Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review
Abstract
:1. Introduction
2. Updated Epidemiological Data
3. Lipid-Derived Biomarkers
3.1. Low-Density Lipoprotein Cholesterol
3.2. Triglyceride-to-High-Density Lipoprotein Cholesterol Ratio
3.3. Oxylipin
3.4. Lipoprotein-Associated Phospholipase A2 (LP-PLA2)
3.5. Lipoprotein (a)
3.6. Apolipoprotein A-I
3.7. Apolipoprotein B
4. Therapeutic Approaches Targeting Lipid-Derived Biomarkers
5. Future Research Directions
6. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Roth, G.A.; Mensah, G.A.; Johnson, C.O.; Addolorato, G.; Ammirati, E.; Baddour, L.M.; Barengo, N.C.; Beaton, A.Z.; Benjamin, E.J.; Benziger, C.P.; et al. Global Burden of Cardiovascular Diseases and Risk Factors, 1990–2019: Update From the GBD 2019 Study [published correction appears in J. Am. Coll. Cardiol. 2021, 77, 1958–1959]. J. Am. Coll. Cardiol. 2020, 76, 2982–3021. [Google Scholar] [CrossRef]
- Movsisyan, N.K.; Vinciguerra, M.; Medina-Inojosa, J.R.; Lopez-Jimenez, F. Cardiovascular Diseases in Central and Eastern Europe: A Call for More Surveillance and Evidence-Based Health Promotion. Ann. Glob. Health 2020, 86, 21. [Google Scholar] [CrossRef] [PubMed]
- Fan, J.; Li, X.; Yu, X.; Liu, Z.; Jiang, Y.; Fang, Y.; Zong, M.; Suo, C.; Man, Q.; Xiong, L. Global Burden, Risk Factor Analysis, and Prediction Study of Ischemic Stroke, 1990–2030. Neurology 2023, 101, e137–e150. [Google Scholar] [CrossRef] [PubMed]
- Masaebi, F.; Salehi, M.; Kazemi, M.; Vahabi, N.; Looha, M.A.; Zayeri, F. Trend analysis of disability adjusted life years due to cardiovascular diseases: Results from the global burden of disease study 2019. BMC Public Health 2021, 21, 1268. [Google Scholar] [CrossRef] [PubMed]
- Gurková, E.; Štureková, L.; Mandysová, P.; Šaňák, D. Factors affecting the quality of life after ischemic stroke in young adults: A scoping review. Health Qual. Life Outcomes 2023, 21, 4. [Google Scholar] [CrossRef] [PubMed]
- Strilciuc, S.; Grad, D.A.; Radu, C.; Chira, D.; Stan, A.; Ungureanu, M.; Gheorghe, A.; Muresanu, F.D. The economic burden of stroke: A systematic review of cost of illness studies. J. Med. Life 2021, 14, 606–619. [Google Scholar] [CrossRef] [PubMed]
- Lucas-Noll, J.; Clua-Espuny, J.L.; Lleixà-Fortuño, M.; Gavaldà-Espelta, E.; Queralt-Tomas, L.; Panisello-Tafalla, A.; Carles-Lavila, M. The costs associated with stroke care continuum: A systematic review. Health Econ. Rev. 2023, 13, 32. [Google Scholar] [CrossRef] [PubMed]
- Luengo-Fernandez, R.; Violato, M.; Candio, P.; Leal, J. Economic burden of stroke across Europe: A population-based cost analysis. Eur. Stroke J. 2019, 5, 17–25. [Google Scholar] [CrossRef] [PubMed]
- Hajat, C.; Siegal, Y.; Adler-Waxman, A. Clustering and Healthcare Costs With Multiple Chronic Conditions in a US Study. Front. Public Health 2021, 8, 607528. [Google Scholar] [CrossRef]
- Winchester, D.; Cibotti-Sun, M. 2023 Chronic Coronary Disease Guideline-at-a-Glance. J. Am. Coll. Cardiol. 2023, 82, 956–960. [Google Scholar] [CrossRef]
- Kloner, R.A.; Chaitman, B. Angina and Its Management. J. Cardiovasc. Pharmacol. Ther. 2017, 22, 199–209. [Google Scholar] [CrossRef]
- Murray, C.J.L. The Global Burden of Disease Study at 30 years. Nat. Med. 2022, 28, 2019–2026. [Google Scholar] [CrossRef] [PubMed]
- Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.; Cushman, M.; Delling, F.N.; Deo, R.; et al. American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2018 Update: A Report From the American Heart Association. Circulation 2018, 137, e67–e492. [Google Scholar] [CrossRef] [PubMed]
- Saini, V.; Guada, L.; Yavagal, D.R. Global Epidemiology of Stroke and Access to Acute Ischemic Stroke Interventions. Neurology 2021, 97, S6–S16. [Google Scholar] [CrossRef] [PubMed]
- GBD 2019 Bangladesh Burden of Disease Collaborators. The burden of diseases and risk factors in Bangladesh, 1990-2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Glob. Health 2023, 11, e1931–e1942. [Google Scholar] [CrossRef] [PubMed]
- Hewage, S.; Jadamba, A.; Brain, D.; Parsonage, W.; McPhail, S.; Kularatna, S. Global and regional burden of ischemic stroke associated with atrial fibrillation, 2009–2019. Prev. Med. 2023, 173, 107584. [Google Scholar] [CrossRef] [PubMed]
- Pu, L.; Wang, L.; Zhang, R.; Zhao, T.; Jiang, Y.; Han, L. Projected Global Trends in Ischemic Stroke Incidence, Deaths and Disability-Adjusted Life Years From 2020 to 2030. Stroke 2023, 54, 1330–1339. [Google Scholar] [CrossRef]
- Bostan, M.M.; Stătescu, C.; Anghel, L.; Șerban, I.L.; Cojocaru, E.; Sascău, R. Post-Myocardial Infarction Ventricular Remodeling Biomarkers-The Key Link between Pathophysiology and Clinic. Biomolecules 2020, 10, 1587. [Google Scholar] [CrossRef] [PubMed]
- Holmes, M.V.; Ala-Korpela, M. What is ‘LDL cholesterol’? Nat. Rev. Cardiol. 2019, 16, 197–198. [Google Scholar] [CrossRef] [PubMed]
- Itabe, H.; Sawada, N.; Makiyama, T.; Obama, T. Structure and Dynamics of Oxidized Lipoproteins In Vivo: Roles of High-Density Lipoprotein. Biomedicines 2021, 9, 655. [Google Scholar] [CrossRef] [PubMed]
- Yoshida, H.; Ito, K.; Manita, D.; Sato, R.; Hiraishi, C.; Matsui, S.; Hirowatari, Y. Clinical Significance of Intermediate-Density Lipoprotein Cholesterol Determination as a Predictor for Coronary Heart Disease Risk in Middle-Aged Men. Front. Cardiovasc. Med. 2021, 8, 756057. [Google Scholar] [CrossRef]
- Grundy, S.M.; Stone, N.J.; Bailey, A.L.; Beam, C.; Birtcher, K.K.; Blumenthal, R.S.; Braun, L.T.; De Ferranti, S.; Faiella-Tommasino, J.; Forman, D.E.; et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA 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. 2019, 73, e285–e350. [Google Scholar] [CrossRef] [PubMed]
- Yanai, H.; Yoshida, H. Secondary dyslipidemia: Its treatments and association with atherosclerosis. Glob. Health Med. 2021, 3, 15–23. [Google Scholar] [CrossRef] [PubMed]
- Lu, Y.; Cui, X.; Zhang, L.; Wang, X.; Xu, Y.; Qin, Z.; Liu, G.; Wang, Q.; Tian, K.; Lim, K.S.; et al. The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy. Aging Dis. 2022, 13, 491–520. [Google Scholar] [CrossRef]
- Jung, E.; Kong, S.Y.; Ro, Y.S.; Ryu, H.H.; Shin, S.D. Serum Cholesterol Levels and Risk of Cardiovascular Death: A Systematic Review and a Dose-Response Meta-Analysis of Prospective Cohort Studies. Int. J. Environ. Res. Public Health 2022, 19, 8272. [Google Scholar] [CrossRef] [PubMed]
- Liang, Y.; Yan, Z.; Hao, Y.; Wang, Q.; Zhang, Z.; She, R.; Wang, P.; Du, Y.; Lau, J.T.; Dekker, J.; et al. Metabolic syndrome in patients with first-ever ischemic stroke: Prevalence and association with coronary heart disease. Sci. Rep. 2022, 12, 13042. [Google Scholar] [CrossRef] [PubMed]
- Aygun, S.; Tokgozoglu, L. Comparison of Current International Guidelines for the Management of Dyslipidemia. J. Clin. Med. 2022, 11, 7249. [Google Scholar] [CrossRef] [PubMed]
- Xu, L.; Yan, X.; Tang, Z.; Feng, B. Association between circulating oxidized OxLDL/LDL-C ratio and the severity of coronary atherosclerosis, along with other emerging biomarkers of cardiovascular disease in patients with type 2 diabetes. Diabetes Res. Clin. Pract. 2022, 191, 110040. [Google Scholar] [CrossRef] [PubMed]
- Shamloul, G.; Khachemoune, A. An updated review of the sebaceous gland and its role in health and diseases Part 1: Embryology, evolution, structure, and function of sebaceous glands. Dermatol. Ther. 2021, 34, e14695. [Google Scholar] [CrossRef]
- E Kosmas, C.; Martinez, I.; Sourlas, A.; Bouza, K.V.; Campos, F.N.; Torres, V.; Montan, P.D.; Guzman, E. High-density lipoprotein (HDL) functionality and its relevance to atherosclerotic cardiovascular disease. Drugs Context 2018, 7, 212525. [Google Scholar] [CrossRef]
- Franczyk, B.; Rysz, J.; Ławiński, J.; Rysz-Górzyńska, M.; Gluba-Brzózka, A. Is a High HDL-Cholesterol Level Always Beneficial? Biomedicines 2021, 9, 1083. [Google Scholar] [CrossRef]
- Trites, M.J.; Stebbings, B.M.; Aoki, H.; Phanse, S.; Akl, M.G.; Li, L.; Babu, M.; Widenmaier, S.B. HDL functionality is dependent on hepatocyte stress defense factors Nrf1 and Nrf2. Front. Physiol. 2023, 14, 1212785. [Google Scholar] [CrossRef] [PubMed]
- Kosmas, C.E.; Rodriguez Polanco, S.; Bousvarou, M.D.; Papakonstantinou, E.J.; Peña Genao, E.; Guzman, E.; Kostara, C.E. The Triglyceride/High-Density Lipoprotein Cholesterol (TG/HDL-C) Ratio as a Risk Marker for Metabolic Syndrome and Cardiovascular Disease. Diagnostics 2023, 13, 929. [Google Scholar] [CrossRef] [PubMed]
- Nie, G.; Hou, S.; Zhang, M.; Peng, W. High TG/HDL ratio suggests a higher risk of metabolic syndrome among an elderly Chinese population: A cross-sectional study. BMJ Open 2021, 11, e041519. [Google Scholar] [CrossRef]
- Lelis, D.d.F.; Calzavara, J.V.S.; Santos, R.D.; Sposito, A.C.; Griep, R.H.; Barreto, S.M.; Molina, M.d.C.B.; Schmidt, M.I.; Duncan, B.B.; Bensenor, I.; et al. Reference values for the triglyceride to high-density lipoprotein ratio and its association with cardiometabolic diseases in a mixed adult population: The ELSA-Brasil study. J. Clin. Lipidol. 2021, 15, 699–711. [Google Scholar] [CrossRef] [PubMed]
- Nosrati, M.; Safari, M.; Alizadeh, A.; Ahmadi, M.; Mahrooz, A. The Atherogenic Index Log (Triglyceride/HDL-Cholesterol) as a Biomarker to Identify Type 2 Diabetes Patients with Poor Glycemic Control. Int. J. Prev. Med. 2021, 12, 160. [Google Scholar] [PubMed]
- Sato, F.; Nakamura, Y.; Kayaba, K.; Ishikawa, S. TG/HDL-C ratio as a predictor of stroke in the population with healthy BMI: The Jichi Medical School Cohort Study. Nutr. Metab. Cardiovasc. Dis. 2022, 32, 1872–1879. [Google Scholar] [CrossRef] [PubMed]
- Coban, E.K. Can TG/HDL Ratio be an Accurate Predictor in the Determination of the Risk of Cerebrovascular Events in Youngsters? Sisli Etfal Hastan. Tıp Bul. 2018, 52, 201–205. [Google Scholar] [CrossRef] [PubMed]
- Nam, K.W.; Kwon, H.M.; Jeong, H.Y.; Park, J.H.; Kwon, H.; Jeong, S.M. High triglyceride/HDL cholesterol ratio is associated with silent brain infarcts in a healthy population. BMC Neurol. 2019, 19, 147. [Google Scholar] [CrossRef] [PubMed]
- Deng, Q.W.; Li, S.; Wang, H.; Lei, L.; Zhang, H.Q.; Gu, Z.T.; Xing, F.L.; Yan, F.L. The Short-term Prognostic Value of the Triglyceride-to-high-density Lipoprotein Cholesterol Ratio in Acute Ischemic Stroke. Aging Dis. 2018, 9, 498–506. [Google Scholar] [CrossRef]
- Sugimoto, K.; Allmann, S.; Kolomiets, M.V. Editorial: Oxylipins: The Front Line of Plant Interactions. Front. Plant Sci. 2022, 13, 878765. [Google Scholar] [CrossRef]
- Le, D.E.; García-Jaramillo, M.; Bobe, G.; Magana, A.A.; Vaswani, A.; Minnier, J.; Jump, D.B.; Rinkevich, D.; Alkayed, N.J.; Maier, C.S.; et al. Plasma Oxylipins: A Potential Risk Assessment Tool in Atherosclerotic Coronary Artery Disease. Front. Cardiovasc. Med. 2021, 8, 645786. [Google Scholar] [CrossRef] [PubMed]
- Misheva, M.; Johnson, J.; McCullagh, J. Role of Oxylipins in the Inflammatory-Related Diseases NAFLD, Obesity, and Type 2 Diabetes. Metabolites 2022, 12, 1238. [Google Scholar] [CrossRef] [PubMed]
- Shinto, L.H.; Raber, J.; Mishra, A.; Roese, N.; Silbert, L.C. A Review of Oxylipins in Alzheimer’s Disease and Related Dementias (ADRD): Potential Therapeutic Targets for the Modulation of Vascular Tone and Inflammation. Metabolites 2022, 12, 826. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Gu, Y.; Kumar, S.; Amin, S.; Guo, Q.; Wang, J.; Fang, C.-L.; Cao, X.; Wan, M. Oxylipin-PPARγ-initiated adipocyte senescence propagates secondary senescence in the bone marrow. Cell Metab. 2023, 35, 667–684.e6. [Google Scholar] [CrossRef] [PubMed]
- Yu, D.; Liang, N.; Zebarth, J.; Shen, Q.; Ozzoude, M.; Goubran, M.; Rabin, J.S.; Ramirez, J.; Scott, C.J.M.; Gao, F.; et al. Soluble Epoxide Hydrolase Derived Linoleic Acid Oxylipins, Small Vessel Disease Markers, and Neurodegeneration in Stroke. J. Am. Heart Assoc. 2023, 12, e026901. [Google Scholar] [CrossRef] [PubMed]
- Teder, T.; Haeggström, J.Z.; Airavaara, M.; Lõhelaid, H. Cross-talk between bioactive lipid mediators and the unfolded protein response in ischemic stroke. Prostaglandins Other Lipid Mediat. 2023, 168, 106760. [Google Scholar] [CrossRef] [PubMed]
- Bonetti, N.R.; Liberale, L.; Akhmedov, A.; Pasterk, L.; Gobbato, S.; Puspitasari, Y.M.; Vukolic, A.; Saravi, S.S.S.; Coester, B.; Horvath, C.; et al. Long-term dietary supplementation with plant-derived omega-3 fatty acid improves outcome in experimental ischemic stroke. Atherosclerosis 2021, 325, 89–98. [Google Scholar] [CrossRef] [PubMed]
- Xu, Q.; Du, L.; Gu, H.; Ji, M.; Zhan, L. The effect of omega-3 polyunsaturated fatty acids on stroke treatment and prevention: A systematic review and meta-analysis. Nutr. Hosp. 2022, 39, 924–935. [Google Scholar] [CrossRef] [PubMed]
- Huang, F.; Wang, K.; Shen, J. Lipoprotein-associated phospholipase A2: The story continues. Med. Res. Rev. 2020, 40, 79–134. [Google Scholar] [CrossRef]
- Mourouzis, K.; Siasos, G.; Oikonomou, E.; Zaromitidou, M.; Tsigkou, V.; Antonopoulos, A.; Bletsa, E.; Stampouloglou, P.; Vlasis, K.; Vavuranakis, M.; et al. Lipoprotein-associated phospholipase A2 levels, endothelial dysfunction and arterial stiffness in patients with stable coronary artery disease. Lipids Health Dis. 2021, 20, 12. [Google Scholar] [CrossRef]
- Cao, J.; Yan, P.; Zhou, Y.; Zhou, X.; Sun, Z.; Zhu, X.Q. Clinical Utility of the Serum Level of Lipoprotein-Related Phospholipase A2 in Acute Ischemic Stroke With Cerebral Artery Stenosis. Front. Neurol. 2021, 12, 642483. [Google Scholar] [CrossRef]
- Li, X.; Xu, L.; Xu, Z. The diagnostic and prognostic performance of Lp-PLA2 in acute ischemic stroke. Med. Clin. 2021, 156, 437–443. [Google Scholar] [CrossRef]
- Qiao, J.; Zhou, K.; Huang, C.; Fu, S.; Xing, Y.; Zhang, B. Comparison of serum Lp-PLA2 levels in ischemic stroke patients with H-type hypertension or non-H-type hypertension. J. Clin. Lab. Anal. 2020, 34, e23068. [Google Scholar] [CrossRef]
- Li, Y.; Wang, W.; Yang, H.; Guo, W.; Feng, J.; Yang, D.; Guo, L.; Tan, G. Negative correlation between early recovery and lipoprotein-associated phospholipase A2 levels after intravenous thrombolysis. J. Int. Med. Res. 2022, 50, 3000605221093303. [Google Scholar] [CrossRef] [PubMed]
- Ugovšek, S.; Šebeštjen, M. Lipoprotein(a)-The Crossroads of Atherosclerosis, Atherothrombosis and Inflammation. Biomolecules 2021, 12, 26. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Wang, Y.; Gong, F.; Yu, X.; Zhang, T. A novel deletion mutation in the LPA gene in a middle-aged woman with ischaemic stroke. BMC Med. Genom. 2021, 14, 132. [Google Scholar] [CrossRef]
- Klingel, R.; Heibges, A.; Fassbender, C. Lipoprotein(a) and mortality-a high risk relationship. Clin. Res. Cardiol. Suppl. 2019, 14 (Suppl. 1), 13–19. [Google Scholar] [CrossRef]
- Riches, K.; Porter, K.E. Lipoprotein(a): Cellular Effects and Molecular Mechanisms. Cholesterol 2012, 2012, 923289. [Google Scholar] [CrossRef] [PubMed]
- Nurmohamed, N.S.; Moriarty, P.M.; Stroes, E.S. Considerations for routinely testing for high lipoprotein(a). Curr. Opin. Lipidol. 2023, 34, 174–179. [Google Scholar] [CrossRef]
- Liu, H.-H.; Guo, Y.-L.; Zhu, C.-G.; Wu, N.-Q.; Gao, Y.; Xu, R.-X.; Dong, Q.; Qian, J.; Dou, K.-F.; Li, J.-J. Synergistic effect of the commonest residual risk factors, remnant cholesterol, lipoprotein(a), and inflammation, on prognosis of statin-treated patients with chronic coronary syndrome. J. Transl. Med. 2022, 20, 243. [Google Scholar] [CrossRef]
- Leistner, D.M.; Laguna-Fernandez, A.; Haghikia, A.; Abdelwahed, Y.S.; Schatz, A.S.; Erbay, A.; Roehle, R.; Fonseca, A.F.; Ferber, P.; Landmesser, U. Impact of elevated lipoprotein(a) on coronary artery disease phenotype and severity. Eur. J. Prev. Cardiol. 2024, zwae007. [Google Scholar] [CrossRef]
- Brosolo, G.; Da Porto, A.; Marcante, S.; Picci, A.; Capilupi, F.; Capilupi, P.; Bulfone, L.; Vacca, A.; Bertin, N.; Vivarelli, C.; et al. Lipoprotein(a): Just an Innocent Bystander in Arterial Hypertension? Int. J. Mol. Sci. 2023, 24, 13363. [Google Scholar] [PubMed]
- Kumar, P.; Swarnkar, P.; Misra, S.; Nath, M. Lipoprotein (a) level as a risk factor for stroke and its subtype: A systematic review and meta-analysis. Sci. Rep. 2021, 11, 15660. [Google Scholar] [CrossRef] [PubMed]
- Jiang, X.; Xu, J.; Hao, X.; Xue, J.; Li, K.; Jin, A.; Lin, J.; Meng, X.; Zheng, L.; Wang, Y. Elevated lipoprotein(a) and lipoprotein-associated phospholipase A2 are associated with unfavorable functional outcomes in patients with ischemic stroke. J. Neuroinflamm. 2021, 18, 307. [Google Scholar]
- Bhale, A.S.; Venkataraman, K. Leveraging knowledge of HDLs major protein ApoA1: Structure, function, mutations, and potential therapeutics. Biomed. Pharmacother. Biomed. Pharmacother. 2022, 154, 113634. [Google Scholar] [CrossRef]
- Georgila, K.; Vyrla, D.; Drakos, E. Apolipoprotein A-I (ApoA-I), Immunity, Inflammation and Cancer. Cancers 2019, 11, 1097. [Google Scholar] [CrossRef]
- Karjalainen, M.K.; Holmes, M.V.; Wang, Q.; Anufrieva, O.; Kähönen, M.; Lehtimäki, T.; Havulinna, A.S.; Kristiansson, K.; Salomaa, V.; Perola, M.; et al. Apolipoprotein A-I concentrations and risk of coronary artery disease: A Mendelian randomization study. Atherosclerosis 2020, 299, 56–63. [Google Scholar] [CrossRef]
- Abudukeremu, A.; Huang, C.; Li, H.; Sun, R.; Liu, X.; Wu, X.; Xie, X.; Huang, J.; Zhang, J.; Bao, J.; et al. Efficacy and Safety of High-Density Lipoprotein/Apolipoprotein A1 Replacement Therapy in Humans and Mice With Atherosclerosis: A Systematic Review and Meta-Analysis. Front. Cardiovasc. Med. 2021, 8, 700233. [Google Scholar] [CrossRef]
- Ohtani, R.; Nirengi, S.; Sakane, N. Association Between Serum Apolipoprotein A1 Levels, Ischemic Stroke Subtypes and Plaque Properties of the Carotid Artery. J. Clin. Med. Res. 2020, 12, 598–603. [Google Scholar] [CrossRef]
- Cole, J.; Zubirán, R.; Wolska, A.; Jialal, I.; Remaley, A.T. Use of Apolipoprotein B in the Era of Precision Medicine: Time for a Paradigm Change? J. Clin. Med. 2023, 12, 5737. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef] [PubMed]
- Johannesen, C.D.L.; Mortensen, M.B.; Langsted, A.; Nordestgaard, B.G. Apolipoprotein B and Non-HDL Cholesterol Better Reflect Residual Risk Than LDL Cholesterol in Statin-Treated Patients. J. Am. Coll. Cardiol. 2021, 77, 1439–1450. [Google Scholar] [CrossRef] [PubMed]
- Marston, N.A.; Giugliano, R.P.; Melloni, G.E.M.; 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. 2022, 7, 250–256. [Google Scholar] [CrossRef] [PubMed]
- Deng, F.; Li, D.; Lei, L.; Yang, Q.; Li, Q.; Wang, H.; Deng, J.; Zheng, Q.; Jiang, W. Association between apolipoprotein B/A1 ratio and coronary plaque vulnerability in patients with atherosclerotic cardiovascular disease: An intravascular optical coherence tomography study. Cardiovasc. Diabetol. 2021, 20, 188. [Google Scholar] [CrossRef] [PubMed]
- Au, A.; Griffiths, L.R.; Irene, L.; Kooi, C.W.; Wei, L.K. The impact of APOA5, APOB, APOC3 and ABCA1 gene polymorphisms on ischemic stroke: Evidence from a meta-analysis. Atherosclerosis 2017, 265, 60–70. [Google Scholar] [CrossRef] [PubMed]
- Sun, Y.; Hou, X.H.; Wang, D.D.; Ma, Y.H.; Tan, C.C.; Sun, F.R.; Cui, M.; Dong, Q.; Tan, L.; Yu, J.T. Apolipoprotein B/AI ratio as an independent risk factor for intracranial atherosclerotic stenosis. Aging 2019, 11, 6851–6862. [Google Scholar] [CrossRef] [PubMed]
- O’donnell, M.J.; McQueen, M.; Sniderman, A.; Pare, G.; Wang, X.; Hankey, G.J.; Rangarajan, S.; Chin, S.L.; Rao-Melacini, P.; Ferguson, J.; et al. Association of Lipids, Lipoproteins, and Apolipoproteins with Stroke Subtypes in an International Case Control Study (INTERSTROKE). J. Stroke 2022, 24, 224–235. [Google Scholar] [CrossRef]
- Feingold, K.R. Cholesterol Lowering Drugs. In Endotext; Feingold, K.R., Anawalt, B., Blackman, M.R., Eds.; MDText.com, Inc.: South Dartmouth, MA, USA, 2021. [Google Scholar]
- Laakso, M.; Fernandes Silva, L. Statins and risk of type 2 diabetes: Mechanism and clinical implications. Front. Endocrinol. 2023, 14, 1239335. [Google Scholar] [CrossRef]
- Yin, Y.; Zhang, L.; Marshall, I.; Wolfe, C.; Wang, Y. Statin Therapy for Preventing Recurrent Stroke in Patients with Ischemic Stroke: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Observational Cohort Studies. Neuroepidemiology 2022, 56, 240–249. [Google Scholar] [CrossRef]
- Yu, M.; Liang, C.; Kong, Q.; Wang, Y.; Li, M. Efficacy of combination therapy with ezetimibe and statins versus a double dose of statin monotherapy in participants with hypercholesterolemia: A meta-analysis of literature. Lipids Health Dis. 2020, 19, 1. [Google Scholar] [CrossRef]
- Wang, Y.; Zhan, S.; Du, H.; Li, J.; Khan, S.U.; Aertgeerts, B.; Guyatt, G.; Hao, Q.; Bekkering, G.; Li, L.; et al. Safety of ezetimibe in lipid-lowering treatment: Systematic review and meta-analysis of randomised controlled trials and cohort studies. BMJ Med. 2022, 1, e000134. [Google Scholar] [CrossRef] [PubMed]
- Stanciu, M.-C.; Nichifor, M.; Teacă, C.-A. Bile Acid Sequestrants Based on Natural and Synthetic Gels. Gels 2023, 9, 500. [Google Scholar] [CrossRef] [PubMed]
- Esan, O.; Viljoen, A.; Wierzbicki, A.S. Colesevelam—A bile acid sequestrant for treating hypercholesterolemia and improving hyperglycemia. Expert Opin. Pharmacother. 2022, 23, 1363–1370. [Google Scholar] [CrossRef] [PubMed]
- Ruscica, M.; Greco, M.F.; Ferri, N.; Corsini, A. Lipoprotein(a) and PCSK9 inhibition: Clinical evidence. Eur. Heart J. Suppl. J. Eur. Soc. Cardiol. 2020, 22 (Suppl. L), L53–L56. [Google Scholar] [CrossRef] [PubMed]
- Hajar, R. PCSK 9 Inhibitors: A Short History and a New Era of Lipid-lowering Therapy. Heart Views 2019, 20, 74–75. [Google Scholar] [CrossRef]
- Nissen, S.E.; Lincoff, A.M.; Brennan, D.; Ray, K.K.; Mason, D.; Kastelein, J.J.; Thompson, P.D.; Libby, P.; Cho, L.; Plutzky, J.; et al. Bempedoic Acid and Cardiovascular Outcomes in Statin-Intolerant Patients. N. Engl. J. Med. 2023, 388, 1353–1364. [Google Scholar] [CrossRef] [PubMed]
- Larrey, D.; D’Erasmo, L.; O’Brien, S.; Arca, M. Italian Working Group on Lomitapide. Long-term hepatic safety of lomitapide in homozygous familial hypercholesterolaemia. Liver Int. 2023, 43, 413–423. [Google Scholar] [CrossRef] [PubMed]
- White, R.T.; Sankey, K.H.; Nawarskas, J.J. Evinacumab-dgnb (Evkeeza-REGN1500), A Novel Lipid-Lowering Therapy for Homozygous Familial Hypercholesterolemia. Cardiol. Rev. 2023, 32, 180–185. [Google Scholar] [CrossRef] [PubMed]
- Alhamadani, F.; Zhang, K.; Parikh, R.; Wu, H.; Rasmussen, T.P.; Bahal, R.; Zhong, X.-B.; Manautou, J.E. Adverse Drug Reactions and Toxicity of the Food and Drug Administration-Approved Antisense Oligonucleotide Drugs. Drug Metab. Dispos. 2022, 50, 879–887. [Google Scholar] [CrossRef]
- Branchi, A.; Fiorenza, A.M.; Rovellini, A.; Torri, A.; Muzio, F.; Macor, S.; Sommariva, D. Lowering effects of four different statins on serum triglyceride level. Eur. J. Clin. Pharmacol. 1999, 55, 499–502. [Google Scholar] [CrossRef]
- Li, S.; Yang, B.; Du, Y.; Lin, Y.; Liu, J.; Huang, S.; Zhang, A.; Jia, Z.; Zhang, Y. Targeting PPARα for the Treatment and Understanding of Cardiovascular Diseases. Cell. Physiol. Biochem. 2018, 51, 2760–2775. [Google Scholar] [CrossRef]
- Julius, U. Niacin as antidyslipidemic drug. Can. J. Physiol. Pharmacol. 2015, 93, 1043–1054. [Google Scholar] [CrossRef]
- Zeman, M.; Vecka, M.; Perlík, F.; Hromádka, R.; Staňková, B.; Tvrzická, E.; Žák, A. Niacin in the Treatment of Hyperlipidemias in Light of New Clinical Trials: Has Niacin Lost its Place? Med. Sci. Monit. 2015, 21, 2156. [Google Scholar] [CrossRef] [PubMed]
- Preston Mason, R. New Insights into Mechanisms of Action for Omega-3 Fatty Acids in Atherothrombotic Cardiovascular Disease. Curr. Atheroscler. Rep. 2019, 21, 2. [Google Scholar] [CrossRef]
- von Gerichten, J.; West, A.L.; Irvine, N.A.; Miles, E.A.; Calder, P.C.; Lillycrop, K.A.; Burdge, G.C.; Fielding, B.A. Oxylipin secretion by human CD3+ T lymphocytes in vitro is modified by the exogenous essential fatty acid ratio and life stage. Front. Immunol. 2023, 14, 1206733. [Google Scholar] [CrossRef] [PubMed]
- Braun, L.T.; Davidson, M.H. Lp-PLA2: A new target for statin therapy. Curr. Atheroscler. Rep. 2010, 12, 29–33. [Google Scholar] [CrossRef] [PubMed]
- Karakas, M.; Koenig, W. Lp-PLA2 Inhibition—The Atherosclerosis Panacea? Pharmaceuticals 2010, 3, 1360–1373. [Google Scholar] [CrossRef]
- Fras, Z.; Tršan, J.; Banach, M. On the present and future role of Lp-PLA2 in atherosclerosis-related cardiovascular risk prediction and management. Arch. Med. Sci. 2020, 17, 954–964. [Google Scholar] [CrossRef]
- Giubilato, S.; Lucà, F.; Abrignani, M.G.; Gatto, L.; Rao, C.M.; Ingianni, N.; Amico, F.; Rossini, R.; Caretta, G.; Cornara, S.; et al. Management of Residual Risk in Chronic Coronary Syndromes. Clinical Pathways for a Quality-Based Secondary Prevention. J. Clin. Med. 2023, 12, 5989. [Google Scholar] [CrossRef]
Characteristics of the Biomarker | Detailed Clinical Situation |
---|---|
High sensitivity | Rapid release that allows fast diagnosis |
Long half-life that allows repeatedly monitoring | |
Correlated with disease severity | |
High specificity | Absent in healthy persons |
Absent in other tissues except the heart and brain | |
Absent in differential diagnosis disorders | |
Assay-related parameters | Cost-effective |
Non-invasive or minimally invasive sample obtaining | |
Short processing time | |
Standardized method (with clear thresholds) | |
Clinical setting | Useful for early detection |
Useful for therapy monitoring | |
Useful for predictions and prognosis |
Lipid-Derived Biomarker | Utility in Chronic Coronary Syndromes | Utility in Ischemic Stroke |
---|---|---|
Low-density lipoprotein cholesterol | Associated with an increased risk of CV events. Favorable correlation between the ox-LDL/LDL ratio and the Gensini score for CAD | Associated with increased risk of developing IS Helpful in the secondary prevention of IS The main target of cholesterol-lowering drugs |
Triglyceride-to-high-density-lipoprotein cholesterol ratio | Associated with the presence and burden of coronary plaque. Independent predictors of the non-calcified plaque burden | Helpful in evaluating the stroke hazard ratio. Correlated with mortality |
Oxylipin | Indicator of chronic hypoxia. Potential correlation with the number of affected coronary arteries | Early detection of subclinical changes in IS. Potential treatment for the chronic post-stroke phase |
Lipoprotein-associated phospholipase A2 | Predictor of CV events such as myocardial infarction and CV death. Predictor for atherosclerotic carotid disease | Complementary biomarker to current imaging methods in predicting and diagnosing acute IS. Helpful in monitoring the outcome of therapeutic measures in acute and chronic IS |
Lipoprotein (a) | Associated with the severity of CAD. Potential correlation with other CV risk factors (hypertension). Independent CV risk factor | Associated with increased risk of large artery atherosclerotic IS. Correlated with functional outcome and prognosis |
Apolipoprotein A-I | Potential protective factors, When combined with ApoB (ApoB/A1 ratio), it is an independent predictor for plaque modifications | Predictor for atherothrombotic IS. Correlated with carotid plaque phenotype |
Apolipoprotein B | More stable biomarkers in evaluating CV risk compared to cholesterol. Significantly associated with incident myocardial infarction | Independent predictor for intracranial artery stenosis. Strong association with large vessel IS |
Drug | Molecular Mechanism | Targeted Lipid-Derived Biomarker | Current Clinical Status |
---|---|---|---|
Statins | Inhibition of HMG-CoA reductase | Low-density lipoprotein cholesterol Triglyceride-to-high-density-lipoprotein cholesterol ratio Lipoprotein-associated phospholipase A2 Apolipoprotein B | First-line therapy |
Ezetimibe | Inhibition of intestinal cholesterol absorption | Low-density lipoprotein cholesterol Apolipoprotein B | Add-on therapy to statins |
Bile acid sequestrants | Decrease in bile acid absorption | Low-density lipoprotein cholesterol | Used in combination with niacin and ezetimibe |
PCSK9 inhibitors | Inhibition of LDL receptor degradation | Low-density lipoprotein cholesterol Lipoprotein (a) Apolipoprotein B | Adjunct to diet, used alone or combined with other LDL-C lowering therapies |
Bempedoic acid | Inhibition of hepatic ATP citrate lyase activity | Low-density lipoprotein cholesterol Apolipoprotein B | Adjunct to maximally tolerated statin therapy |
Lomitapide | Inhibition of the microsomal triglyceride transfer protein | Low-density lipoprotein cholesterol Apolipoprotein B | Adjunct to diet, combined with other LDL-C-lowering therapies |
Evinacumab | Inhibition of angiopoietin-like protein 3 activity | Low-density lipoprotein cholesterol | Adjunct to other cholesterol-lowering treatments |
Mipomersen | Reduction in VLDL formation and synthesis | Low-density lipoprotein cholesterol Apolipoprotein B | Discontinued |
Niacin | Modulation of liver synthesis of triglycerides, and limitation of VLDL assembly | Triglyceride-to-high-density-lipoprotein cholesterol ratio Lipoprotein (a) Apolipoprotein B | Adjunct to other cholesterol-lowering treatments |
Fibric acid derivates | Increasing fatty acid oxidation, triglyceride-rich particle elimination, and VLDL catabolism | Triglyceride-to-high-density-lipoprotein cholesterol ratio Apolipoprotein B | Adjunct to other cholesterol-lowering treatments |
Omega 3 fatty acids | Reduction in lipogenic gene expression | Triglyceride-to-high-density-lipoprotein cholesterol ratio | Adjunct to other cholesterol-lowering treatments |
Dabigatran | Binding competitively to the active site on human thrombin Pleiotropic effect of ApoB-lowering | Apolipoprotein B | Not primarily used ApoB-lowering medication |
LP-PLA2 inhibitors | Inhibition of LP-PLA2 | Lipoprotein-associated phospholipase A2 | Clinical studies |
Oxylipins | Modulation of pro- and anti-inflammatory pathways | - | Clinical studies |
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content. |
© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Schreiner, T.G.; Ignat, B.E.; Grosu, C.; Costache, A.D.; Leon, M.M.; Mitu, F. Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review. Medicina 2024, 60, 561. https://doi.org/10.3390/medicina60040561
Schreiner TG, Ignat BE, Grosu C, Costache AD, Leon MM, Mitu F. Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review. Medicina. 2024; 60(4):561. https://doi.org/10.3390/medicina60040561
Chicago/Turabian StyleSchreiner, Thomas Gabriel, Bogdan Emilian Ignat, Cristina Grosu, Alexandru Dan Costache, Maria Magdalena Leon, and Florin Mitu. 2024. "Lipid-Derived Biomarkers as Therapeutic Targets for Chronic Coronary Syndrome and Ischemic Stroke: An Updated Narrative Review" Medicina 60, no. 4: 561. https://doi.org/10.3390/medicina60040561