{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:42:35Z","timestamp":1777088555018,"version":"3.51.4"},"reference-count":49,"publisher":"Japanese Circulation Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Circ J"],"published-print":{"date-parts":[[2026,4,24]]},"DOI":"10.1253\/circj.cj-25-0504","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T22:07:01Z","timestamp":1762985221000},"page":"502-512","source":"Crossref","is-referenced-by-count":2,"title":["Lipid Variability and the Risk of Incident Peripheral Artery Disease"],"prefix":"10.1253","volume":"90","author":[{"given":"Ying-Chang","family":"Tung","sequence":"first","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"},{"name":"College of Medicine, Chang Gung University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tsung-Han","family":"Tsai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Jui","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzyy-Jer","family":"Hsu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fu-Chih","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chia-Pin","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pao-Hsien","family":"Chu","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine"},{"name":"College of Medicine, Chang Gung University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"330","reference":[{"key":"1","doi-asserted-by":"crossref","unstructured":"1. Fowkes FGR, Rudan D, Rudan I, Aboyans V, Denenberg JO, McDermott MM, et al. Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis. <i>Lancet<\/i> 2013; 382: 1329\u20131340.","DOI":"10.1016\/S0140-6736(13)61249-0"},{"key":"2","doi-asserted-by":"crossref","unstructured":"2. Criqui MH, Matsushita K, Aboyans V, Hess CN, Hicks CW, Kwan TW, et al. Lower extremity peripheral artery disease: Contemporary epidemiology, management gaps, and future directions: A scientific statement from the American Heart Association. <i>Circulation<\/i> 2021; 144: e171\u2013e191.","DOI":"10.1161\/CIR.0000000000001005"},{"key":"3","doi-asserted-by":"crossref","unstructured":"3. Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda AL, Kanevsky E, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: Insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). <i>Circulation<\/i> 2018; 137: 338\u2013350.","DOI":"10.1161\/CIRCULATIONAHA.117.032235"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4. Criqui MH, Aboyans V. Epidemiology of peripheral artery disease. <i>Circ Res<\/i> 2015; 116: 1509\u20131526.","DOI":"10.1161\/CIRCRESAHA.116.303849"},{"key":"5","doi-asserted-by":"crossref","unstructured":"5. McDermott MM, Mandapat AL, Moates A, Albay M, Chiou E, Celic L, et al. Knowledge and attitudes regarding cardiovascular disease risk and prevention in patients with coronary or peripheral arterial disease. <i>Arch Intern Med<\/i> 2003; 163: 2157\u20132162.","DOI":"10.1001\/archinte.163.18.2157"},{"key":"6","doi-asserted-by":"crossref","unstructured":"6. Hirsch AT, Criqui MH, Treat-Jacobson D, Regensteiner JG, Creager MA, Olin JW, et al. Peripheral arterial disease detection, awareness, and treatment in primary care. <i>JAMA<\/i> 2001; 286: 1317\u20131324.","DOI":"10.1001\/jama.286.11.1317"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7. Takei T, Tokuda T, Yoshioka N, Ogata K, Tanaka A, Kojima S, et al. Impact of guideline-directed medical therapy on 2-year mortality in Japanese patients undergoing endovascular therapy for femoropopliteal lesions: Results of the multicenter GEMINI-FP study. <i>Circ J<\/i> 2025; 89: 638\u2013646.","DOI":"10.1253\/circj.CJ-25-0086"},{"key":"8","unstructured":"8. Virani SS, Alonso A, Aparicio HJ, Benjamin EJ, Bittencourt MS, Callaway CW, et al. Heart disease and stroke statistics \u2013 2021 update: A report from the American Heart Association. <i>Circulation<\/i> 2021; 143: e254\u2013e743."},{"key":"9","doi-asserted-by":"crossref","unstructured":"9. Aday AW, Everett BM. Dyslipidemia profiles in patients with peripheral artery disease. <i>Curr Cardiol Rep<\/i> 2019; 21: 1\u20139.","DOI":"10.1007\/s11886-019-1129-5"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10. Simpson WG. Biomarker variability and cardiovascular disease residual risk. <i>Curr Opin Cardiol<\/i> 2019; 34: 413\u2013417.","DOI":"10.1097\/HCO.0000000000000627"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11. Messerli FH, Hofstetter L, Rimoldi SF, Rexhaj E, Bangalore S. Risk factor variability and cardiovascular outcome: JACC review topic of the week. <i>J Am Coll Cardiol<\/i> 2019; 73: 2596\u20132603.","DOI":"10.1016\/j.jacc.2019.02.063"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12. Bangalore S, Breazna A, DeMicco DA, Wun CC, Messerli FH; TNT Steering Committee and Investigators. Visit-to-visit low-density lipoprotein cholesterol variability and risk of cardiovascular outcomes: Insights from the TNT trial. <i>J Am Coll Cardiol<\/i> 2015; 65: 1539\u20131548.","DOI":"10.1016\/j.jacc.2015.02.017"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13. Waters DD, Bangalore S, Fayyad R, DeMicco DA, Laskey R, Melamed S, et al. Visit-to-visit variability of lipid measurements as predictors of cardiovascular events. <i>J Clin Lipidol<\/i> 2018; 12: 356\u2013366.","DOI":"10.1016\/j.jacl.2017.12.003"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14. Kreger BE, Odell PM, D\u2019Agostino RB, Wilson PF. Long-term intraindividual cholesterol variability: Natural course and adverse impact on morbidity and mortality \u2013 the Framingham Study. <i>Am Heart J<\/i> 1994; 127: 1607\u20131614.","DOI":"10.1016\/0002-8703(94)90393-X"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15. Aday AW, Lawler PR, Cook NR, Ridker PM, Mora S, Pradhan AD. Lipoprotein particle profiles, standard lipids, and peripheral artery disease incidence: Prospective data from the Women\u2019s Health Study. <i>Circulation<\/i> 2018; 138: 2330\u20132341.","DOI":"10.1161\/CIRCULATIONAHA.118.035432"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16. Murabito JM, Evans JC, Nieto K, Larson MG, Levy D, Wilson PW. Prevalence and clinical correlates of peripheral arterial disease in the Framingham Offspring Study. <i>Am Heart J<\/i> 2002; 143: 961\u2013965.","DOI":"10.1067\/mhj.2002.122871"},{"key":"17","doi-asserted-by":"crossref","unstructured":"17. Jansen-Chaparro S, L\u00f3pez-Carmona MD, Cobos-Palacios L, Sanz-C\u00e1novas J, Bernal-L\u00f3pez MR, G\u00f3mez-Huelgas R. Statins and peripheral arterial disease: A narrative review. <i>Front Cardiovasc Med<\/i> 2021; 8: 777016.","DOI":"10.3389\/fcvm.2021.777016"},{"key":"18","doi-asserted-by":"crossref","unstructured":"18. Murabito JM, D\u2019Agostino RB, Silbershatz H, Wilson PW. Intermittent claudication: A risk profile from the Framingham Heart Study. <i>Circulation<\/i> 1997; 96: 44\u201349.","DOI":"10.1161\/01.CIR.96.1.44"},{"key":"19","doi-asserted-by":"crossref","unstructured":"19. Newman AB, Siscovick DS, Manolio TA, Polak J, Fried LP, Borhani NO, et al. Ankle-arm index as a marker of atherosclerosis in the Cardiovascular Health Study. Cardiovascular Heart Study (CHS) Collaborative Research Group. <i>Circulation<\/i> 1993; 88: 837\u2013845.","DOI":"10.1161\/01.CIR.88.3.837"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20. Fowkes FG, Housley E, Riemersma RA, Macintyre CC, Cawood EH, Prescott RJ, et al. Smoking, lipids, glucose intolerance, and blood pressure as risk factors for peripheral atherosclerosis compared with ischemic heart disease in the Edinburgh Artery Study. <i>Am J Epidemiol<\/i> 1992; 135: 331\u2013340.","DOI":"10.1093\/oxfordjournals.aje.a116294"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21. Shao SC, Chan YY, Kao Yang YH, Lin SJ, Hung MJ, Chien RN, et al. The Chang Gung Research Database: A multi-institutional electronic medical records database for real-world epidemiological studies in Taiwan. <i>Pharmacoepidemiol Drug Saf<\/i> 2019; 28: 593\u2013600.","DOI":"10.1002\/pds.4713"},{"key":"22","doi-asserted-by":"crossref","unstructured":"22. Tsai MS, Lin MH, Lee CP, Yang YH, Chen WC, Chang GH, et al. Chang Gung Research Database: A multi-institutional database consisting of original medical records. <i>Biomed J<\/i> 2017; 40: 263\u2013269.","DOI":"10.1016\/j.bj.2017.08.002"},{"key":"23","doi-asserted-by":"crossref","unstructured":"23. Tung YC, Hsiao FC, Lin CP, Ho CT, Hsu TJ, Chiang HY, et al. High triglyceride variability increases the risk of first attack of acute pancreatitis. <i>Am J Gastroenterol<\/i> 2023; 118: 1080\u20131090.","DOI":"10.14309\/ajg.0000000000002198"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24. Mena LJ, Felix VG, Melgarejo JD, Maestre GE. 24-Hour blood pressure variability assessed by average real variability: A systematic review and meta-analysis. <i>J Am Heart Assoc<\/i> 2017; 6: e006895.","DOI":"10.1161\/JAHA.117.006895"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25. Rothwell PM, Howard SC, Dolan E, O\u2019Brien E, Dobson JE, Dahl\u00f6f B, et al. Prognostic significance of visit-to-visit variability, maximum systolic blood pressure, and episodic hypertension. <i>Lancet<\/i> 2010; 375: 895\u2013905.","DOI":"10.1016\/S0140-6736(10)60308-X"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26. Yano Y. Visit-to-visit blood pressure variability: What is the current challenge? <i>Am J Hypertens<\/i> 2017; 30: 112\u2013114.","DOI":"10.1093\/ajh\/hpw124"},{"key":"27","doi-asserted-by":"publisher","unstructured":"27. Hsiao FC, Lin CP, Tung YC, Wu CT, Chu PH. Major adverse limb events in type 2 diabetes patients receiving glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors: A retrospective multi-institutional study. <i>Diabetes Res Clin Pract<\/i> 2021; 180: 109076, doi:10.1016\/j.diabres.2021.109076.","DOI":"10.1016\/j.diabres.2021.109076"},{"key":"28","doi-asserted-by":"publisher","unstructured":"28. Hsiao FC, Chan YH, Tung YC, Lin CP, Lee TH, Wang YC, et al. Visit-to-visit hemoglobin A1c variation and long-term risk of major adverse limb events in patients with type 2 diabetes. <i>J Clin Endocrinol Metab<\/i> 2023; 108: 2500\u20132509, doi:10.1210\/clinem\/dgad203.","DOI":"10.1210\/clinem\/dgad203"},{"key":"29","doi-asserted-by":"crossref","unstructured":"29. Kim MK, Han K, Kim HS, Park YM, Kwon HS, Yoon KH, et al. Cholesterol variability and the risk of mortality, myocardial infarction, and stroke: A nationwide population-based study. <i>Eur Heart J<\/i> 2017; 38: 3560\u20133566.","DOI":"10.1093\/eurheartj\/ehx585"},{"key":"30","doi-asserted-by":"crossref","unstructured":"30. Clark D III, Nicholls SJ, St John J, Elshazly MB, Kapadia SR, Tuzcu EM, et al. Visit-to-visit cholesterol variability correlates with coronary atheroma progression and clinical outcomes. <i>Eur Heart J<\/i> 2018; 39: 2551\u20132558.","DOI":"10.1093\/eurheartj\/ehy209"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31. Manemann SM, Bielinski SJ, Moser ED, St Sauver JL, Takahashi PY, Roger VL, et al. Variability in lipid levels and risk for cardiovascular disease: An electronic health record-based population cohort study. <i>J Am Heart Assoc<\/i> 2023; 12: e027639.","DOI":"10.1161\/JAHA.122.027639"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32. Li S, Hou L, Zhu S, Yi Q, Liu W, Zhao Y, et al. Lipid variability and risk of cardiovascular diseases and all-cause mortality: A systematic review and meta-analysis of cohort studies. <i>Nutrients<\/i> 2022; 14: 2450.","DOI":"10.3390\/nu14122450"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33. Meijer WT, Grobbee DE, Hunink MM, Hofman A, Hoes AW. Determinants of peripheral arterial disease in the elderly: The Rotterdam Study. <i>Arch Intern Med<\/i> 2000; 160: 2934\u20132938.","DOI":"10.1001\/archinte.160.19.2934"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34. Besterman E. Experimental coronary atherosclerosis in rabbits. <i>Atherosclerosis<\/i> 1970; 12: 75\u201383.","DOI":"10.1016\/0021-9150(70)90085-7"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35. Lee SH, Kim MK, Rhee EJ. Effects of cardiovascular risk factor variability on health outcomes. <i>Endocrinol Metabol<\/i> 2020; 35: 217\u2013226.","DOI":"10.3803\/EnM.2020.35.2.217"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36. Chen H, Ren JY, Xing Y, Zhang WL, Liu X, Wu P, et al. Short-term withdrawal of simvastatin induces endothelial dysfunction in patients with coronary artery disease: A dose\u2013response effect dependent on endothelial nitric oxide synthase. <i>Int J Cardiol<\/i> 2009; 131: 313\u2013320.","DOI":"10.1016\/j.ijcard.2007.10.044"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37. Shapiro MD, Fazio S. From lipids to inflammation: New approaches to reducing atherosclerotic risk. <i>Circ Res<\/i> 2016; 118: 732\u2013749.","DOI":"10.1161\/CIRCRESAHA.115.306471"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38. Lee S, Zhou J, Wong WT, Liu T, Wu WK, Wong ICK, et al. Glycemic and lipid variability for predicting complications and mortality in diabetes mellitus using machine learning. <i>BMC Endocr Disord<\/i> 2021; 21: 94.","DOI":"10.1186\/s12902-021-00751-4"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39. Lewis GF, Rader DJ. New insights into the regulation of HDL metabolism and reverse cholesterol transport. <i>Circ Res<\/i> 2005; 96: 1221\u20131232.","DOI":"10.1161\/01.RES.0000170946.56981.5c"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40. Navab M, Yu R, Gharavi N, Huang W, Ezra N, Lotfizadeh A, et al. High-density lipoprotein: Antioxidant and anti-inflammatory properties. <i>Curr Atheroscler Rep<\/i> 2007; 9: 244\u2013248.","DOI":"10.1007\/s11883-007-0026-3"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41. Mineo C, Deguchi H, Griffin JH, Shaul PW. Endothelial and antithrombotic actions of HDL. <i>Circ Res<\/i> 2006; 98: 1352\u20131364.","DOI":"10.1161\/01.RES.0000225982.01988.93"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42. Ko DT, Alter DA, Guo H, Koh M, Lau G, Austin PC, et al. High-density lipoprotein cholesterol and cause-specific mortality in individuals without previous cardiovascular conditions: The CANHEART study. <i>J Am Coll Cardiol<\/i> 2016; 68: 2073\u20132083.","DOI":"10.1016\/j.jacc.2016.08.038"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43. Roberts CK, Ng C, Hama S, Eliseo AJ, Barnard RJ. Effect of a short-term diet and exercise intervention on inflammatory\/anti-inflammatory properties of HDL in overweight\/obese men with cardiovascular risk factors. <i>J Appl Physiol<\/i> 2006; 101: 1727\u20131732.","DOI":"10.1152\/japplphysiol.00345.2006"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44. Parvaresh Rizi E, Baig S, Loh TP, Toh SA, Khoo CM, Tai ES. Two-hour postprandial lipoprotein particle concentration differs between lean and obese individuals. <i>Front Physiol<\/i> 2019; 10: 856.","DOI":"10.3389\/fphys.2019.00856"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45. De Bruin T, Brouwer CB, Gimpel JA, Erkelens DW. Postprandial decrease in HDL cholesterol and HDL apo AI in normal subjects in relation to triglyceride metabolism. <i>Am J Physiol<\/i> 1991; 260: E492\u2013E498.","DOI":"10.1152\/ajpendo.1991.260.3.E492"},{"key":"46","doi-asserted-by":"crossref","unstructured":"46. Mann DM, Glazer NL, Winter M, Paasche-Orlow MK, Muntner P, Shimbo D, et al. A pilot study identifying statin nonadherence with visit-to-visit variability of low-density lipoprotein cholesterol. <i>Am J Cardiol<\/i> 2013; 111: 1437\u20131442.","DOI":"10.1016\/j.amjcard.2013.01.297"},{"key":"47","doi-asserted-by":"crossref","unstructured":"47. Marinho LL, Everett BM, Aday AW, Visseren FL, MacFadyen JG, Zaharris E, et al. Effect of pemafibrate on diabetic foot ulceration and gangrene: An exploratory analysis from PROMINENT. <i>J Am Coll Cardiol<\/i> 2024; 84: 408\u2013410.","DOI":"10.1016\/j.jacc.2024.05.028"},{"key":"48","doi-asserted-by":"crossref","unstructured":"48. Thomas PE, Vedel-Krogh S, Kamstrup PR. High lipoprotein (a) is a risk factor for peripheral artery disease, abdominal aortic aneurysms, and major adverse limb events. <i>Curr Opin Lipidol<\/i> 2024; 39: 511\u2013519.","DOI":"10.1097\/HCO.0000000000001168"},{"key":"49","doi-asserted-by":"crossref","unstructured":"49. Tomoi Y, Takahara M, Soga Y, Hirano T, Tsunoda K, Katsuki T, et al. Impact of high lipoprotein (a) levels on delayed wound healing in patients with chronic limb-threatening ischemia after peripheral endovascular therapy. <i>Circ J<\/i> 2025; 89: 550\u2013556.","DOI":"10.1253\/circj.CJ-24-0383"}],"container-title":["Circulation Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/90\/5\/90_CJ-25-0504\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,25]],"date-time":"2026-04-25T03:18:59Z","timestamp":1777087139000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/circj\/90\/5\/90_CJ-25-0504\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,24]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026]]}},"URL":"https:\/\/doi.org\/10.1253\/circj.cj-25-0504","relation":{},"ISSN":["1346-9843","1347-4820"],"issn-type":[{"value":"1346-9843","type":"print"},{"value":"1347-4820","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,24]]},"article-number":"CJ-25-0504"}}