肥胖与颅内动脉粥样硬化性狭窄相关研究进展
Research Progress on the Association between Obesity and Intracranial Atherosclerotic Stenosis
摘要: 肥胖作为全球日益严重的公共卫生问题,与多种慢性疾病的发生密切相关,特别是与颅内动脉粥样硬化性狭窄(ICAS)的关系受到广泛关注。然而,不同肥胖评估指标与颅内动脉粥样硬化性狭窄风险的关系需进一步探讨,以及肥胖在颅内动脉粥样硬化性狭窄的具体作用机制及其干预策略仍需深入研究。文章通过系统检索并查阅国内外相关文献,从肥胖评估指标与颅内动脉粥样硬化性狭窄的关系、肥胖影响颅内动脉粥样硬化性狭窄发生与发展的潜在机制,以及颅内动脉粥样硬化性狭窄防治中肥胖相关的管理策略三个方面进行综述。
Abstract: Obesity, as an increasingly serious global public health issue, is closely associated with the onset of various chronic diseases, particularly intracranial atherosclerotic stenosis (ICAS), which has garnered significant attention. However, the relationship between different obesity assessment indices and the risk of ICAS warrants further investigation, as does the specific role of obesity in the pathogenesis and progression of ICAS, along with potential intervention strategies. This review systematically examines domestic and international literature to explore three key aspects: the relationship between obesity assessment indices and ICAS, the underlying mechanisms by which obesity influences the development and progression of ICAS, and the management strategies for obesity in the prevention and treatment of ICAS.
文章引用:孔祥龙, 王巧. 肥胖与颅内动脉粥样硬化性狭窄相关研究进展[J]. 临床医学进展, 2025, 15(3): 520-529. https://doi.org/10.12677/acm.2025.153644

参考文献

[1] Powell-Wiley, T.M., Poirier, P., Burke, L.E., Després, J., Gordon-Larsen, P., Lavie, C.J., et al. (2021) Obesity and Cardiovascular Disease: A Scientific Statement from the American Heart Association. Circulation, 143, e984-e1010. [Google Scholar] [CrossRef] [PubMed]
[2] Derdeyn, C.P., Chimowitz, M.I., Lynn, M.J., Fiorella, D., Turan, T.N., Janis, L.S., et al. (2014) Aggressive Medical Treatment with or without Stenting in High-Risk Patients with Intracranial Artery Stenosis (SAMMPRIS): The Final Results of a Randomised Trial. The Lancet, 383, 333-341. [Google Scholar] [CrossRef] [PubMed]
[3] Sangha, R.S., Naidech, A.M., Corado, C., Ansari, S.A. and Prabhakaran, S. (2017) Challenges in the Medical Management of Symptomatic Intracranial Stenosis in an Urban Setting. Stroke, 48, 2158-2163. [Google Scholar] [CrossRef] [PubMed]
[4] Gutierrez, J., Turan, T.N., Hoh, B.L. and Chimowitz, M.I. (2022) Intracranial Atherosclerotic Stenosis: Risk Factors, Diagnosis, and Treatment. The Lancet Neurology, 21, 355-368. [Google Scholar] [CrossRef] [PubMed]
[5] Loos, R.J.F. (2012) Genetic Determinants of Common Obesity and Their Value in Prediction. Best Practice & Research Clinical Endocrinology & Metabolism, 26, 211-226. [Google Scholar] [CrossRef] [PubMed]
[6] Sallis, J.F. and Glanz, K. (2009) Physical Activity and Food Environments: Solutions to the Obesity Epidemic. The Milbank Quarterly, 87, 123-154. [Google Scholar] [CrossRef] [PubMed]
[7] Sommer, I., Griebler, U., Mahlknecht, P., Thaler, K., Bouskill, K., Gartlehner, G., et al. (2015) Socioeconomic Inequalities in Non-Communicable Diseases and Their Risk Factors: An Overview of Systematic Reviews. BMC Public Health, 15, Article No. 914. [Google Scholar] [CrossRef] [PubMed]
[8] Gebreab, S.Z., Vandeleur, C.L., Rudaz, D., Strippoli, M.F., Gholam-Rezaee, M., Castelao, E., et al. (2018) Psychosocial Stress over the Lifespan, Psychological Factors, and Cardiometabolic Risk in the Community. Psychosomatic Medicine, 80, 628-639. [Google Scholar] [CrossRef] [PubMed]
[9] Kahn, S.E., Hull, R.L. and Utzschneider, K.M. (2006) Mechanisms Linking Obesity to Insulin Resistance and Type 2 Diabetes. Nature, 444, 840-846. [Google Scholar] [CrossRef] [PubMed]
[10] Marini, S., Merino, J., Montgomery, B.E., Malik, R., Sudlow, C.L., Dichgans, M., et al. (2020) Mendelian Randomization Study of Obesity and Cerebrovascular Disease. Annals of Neurology, 87, 516-524. [Google Scholar] [CrossRef] [PubMed]
[11] Ma, Y., Leng, X., Dong, Y., Xu, W., Cao, X., Ji, X., et al. (2019) Risk Factors for Intracranial Atherosclerosis: A Systematic Review and Meta-Analysis. Atherosclerosis, 281, 71-77. [Google Scholar] [CrossRef] [PubMed]
[12] Bouchi, R., Takeuchi, T., Akihisa, M., Ohara, N., Nakano, Y., Nishitani, R., et al. (2015) High Visceral Fat with Low Subcutaneous Fat Accumulation as a Determinant of Atherosclerosis in Patients with Type 2 Diabetes. Cardiovascular Diabetology, 14, Article No. 136. [Google Scholar] [CrossRef] [PubMed]
[13] Kahn, H.S. (2005) The “Lipid Accumulation Product” Performs Better than the Body Mass Index for Recognizing Cardiovascular Risk: A Population-Based Comparison. BMC Cardiovascular Disorders, 5, Article No. 26. [Google Scholar] [CrossRef] [PubMed]
[14] Amato, M.C., Giordano, C., Galia, M., Criscimanna, A., Vitabile, S., Midiri, M., et al. (2010) Visceral Adiposity Index: A Reliable Indicator of Visceral Fat Function Associated with Cardiometabolic Risk. Diabetes Care, 33, 920-922. [Google Scholar] [CrossRef] [PubMed]
[15] Krakauer, N.Y. and Krakauer, J.C. (2012) A New Body Shape Index Predicts Mortality Hazard Independently of Body Mass Index. PLOS ONE, 7, e39504. [Google Scholar] [CrossRef] [PubMed]
[16] Xia, M., Chen, Y., Lin, H., Ma, H., Li, X., Aleteng, Q., et al. (2016) A Indicator of Visceral Adipose Dysfunction to Evaluate Metabolic Health in Adult Chinese. Scientific Reports, 6, Article No. 38214. [Google Scholar] [CrossRef] [PubMed]
[17] Wong, K.S., Ng, P.W., Tang, A., Liu, R., Yeung, V. and Tomlinson, B. (2007) Prevalence of Asymptomatic Intracranial Atherosclerosis in High-Risk Patients. Neurology, 68, 2035-2038. [Google Scholar] [CrossRef] [PubMed]
[18] Okorodudu, D.O., Jumean, M.F., Montori, V.M., Romero-Corral, A., Somers, V.K., Erwin, P.J., et al. (2010) Diagnostic Performance of Body Mass Index to Identify Obesity as Defined by Body Adiposity: A Systematic Review and Meta-Analysis. International Journal of Obesity, 34, 791-799. [Google Scholar] [CrossRef] [PubMed]
[19] Li, R., Li, Q., Cui, M., Ying, Z., Li, L., Zhong, T., et al. (2017) Visceral Adiposity Index, Lipid Accumulation Product and Intracranial Atherosclerotic Stenosis in Middle-Aged and Elderly Chinese. Scientific Reports, 7, Article No. 7951. [Google Scholar] [CrossRef] [PubMed]
[20] Eickemberg, M., Amorim, L.D.A.F., de Almeida, M.C.C., de Aquino, E.M.L., de Fonseca, M.J.M., de Souza Santos, I., et al. (2018) Indicators of Abdominal Adiposity and Carotid Intima-Media Thickness: Results from the Longitudinal Study of Adult Health (ELSA-Brazil). Arquivos Brasileiros de Cardiologia, 112, 220-227. [Google Scholar] [CrossRef] [PubMed]
[21] Lorenz, M.W., Markus, H.S., Bots, M.L., Rosvall, M. and Sitzer, M. (2007) Prediction of Clinical Cardiovascular Events with Carotid Intima-Media Thickness: A Systematic Review and Meta-Analysis. Circulation, 115, 459-467. [Google Scholar] [CrossRef] [PubMed]
[22] Sun, J., Meng, X., Huang, H., Jing, J., Pan, Y., Mei, L., et al. (2023) Higher Visceral Adiposity Index and Lipid Accumulation Product in Relation to Increased Risk of Atherosclerotic Burden in Community-Dwelling Older Adults. Experimental Gerontology, 174, Article 112115. [Google Scholar] [CrossRef] [PubMed]
[23] Zhao, W., Ma, X., Ju, J., Zhao, Y., Wang, X., Li, S., et al. (2023) Association of Visceral Adiposity Index with Asymptomatic Intracranial Arterial Stenosis: A Population-Based Study in Shandong, China. Lipids in Health and Disease, 22, Article No. 64. [Google Scholar] [CrossRef] [PubMed]
[24] Ma, X., Chen, L., Hu, W. and He, L. (2022) Association between a Body Shape Index and Subclinical Carotid Atherosclerosis in Population Free of Cardiovascular and Cerebrovascular Diseases. Journal of Atherosclerosis and Thrombosis, 29, 1140-1152. [Google Scholar] [CrossRef] [PubMed]
[25] Abete, I., Arriola, L., Etxezarreta, N., Mozo, I., Moreno-Iribas, C., Amiano, P., et al. (2014) Association between Different Obesity Measures and the Risk of Stroke in the EPIC Spanish Cohort. European Journal of Nutrition, 54, 365-375. [Google Scholar] [CrossRef] [PubMed]
[26] Lv, Z., Ji, Y., Xu, S., Li, C. and Cai, W. (2024) Chinese Visceral Adiposity Index and Its Transition Patterns: Impact on Cardiovascular and Cerebrovascular Diseases in a National Cohort Study. Lipids in Health and Disease, 23, Article No. 124. [Google Scholar] [CrossRef] [PubMed]
[27] Li, B., Lai, X., Yan, C., Jia, X. and Li, Y. (2020) The Associations between Neutrophil-to-Lymphocyte Ratio and the Chinese Visceral Adiposity Index, and Carotid Atherosclerosis and Atherosclerotic Cardiovascular Disease Risk. Experimental Gerontology, 139, Article 111019. [Google Scholar] [CrossRef] [PubMed]
[28] Vilahur, G., Ben-Aicha, S. and Badimon, L. (2017) New Insights into the Role of Adipose Tissue in Thrombosis. Cardiovascular Research, 113, 1046-1054. [Google Scholar] [CrossRef] [PubMed]
[29] Ellulu, M.S., Patimah, I., Khaza’ai, H., Rahmat, A. and Abed, Y. (2017) Obesity and Inflammation: The Linking Mechanism and the Complications. Archives of Medical Science, 4, 851-863. [Google Scholar] [CrossRef] [PubMed]
[30] Yang, J., Ran, M., Li, H., Lin, Y., Ma, K., Yang, Y., et al. (2022) New Insight into Neurological Degeneration: Inflammatory Cytokines and Blood-Brain Barrier. Frontiers in Molecular Neuroscience, 15, Article 1013933. [Google Scholar] [CrossRef] [PubMed]
[31] Prakash, R. and Carmichael, S.T. (2015) Blood-Brain Barrier Breakdown and Neovascularization Processes after Stroke and Traumatic Brain Injury. Current Opinion in Neurology, 28, 556-564. [Google Scholar] [CrossRef] [PubMed]
[32] O’Carroll, S.J., Kho, D.T., Wiltshire, R., Nelson, V., Rotimi, O., Johnson, R., et al. (2015) Pro-Inflammatory TNFα and IL-1β Differentially Regulate the Inflammatory Phenotype of Brain Microvascular Endothelial Cells. Journal of Neuroinflammation, 12, Article No. 131. [Google Scholar] [CrossRef] [PubMed]
[33] Stancu, C.S., Toma, L. and Sima, A.V. (2012) Dual Role of Lipoproteins in Endothelial Cell Dysfunction in Atherosclerosis. Cell and Tissue Research, 349, 433-446. [Google Scholar] [CrossRef] [PubMed]
[34] Jickling, G.C., Liu, D., Ander, B.P., Stamova, B., Zhan, X. and Sharp, F.R. (2015) Targeting Neutrophils in Ischemic Stroke: Translational Insights from Experimental Studies. Journal of Cerebral Blood Flow & Metabolism, 35, 888-901. [Google Scholar] [CrossRef] [PubMed]
[35] Liu, R., Hong, J., Xu, X., Feng, Q., Zhang, D., Gu, Y., et al. (2017) Gut Microbiome and Serum Metabolome Alterations in Obesity and after Weight-Loss Intervention. Nature Medicine, 23, 859-868. [Google Scholar] [CrossRef] [PubMed]
[36] Valdes, A.M., Walter, J., Segal, E. and Spector, T.D. (2018) Role of the Gut Microbiota in Nutrition and Health. BMJ, 361, k2179. [Google Scholar] [CrossRef] [PubMed]
[37] Koeth, R.A., Wang, Z., Levison, B.S., Buffa, J.A., Org, E., Sheehy, B.T., et al. (2013) Intestinal Microbiota Metabolism of L-Carnitine, a Nutrient in Red Meat, Promotes Atherosclerosis. Nature Medicine, 19, 576-585. [Google Scholar] [CrossRef] [PubMed]
[38] Gao, R., Zhu, C., Li, H., Yin, M., Pan, C., Huang, L., et al. (2017) Dysbiosis Signatures of Gut Microbiota along the Sequence from Healthy, Young Patients to Those with Overweight and Obesity. Obesity, 26, 351-361. [Google Scholar] [CrossRef] [PubMed]
[39] Crovesy, L., Masterson, D. and Rosado, E.L. (2020) Profile of the Gut Microbiota of Adults with Obesity: A Systematic Review. European Journal of Clinical Nutrition, 74, 1251-1262. [Google Scholar] [CrossRef] [PubMed]
[40] Zhang, G., Zhong, X., Chen, J., Yang, C., Liu, Y., LI, R., et al. (2024) The Gut Microbiome and Serum Metabolome Are Altered and Interrelated in Patients with Intracranial Atherosclerotic Stenosis. Journal of Stroke and Cerebrovascular Diseases, 33, Article 107887. [Google Scholar] [CrossRef] [PubMed]
[41] Jiang, S., Yu, C., Lv, B., He, S., Zheng, Y., Yang, W., et al. (2024) Two-Sample Mendelian Randomization to Study the Causal Association between Gut Microbiota and Atherosclerosis. Frontiers in Immunology, 14, Article 1282072. [Google Scholar] [CrossRef] [PubMed]
[42] Peoples, J.N., Saraf, A., Ghazal, N., Pham, T.T. and Kwong, J.Q. (2019) Mitochondrial Dysfunction and Oxidative Stress in Heart Disease. Experimental & Molecular Medicine, 51, 1-13. [Google Scholar] [CrossRef] [PubMed]
[43] Qiu, H. and Schlegel, V. (2018) Impact of Nutrient Overload on Metabolic Homeostasis. Nutrition Reviews, 76, 693-707. [Google Scholar] [CrossRef] [PubMed]
[44] Rauf, A., Khalil, A.A., Awadallah, S., Khan, S.A., Abu‐Izneid, T., Kamran, M., et al. (2023) Reactive Oxygen Species in Biological Systems: Pathways, Associated Diseases, and Potential Inhibitors—A Review. Food Science & Nutrition, 12, 675-693. [Google Scholar] [CrossRef] [PubMed]
[45] Krüger-Genge, A., Blocki, A., Franke, R. and Jung, F. (2019) Vascular Endothelial Cell Biology: An Update. International Journal of Molecular Sciences, 20, Article 4411. [Google Scholar] [CrossRef] [PubMed]
[46] Obeagu, E.I., Igwe, M.C. and Obeagu, G.U. (2024) Oxidative Stress’s Impact on Red Blood Cells: Unveiling Implications for Health and Disease. Medicine, 103, e37360. [Google Scholar] [CrossRef] [PubMed]
[47] Look AHEAD Research Group (2016) Association of the Magnitude of Weight Loss and Changes in Physical Fitness with Long-Term Cardiovascular Disease Outcomes in Overweight or Obese People with Type 2 Diabetes: A Post-Hoc Analysis of the Look AHEAD Randomised Clinical Trial. The Lancet Diabetes & Endocrinology, 4, 913-921. [Google Scholar] [CrossRef
[48] Hoak, D.A. and Lutsep, H.L. (2016) Management of Symptomatic Intracranial Stenosis. Current Cardiology Reports, 18, Article No. 83. [Google Scholar] [CrossRef] [PubMed]
[49] Ellulu, M.S. (2017) Obesity, Cardiovascular Disease, and Role of Vitamin C on Inflammation: A Review of Facts and Underlying Mechanisms. Inflammopharmacology, 25, 313-328. [Google Scholar] [CrossRef] [PubMed]
[50] Soleimani, M., Barone, S., Luo, H. and Zahedi, K. (2023) Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt. International Journal of Molecular Sciences, 24, Article 4294. [Google Scholar] [CrossRef] [PubMed]
[51] Filippou, C.D., Tsioufis, C.P., Thomopoulos, C.G., Mihas, C.C., Dimitriadis, K.S., Sotiropoulou, L.I., et al. (2020) Dietary Approaches to Stop Hypertension (DASH) Diet and Blood Pressure Reduction in Adults with and without Hypertension: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Advances in Nutrition, 11, 1150-1160. [Google Scholar] [CrossRef] [PubMed]
[52] Chen, W., Zhang, S., Hu, X., Chen, F. and Li, D. (2023) A Review of Healthy Dietary Choices for Cardiovascular Disease: From Individual Nutrients and Foods to Dietary Patterns. Nutrients, 15, Article 4898. [Google Scholar] [CrossRef] [PubMed]
[53] Aune, D., Norat, T., Leitzmann, M., Tonstad, S. and Vatten, L.J. (2015) Physical Activity and the Risk of Type 2 Diabetes: A Systematic Review and Dose-Response Meta-Analysis. European Journal of Epidemiology, 30, 529-542. [Google Scholar] [CrossRef] [PubMed]
[54] Diaz, K.M. and Shimbo, D. (2013) Physical Activity and the Prevention of Hypertension. Current Hypertension Reports, 15, 659-668. [Google Scholar] [CrossRef] [PubMed]
[55] Mouradian, M.S., Majumdar, S.R., Senthilselvan, A., Khan, K. and Shuaib, A. (2002) How Well Are Hypertension, Hyperlipidemia, Diabetes, and Smoking Managed after a Stroke or Transient Ischemic Attack? Stroke, 33, 1656-1659. [Google Scholar] [CrossRef] [PubMed]
[56] Yang, D., Liu, M., Willey, J.Z., Khasiyev, F., Tom, S.E., Rundek, T., et al. (2023) Physical Activity Is Inversely Associated with Severe Intracranial Stenosis in Stroke-Free Participants of Nomas. Stroke, 54, 159-166. [Google Scholar] [CrossRef] [PubMed]
[57] Piercy, K.L., Troiano, R.P., Ballard, R.M., Carlson, S.A., Fulton, J.E., Galuska, D.A., et al. (2018) The Physical Activity Guidelines for Americans. JAMA, 320, 2020-2028. [Google Scholar] [CrossRef] [PubMed]
[58] Bray, G.A., Frühbeck, G., Ryan, D.H. and Wilding, J.P.H. (2016) Management of Obesity. The Lancet, 387, 1947-1956. [Google Scholar] [CrossRef] [PubMed]
[59] Kadri, S., El Ayed, M., Kadri, A., Limam, F., Aouani, E. and Mokni, M. (2021) Protective Effect of Grape Seed Extract and Orlistat Co-Treatment against Stroke: Effect on Oxidative Stress and Energy Failure. Biomedicine & Pharmacotherapy, 136, Article 111282. [Google Scholar] [CrossRef] [PubMed]
[60] Sun, J., Ling, Z., Wang, F., Chen, W., Li, H., Jin, J., et al. (2016) Clostridium Butyricum Pretreatment Attenuates Cerebral Ischemia/Reperfusion Injury in Mice via Anti-Oxidation and Anti-Apoptosis. Neuroscience Letters, 613, 30-35. [Google Scholar] [CrossRef] [PubMed]
[61] Benakis, C., Brea, D., Caballero, S., Faraco, G., Moore, J., Murphy, M., et al. (2016) Commensal Microbiota Affects Ischemic Stroke Outcome by Regulating Intestinal γδ T Cells. Nature Medicine, 22, 516-523. [Google Scholar] [CrossRef] [PubMed]
[62] Hubbard, V.S. and Hall, W.H. (1991) Gastrointestinal Surgery for Severe Obesity. Obesity Surgery, 1, 257-265.
[63] Sjöström, L., Peltonen, M., Jacobson, P., Sjöström, C.D., Karason, K., Wedel, H., et al. (2012) Bariatric Surgery and Long-Term Cardiovascular Events. JAMA, 307, 56-65. [Google Scholar] [CrossRef] [PubMed]