; 22: 665–9.

Wilson PW., Polonsky TS., Miedema MD., Khera A., Kosinski AS., Kuvin JT., (2019) Systematic Review for the Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. Jun 25; 73 (24): 3210-3227.

Wolf, D. & Ley, K. Immunity and Inflammation in Atherosclerosis. Circ. Res. 124, 315–327 (2019).

Xepapadaki, E.; Zvintzou, E.; Kalogeropoulou, C.; Filou, S.; Kypreos, K.E. Tauhe Antioxidant Function of HDL in Atherosclerosis. Angiology 2020, 71, 112–121.

Yamanashi, Y.; Takada, T.; Yamamoto, H.; Suzuki, H. NPC1L1 facilitates sphingomyelin absorption and regulates diet-induced production of VLDL/LDL-associated S1P. Nutrients 2020, 12, 2641.

Yang, X, Li, Y. Li, Y. et al., “Oxidative Stress-Mediated Atherosclerosis: Mechanisms and Therapies,” Frontiers in Physiology, vol. 8, 2017.

Zmyslowski, A and Szterk, A “Current knowledge on the mechanism of atherosclerosis and pro-atherosclerotic properties of oxysterols,” Lipids in Health and Disease, vol. 16, no. 1, p. 188, 2017.

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