Document Type : Original Article

Authors

1 Ph.D. Student in Exercise Physiology, Department of Physical Education and Sport Sciences, Neyshabour Branch, Islamic Azad University, Neyshabur, Iran.

2 Professor at Department of Exercise Physiology, Faculty of Sport Science, Ferdowsi University of Mashhad, Mashhad, Iran.

3 Assistant Professor at Department of Physical Education and Sport Sciences, Neyshabour Branch, Islamic Azad University, Neyshabur, Iran.

Abstract

Extended Abstract
Background and Aim: Cardiovascular diseases (CVDs) remain among the leading causes of mortality worldwide, with coronary artery disease (CAD) playing a significant role (2, 3). CAD occurs due to the narrowing or blockage of coronary arteries caused by atherosclerosis, which results from lipid accumulation and blood clot formation, potentially leading to myocardial infarction. Coronary artery bypass grafting (CABG) surgery is a widely used treatment to improve myocardial blood flow; however, the risk of recurrent atherosclerosis remains.
Key risk factors for CAD include elevated total cholesterol (TC) and low-density lipoprotein (LDL) levels, along with reduced high-density lipoprotein (HDL) (4). Additionally, apolipoprotein B (ApoB) is a crucial atherogenic marker that plays a fundamental role in atherosclerosis progression (11). Research suggests that physical exercise, particularly endurance training, has a beneficial impact on reducing ApoB levels and improving lipid profiles. However, some studies have reported conflicting results (12). Given these inconsistencies, this study aims to investigate the effects of combined aerobic-resistance training on lipid profile, ApoB levels, and atherogenic indices in middle-aged men following CABG surgery.
Materials and Methods: This study employed a quasi-experimental pre test-post test design with a control group. The statistical population comprised of men aged 50–65 years who had undergone CABG surgery within the past year. Based on G*Power software calculations, with a 95% confidence level and 80% statistical power, 22 participants were initially selected. To account for potential dropouts, the final sample size was increased to 25. After obtaining ethical approval and clinical trial registration, participants (mean age: 56 ± 3.8 years; weight: 75 ± 7.13 kg) were purposively selected from patients based on inclusion criteria, including cognitive health, absence of movement restrictions, body mass index (BMI) between 25–30 kg/m², and no use of non-specific medications. Participants were then randomly assigned to an exercise group (n= 14) and a control group (n= 11). The intervention consisted of an eight-week combined training program (aerobic-resistance), performed three times per week. Aerobic exercises included treadmill walking (20–30 min), cycling on an ergometer (10–12 min), and hand cycling (10 min). Exercise intensity was progressively increased based on the Borg scale and heart rate reserve, starting at 55% and reaching 80% during the final ten sessions. The resistance training component involved selected exercises using TheraBand resistance bands, beginning with low resistance and gradually increasing repetitions (from 8 to 15), followed by progressive resistance increments. All exercises were supervised by a cardiologist and a sports medicine specialist. Before and after the intervention, body composition, blood pressure, heart rate, and dietary intake were assessed. Fasting blood samples were collected, and plasma levels of ApoB, LDL, HDL, and TC were measured using ELISA and enzymatic methods. Data analysis was conducted using SPSS version 21 with repeated-measures ANOVA, considering a significance level of p<0.05.
Finding: The findings demonstrated that combined aerobic-resistance training significantly improved several lipid profile and atherogenic indices in CABG patients. Statistical analysis revealed significant between-group differences in plasma levels of TC (p=0.01, F=7.15), HDL (p=0.01, F=6.35), LDL/HDL ratio (p=0.02, F=5.86), and atherogenic index (TC - HDL/HDL) (p=0.001, F=13.87). Specifically, the eight-week intervention led to a significant reduction in TC (3.95%), LDL/HDL ratio (8.19%), and atherogenic index (14.28%), along with a significant increase in HDL (6.87%). However, the between-group differences in LDL levels were not statistically significant (p=0.15, F=2.21). Additionally, significant changes were observed in plasma ApoB levels (p=0.01, F=6.90), with a significant reduction of 4.4% in the training group (p=0.005, F=11.11). Furthermore, significant reductions were observed in body weight (p=0.004, F=10.39), body fat mass (p=0.02, F=5.12), and BMI (p=0.004, F=10.27). Specifically, the intervention led to a significant decrease in body weight (1.46%), fat mass (10.85%), and BMI (1.45%) in the exercise group. 
Conclusion: The results suggest that reducing ApoB levels may serve as a more reliable indicator than LDL for assessing CVD risk, as ApoB reflects the number of LDL particles and has a stronger association with atherosclerosis. Previous studies, such as those by Jafari et al. (2018) and Mozzella et al. (2020), have confirmed a reduction in ApoB following exercise interventions. In contrast, other studies (Azizi et al., 2016; Behr et al., 2010) have reported no significant changes in ApoB, possibly due to variations in exercise intensity and duration. The reduction in atherogenic indices observed in this study suggests that combined training effectively improves lipid profiles. Notably, the LDL/HDL ratio, a strong predictor of CVD risk, significantly decreased. While some previous studies support these findings, others suggest that the effectiveness of exercise on lipid profiles depends on factors such as training intensity, diet, and individual participant characteristics.
The findings of this study indicate that an eight-week combined aerobic-resistance training program exerts a beneficial effect on lipid profiles, plasma ApoB levels, and atherogenic indices in middle-aged men following CABG surgery. The reduction in TC, LDL/HDL ratio, and atherogenic index, along with the increase in HDL, reinforces  the positive impact of such training on cardiovascular health. Moreover, the significant reduction in ApoB, despite no significant change in LDL levels, highlights the potential of ApoB as a more precise and reliable marker for CVD risk assessment. Improvements in body composition, including reductions in body weight and fat mass, further confirm the positive role of physical activity in managing metabolic risk factors. Therefore, incorporating combined aerobic-resistance training into cardiac rehabilitation programs is recommended to enhance cardiovascular function and prevent recurrent atherosclerosis. Future research should focus on investigating the long-term effects of such training interventions.
Keywords: Exercise training, Apolipoprotein B, Lipid profile, Coronary artery bypass grafting
Ethical Considerations
All ethical principles in this research were meticulously adhered to by the researchers.
Compliance with ethical guideline
To conduct the research, the consent form was completed by the participants after they were fully informed about the research process, including its risks and benefits.
Funding
The authors of this article declare that they have not received any financial support from any organization.
Conflicts of interest
The authors report no conflicts of interest in relation to this manuscript.

Keywords

1. WHO. Cardiovascular diseases (CVDs): WHO; 2021 [updated 11 June 2021]. Available from: https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds).
2. Schumacher T, Benndorf RA. ABC transport proteins in cardiovascular disease—A brief summary. Molecules. 2017;22(4):589. https://doi.org/10.3390/molecules22040589
3. Anderson L, Thompson DR, Oldridge N, Zwisler AD, Rees K, Martin N, et al. Exercise‐based cardiac rehabilitation for coronary heart disease. Cochrane Database of Systematic Reviews. 2016;67(1): 1-12. https://doi.org/10.1002/14651858.cd001800.pub3
4. Van Ta Q. Atherosclerosis in Cardiovascular Disease: An Overview. TTU Review. 2021;2(1):15-8.
5. Poznyak AV, Wu W-K, Melnichenko AA, Wetzker R, Sukhorukov V, Markin AM, et al. Signaling pathways and key genes involved in regulation of foam cell formation in atherosclerosis. Cells. 2020;9(3):584. https://doi.org/10.3390/cells9030584
6. Zhang T, Chen S, Saito A. A meta-analysis of the effects of green tea combined with physical activity on blood lipids in humans. Revista Brasileira de Medicina do Esporte. 2020;26:454-60.  https://doi.org/10.1590/1517-869220202605212295
7. Holme SA, Sigsgaard T, Holme JA, Holst GJ. Effects of particulate matter on atherosclerosis: a link via high-density lipoprotein (HDL) functionality? Particle and Fibre Toxicology. 2020;17:1-12. https://doi.org/10.1186/s12989-020-00367-x
8. Singh K, Thanassoulis G, Dufresne L, Nguyen A, Gupta R, Narayan KV, et al. A comparison of lipids and apoB in Asian Indians and Americans. Global Heart. 2021;16(1):7. https://doi.org/10.5334/gh.882
9. Erqou S, Thompson A, Di Angelantonio E, Saleheen D, Kaptoge S, Marcovina S, et al. Apolipoprotein (a) isoforms and the risk of vascular disease: systematic review of 40 studies involving 58,000 participants. Journal of the American College of Cardiology. 2010;55(19):2160-7. https://doi.org/10.1016/j.jacc.2009.10.080
10. Mahdieh N, Heshmatzad K, Rabbani B. A systematic review of LDLR, PCSK9, and APOB variants in Asia. Atherosclerosis. 2020;305:50-7.   https://doi.org/10.1016/j.atherosclerosis.2020.05.004
11. Cibicková L, Langová K, Vaverková H, Lukeš J, Cibicek N, Karásek D. Superior role of waist circumference to body-mass index in the prediction of cardiometabolic risk in dyslipidemic patients. Physiological Research. 2019;68(6):931-8. https://doi.org/10.33549/physiolres.934176
12. Muscella A, Stefàno E, Marsigliante S. The effects of exercise training on lipid metabolism and coronary heart disease. American Journal of Physiology-Heart and Circulatory Physiology. 2020;319(1):H76-H88. https://doi.org/10.1152/ajpheart.00708.2019
13. Khajei R, Haghighi AH, Hamedinia MR, Lamir AR. Effects of eight week aerobic training on monocytes ABCG5 gene expression in middle-aged men after heart bypass surgery. Journal of Sabzevar University of Medical Sciences. 2017;24(1):79-88. [In Persian]. http://eprints.medsab.ac.ir/id/eprint/111
14. Joseph LJ, Davey SL, Evans WJ, Campbell WW. Differential effect of resistance training on the body composition and liporotein-lipid profile in older men and women. Metabolism. 1999;48(11):1474-80. https://doi.org/10.1016/s0026-0495(99)90162-2
15. Silva RG, Silva DR, Pina FL, Nascimento MA, Ribeiro AS, Cyrino ES. Effect of two different weekly resistance training frequencies on muscle strength and blood pressure in normotensive older women. Revista Brasileira de Cineantropometria & Desempenho Humano. 2017;19(1):118-27. https://doi.org/10.70252/qsom3270
16. Kang H. Sample size determination and power analysis using the G* Power software. Journal of Educational Evaluation for Health Professions. 2021;18. https://doi.org/10.3352/jeehp.2021.18.17
17. Hamidi A, Rashidlamir A, Khajei R, Zarei M, Zendedel A. The effect of aerobic-resistance training on plasma levels of bFGF in coronary artery disease after CABG. Journal of Arak University of Medical Sciences. 2020;23(3):314-25. [In Persian]. https://doi.org/10.32598/jams.23.3.6056.1
18. Jafari M, Rashidlamir A, Dastani M, Fathi M, Alavinya SE. The effect of cardiac rehabilitation on ApoA1 and ApoB in men with coronary heart disease (CHD) after coronary artery bypass graft (CABG). Medical Science Journal of Islamic Azad Univesity-Tehran Medical Branch. 2018;28(2):117-23. [In Persian]. https://doi.org/10.29252/iau.28.2.117
19. Wang Y, Xu D. Effects of aerobic exercise on lipids and lipoproteins. Lipids in Health and Disease. 2017;16:1-8. https://doi.org/10.1186/s12944-017-0515-5
20. Goldfield GS, Kenny GP, Alberga AS, Prud’homme D, Hadjiyannakis S, Gougeon R, et al. Effects of aerobic training, resistance training, or both on psychological health in adolescents with obesity: The HEARTY randomized controlled trial. Journal of Consulting and Clinical Psychology. 2015;83(6):1123. https://doi.org/10.1037/ccp0000038
21. Kadoglou NP, Fotiadis G, Athanasiadou Z, Vitta I, Lampropoulos S, Vrabas IS. The effects of resistance training on ApoB/ApoA-I ratio, Lp (a) and inflammatory markers in patients with type 2 diabetes. Endocrine. 2012;42:561-9. https://doi.org/10.1007/s12020-012-9650-y
22. Sarlak Z. Effects of Eight Weeks Aerobic Training on Serum Apo AI, APO B and lipid profile in Overweight Women. Sport Physiology. 2016;7(28):45-58. [In Persian]. DOR: 20.1001.1.2322164.1394.7.28.3.9
23. Azizi M, Hussein Pordelavr S, Roozbahani S. The Comparison Effects of Submaximal Aerobic Exercise on Lipid Profiles and Apolioprotein A-1 and B in Overweight Women. Jundishapur Scientific Medical Journal. 2016;15(5):507-16. [In Persian].
24. Behre C, Bergström G, Schmidt C. Moderate physical activity is associated with lower ApoB/ApoA-I ratios independently of other risk factors in healthy, middle-aged men. Angiology. 2010;61(8):775-9. https://doi.org/10.1177/0003319710373746
25. Carr SS, Hooper AJ, Sullivan DR, Burnett JR. Non-HDL-cholesterol and apolipoprotein B compared with LDL-cholesterol in atherosclerotic cardiovascular disease risk assessment. Pathology. 2019;51(2):148-54. https://doi.org/10.1016/j.pathol.2018.11.006
26. Marchini T, Hansen S, Wolf D. ApoB-specific CD4+ T cells in mouse and human atherosclerosis. Cells. 2021;10(2):446. https://doi.org/10.3390/cells10020446
27. da Silva JL, Vinagre CG, Morikawa AT, Alves MJN, Mesquita CH, Maranhão RC. Resistance training changes LDL metabolism in normolipidemic subjects: a study with a nanoemulsion mimetic of LDL. Atherosclerosis. 2011;219(2):532-7. https://doi.org/10.1016/j.atherosclerosis.2011.08.014
28. Kharaba ZJ, Buabeid MA, Ibrahim NA, Jirjees FJ, Al Obaidi HJ, Kaddaha A, et al. Testosterone therapy in hypogonadal patients and the associated risks of cardiovascular events. Biomedicine & Pharmacotherapy. 2020;129:110423. https://doi.org/10.1016/j.biopha.2020.110423
29. Sultani R, Tong DC, Peverelle M, Lee YS, Baradi A, Wilson AM. Elevated triglycerides to high-density lipoprotein cholesterol (TG/HDL-C) ratio predicts long-term mortality in high-risk patients. Heart, Lung and Circulation. 2020;29(3):414-21.‌ https://doi.org/10.1016/j.hlc.2019.03.019
30. Hajighasemi A, Ravasi AA, Kordi MR, Rashidlamir A. The Effect of Moderate Resistance Training on Lymphocyte Cells ABCA1 Gene Expression, HDL and LDL in male with Coronary Artery Disease. Journal of Sport Biosciences. 2024 Mar 20;16(1):5-15. [In Persian]. https://doi.org/10.22059/jsb.2022.206134.1075
31. Keihaniyan A, Arazi H, Kargarfard M. The Effect of Eight-Week Resistance and Aerobic Training on Lipid Profile and Serum Levels of Hepatokine HFREP1 in Obese Men with Type 2 Diabetes. Sport Physiology. 2018;10(40):85-98. [In Persian]. https://doi.org/10.22089/spj.2018.5891.1773
32. Shono N, Urata H, Saltin B, Mizuno M, Harada T, Shindo M, et al. Effects of low intensity aerobic training on skeletal muscle capillary and blood lipoprotein profiles. Journal of Atherosclerosis and Thrombosis. 2002;9(1):78-85. https://doi.org/10.5551/jat.9.78
33. Abdi M, Marefati H, Moazenzadeh M. The Effect of Cardiac Rehabilitation on the Serum Levels of Adiponectin and Lipoproteins in Male Atherosclerotic Patients. Journal of Kerman University of Medical Sciences. 2012;19(5):317-25. [In Persian]. https://jkmu.kmu.ac.ir/article_16504.html
34. Shamsizadeh M, Hejazi SM, Minaee S, Haghir H, Rajayi L. The effect of eight weeks of aerobic training on serum lipid profile and serum level of fibrinogen in middle-aged men with heart failure. Payavard Salamat. 2020;14(1):86-95. [In Persian]. http://payavard.tums.ac.ir/article-1-6944-en.html
35. Banz WJ, Maher MA, Thompson WG, Bassett DR, Moore W, Ashraf M, et al. Effects of resistance versus aerobic training on coronary artery disease risk factors. Experimental Biology and Medicine. 2003;228(4):434-40. https://doi.org/10.1177/153537020322800414
36. Asad M. Effect of 8 weeks aerobic, resistance and concurrent training on cholestrol, LDL, HDL and cardiovascular fitness in obesity male. Applied Research in Sport Management. 2013;1(3):57-64. [In Persian]. DOR: 20.1001.1.23455551.1391.1.3.7.8
37. Elliott K, Sale C, Cable N. Effects of resistance training and detraining on muscle strength and blood lipid profiles in postmenopausal women. British Journal of Sports Medicine. 2002;36(5):340-4. https://doi.org/10.1136/bjsm.36.5.340
38. Stoedefalke K, Armstrong N, Kirby B, Welsman J. Effect of training on peak oxygen uptake and blood lipids in 13 to 14‐year‐old girls. Acta Paediatrica. 2000;89(11):1290-4. https://doi.org/10.1111/j.1651-2227.2000.tb00753.x
39. Welsman JR, Armstrong N, Withers S. Responses of young girls to two modes of aerobic training. British Journal of Sports Medicine. 1997;31(2):139-42. https://doi.org/10.1136/bjsm.31.2.139
40. Durstine JL, Grandjean PW, Cox CA, Thompson PD. Lipids, lipoproteins, and exercise. Journal of Cardiopulmonary Rehabilitation and Prevention. 2002;22(6):385-98. https://doi.org/10.1097/00008483-200211000-00002
41. Sarmadiyan M, Khorshidi D. Effect of combined training on body composition, lipids levels and indicators of metabolic syndrome in overweight and obesed postmenopausal women. Journal of Gerontology. 2016;1(2):36-44. https://doi.org/10.18869/acadpub.joge.1.2.36
42. Triantafyllidi H, Benas D, Schoinas A, Varoudi M, Thymis J, Kostelli G, et al. Sex‐related associations of high‐density lipoprotein cholesterol with aortic stiffness and endothelial glycocalyx integrity in treated hypertensive patients. The Journal of Clinical Hypertension. 2020;22(10):1827-34. https://doi.org/10.1111/jch.14002
43. Li H-M, Mo Z-W, Peng Y-M, Li Y, Dai W-P, Yuan H-Y, et al. Angiogenic and Antiangiogenic mechanisms of high density lipoprotein from healthy subjects and coronary artery diseases patients. Redox Biology. 2020;36:101642. https://doi.org/10.1016/j.redox.2020.101642