The Effect of Resistance Training on Proprotein Subtilisin Convertase Kexin 9 Level After Coronary Bypass Surgery

NCT02674659 — Not applicable, Completed, 87 participants, National Cardiovascular Center Harapan Kita Hospital Indonesia

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The Effect of Resistance Training on Proprotein Subtilisin Convertase Kexin 9 (PCSK-9) Level in Patients After Coronary Bypass Surgery

RegistryNCT02674659
StatusCompleted
PhaseNot applicable
Study typeInterventional; randomized, parallel, masking: single, prevention
Enrollment87 (Actual)
SponsorNational Cardiovascular Center Harapan Kita Hospital Indonesia (Other)
ConditionsCoronary Artery Disease
Interventionsresistance training, aerobic training (Behavioral)
Datesstart 2016-02-10, primary completion 2016-09-23, completion 2016-12-18, first posted 2016-02-04, last updated 2020-01-21

Related Papers Related Patents Related Grants Related Experts
All trials for Coronary Artery Disease All trials of resistance training All trials of aerobic training

-Summary

This research add resistance training to patients who undergo cardiac rehabilitation program after coronary bypass surgery, comparing the level of PCSK9 level on that group to another group who receives conventional rehabilitation program (only aerobic exercise)

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+Detailed description

The PCSK9 level measured before and after cardiac rehabilitation program (around 3-4 weeks), and compared between two groups. ELISA method will be used to measure plasma PCSK9 level.

Resistance training will be given by professional trainer in gymnasium of National Cardiovascular Center Harapan Kita supervised by cardiologists, following rules from American College of Sports Medicine guideline regarding to exercise after cardiac event.

+Arms and interventions

ArmTypeInterventionsDescription
Control groupExperimentalBehavioral: aerobic trainingPatients after coronary bypass surgery who undergo conventional cardiac rehabilitation program (aerobic training only)
Intervention groupExperimentalBehavioral: resistance training; Behavioral: aerobic trainingPatients after coronary bypass surgery who undergo conventional cardiac rehabilitation program plus resistance training (aerobic and resistance training as well)
  • resistance training (Behavioral): resistance training consists of lower and upper extremities exercises. We focus on biceps and hamstring to be trained. One session was held for around 30 minutes.
  • aerobic training (Behavioral): aerobic exercise consists of warming up session, treadmill exercise (around 20-30 minutes), and wrap-up session (for all session about 1 hour)

+Outcome measures

Primary outcomes

  • PCSK-9 Level [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking patient's blood sample after cardiac rehabilitation program. The method that we use to check PCSK-9 level is ELISA method

Secondary outcomes

  • Low Density Lipoprotein [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking patient's blood sample after cardiac rehabilitation program
  • Body Mass Index [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: Body Mass Index is calculated by calculating the measured body weight divided by the height square in measure. We take BMI data after cardiac rehabilitation program in every participant.
  • High-Density Lipoprotein [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking patient's blood sample after cardiac rehabilitation program
  • Total Cholesterol [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking patient's blood sample after cardiac rehabilitation program
  • Triglyceride [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: This outcome measurement will be achieved by taking the patient's blood sample after cardiac rehabilitation program
  • Fasting Blood Glucose [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: Blood glucose concentration was taken after 10-12-hour fasting. This outcome measurement will be achieved by taking the patient's blood sample after cardiac rehabilitation program
  • Systolic Blood Pressure [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking the patient's blood pressure after cardiac rehabilitation program
  • Diastolic Blood Pressure [3-4 weeks (after completion of 12 sessions of cardiac rehabilitation program)]: this outcome measurement will be achieved by taking the patient's blood pressure after cardiac rehabilitation program

+Eligibility

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

* post elective coronary artery bypass surgery
* > 18 years old
* sign informed consent

Exclusion Criteria:

* contraindications of resistance training (unstable angina, uncontrolled blood pressure (systolic > 160 mmHg diastolic > 100 mmHg), acute heart failure, pulmonary diseases, arrhythmia malignant)
* musculoskeletal pain, visual analog scale >3
* post congenital heart disease surgery
* post elective coronary artery bypass surgery with malfunction valves (operated or not)

+Posted results

Participant flow

MilestoneControl GroupIntervention Group
Started4344
Completed3940
Not completed44

Outcome results

  • PCSK-9 Level (Primary), Mean, ng/ml: Control Group 377.5 +/- 118.9; Intervention Group 322.53 +/- 107.5
  • Low Density Lipoprotein (Secondary), Mean, mg/dL: Control Group 106.3 +/- 26.6; Intervention Group 96.2 +/- 24.9
  • Body Mass Index (Secondary), Mean, kg/m^2: Control Group 25.3 +/- 2.9; Intervention Group 24.7 +/- 3.0
  • High-Density Lipoprotein (Secondary), Mean, mg/dL: Control Group 36.1 +/- 7.0; Intervention Group 37.4 +/- 7.9
  • Total Cholesterol (Secondary), Mean, mg/dL: Control Group 162.2 +/- 32.6; Intervention Group 162.1 +/- 35.5
  • Triglyceride (Secondary), Mean, mg/dL: Control Group 145.7 +/- 50.2; Intervention Group 139.4 +/- 50.7
  • Fasting Blood Glucose (Secondary), Mean, mg/dL: Control Group 107.7 +/- 24.6; Intervention Group 102.4 +/- 22.9
  • Systolic Blood Pressure (Secondary), Mean, mmHg: Control Group 117.3 +/- 11.4; Intervention Group 118.8 +/- 12.5
  • Diastolic Blood Pressure (Secondary), Mean, mmHg: Control Group 73.8 +/- 6.3; Intervention Group 74.8 +/- 10.3

Adverse events

Time frame: 2 months

ArmDeathsSerious adverse eventsOther adverse events
Control Group0/43 (0.0%)1/43 (2.3%)2/43 (4.7%)
Intervention Group0/44 (0.0%)1/44 (2.3%)0/44 (0.0%)

Serious adverse events by term

TermOrgan systemControl GroupIntervention Group
Acute heart failureCardiac disorders1/431/44

Other adverse events by term

TermOrgan systemControl GroupIntervention Group
wound infectionSkin and subcutaneous tissue disorders2/430/44

Limitations and caveats: This study only investigated selected population of patients (post CABG patients) and cannot explain further the mechanism of reduced PCSK9 level by doing resistance training

+Publications

  • Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, Skidmore B, Stone JA, Thompson DR, Oldridge N. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004 May 15;116(10):682-92. doi: 10.1016/j.amjmed.2004.01.009. PMID 15121495
  • Cornelissen VA, Fagard RH, Coeckelberghs E, Vanhees L. Impact of resistance training on blood pressure and other cardiovascular risk factors: a meta-analysis of randomized, controlled trials. Hypertension. 2011 Nov;58(5):950-8. doi: 10.1161/HYPERTENSIONAHA.111.177071. Epub 2011 Sep 6. PMID 21896934
  • Results publication: Ghroubi S, Elleuch W, Abid L, Abdenadher M, Kammoun S, Elleuch MH. Effects of a low-intensity dynamic-resistance training protocol using an isokinetic dynamometer on muscular strength and aerobic capacity after coronary artery bypass grafting. Ann Phys Rehabil Med. 2013 Mar;56(2):85-101. doi: 10.1016/j.rehab.2012.10.006. Epub 2012 Dec 7. PMID 23414745
  • Results publication: Busch JC, Lillou D, Wittig G, Bartsch P, Willemsen D, Oldridge N, Bjarnason-Wehrens B. Resistance and balance training improves functional capacity in very old participants attending cardiac rehabilitation after coronary bypass surgery. J Am Geriatr Soc. 2012 Dec;60(12):2270-6. doi: 10.1111/jgs.12030. Epub 2012 Nov 23. PMID 23176104
  • Results publication: Kamani CH, Gencer B, Montecucco F, Courvoisier D, Vuilleumier N, Meyer P, Mach F. Stairs instead of elevators at the workplace decreases PCSK9 levels in a healthy population. Eur J Clin Invest. 2015 Oct;45(10):1017-24. doi: 10.1111/eci.12480. Epub 2015 Aug 26. PMID 26081791
  • Results publication: Urban D, Poss J, Bohm M, Laufs U. Targeting the proprotein convertase subtilisin/kexin type 9 for the treatment of dyslipidemia and atherosclerosis. J Am Coll Cardiol. 2013 Oct 15;62(16):1401-8. doi: 10.1016/j.jacc.2013.07.056. Epub 2013 Aug 21. PMID 23973703
  • Results publication: Kim HS, Wu Y, Lin SJ, Deerochanawong C, Zambahari R, Zhao L, Zhang Q, Yan P. Current status of cholesterol goal attainment after statin therapy among patients with hypercholesterolemia in Asian countries and region: the Return on Expenditure Achieved for Lipid Therapy in Asia (REALITY-Asia) study. Curr Med Res Opin. 2008 Jul;24(7):1951-63. doi: 10.1185/03007990802138731. Epub 2008 Jun 10. PMID 18547466
  • Results publication: Sullivan D, Olsson AG, Scott R, Kim JB, Xue A, Gebski V, Wasserman SM, Stein EA. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012 Dec 19;308(23):2497-506. doi: 10.1001/jama.2012.25790. PMID 23128163
  • Results publication: Cohen JC, Boerwinkle E, Mosley TH Jr, Hobbs HH. Sequence variations in PCSK9, low LDL, and protection against coronary heart disease. N Engl J Med. 2006 Mar 23;354(12):1264-72. doi: 10.1056/NEJMoa054013. PMID 16554528
  • Results publication: Lagace TA, Curtis DE, Garuti R, McNutt MC, Park SW, Prather HB, Anderson NN, Ho YK, Hammer RE, Horton JD. Secreted PCSK9 decreases the number of LDL receptors in hepatocytes and in livers of parabiotic mice. J Clin Invest. 2006 Nov;116(11):2995-3005. doi: 10.1172/JCI29383. PMID 17080197
  • Results publication: Zhang DW, Lagace TA, Garuti R, Zhao Z, McDonald M, Horton JD, Cohen JC, Hobbs HH. Binding of proprotein convertase subtilisin/kexin type 9 to epidermal growth factor-like repeat A of low density lipoprotein receptor decreases receptor recycling and increases degradation. J Biol Chem. 2007 Jun 22;282(25):18602-18612. doi: 10.1074/jbc.M702027200. Epub 2007 Apr 23. PMID 17452316
  • Results publication: Wen S, Jadhav KS, Williamson DL, Rideout TC. Treadmill Exercise Training Modulates Hepatic Cholesterol Metabolism and Circulating PCSK9 Concentration in High-Fat-Fed Mice. J Lipids. 2013;2013:908048. doi: 10.1155/2013/908048. Epub 2013 Jun 19. PMID 23862065
  • Results publication: European Association of Cardiovascular Prevention and Rehabilitation Committee for Science Guidelines; EACPR; Corra U, Piepoli MF, Carre F, Heuschmann P, Hoffmann U, Verschuren M, Halcox J; Document Reviewers; Giannuzzi P, Saner H, Wood D, Piepoli MF, Corra U, Benzer W, Bjarnason-Wehrens B, Dendale P, Gaita D, McGee H, Mendes M, Niebauer J, Zwisler AD, Schmid JP. Secondary prevention through cardiac rehabilitation: physical activity counselling and exercise training: key components of the position paper from the Cardiac Rehabilitation Section of the European Association of Cardiovascular Prevention and Rehabilitation. Eur Heart J. 2010 Aug;31(16):1967-74. doi: 10.1093/eurheartj/ehq236. Epub 2010 Jul 19. PMID 20643803
  • Results publication: Fiorina C, Vizzardi E, Lorusso R, Maggio M, De Cicco G, Nodari S, Faggiano P, Dei Cas L. The 6-min walking test early after cardiac surgery. Reference values and the effects of rehabilitation programme. Eur J Cardiothorac Surg. 2007 Nov;32(5):724-9. doi: 10.1016/j.ejcts.2007.08.013. Epub 2007 Sep 18. PMID 17881241
  • Results publication: Wang J, Yu W, Zhao D, Liu N, Yu Y. In-Hospital and Long-Term Mortality in 35,173 Chinese Patients Undergoing Coronary Artery Bypass Grafting in Beijing: Impact of Sex, Age, Myocardial Infarction, and Cardiopulmonary Bypass. J Cardiothorac Vasc Anesth. 2017 Feb;31(1):26-31. doi: 10.1053/j.jvca.2016.08.004. Epub 2016 Aug 4. PMID 27771273
  • Results publication: Mozaffarian D, Benjamin EJ, Go AS, Arnett DK, Blaha MJ, Cushman M, de Ferranti S, Despres JP, Fullerton HJ, Howard VJ, Huffman MD, Judd SE, Kissela BM, Lackland DT, Lichtman JH, Lisabeth LD, Liu S, Mackey RH, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Muntner P, Mussolino ME, Nasir K, Neumar RW, Nichol G, Palaniappan L, Pandey DK, Reeves MJ, Rodriguez CJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Willey JZ, Woo D, Yeh RW, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation. 2015 Jan 27;131(4):e29-322. doi: 10.1161/CIR.0000000000000152. Epub 2014 Dec 17. No abstract available. PMID 25520374
  • Results publication: Pieri M, Belletti A, Monaco F, Pisano A, Musu M, Dalessandro V, Monti G, Finco G, Zangrillo A, Landoni G. Outcome of cardiac surgery in patients with low preoperative ejection fraction. BMC Anesthesiol. 2016 Oct 18;16(1):97. doi: 10.1186/s12871-016-0271-5. PMID 27760527
  • Results publication: Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, Cruaud C, Benjannet S, Wickham L, Erlich D, Derre A, Villeger L, Farnier M, Beucler I, Bruckert E, Chambaz J, Chanu B, Lecerf JM, Luc G, Moulin P, Weissenbach J, Prat A, Krempf M, Junien C, Seidah NG, Boileau C. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003 Jun;34(2):154-6. doi: 10.1038/ng1161. PMID 12730697
  • Results publication: Careskey HE, Davis RA, Alborn WE, Troutt JS, Cao G, Konrad RJ. Atorvastatin increases human serum levels of proprotein convertase subtilisin/kexin type 9. J Lipid Res. 2008 Feb;49(2):394-8. doi: 10.1194/jlr.M700437-JLR200. Epub 2007 Nov 21. PMID 18033751
  • Results publication: Boyer M, Levesque V, Poirier P, Marette A, Mathieu P, Despres JP, Larose E, Arsenault BJ. Impact of a 1-year lifestyle modification program on plasma lipoprotein and PCSK9 concentrations in patients with coronary artery disease. J Clin Lipidol. 2016 Nov-Dec;10(6):1353-1361. doi: 10.1016/j.jacl.2016.08.014. Epub 2016 Sep 2. PMID 27919352
  • Results publication: Baass A, Dubuc G, Tremblay M, Delvin EE, O'Loughlin J, Levy E, Davignon J, Lambert M. Plasma PCSK9 is associated with age, sex, and multiple metabolic markers in a population-based sample of children and adolescents. Clin Chem. 2009 Sep;55(9):1637-45. doi: 10.1373/clinchem.2009.126987. Epub 2009 Jul 23. PMID 19628659
  • Results publication: Chen YW, Hubal MJ, Hoffman EP, Thompson PD, Clarkson PM. Molecular responses of human muscle to eccentric exercise. J Appl Physiol (1985). 2003 Dec;95(6):2485-94. doi: 10.1152/japplphysiol.01161.2002. Epub 2003 Aug 22. PMID 12937035
  • Results publication: Brooks N, Layne JE, Gordon PL, Roubenoff R, Nelson ME, Castaneda-Sceppa C. Strength training improves muscle quality and insulin sensitivity in Hispanic older adults with type 2 diabetes. Int J Med Sci. 2006 Dec 18;4(1):19-27. doi: 10.7150/ijms.4.19. PMID 17211497
  • Results publication: Arsenault BJ, Pelletier-Beaumont E, Almeras N, Tremblay A, Poirier P, Bergeron J, Despres JP. PCSK9 levels in abdominally obese men: association with cardiometabolic risk profile and effects of a one-year lifestyle modification program. Atherosclerosis. 2014 Oct;236(2):321-6. doi: 10.1016/j.atherosclerosis.2014.07.010. Epub 2014 Jul 26. PMID 25128757
  • Results publication: Shaibi GQ, Cruz ML, Ball GD, Weigensberg MJ, Salem GJ, Crespo NC, Goran MI. Effects of resistance training on insulin sensitivity in overweight Latino adolescent males. Med Sci Sports Exerc. 2006 Jul;38(7):1208-15. doi: 10.1249/01.mss.0000227304.88406.0f. PMID 16826016
  • Results publication: Kelley GA, Kelley KS. Progressive resistance exercise and resting blood pressure : A meta-analysis of randomized controlled trials. Hypertension. 2000 Mar;35(3):838-43. doi: 10.1161/01.hyp.35.3.838. PMID 10720604
  • Results publication: Dwiputra B, Santoso A, Purwowiyoto BS, Radi B, Ambari AM. The effect of resistance training on PCSK9 levels in patients undergoing cardiac rehabilitation after coronary artery bypass grafting: a randomized study. BMC Cardiovasc Disord. 2023 Nov 9;23(1):549. doi: 10.1186/s12872-023-03571-7. PMID 37946122

+Investigators