Literature Review of Visit to Visit Lipid Variability as a Predictor of Cardiovascular Events
Abstract
Cardiovascular disease remains a major global health problem due to its substantial contribution to morbidity and mortality. The World Health Organization reports that cardiovascular disease is the leading cause of death worldwide, accounting for approximately 17.9 million deaths each year. In Indonesia, reports from the Ministry of Health show a persistent increase in cardiovascular disease prevalence. Dyslipidemia, defined as an imbalance in blood lipid levels, is a major modifiable risk factor associated with cardiovascular events, making lipid control a key focus of preventive strategies. Visit to visit lipid variability (VLV) refers to fluctuations in lipid parameters such as total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides across different clinical visits over a certain period. Recent studies indicate that higher variability in lipid levels is independently associated with an increased risk of coronary heart disease, stroke, and cardiovascular mortality. This study adopted a literature review design to examine the role of VLV as a predictor of cardiovascular events. Ten national and international journal articles were selected based on predefined inclusion and exclusion criteria. The reviewed evidence consistently shows that high variability in lipid levels, particularly LDL-C and HDL-C, is linked to a greater risk of myocardial infarction, stroke, acute coronary syndrome, and cardiovascular-related death in various populations, including patients with diabetes mellitus and familial hypercholesterolemia. Conversely, maintaining stable lipid levels over time is associated with a reduced risk of adverse cardiovascular outcomes. These findings highlight the importance of continuous lipid monitoring and long-term lipid stability as essential components in efforts to prevent and control cardiovascular disease.
References
Ahlers, M., John, S., Bhatia, H., Le, V., & Taub, P. (2025). Identification and management of patients at high-risk for cardiovascular disease in primary prevention. American Journal of Preventive Cardiology, 101265. https://doi.org/10.1016/j.ajpc.2025.101265
Alanzi, S. S., Almayouf, S. M. A., Alotaibi, K. M. N., Alanazi, A. O. A., Ghuwayzi, H., Alharbi, O. N., & Aldajani, O. H. O. (2025). Global Burden, Risk Factors, and Evidence-Based Strategies for Cardiovascular Disease Prevention: A Comprehensive Systematic Review. Journal of Angiotherapy, 9(1), 1-20. https://doi.org/10.25163/angiotherapy.9110348
Campbell, M. K., Chew, N. W., & Mehta, A. (2025). Beyond cholesterol: unraveling residual lipidomic risk in cardiovascular health. Current Atherosclerosis Reports, 27(1), 37. https://doi.org/10.1007/s11883-025-01284-0
Cao, Y.-X., Li, L., Zhang, H.-W., Jin, J.-L., Liu, H.-H., Guo, Y.-L., Wu, N.-Q., Zhu, C.-G., Dong, Q., Xu, R.-X., Sun, J., & Li, J.-J. (2021). Visit-to-visit Variability of Lipid and Cardiovascular Events in Patients with Familial Hypercholesterolemia. Annals of Translational Medicine, 9(7), 556–556. https://doi.org/10.21037/atm-20-5324
Faggiano, P., Ruscica, M., Bettari, S., Cherubini, A., Carugo, S., Corsini, A., Barbati, G., & Di Lenarda, A. (2023). LDL Cholesterol Variability Impacts the Prognosis of Patients with Chronic Ischemic Heart Disease: A Real-World Italian Experience. Journal of Clinical Medicine, 12(19), 6231. https://doi.org/10.3390/jcm12196231
Formichi, C., Caprio, S., Nigi, L., & Dotta, F. (2025). The impact of environmental pollution on metabolic health and the risk of non-communicable chronic metabolic diseases in humans. Nutrition, Metabolism and Cardiovascular Diseases, 103975. https://doi.org/10.1016/j.numecd.2025.103975
Frąk, W., Wojtasińska, A., Lisińska, W., Młynarska, E., Franczyk, B., & Rysz, J. (2022). Pathophysiology of Cardiovascular Diseases: New Insights into Molecular Mechanisms of Atherosclerosis, Arterial Hypertension, and Coronary Artery Disease. Biomedicines, 10(8), 1938. https://doi.org/10.3390/biomedicines10081938
Grinspoon, S. K., Watanabe, M., Ribaudo, H. J., Bloomfield, G. S., Fichtenbaum, C. J., Umbleja, T., ... & Zanni, M. V. (2025). Factors Affecting Risk of Cardiovascular Disease (CVD) Events in a Global CVD Prevention Cohort of People With Human Immunodeficiency Virus (HIV). Clinical Infectious Diseases, ciaf210. https://doi.org/10.1093/cid/ciaf210
He, P., Gan, X., Wu, Q., Ye, Z., Yang, S., Zhang, Y., Li, H., Zhou, C., Zhang, Y., Liu, M., & Qin, X. (2022). Joint Effect of Visit-to-visit Variability in LDL-cholesterol, HDL-cholesterol and HbA1c on Cardiovascular and Total Mortality in Patients with Diabetes. Diabetology & Metabolic Syndrome, 14(1), 132. https://doi.org/10.1186/s13098-022-00905-x
Hodeda, L., Eisen, A., Rotholz, A., Kornowski, R., & Gurevitz, C. (2025). Sex Differences in the Treatment with PCSK9 Monoclonal Antibodies-Real World Experience from a Dedicated Preventive Cardiology Clinic. American Journal of Preventive Cardiology, 101022. https://doi.org/10.1016/j.ajpc.2025.101022
Hosseini, K. (2025). Effects of Familial Hypercholesterolemia on Major Adverse Cardiac and Cerebrovascular Events in Patients with Premature Coronary Artery Disease: A Retrospective Cohort Study. The Research in Heart Yield and Translational Medicine (RHYTHM), 20(1), 47-54. https://doi.org/10.18502/jthc.v20i1.19221
Kamrani, F., Imannezhad, M., Rezaee, A., Darroudi, S., Yavari Kondori, A., Sadatian, S., ... & Moohebati, M. (2025). Emerging importance of remnant cholesterol compared with low-density lipoprotein cholesterol in cardiovascular risk assessment. Scientific Reports, 15(1), 44094. https://doi.org/10.1038/s41598-025-27681-8
Kang, K., Wang, Q., Li, Y., Liu, C., Yu, H., & Li, N. (2025). Global and Chinese perspectives on the growing burden of heart failure: trends, gender, and age-related differences (1990–2021) based on GBD 2021 data. BMC Cardiovascular Disorders, 25(1), 510. https://doi.org/10.1186/s12872-025-04954-8
Karnan, N., Abdirahman, A. H., Kilaru, G., Kaur, A. R., Majumder, K., & Abou Al Fadel, L. A. S. (2025). Assessing disparity in mortality rates for ischemic heart disease using CDC-WONDER database: A retrospective analysis. Global Cardiology Science & Practice, 2025(1), e202514. https://doi.org/10.21542/gcsp.2025.14
Kindborg, G., Eriksson Hogling, D., Häbel, H., Yan, J., Hallerbäck, T., Lindhe, Ö., ... & Brinck, J. (2025). Major cardiovascular events in first-degree relatives of individuals with elevated plasma lipoprotein (a): a registry-based cohort study. European Heart Journal, ehaf677. https://doi.org/10.1093/eurheartj/ehaf677
Li, S., Hou, L., Zhu, S., Yi, Q., Liu, W., Zhao, Y., Wu, F., Li, X., Pan, A., & Song, P. (2022). Lipid Variability and Risk of Cardiovascular Diseases and All-Cause Mortality: A Systematic Review and Meta-Analysis of Cohort Studies. Nutrients, 14(12), 2450. https://doi.org/10.3390/nu14122450
Lim, Y.-J., Oh, M., Park, S. G., Kim, H., & Yoo, S. (2023). Visit-to-visit Variability of Metabolic Parameters and Progression of Atherosclerosis in Computed Tomography: Follow up of an Asymptomatic Cohort. Cardiovascular Diagnosis and Therapy, 13(5), 855–865. https://doi.org/10.21037/cdt-23-75
Liu, Q., Liu, M., Liang, W., Li, X., Jing, W., Chen, Z., & Liu, J. (2025). Global distribution and health impact of infectious disease outbreaks, 1996–2023: a worldwide retrospective analysis of World Health Organization emergency event reports. Journal of Global Health, 15, 04151. https://doi.org/10.7189/jogh.15.04151
Liu, X., Wu, S., Song, Q., & Wang, X. (2020). Visit-to-visit Variability of Lipid Measurements and the Risk of Myocardial Infarction and All-Cause Mortality: A Prospective Cohort Study. Atherosclerosis, 312, 110–116. https://doi.org/10.1016/j.atherosclerosis.2020.09.003
Manemann, S. M., Bielinski, S. J., Moser, E. D., St. Sauver, J. L., Takahashi, P. Y., Roger, V. L., Olson, J. E., Chamberlain, A. M., Remaley, A. T., Decker, P. A., Killian, J. M., & Larson, N. B. (2023). Variability in Lipid Levels and Risk for Cardiovascular Disease: An Electronic Health Record–Based Population Cohort Study. Journal of the American Heart Association, 12(5). https://doi.org/10.1161/JAHA.122.027639
Nakano, S., Otake, H., Kawamori, H., Toba, T., Sugizaki, Y., Nagasawa, A., Takeshige, R., Matsuoka, Y., Tanimura, K., Takahashi, Y., Fukuyama, Y., Shite, J., Kozuki, A., Iwasaki, M., Kuroda, K., Takaya, T., & Hirata, K. (2021). Association Between Visit-to-Visit Variability in Low-Density Lipoprotein Cholesterol and Plaque Rupture That Leads to Acute Coronary Syndrome. Circulation Reports, 3, 540–549. https://doi.org/10.1253/circrep.CR-21-0080
Park, J.-B., Shin, E., Lee, J.-E., Lee, S. J., Lee, H., Choi, S.-Y., Choe, E. K., Choi, S. H., & Park, H. E. (2022). Genetic Determinants of Visit-to-Visit Lipid Variability: Genome-Wide Association Study in Statin-Naïve Korean Population. Frontiers in Cardiovascular Medicine, 9. https://doi.org/10.3389/fcvm.2022.811657
Rodriguez, C. P., Burka, S., & Michos, E. D. (2025). Impact of Sex Differences on Lipids and Statin Utilization. Current atherosclerosis reports, 27(1), 1-13. https://doi.org/10.1007/s11883-025-01286-y
Sheng, C.-S., Miao, Y., Ding, L., Cheng, Y., Wang, D., Yang, Y., & Tian, J. (2022). Prognostic Significance of Visit-to-visit Variability, and Maximum and Minimum LDL cholesterol in Diabetes Mellitus. Lipids in Health and Disease, 21(1), 19. https://doi.org/10.1186/s12944-022-01628-8
Sherlock, L., Lee, S. F., Cukierman-Yaffe, T., Leong, D., Gerstein, H. C., Bosch, J., Muniz-Terrera, G., & Whiteley, W. N. (2024). Visit-to-visit Variability in Multiple Biological Measurements and Cognitive Performance and Risk of Cardiovascular Disease: A Cohort Study. Cerebral Circulation - Cognition and Behavior, 6, 100223. https://doi.org/10.1016/j.cccb.2024.100223
Sosnowska, B., Bytyci, I., Lewek, J., Bielecka-Dabrowa, A., Burzyńska, M., Jankowski, P., ... & Banach, M. (2025). Determinants of lack of atherosclerosis progression in adult patients with elevated lipoprotein (a): results from the STAR-Lp (a) study. Archives of Medical Science: AMS, 21(5), 1730. https://doi.org/10.5114/aoms/209946
Stoicescu, C., Vacarescu, C., & Cozma, D. (2025). HDL function versus small dense LDL: Cardiovascular benefits and implications. Journal of Clinical Medicine, 14(14), 4945. https://doi.org/10.3390/jcm14144945
Sun, Q., Liu, J., Wu, L., Sun, Y., Jin, J., Wang, S., Wu, J., Jing, Y., Zhou, H., & Dong, C. (2021). Associations of Visit-to-visit Variabilities and Trajectories of Serum Lipids with the Future Probability of Type 2 Diabetes Mellitus. Lipids in Health and Disease, 20(1), 168. https://doi.org/10.1186/s12944-021-01592-9
Sun, Y., Guo, Y., Ma, S., Mao, Z., Meng, D., Xuan, K., ... & Zhu, X. (2025). Association of C-reactive protein-triglyceride glucose index with the incidence and mortality of cardiovascular disease: a retrospective cohort study. Cardiovascular diabetology, 24(1), 313.
Tang, N., Chen, X., Li, H., Cheng, S., Hu, Y. N., Wang, L., ... & Qi, C. (2025). Association of C reactive protein triglyceride glucose index with mortality in coronary heart disease and type 2 diabetes from NHANES data. Scientific Reports, 15(1), 24687. https://doi.org/10.1038/s41598-025-10184-x
Teekaput, C., Thiankhaw, K., Wongcharoen, W., Prasertwitayakij, N., Gunaparn, S., & Phrommintikul, A. (2025). Visit-to-visit Lipid Variability on Long-term Major Adverse Cardiovascular Events: a Prospective Multicentre Cohort Ffom the CORE-Thailand Registry. Scientific Reports, 15(1), 1953. https://doi.org/10.1038/s41598-025-85453-w
Wan, E. Y. F., Yu, E. Y. T., Chin, W. Y., Barrett, J. K., Mok, A. H. Y., Lau, C. S. T., Wang, Y., Wong, I. C. K., Chan, E. W. Y., & Lam, C. L. K. (2020). Greater Variability in Lipid Measurements Associated with Cardiovascular Disease and Mortality: A 10‐Year Diabetes Cohort Study. Diabetes, Obesity and Metabolism, 22(10), 1777–1788. https://doi.org/10.1111/dom.14093
Wang, A., Li, H., Yuan, J., Zuo, Y., Zhang, Y., Chen, S., Wu, S., & Wang, Y. (2020). Visit-to-Visit Variability of Lipids Measurements and the Risk of Stroke and Stroke Types: A Prospective Cohort Study. Journal of Stroke, 22(1), 119–129. https://doi.org/10.5853/jos.2019.02075
Wazir, M., Olanrewaju, O. A., Yahya, M., Kumari, J., Kumar, N., Singh, J., Abbas Al-itbi, A. Y., Kumari, K., Ahmed, A., Islam, T., Varrassi, G., Khatri, M., Kumar, S., Wazir, H., & Raza, S. S. (2023). Lipid Disorders and Cardiovascular Risk: A Comprehensive Analysis of Current Perspectives. Cureus, 15(12). https://doi.org/10.7759/cureus.51395
Yum, Y., Koh, S., Park, S., Joo, H. J., Kim, Y. H., & Kim, E. J. (2024). Impact of Cholesterol Variability as a Potential Residual Cardiovascular Risk Factor in the Elderly: Large Multicenter Common Data Model Database Analysis. CardioMetabolic Syndrome Journal, 4(1), 22. https://doi.org/10.51789/cmsj.2024.4.e2
Zhang, N., Wang, Y., Li, W., Wang, Y., Zhang, H., Xu, D., ... & Tang, H. (2025). Association between serum vitamin D level and cardiovascular disease in Chinese patients with type 2 diabetes mellitus: a cross-sectional study. Scientific Reports, 15(1), 6454. https://doi.org/10.1038/s41598-025-90785-8
Copyright (c) 2026 Journal La Medihealtico
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.
