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Published in: Cardiovascular Diabetology 1/2023

Open Access 01-12-2023 | Heart Failure | Research

Association between fingertip-measured advanced glycation end products and cardiovascular events in outpatients with cardiovascular disease

Authors: Tomoya Hirai, Kazuhiro Fujiyoshi, Satoru Yamada, Takuya Matsumoto, Junko Kikuchi, Kohki Ishida, Miwa Ishida, Kyo Shigeta, Taiki Tojo

Published in: Cardiovascular Diabetology | Issue 1/2023

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Abstract

Background

The accumulation of advanced glycation end products (AGEs) is associated with cardiovascular events in patients with cardiovascular disease (CVD). However, the relationship between the AGEs measured by an AGEs sensor noninvasively at the fingertip and prognosis in patients with CVD remains unclear. Therefore, this study aimed to determine the relationship between AGEs score and prognosis among patients with CVD.

Methods

A total of 191 outpatients with CVD were included. AGEs score were measured using an AGEs sensor and the patients were classified into groups by the median value of AGEs score. The incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at 30 months was compared between high- and low-AGEs score groups. In addition, receiver operating characteristic (ROC) curve analysis was used to calculate cutoff value for the AGEs score, which discriminates the occurrence of MACCE. Cox regression analysis was performed to identify the factors associated with the presence of MACCE. MACCE included cardiac death, myocardial infarction, percutaneous coronary intervention, heart failure, and stroke.

Results

AGEs score was normally distributed, with a median value of 0.51. No significant intergroup differences were found in laboratory findings, physical functions, or medications. The high-AGEs score group had a significantly higher incidence of MACCE than the low-AGEs score group (27.1 vs. 10.5%, P = 0.007). A high-AGEs score was a risk factor for MACCE (hazard ratio, 2.638; 95% confidence interval, 1.271–5.471; P = 0.009). After the adjustment for confounders other than 6-min walking distance, the AGEs score remained a factor associated with the occurrence of MACCE. The best cutoff AGEs score for the detection of MACCE was 0.51 (area under the curve, 0.642; P = 0.008; sensitivity, 72.2%; specificity, 54.8%).

Conclusions

AGEs score measured at the fingertip in patients with CVD is associated with MACCE. AGEs score, which can be measured noninvasively and easily, may be useful as an assessment for the secondary prevention of CVD in patients with CVD.
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Literature
1.
go back to reference Lippi G, Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AME Med J. 2020;5(15):1–6. Lippi G, Sanchis-Gomar F. Global epidemiology and future trends of heart failure. AME Med J. 2020;5(15):1–6.
2.
go back to reference Okura Y, Ramadan MM, Ohno Y, Mitsuma W, Tanaka K, Ito M, et al. Impending epidemic: future projection of heart failure in Japan to the year 2055. Circ J. 2008;72(3):489–91.CrossRefPubMed Okura Y, Ramadan MM, Ohno Y, Mitsuma W, Tanaka K, Ito M, et al. Impending epidemic: future projection of heart failure in Japan to the year 2055. Circ J. 2008;72(3):489–91.CrossRefPubMed
3.
go back to reference Ishihara S, Kawakami R, Nogi M, Hirai K, Hashimoto Y, Nakada Y, et al. Incidence and clinical significance of 30-day and 90-day rehospitalization for heart failure among patients with acute decompensated heart failure in Japan—from the NARA-HF study. Circ J. 2020;84(2):194–202.CrossRefPubMed Ishihara S, Kawakami R, Nogi M, Hirai K, Hashimoto Y, Nakada Y, et al. Incidence and clinical significance of 30-day and 90-day rehospitalization for heart failure among patients with acute decompensated heart failure in Japan—from the NARA-HF study. Circ J. 2020;84(2):194–202.CrossRefPubMed
4.
go back to reference Chainani V, Shaharyar S, Dave K, Choksi V, Ravindranthan S, Hanno R, et al. Objective measures of the frailty syndrome (hand grip strength and gait speed) and cardiovascular mortality: a systematic review. Int J Cardiol. 2016;215:487–93.CrossRefPubMed Chainani V, Shaharyar S, Dave K, Choksi V, Ravindranthan S, Hanno R, et al. Objective measures of the frailty syndrome (hand grip strength and gait speed) and cardiovascular mortality: a systematic review. Int J Cardiol. 2016;215:487–93.CrossRefPubMed
5.
go back to reference Nakamura T, Kamiya K, Hamazaki N, Matsuzawa R, Nozaki K, Ichikawa T, et al. Quadriceps strength and mortality in older patients with heart failure. Can J Cardiol. 2021;37(3):476–83.CrossRefPubMed Nakamura T, Kamiya K, Hamazaki N, Matsuzawa R, Nozaki K, Ichikawa T, et al. Quadriceps strength and mortality in older patients with heart failure. Can J Cardiol. 2021;37(3):476–83.CrossRefPubMed
6.
go back to reference Beatty AL, Schiller NB, Whooley MA. Six-minute walk test as a prognostic tool in stable coronary heart disease: data from the heart and soul study. Arch Intern Med. 2012;172(14):1096–102.CrossRefPubMedPubMedCentral Beatty AL, Schiller NB, Whooley MA. Six-minute walk test as a prognostic tool in stable coronary heart disease: data from the heart and soul study. Arch Intern Med. 2012;172(14):1096–102.CrossRefPubMedPubMedCentral
7.
go back to reference Roul G, Germain P, Bareiss P. Does the 6-minute walk test predict the prognosis in patients with NYHA class II or III chronic heart failure? Am Heart J. 1998;136(3):449–57.CrossRefPubMed Roul G, Germain P, Bareiss P. Does the 6-minute walk test predict the prognosis in patients with NYHA class II or III chronic heart failure? Am Heart J. 1998;136(3):449–57.CrossRefPubMed
8.
go back to reference Kateyian ST, Brawner CA, Savage PD, Ehrman JK, Schairer J, Divine G, et al. Peak aerobic capacity predicts prognosis in patients with coronary heart disease. Am Heart J. 2008;156(2):292–300.CrossRef Kateyian ST, Brawner CA, Savage PD, Ehrman JK, Schairer J, Divine G, et al. Peak aerobic capacity predicts prognosis in patients with coronary heart disease. Am Heart J. 2008;156(2):292–300.CrossRef
9.
go back to reference Makita S, Yasu T, Akashi YJ, Adachi H, Izawa H, Ishihara S, et al. JCS/JACR 2021 guideline on rehabilitation in patients with cardiovascular disease. Circ J. 2022;87(1):155–235.CrossRefPubMed Makita S, Yasu T, Akashi YJ, Adachi H, Izawa H, Ishihara S, et al. JCS/JACR 2021 guideline on rehabilitation in patients with cardiovascular disease. Circ J. 2022;87(1):155–235.CrossRefPubMed
10.
go back to reference Polak JF, O’Leary DH. Carotid intima-media thickness as surrogate for and predictor of CVD. Glob Heart. 2016;11(3):295-321.e3.CrossRefPubMed Polak JF, O’Leary DH. Carotid intima-media thickness as surrogate for and predictor of CVD. Glob Heart. 2016;11(3):295-321.e3.CrossRefPubMed
11.
go back to reference Blacher J, Asmer R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33(5):1111–7.CrossRefPubMed Blacher J, Asmer R, Djane S, London GM, Safar ME. Aortic pulse wave velocity as a marker of cardiovascular risk in hypertensive patients. Hypertension. 1999;33(5):1111–7.CrossRefPubMed
12.
go back to reference Nin JW, Jorsal A, Ferreira I, Schalkwijk CG, Prins MH, Parving HH, et al. Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study. Diabetes Care. 2011;34(2):442–7.CrossRefPubMedPubMedCentral Nin JW, Jorsal A, Ferreira I, Schalkwijk CG, Prins MH, Parving HH, et al. Higher plasma levels of advanced glycation end products are associated with incident cardiovascular disease and all-cause mortality in type 1 diabetes: a 12-year follow-up study. Diabetes Care. 2011;34(2):442–7.CrossRefPubMedPubMedCentral
13.
go back to reference Reichert S, Triebert U, Santos AN, Hofmann B, Schaller HG, Schlitt A, et al. Soluble form of receptor for advanced glycation end products and incidence of new cardiovascular events among patients with cardiovascular disease. Atherosclerosis. 2017;266:234–9.CrossRefPubMed Reichert S, Triebert U, Santos AN, Hofmann B, Schaller HG, Schlitt A, et al. Soluble form of receptor for advanced glycation end products and incidence of new cardiovascular events among patients with cardiovascular disease. Atherosclerosis. 2017;266:234–9.CrossRefPubMed
14.
go back to reference Hanssen NMJ, Beulens JWJ, Dieren SV, Scheijen JLJM, Daphne LA, Spijkerman AMW, et al. Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes. 2015;64(1):257–65.CrossRefPubMed Hanssen NMJ, Beulens JWJ, Dieren SV, Scheijen JLJM, Daphne LA, Spijkerman AMW, et al. Plasma advanced glycation end products are associated with incident cardiovascular events in individuals with type 2 diabetes: a case-cohort study with a median follow-up of 10 years (EPIC-NL). Diabetes. 2015;64(1):257–65.CrossRefPubMed
15.
go back to reference Yamanaka M, Matsumura T, Ohno R, Fujiwara Y, Shinagawa M, Sugawa H, et al. Non-invasive measurement of skin autofluorescence to evaluate diabetic complications. J Clin Biochem Nutr. 2016;58(2):135–40.CrossRefPubMedPubMedCentral Yamanaka M, Matsumura T, Ohno R, Fujiwara Y, Shinagawa M, Sugawa H, et al. Non-invasive measurement of skin autofluorescence to evaluate diabetic complications. J Clin Biochem Nutr. 2016;58(2):135–40.CrossRefPubMedPubMedCentral
16.
go back to reference Hirai T, Fujiyoshi K, Yamada S, Matsumoto T, Kikuchi J, Ishida K, et al. Advanced glycation end products are associated with diabetes status and physical functions in patients with cardiovascular disease. Nutrients. 2022;14(15):3032.CrossRefPubMedPubMedCentral Hirai T, Fujiyoshi K, Yamada S, Matsumoto T, Kikuchi J, Ishida K, et al. Advanced glycation end products are associated with diabetes status and physical functions in patients with cardiovascular disease. Nutrients. 2022;14(15):3032.CrossRefPubMedPubMedCentral
17.
go back to reference Kunimoto M, Yokoyama M, Shimada K, Matsubara T, Aikawa T, Ouchi S, et al. Relationship between skin autofluorescence levels and clinical events in patients with heart failure undergoing cardiac rehabilitation. Cardiovasc Diabetol. 2021;20(1):208.CrossRefPubMedPubMedCentral Kunimoto M, Yokoyama M, Shimada K, Matsubara T, Aikawa T, Ouchi S, et al. Relationship between skin autofluorescence levels and clinical events in patients with heart failure undergoing cardiac rehabilitation. Cardiovasc Diabetol. 2021;20(1):208.CrossRefPubMedPubMedCentral
18.
go back to reference Morita Y, Yagi M, Ishizaki K, Takabe W, Komatsu T, Nakazawa M, et al. Evaluation of the glycative stress by non-invansive skin AGEs measurement devices. Glycation Stress Research. 2019;6(2):92–102. Morita Y, Yagi M, Ishizaki K, Takabe W, Komatsu T, Nakazawa M, et al. Evaluation of the glycative stress by non-invansive skin AGEs measurement devices. Glycation Stress Research. 2019;6(2):92–102.
19.
go back to reference Takayanagi Y, Yamanaka M, Fujihara J, Matsuoka Y, Gohto Y, Obana A, et al. Evaluation of relevance between advanced glycation end products and diabetic retinopathy stages using skin autofluorescence. Antioxidants. 2020;9(11):1100.CrossRefPubMedPubMedCentral Takayanagi Y, Yamanaka M, Fujihara J, Matsuoka Y, Gohto Y, Obana A, et al. Evaluation of relevance between advanced glycation end products and diabetic retinopathy stages using skin autofluorescence. Antioxidants. 2020;9(11):1100.CrossRefPubMedPubMedCentral
20.
go back to reference ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7.CrossRef ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002;166(1):111–7.CrossRef
21.
go back to reference Meerwaldt R, Hartog JWL, Graaff R, Huisman RJ, Links TP, Hokkander NC, et al. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16(12):3687–93.CrossRefPubMed Meerwaldt R, Hartog JWL, Graaff R, Huisman RJ, Links TP, Hokkander NC, et al. Skin autofluorescence, a measure of cumulative metabolic stress and advanced glycation end products, predicts mortality in hemodialysis patients. J Am Soc Nephrol. 2005;16(12):3687–93.CrossRefPubMed
22.
go back to reference Mulder DJ, Haelst PL, Graaff R, Gans RO, Zijlstra F, Smit AJ. Skin autofluorescence is elevated in acute myocardial infarction and is associated with the one-year incidence of major adverse cardiac events. Nath Heart J. 2009;17(4):162–8.CrossRef Mulder DJ, Haelst PL, Graaff R, Gans RO, Zijlstra F, Smit AJ. Skin autofluorescence is elevated in acute myocardial infarction and is associated with the one-year incidence of major adverse cardiac events. Nath Heart J. 2009;17(4):162–8.CrossRef
23.
go back to reference Cavero-Redondo I, Soriano-Cano A, Álvarez-Bueno C, Cunha PG, Hortelano JAM, Miguei MG, et al. Skin autofluorescence-indicated advanced glycation end products as predictors of cardiovascular and all-cause mortality in high-risk subjects: a systematic review and meta-analysis. J Am Heart Assoc. 2018;7(18): e009833.CrossRefPubMedPubMedCentral Cavero-Redondo I, Soriano-Cano A, Álvarez-Bueno C, Cunha PG, Hortelano JAM, Miguei MG, et al. Skin autofluorescence-indicated advanced glycation end products as predictors of cardiovascular and all-cause mortality in high-risk subjects: a systematic review and meta-analysis. J Am Heart Assoc. 2018;7(18): e009833.CrossRefPubMedPubMedCentral
24.
go back to reference Chen Q, Huang Q, Liu W, Zhou X. Advanced glycation end products via skin autofluorescence as a new biomarker for major adverse cardiovascular events: a meta-analysis of prospective studies. Nutr Metab Cardiovasc Dis. 2022;32(5):1083–92.CrossRefPubMed Chen Q, Huang Q, Liu W, Zhou X. Advanced glycation end products via skin autofluorescence as a new biomarker for major adverse cardiovascular events: a meta-analysis of prospective studies. Nutr Metab Cardiovasc Dis. 2022;32(5):1083–92.CrossRefPubMed
25.
go back to reference Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597–605.CrossRefPubMed Goldin A, Beckman JA, Schmidt AM, Creager MA. Advanced glycation end products: sparking the development of diabetic vascular injury. Circulation. 2006;114(6):597–605.CrossRefPubMed
26.
go back to reference Saz-Lara A, Álvarez-Bueno C, Martínez-Vizcaíno V, Notario-Pacheco B, Sequí-Dominguez I, Cavero-Redondo I. Are advanced glycation end products in skin associated with vascular dysfunction markers? A meta-analysis. Int J Environ Res Public Health. 2020;17(18):6936.CrossRefPubMedPubMedCentral Saz-Lara A, Álvarez-Bueno C, Martínez-Vizcaíno V, Notario-Pacheco B, Sequí-Dominguez I, Cavero-Redondo I. Are advanced glycation end products in skin associated with vascular dysfunction markers? A meta-analysis. Int J Environ Res Public Health. 2020;17(18):6936.CrossRefPubMedPubMedCentral
27.
go back to reference Kunimoto M, Shimada K, Yokoyama M, Matsubara T, Aikawa T, Ouchi S, et al. Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients. BMC Cardiovasc Disord. 2020;20(1):195.CrossRefPubMedPubMedCentral Kunimoto M, Shimada K, Yokoyama M, Matsubara T, Aikawa T, Ouchi S, et al. Association between the tissue accumulation of advanced glycation end products and exercise capacity in cardiac rehabilitation patients. BMC Cardiovasc Disord. 2020;20(1):195.CrossRefPubMedPubMedCentral
28.
go back to reference Kovacic JC, Castellano JM, Farkouh ME, Fuster V. The relationships between cardiovascular disease and diabetes: focus on pathogenesis. Endocrinol Metab Clin North Am. 2014;43(1):41–57.CrossRefPubMed Kovacic JC, Castellano JM, Farkouh ME, Fuster V. The relationships between cardiovascular disease and diabetes: focus on pathogenesis. Endocrinol Metab Clin North Am. 2014;43(1):41–57.CrossRefPubMed
29.
30.
go back to reference Miyata T, Strihou CY. Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors: implication of radical scavenging and transition metal chelation in inhibition of advanced glycation end product formation. Arch Biochem Biophys. 2003;419(1):50–4.CrossRefPubMed Miyata T, Strihou CY. Angiotensin II receptor blockers and angiotensin converting enzyme inhibitors: implication of radical scavenging and transition metal chelation in inhibition of advanced glycation end product formation. Arch Biochem Biophys. 2003;419(1):50–4.CrossRefPubMed
31.
go back to reference Miyata T, Strihou CY, Ueda Y, Ichimori K, Inagi R, Onogi H, et al. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol. 2002;13(10):2478–87.CrossRefPubMed Miyata T, Strihou CY, Ueda Y, Ichimori K, Inagi R, Onogi H, et al. Angiotensin II receptor antagonists and angiotensin-converting enzyme inhibitors lower in vitro the formation of advanced glycation end products: biochemical mechanisms. J Am Soc Nephrol. 2002;13(10):2478–87.CrossRefPubMed
32.
go back to reference Guilbaud A, Niquet-Leridon C, Boulanger E, Tessier FJ. How can diet affect the accumulation of advanced glycation end-products in the human body? Foods. 2016;5(4):84.CrossRefPubMedPubMedCentral Guilbaud A, Niquet-Leridon C, Boulanger E, Tessier FJ. How can diet affect the accumulation of advanced glycation end-products in the human body? Foods. 2016;5(4):84.CrossRefPubMedPubMedCentral
33.
go back to reference Yamagishi S, Ueda S, Okuda S. Food-derived advanced glycation end products (AGEs): a novel therapeutic target for various disorders. Curr Pharm Des. 2007;13(27):2832–6.CrossRefPubMed Yamagishi S, Ueda S, Okuda S. Food-derived advanced glycation end products (AGEs): a novel therapeutic target for various disorders. Curr Pharm Des. 2007;13(27):2832–6.CrossRefPubMed
34.
go back to reference Drenth H, Zuidema SU, Krijnen WP, Bautmans I, Smit AJ, Schans C, et al. Advanced glycation end products are associated with physical activity and physical functioning in the older population. J Gerontol A Biol Sci Med Sci. 2018;73(11):1545–51.CrossRefPubMed Drenth H, Zuidema SU, Krijnen WP, Bautmans I, Smit AJ, Schans C, et al. Advanced glycation end products are associated with physical activity and physical functioning in the older population. J Gerontol A Biol Sci Med Sci. 2018;73(11):1545–51.CrossRefPubMed
35.
go back to reference Chen JH, Lin X, Bu C, Zhang X. Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutr Metab (Lond). 2018;15:72.CrossRefPubMed Chen JH, Lin X, Bu C, Zhang X. Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutr Metab (Lond). 2018;15:72.CrossRefPubMed
36.
go back to reference Ambrosetti M, Abreu A, Corrà U, Davos CH, Hansen D, Frederix I, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: from knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2020;28(5):460–95.CrossRef Ambrosetti M, Abreu A, Corrà U, Davos CH, Hansen D, Frederix I, et al. Secondary prevention through comprehensive cardiovascular rehabilitation: from knowledge to implementation. 2020 update. A position paper from the Secondary Prevention and Rehabilitation Section of the European Association of Preventive Cardiology. Eur J Prev Cardiol. 2020;28(5):460–95.CrossRef
37.
go back to reference Pratesi A, Baldasseroni S, Burgisser C, Orso F, Barucci R, Sliverii MV, et al. Long-term functional outcomes after cardiac rehabilitation in older patients data from the Cardiac Rehabilitation in Advanced aGE: EXercise TRaining and Active follow-up (CR-AGE EXTRA) randomised study. Eur J Prev Cardiol. 2019;26(14):1470–8.CrossRefPubMed Pratesi A, Baldasseroni S, Burgisser C, Orso F, Barucci R, Sliverii MV, et al. Long-term functional outcomes after cardiac rehabilitation in older patients data from the Cardiac Rehabilitation in Advanced aGE: EXercise TRaining and Active follow-up (CR-AGE EXTRA) randomised study. Eur J Prev Cardiol. 2019;26(14):1470–8.CrossRefPubMed
38.
go back to reference Bierbauer W, Scholz U, Bermudez T, Debeer D, Coch M, Silvestri RF, et al. Improvements in exercise capacity of older adults during cardiac rehabilitation. Eur J Prev Cardiol. 2020;27(16):1747–55.CrossRefPubMed Bierbauer W, Scholz U, Bermudez T, Debeer D, Coch M, Silvestri RF, et al. Improvements in exercise capacity of older adults during cardiac rehabilitation. Eur J Prev Cardiol. 2020;27(16):1747–55.CrossRefPubMed
Metadata
Title
Association between fingertip-measured advanced glycation end products and cardiovascular events in outpatients with cardiovascular disease
Authors
Tomoya Hirai
Kazuhiro Fujiyoshi
Satoru Yamada
Takuya Matsumoto
Junko Kikuchi
Kohki Ishida
Miwa Ishida
Kyo Shigeta
Taiki Tojo
Publication date
01-12-2023
Publisher
BioMed Central
Keyword
Heart Failure
Published in
Cardiovascular Diabetology / Issue 1/2023
Electronic ISSN: 1475-2840
DOI
https://doi.org/10.1186/s12933-023-01953-x

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