Background: This study was designed to examine the influence of exercise training on leptin
levels in patients with stable coronary artery disease (CAD).
Methods: Sixty-four male patients, mean age 55.6 &#177; 6.0 years, were randomized either to six
weeks of aerobic training, three times a week, at 60&#8211;80% of maximal heart rate (training
group, Ex, n = 32) or to a control group (n = 32). Exercise stress test was performed and body
mass index (BMI), waist-to-hip ratio (WHR), waist circumference and plasma leptin levels
were measured at the beginning and end of the study.
Results: Physical capacity increased significantly only in Ex patients (max workload in
METs from 7.7 &#177; 1.4 to 8.2 &#177; 1.4, p < 0.05). There were no significant differences between
initial and final results in either group in terms of BMI, WHR or waist circumference.
Although, at the end of the study, leptin levels did not change in Ex patients (6.7 &#177; 3.2 vs
6.9 &#177; 3.6 ng/mL, NS), they did increase significantly in the control group (8.0 &#177; 4.0 vs 9.3 &#177; 5.2 ng/mL, p < 0.02).
Conclusions: A short period of exercise training in CAD patients improved their physical
capacity, but did not influence BMI, WHR and waist circumference. Exercise training prevented
an increase in leptin levels during the study period. (Cardiol J 2010; 17, 5: 477-481

Bilińska, Maria

Janas, Jadwiga

Kosydar-Piechna, Magdalena

Piotrowicz, Ryszard

English

Via Medica Journals

477www.cardiologyjournal.orgORIGINAL ARTICLECardiology Journal2010, Vol. 17, No. 5, pp. 477–481Copyright © 2010 Via MedicaISSN 1897–5593Address for correspondence:  Magdalena Kosydar-Piechna, MD, Department of Cardiac Rehabilitation and NoninvasiveElectrocardiology, Institute of Cardiology, Alpejska 42, 04–628 Warszawa, Poland, tel: +48 22 343 44 08, fax: +48 22 343 45 19,e-mail: mkosydar@ikard.plReceived: 5.11.2009 Accepted: 12.03.2010Influence of exercise training onleptin levels in patients with stablecoronary artery disease: A pilot studyMagdalena Kosydar-Piechna1, Maria Bilińska1, Jadwiga Janas2, Ryszard Piotrowicz11Department of Cardiac Rehabilitation and Noninvasive Electrocardiology,Institute of Cardiology, Warsaw, Poland2Department of Clinical Biochemistry, Institute of Cardiology, Warsaw, PolandAbstractBackground: This study was designed to examine the influence of exercise training on leptinlevels in patients with stable coronary artery disease (CAD).Methods: Sixty-four male patients, mean age 55.6 ± 6.0 years, were randomized either to sixweeks of aerobic training, three times a week, at 60–80% of maximal heart rate (traininggroup, Ex, n = 32) or to a control group (n = 32). Exercise stress test was performed and bodymass index (BMI), waist-to-hip ratio (WHR), waist circumference and plasma leptin levelswere measured at the beginning and end of the study.Results: Physical capacity increased significantly only in Ex patients (max workload inMETs from 7.7 ± 1.4 to 8.2 ± 1.4, p < 0.05). There were no significant differences betweeninitial and final results in either group in terms of BMI, WHR or waist circumference.Although, at the end of the study, leptin levels did not change in Ex patients (6.7 ± 3.2 vs6.9 ± 3.6 ng/mL, NS), they did increase significantly in the control group (8.0 ± 4.0 vs 9.3 ±± 5.2 ng/mL, p < 0.02).Conclusions: A short period of exercise training in CAD patients improved their physicalcapacity, but did not influence BMI, WHR and waist circumference. Exercise training pre-vented an increase in leptin levels during the study period. (Cardiol J 2010; 17, 5: 477–481)Key words: coronary artery disease, exercise training, leptin levelsIntroductionAdipose tissue, as an active endocrine organ,releases proteins termed adipokines, including a hor-mone known as leptin. It has been established thatincreased leptin levels are common in obese and dia-betic patients and independently associated with in-sulin resistance [1], cardiovascular diseases [2, 3], andlow-grade chronic inflammation in humans [4, 5].To date, the influence of regular physical ac-tivity on leptin levels has been examined in healthysubjects as well as in obese and diabetic patients.The effects of exercise training on leptin le-vels in patients with coronary artery disease (CAD)are unknown. Therefore, the aim of this pilot studywas to assess the influence of six- weeks of exer-cise training on leptin levels in patients with stablecoronary artery disease.478Cardiology Journal 2010, Vol. 17, No. 5www.cardiologyjournal.orgMethodsWe enrolled consecutive male patients < 65 ye-ars, with stable CAD, who had been referred forour exercise training program between 1 Januaryand 31 December 2007. We excluded patients withheart failure, unstable angina, diabetes mellitus, un-controlled arrhythmias, poorly controlled hyperten-sion, hemodynamically significant valvular heartdisease, those with chronic inflammatory, autoim-mune, neoplastic, or other systemic diseases,chronic hepatic or kidney diseases. All the patientswere clinically stable at least one month before theirinclusion in the program, without any changes inmedical treatment. The subjects received standardmedications such as statin, aspirin, beta-blocker andangiotensin-converting enzyme inhibitor. The dos-es of medications were not changed during thestudy period. The study protocol was approved bythe Local Ethics Committee. Afterwards, a writteninformed consent was obtained from each patient.The patients were randomized into two groups:training group (Ex) and control group. Ex patientsagreed to participate in our training program. Thebaseline evaluation included clinical history andexamination, resting electrocardiogram, chestX-ray, two-dimensional echocardiogram, bloodchemistry (total and high- and low-density lipopro-tein cholesterol, triglycerides, fasting and post-prandial glucose levels, and liver and kidney func-tion tests), We defined patients as non-smokerswhen they had not smoked tobacco for at least oneyear. All the patients were advised to follow a dietcontaining limited amounts of fat and high-carbo-hydrate foods, and not to change the diet during thestudy protocol.AnthropometryFasting body weight and height were measured(B 150 L, Axis, Poland) in all participants wearingonly underclothes, without shoes. Height was mea-sured without shoes to within an accuracy of 1 cm.Waist-to-hip ratio (WHR) was measured as a ratioof the circumference of the waist [cm] to that of thehips [cm]. Body mass index (BMI) was calculatedas [kg/m²].Blood sampling andlaboratory measurementsAll the participants were told to avoid vigor-ous exercise for four days before blood sampling.Blood samples were collected between 8 and 10amafter an overnight fast. EDTA was added to wholeblood for plasma preparation. The parameters ofblood chemistry e.g. glucose, lipids, etc. were mea-sured in fresh plasma by standard methods. Plas-ma samples for leptin measurement were immedi-ately centrifuged (2,000 rpm for 10 min), decantedand frozen at temperature –70°C. Leptin concentra-tion in plasma samples was quantified using HumanLeptin RIA (RadioImmunoAssay) kit from LincoResearch, Inc., St. Charles, Missouri, USA. Sensi-tivity of the assay was 0.5 ng/mL. Intra- and inter-assay coefficients of variation were 4.6% and 6.2%,respectively.Exercise stress testingEach subject performed a symptom-limitedmaximal exercise treadmill test according to themodified Bruce protocol. Blood pressure was moni-tored by using mercurial sphygnomanometer anda 12-lead ECG was recorded at rest, every minuteduring exercise and during recovery, until heart rate(HR) and ECG returned to the baseline values (us-ing the modified Mason-Likar 12-lead system, Mar-quette Case 12; Marquette Electronics, Milwaukee,Wisconsin, USA). All treadmill tests were super-vised by a cardiologist. The main reasons of stop-ping the tests were reaching the age-adjusted limitof HR and/or fatigue. None of the tests were dis-continued because of signs of ischemia in ECG and//or angina. The following parameters were analyzed:duration and distance of exercise stress test, work-load in metabolic equivalents (METs), HR at restand at peak exercise (max HR).Exercise training programEx group patients underwent a six-week con-trolled, standardized exercise training program onbicycle ergometer, three times a week. Each ses-sion included a ten-minute warm-up, 40 minutes ofcycling with telemetry monitoring (the intensity setat 60% at the beginning of the exercise program wasprogressively increased to 80% of peak HR mea-sured during exercise stress testing), and a ten-minute cool-down. The training was documented bya written protocol.Cardiac rhythm was continuously monitored ona three-channel telemetry system in all trained pa-tients and in all sessions throughout the study. Nopatient left the program at any point during the study.Patients in the control group were advised towalk at least three times per week for 30 minutesduring the study period.479Magdalena Kosydar-Piechna et al., Exercise training and leptin levels in CAD patientswww.cardiologyjournal.orgStatistical analysisStatistical analysis was performed using SASstatistical software (Version 9.2, Cary, North Caro-lina, USA). Values are expressed as mean ± stan-dard deviation for normally distributed variables.Normal distribution was evaluated by the Shapiro--Wilk test. The difference in mean values was com-pared with Student’s t-test, either the unpaired oneto detect differences between groups, or the pairedone to detect differences within each group over time.Comparisons of non-normally distributed datawere carried out using the Wilcoxon rank test.A p value of less than 0.05 was considered statisti-cally significant.ResultsBaseline resultsNo significant differences were found betweenEx and control groups regarding age, number ofsmokers, presence of hypertension, history of myo-cardial infarction or left ventricular ejection fraction(Table 1). There were no significant differencesbetween the groups in terms of baseline metabolicparameters considered or BMI (Table 2). Similar-ly, HR at rest and at peak exercise as well as METswere comparable between the two groups at thebeginning of the study (Table 3). Moreover, at theinitial evaluation, leptin levels did not differ signif-icantly between the two groups (Table 2).Final resultsSixty-four patients completed the study. Noadverse events occurred in either group during thestudy period. As shown in Table 2, no significantdifferences were found between the two groups inany of the analyzed metabolic parameters. More-over, BMI, WHR and waist circumference werestable and did not change significantly in eitherstudy group during the study period. After sixweeks, exercise duration and distance improvedsignificantly in both study groups (Table 3). How-ever, in the Ex group only, maximal workload inMETs increased significantly (7.7 ± 1.4 vs 8.2 ±Table 1. Study population.Characteristic Exercise Control Pgroup group(n = 32) (n = 32)Age (years) 54.0 ± 4.8 54.5 ± 5.6 NSCAD (years) 3.9 ± 4.6 2.8 ± 3.7 NSHistory MI 20 (62%) 19 (58%) NSNon-smokers 28 (87%) 27 (83%) NSSmokers 4 (13%) 5 (17%) NSHypertension 25 (78%) 25 (78%) NSCoronaryangiography:1 vessel 5 (16%) 5 (16%) NS2 vessels 11 (34%) 7 (22%) NS3 vessels 16 (50%) 20 (62%) NSMedication:Beta-blocker 32 (100%) 32 (100%) NSACE-I 30 (94%) 30 (94%) NSAT II blocker 3 (9%) 2 (6%) NSStatins 32 (100%) 32 (100%) NSAspirin 31 (98%) 31 (98%) NSClopidogrel/ 2 (6%) 2 (6%) NS/ticlopidineLVEF (%) 60.0 ± 7.5 56.8 ± 8.9 NSCAD — coronary artery disease; MI — myocardial infarction; ACE-I— angiotensin converting enzyme inhibitor; AT II blocker — angio-tensin II receptor blocker; LVEF — left ventricular ejection fraction;NS — non significantTable 2. Metabolic parameters at baseline and at the end of the study.Variables Exercise group (n = 32) Control group (n = 32)Baseline Final Baseline FinalBody mass index [kg/m²] 27.3 ± 2.8 27.4 ± 2.8 28.0 ± 3.2 28.4 ± 3.6Waist circumference [cm] 95.8 ± 7.0 96.0 ± 8.4 99.6 ± 7.6 99.8 ± 7.5Waist-to-hip ratio 1.02 ± 0.05 1.01 ± 0.05 1.03 ± 0.05 1.03 ± 0.06Total cholesterol [mmol/L] 3.9 ± 0.7 3.8 ± 0.8 4.1 ± 0.6 4.2 ± 1.0HDL cholesterol [mmol/L] 1.3 ± 0.4 1.3 ± 0.5 1.3 ± 0.4 1.3 ± 0.3LDL cholesterol [mmol/L] 2.4 ± 0.8 2.3 ± 0.7 2.6 ± 0.8 2.6 ± 0.7Triglycerides [mmol/L] 1.3 ± 0.6 1.4 ± 0.7 1.4 ± 0.7 1.5 ± 0.9Fasting glucose [mmol/L] 5.1 ± 0.7 5.1 ± 0.7 5.2 ± 0.7 5.2 ± 0.6Post-prandial glucose [mmol/L] 5.5 ± 1.5 5.6 ± 1.6 5.7 ± 1.8 5.6 ± 1.5Leptin [ng/mL] 6.7 ± 3.2 6.9 ± 3.6 8.0 ± 4.0 9.3 ± 5.2*All results are presented as mean ± SD; *p < 0.05480Cardiology Journal 2010, Vol. 17, No. 5www.cardiologyjournal.org± 1.4, p < 0.03) compared to the control patients(7.3 ± 1.8 vs 7.7 ± 1.9, p = NS; Table 3).Although, at the end of the study, leptin levelsincreased significantly only in the control patients(15% vs 2% in Ex group), there were no signifi-cant statistical differences between the two studygroups (Table 2).DiscussionThis preliminary study aimed to investigate theeffect of short-term exercise training on plasmaleptin concentrations in stable CAD patients withpreserved left ventricular function.We found that our supervised exercise-train-ing program improved physical capacity and did notaffect leptin levels. On the contrary, in control pa-tients, home-based activity e.g. walking did notchange physical capacity measured in METs andcaused an unfavorable increase in leptin levels.Leptin is secreted by adipose tissue and itsconcentration in humans is known to correlate withweight, BMI [6] and body fat mass [7–9]. Moreover,leptin is thought to exert many potentially proat-herogenic effects such as induction of endothelialcell dysfunction [10] and platelet aggregation [11],stimulation of inflammatory reactions [4, 5], propa-gation of oxidative stress [12], and proliferation ofvascular smooth muscle cells [13].To date, the influence of exercise training onleptin levels has been examined only in healthy,obese or diabetic patients. The majority of thesestudies have documented that short-term exercisetraining does not affect leptin levels.However, Ishii et al. [14] showed that in type 2diabetic patients, exercise training reduced plasmaleptin levels, which was independent of changes inbody fat mass.Ours was the first study to show the influenceof short aerobic training on leptin levels in patientswith CAD. It should be emphasized that BMI,WHR and waist circumference did not change sig-nificantly in either of our study groups. Thus, wecan conclude that an increase in plasma leptin con-centration in the control patients was not asso-ciated with changes in weight or waist circumfe-rence. Since a significant increase of physical ca-pacity measured in METs was observed only in thetrained patients. We suggest that only a properlyapplied training program is able to prevent an in-crease in leptin level in optimally treated, clinicallystable CAD patients.Our findings, although promising, require con-firmation on a larger number of patients to deter-mine whether exercise training has a beneficialimpact on leptin levels. In addition, the mechanismof favorable influence of exercise training on leptinlevels deserves further investigation.It might be of great importance, because se-veral clinical studies have demonstrated that highleptin levels predicted the development of acutecardiovascular events, restenosis after coronaryangioplasty and cerebral stroke, independently oftraditional risk factors [2, 15, 16].Limitations of the studyWhen interpreting our findings, one shouldtake into account that this was a small, short-du-ration pilot study aimed only at determiningwhether exercise training had any impact on lep-tin levels. Our study did not assess the percent-age of body fat. However, Flegal et al. [17] showedthat it positively correlated with waist circumfer-ence in men, which was measured in our patients.We did not include women in this study becauseit is widely recognized that leptin levels are se-veral times higher in women that in men, indepen-dently of fat mass content, suggesting that fe-males have higher leptin levels per unit fat mass[18, 19].Table 3. Parameters during exercise stress test at baseline and at the end of the study.Variables Exercise group (n = 32) Control group (n = 32)Baseline Final Baseline FinalDuration [s] 759.8 ± 96.8 830.1 ± 74.7* 750.5 ± 102.8 781.0 ± 136.5*Distance [m] 672.7 ± 135.5 778.7 ± 117.8* 644.1 ± 152.3 717.6 ± 164.2*Metabolic equivalents 7.7 ± 1.4 8.2 ± 1.4* 7.3 ± 1.8 7.7 ± 1.9Heart rate at rest [bpm] 68.1 ± 11.3 62.9 ± 10.5* 65.1 ± 9.4 64.2 ± 8.2Max heart rate [bpm] 125.9 ± 15.2 124.8 ± 15.6 121.2 ± 16.7 125.4 ± 15.3All results are presented as mean ± SD; *p < 0.05481Magdalena Kosydar-Piechna et al., Exercise training and leptin levels in CAD patientswww.cardiologyjournal.orgConclusions1. A short period of exercise training in CAD pa-tients improved physical capacity, but did notinfluence BMI, WHR or waist circumference.2. Exercise training prevented an increase in lep-tin levels during the study period.AcknowledgementsThe authors do not report any conflict of inte-rest regarding this work.The study was supported by the grant N° 2.11//I/07 from the Institute of Cardiology, Warsaw, Po-land.References1. Segal KR, Landt M, Klein S. Relationship between insulin sensi-tivity and plasma leptin concentration in lean and obese men.Diabetes, 1996; 45: 988–991.2. Wallace AM, McMahon AD, Packard CJ et al. Plasma leptin andthe risk of cardiovascular disease in the west of Scotland coro-nary prevention study (WOSCOPS). Circulation, 2001; 104:3052–3056.3. Wolk R, Berger P, Lennon RJ, Brilakis ES, Johnson BD, Somers VK.Plasma leptin and prognosis in patients with established coro-nary atherosclerosis. J Am Coll Cardiol, 2004; 44: 1819–1824.4. Loffreda S, Yang SQ, Lin HZ et al. Leptin regulates proinflam-matory immune responses. FASEB J, 1998; 12: 57–65.5. Santos-Alvarez J, Goberna R, Sanchez-Margalet V. Human lep-tin stimulates proliferation and activation of human circulatingmonocytes. Cell Immunol, 1999; 194: 6–11.6. Maffei M, Halaas J, Ravussin E et al. Leptin levels in human androdent: Measurement of plasma leptin and ob RNA in obese andweight-reduced subjects. Nat Med, 1995; 1: 1155–1161.7. Murakami T, Shima K. Cloning of rat obese cDNA and its ex-pression in obese rats. Biochem Biophys Res Commun, 1995;209: 944–952.8. Considine RV, Sinha MK, Heiman ML et al. Serum immunore-active-leptin concentrations in normal-weight and obese hu-mans. N Engl J Med, 1996; 334: 292–295.9. Funahashi T, Shimomura I, Hiraoka H et al. Enhanced expres-sion of rat obese (ob) gene in adipose tissues of ventromedialhypothalamus (VMH)-lesioned rats. Biochem Biophys Res Com-mun, 1995; 211: 469–475.10. Knudson JD, Dincer UD, Zhang C et al. Leptin receptors areexpressed in coronary arteries, and hyperleptinemia causes sig-nificant coronary endothelial dysfunction. Am J Physiol HeartCirc Physiol, 2005; 289: H48–H56.11. Nakata M, Yada T, Soejima N, Maruyama I. Leptin promotesaggregation of human platelets via the long form of its receptor.Diabetes, 1999; 48: 426–429.12. Maingrette F, Renier G. Leptin increases lipoprotein lipase se-cretion by macrophages: Involvement of oxidative stress andprotein kinase C. Diabetes, 2003; 52: 2121–2128.13. Li L, Mamputu JC, Wiernsperger N, Renier G. Signaling path-ways involved in human vascular smooth muscle cell prolifera-tion and matrix metalloproteinase-2 expression induced byleptin: Inhibitory effect of metformin. Diabetes, 2005; 54:2227–2234.14. Ishii T, Yamakita T, Yamagami K et al. Effect of exercise train-ing on serum leptin levels in type 2 diabetic patients. Metabo-lism, 2001; 50: 1136–1140.15. Soderberg S, Stegmayr B, Stenlund H et al. Leptin, but notadiponectin, predicts stroke in males. J Intern Med, 2004; 256:128–136.16. Piatti P, Di Mario C, Monti LD et al. 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Influence of exercise training on leptin levels in patients with stable coronary artery disease: A pilot study

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Influence of exercise training on leptin levels in patients with stable coronary artery disease: A pilot study

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