SATOSHI KUROSE

OBJECTIVE: Follistatin (FST)/myostatin (MST) myokine-signaling axis is important for muscle metabolism and pathogenesis of obesity. FST, mainly secreted by skeletal muscle and liver, inhibits MST and affects skeletal muscle synthesis. This study aimed to identify the characteristics of myokines and independent predictors of serum FST levels in patients with obesity. METHODS: In this retrospective cross-sectional study, 226 patients (mean age, 46.6 years; men, 35.4%) with obesity who initially visited an outpatient clinic between June 2014 and September 2020, were included and classified into obesity (25.0 ≤ body mass index (BMI) < 35.0 kg/m2) and severe obesity (BMI ≥35 kg/m2) groups based on the guidelines of the Japan Society for the Study of Obesity. Body composition was measured using bioelectrical impedance analysis and computed tomography. Muscle strength, exercise tolerance, metabolic parameters, and myokines were measured, including serum levels of FST, MST, irisin, and brain-derived neurotrophic factor. RESULTS: Serum FST levels were significantly higher in the severe obesity group than in the obesity group (median: 768.4 vs. 895.1 pg/mL, P = 0.020). However, the levels of other myokines showed no significant differences between the groups. In Model 1, which included factors that significantly correlated with FST levels, stepwise multivariate regression analysis revealed peak oxygen uptake (VO2) as an independent predictor of FST levels based on the significance of the univariate analysis. Additionally, Model 2 was analyzed by adding myokine level to Model 1, revealing that peak VO2, MST, and irisin levels were independent predictors of FST levels. CONCLUSION: Serum FST levels were higher in patients in the severe obesity group compared to those in the obesity group. There was an independent association between low exercise tolerance and elevated serum FST levels.

PURPOSE: This study investigated the associations of personality traits and preoperative lifestyle improvements with early weight loss after sleeve gastrectomy. METHODS: This was a single-center, retrospective study of 57 patients who underwent preoperative lifestyle intervention with a multidisciplinary team approach based on cognitive behavioral therapy before sleeve gastrectomy. All patients underwent preoperative psychological testing with the Neuroticism-Extraversion-Openness Five-Factor Inventory (NEO-FFI) and the Tokyo University Egogram New Version II (TEG II). We investigated the associations of psychological testing results and lifestyle improvements with percent total weight loss (%TWL) one year after surgery. RESULTS: The median %TWL at 1 year was 38.2% for patients with an improved lifestyle and 26.9% for those without improvement (P = 0.0008). Although TEG II factors were not associated with %TWL at 1 year, higher NEO-FFI extraversion (E) scores were significantly associated with a better %TWL at 1 year. The median %TWL at 1 year was 35.2% for patients with higher E scores and 25.4% for those with lower E scores (P = 0.0247). Lifestyle improvement and the NEO-FFI E score significantly influenced %TWL at 1 year based on a logistic regression analysis. CONCLUSION: The NEO-FFI E score and preoperative lifestyle improvement may be predictors of early weight loss after sleeve gastrectomy.

BACKGROUND: A limited number of studies have evaluated the masticatory indices of individuals with obesity who only chew their food a few times and for shorter duration or who were provided with an instructional intervention. This study aimed to examine the effects of a 6-month instructional mastication intervention on the body composition and biochemical indices in female patients with obesity. METHODS: Female patients with obesity were randomly classified into a conventional treatment group (CTG; 12 individuals), which only received normal nutritional and exercise guidance, and a mastication intervention group (MIG; 16 individuals), which received an additional mastication guidance. The MIG received guidance on foods requiring increased number of chews and chewing duration, eating techniques, and the proper method of cutting foods. RESULTS: Changes in the masticatory, body composition, and biochemical indices were compared before and after the 6-month intervention. The values of body composition indices decreased significantly in both groups; however, the rate of change in body mass index significantly decreased in the MIG. In addition, the values of biochemical indices were significantly decreased in the MIG compared with that in the CTG, which is attributed to the addition of mastication instruction to female patients with obesity. CONCLUSION: Increasing the number of chews and duration of chewing times for carbohydrates, which are staple foods, possibly contributed to weight loss and improvement of glucose metabolism. TRIAL REGISTRATION: UMIN, UMIN000025875. Registered on 27 Jan 2017.

BACKGROUND: This study investigated the effects of mobility restrictions (MRs) during the COVID-19 epidemic on physical activity, body composition, and exercise tolerance in patients with obesity. METHODS: We analyzed data of obesity patients participating in a 6-month weight loss program in February 2020, and after, when the epidemic was considered to have had some effect on outdoor activity in Osaka, Japan (MR group). MR group patients were compared to patients with obesity attending the program in 2018 and 2019 (non-MR group) who had a similar number of months as MR group. Changes in physical activity, body composition, and exercise tolerance (O2 consumption; VO2) owing to the weight loss program were analyzed between both groups using analysis of covariance and logistic regression analysis. RESULTS: Decreases in body fat were significantly higher in MR group than in non-MR group. However, increases in physical activity, VO2 at anaerobic threshold, and peak VO2 were significantly lower in MR group; however, increases in peak VO2 owing to the weight loss program were less likely to be achieved in MR group (odds ratio, 0.21; 95% confidence interval, 0.06-0.81). CONCLUSION: MR during the COVID-19 epidemic may have affected the exercise tolerance of patients with obesity.

BACKGROUND: Adiponectin has been reported to be associated with lower skeletal muscle mass and skeletal strength and may be involved in skeletal muscle regulation along with myostatin. This study aims to evaluate the association between serum adiponectin and myostatin levels and identify independent factors using body composition and metabolic parameters in patients with obesity. METHODS: Overall, 148 patients (age, 45.9 ± 14.3 years, body mass index, 37.2 ± 8.0 kg/m2) who initially visited the outpatient clinic of obesity between November 2013 and November 2019 were included. Body composition was measured using InBody 720 and dual energy X-ray absorptiometry. In addition, muscle strength, vascular function, and metabolic parameters were measured. Serum levels of adiponectin, leptin, myostatin, and irisin were measured from blood samples. RESULTS: The serum adiponectin level was 2.9 μg/mL (1.7-4.1 μg/mL), and the serum myostatin level was 2398.4 pg/mL (1,777.1-2952.5 pg/mL). The stepwise regression analysis revealed less leg strength, homeostasis model assessment of insulin resistance, and C-reactive protein as an independent predictor of serum adiponectin levels based on the significance of the univariate analysis (R2 = 0.190, P < 0.001). A high appendicular lean mass/body weight, reactive hyperemia index, and irisin were independent factors for serum myostatin levels (R2 = 0.260, P < 0.001). CONCLUSION: The serum adiponectin level was associated with less muscle strength. Although serum myostatin was associated with a high appendicular lean mass, it is possible that myostatin was regulated by the percentage of body weight from appendicular lean mass.

Objective: DNA methylation is an epigenetic mechanism that regulates gene expression. The obesity-related (FTO) gene is the first gene found to be associated with fat mass and obesity. However, no studies have examined the relationship between weight-loss intervention effect and FTO methylation in obese individuals with whole blood DNA. The purpose of this study was to quantify FTO whole blood DNA methylation and investigate the relationship between body composition, exercise capacity, and blood parameters with a 6-month weight-loss program intervention. Participants and Methods: Eighteen female participants (mean age, 50.6 ±12.1 years, body mass index (BMI), 33.5 ± 6.2 kg/m2) who completed a 6-month weight-loss program at the obesity outpatient department at the Health Science Center of Kansai Medical University Hospital from March 2017 to October 2018 were included in the analysis. Participants were randomized into a normal treatment group (NTG) and a group with additional resistance training (RTG). Body composition, exercise tolerance and metabolic index were measured in each participant. DNA methylation status in whole blood samples was determined using pyrosequencing. All measurements were taken during the first visit and at the 6-month post-intervention visit. Results: The methylation rate was significantly decreased in the NTG in CpG1 (p=0.011) and total value of CpG (p=0.011), whereas in the treatment group containing resistance training (RTG), CpG3 (p=0.038) was increased significantly. Furthermore, the independent factors that determine %CpG3 of RTG were visceral fat area change rate (%VFA) (β = -0.568, P = 0.007, R2 = 0.527) and resistance training (β = 0.517, P = 0.012, R2 = 0.527), which have been extracted. Conclusion: A 6-month weight-loss program, including resistance training, may be associated with decreased visceral fat area changes and increased RTG CpG3 methylation changes. However, further replication studies with larger sample sizes are warranted to verify the findings of this study.

BACKGROUND: Although exercise is a standard treatment for postoperative osteoarthritis, interindividual differences have been reported. Epigenetic modification (DNA methylation), a factor causing interindividual differences, is altered by the environment and may affect all tissues. Performing a tissue biopsy to investigate methylation of skeletal muscle fat metabolism genes is invasive, and less invasive and convenient alternatives such as blood testing are desired. However, the relationship between tissue and blood is still unclear. Here, we examined the relationship between DNA methylation of the PDK4 gene in skeletal muscle and peripheral blood. PATIENTS AND METHODS: Five patients who underwent artificial knee arthroplasty between April 2017 and June 2018 at Kansai Medical University Hospital were included (2 men and 3 women; average age, 75.2 years; body mass index, 26.1 kg/m2). We measured the body composition of the patients using dual-energy X-ray absorptiometry. Peripheral blood was collected at the time of hospitalization and 5 months after surgery; skeletal muscles were collected at the time of surgery and 5 months after surgery. Rehabilitation was performed according to the clinical procedure for 3 months after surgery. Patients performed resistance training and aerobic exercise using an ergometer for 20 min twice a week. Biopsy samples were treated with bisulfite after DNA extraction, and the methylation rate was calculated at different CpG islands downstream from the transcription initiation codon of the PDK4 gene. RESULTS: No significant change in body composition was observed before and after postoperative exercise therapy, and no significant change was noted in the methylation at each position in the promoter region of PDK4 in the skeletal muscle and peripheral blood. However, changes in the methylation rate at CpG1 in peripheral blood significantly correlated with those in skeletal muscle (P = 0.037). Furthermore, the amount of change in the methylation rate of CpG1 in the skeletal muscle was significantly correlated (P = 0.037) with the average methylation rate at the promoter region in peripheral blood. CONCLUSIONS: Methylation rates at CpG1 in the skeletal muscle and peripheral blood were significantly correlated, suggesting that skeletal muscle methylation could be analyzed via peripheral blood rather than skeletal muscle biopsy.

【目的】他動的運動による筋収縮の誘発は、安静時より糖代謝を改善させる可能性がある。本研究は自転車エルゴメーター(EG)、他動的乗馬運動(JB)、座位による食後の短期的な血糖(BG)変化から、JBの有用性を検討することを目的とした。【方法】対象は糖尿病教育入院した2型糖尿病患者22人(58.9±12.3歳)。退院前の薬剤変更がなくなった時点でEG30分、JB30分、座位30分を行うクロスオーバー試験とした。BGは空腹時、介入前、介入15分と30分、介入後60分に測定した。【結果】EGは介入前に比べて15分、30分、介入後60分で有意にBGが低下した。JBは15分、30分では有意なBG変化はなく、介入後60分で有意に低下した。座位は30分で有意にBGが上昇、介入後60分で有意に低下したが、EGやJBより有意に高値を示した。30分のΔBGはEG:-41.7mg/dL、JB:-11.3mg/dL、座位安静:10.7mg/dLで各変化に有意差を認めた。【結論】JBはEGより食後BGの早期低下を認めないが、座位よりは早期低下に有用である。(著者抄録)

BACKGROUND: Toe grip-related training requires individuals to actively exercise muscles that are not frequently used; therefore, it may improve not only toe grip strength but also cognitive function. The purpose of this study was to examine the effects of toe grip-related training on predictors of physical performance and cognitive function in nursing home residents. METHODS: A total of 35 nursing home residents (35 left and 35 right feet; mean age, 82.1 ± 7.9 years) were included in this study. The participants were divided into two groups: a training group and a control group. The Mini-Mental State Examination (MMSE) was used to assess the cognitive function of the participants, and the Fall Risk Index (FRI) was used to evaluate the risk of falls. Toe grip-related physical function was also assessed. Baseline endpoints were evaluated and the effects of toe grip-related training were examined following a 12-week training intervention. RESULTS: The training group showed significant improvements in MMSE score, FRI score, toe grip strength, and the toe skill (TS) test; however, the control group did not show these changes. The training group showed significant increases in Δ MMSE, Δ toe grip strength, and Δ TS (right foot) than the control group. Stepwise regression analysis revealed that Δ toe grip strength is an independent factor of Δ MMSE. CONCLUSIONS: Toe grip training improves not only toe grip strength itself, but also cognitive function. Furthermore, change in toe grip strength was an independent factor of change in MMSE in those populations. TRIAL REGISTRATION: UMIN, UMIN000027437 . Registered on 26 May 2017.

Purpose: DNA methylation is thought to play a role in exercise-induced gene expression. We aimed to examine changes in muscular strength and body composition in elderly patients with end-stage knee osteoarthritis before and after artificial knee arthroplasty and exercise therapy. We aimed to confirm the relationship between DNA methylation and body composition, using the methylation rate of the pyruvate dehydrogenase kinase 4 (PDK4) gene that regulates skeletal muscle and fat metabolism. Patients and methods: Patients underwent artificial knee arthroplasty between April 2017 and June 2017 at Kansai Medical University Hospital. Six patients (seven knees) were included in the analysis (four males/two females; average age, 75.7 years; body mass index, 25.1 kg/m2). Body composition and knee extension muscle strength were measured before surgery and 5 months after surgery. Rehabilitation was performed for 3 months after surgery. In the remaining 2 months, patients performed resistance training and aerobic exercise using an ergometer for 20 mins, twice a week. A biopsy of the vastus medialis was taken during surgery and 5 months post-surgery. Biopsy samples were treated with bisulfite after DNA extraction, and DNA methylation rate was calculated. Results: Body weight (P=0.046), total weight (P=0.027), and total fat mass (P=0.028) were significantly lower 5 months postoperatively than preoperatively. Five months post-surgery, the PDK4 gene was significantly more hypomethylated at eight sites in the CpG island, compared to pre-surgery. There was a significant correlation (r=0.88, P=0.02) between promoter region hypomethylation and weight loss. Total methylation rate and weight loss were significantly correlated (r=0.829, P=0.042). Total methylation rate and decrease in total fat mass showed a positive trending relationship (r=0.812, P=0.05). Conclusion: Rehabilitative exercise resulted in significant decreases in weight and body fat. Hypomethylation of the PDK4 gene promoter region signified the effect of postoperative management focus on exercise therapy on weight and fat loss.

BACKGROUND: Because of the advanced age of patients with cardiovascular disease (CVD), prevention of sleep disorder and dementia is a priority for cardiac rehabilitation (CR) during their long-term care. This study aimed to investigate the association of physical activity with sleep quality and cognitive function in elderly patients with CVD in the CR maintenance phase. METHODS: We conducted a multicenter study through the Clinical Exercise Physiology Association Japan network, which included 102 elderly patients (mean age, 74±7.4 years) with CVD undergoing phase III CR at 6 institutions. Physical activity was assessed using a triaxial accelerometer for 7 consecutive days and was classified as locomotive and household activities. Physical fitness was assessed via 6-min walking distance (6MD), hand grip power, 10-m walking speed, one leg standing time with eyes open, and 10 times sit-to-stand tests. Sleep quality and cognitive function were evaluated using the Pittsburgh sleep quality index (PSQI) and mini-mental state examination (MMSE) scores, respectively. RESULTS: The patients performed 5506.8±3743.6 steps/day and scored 5.8±3.5 points in the PSQI and 28.4±1.7 points in the MMSE. Sleep latency and MMSE scores correlated with locomotive activity, but not with household activity. Locomotive activity and 6MD were independent predictors of sleep latency and MMSE score, respectively. When patients with heart failure were excluded, the relationship between sleep latency and locomotive activity was preserved, but the relationship between exercise tolerance and cognitive function disappeared. CONCLUSION: Locomotive activity and exercise tolerance are associated with sleep latency and cognitive function in elderly patients with CVD continuing phase III CR. However, in this study, the relationship between exercise tolerance and cognitive function was offset by the presence of heart failure.

BACKGROUND: Toe grip strength is the force of a toe on a surface. The objective of this study was to investigate the relationship between falls in middle-aged individuals and physical strength factors such as toe grip strength and knee extension strength. METHODS: The subjects were 194 middle-aged individuals (388 feet) who were independent in daily life, received no nursing care, and participated in a health sports event organized by a sports club. We evaluated the body composition, blood pressure, vascular age, systemic response, bone density, knee extension strength, and toe grip strength, and examined their relationship using a self-administered questionnaire survey. RESULTS: The fall, near-fall, and no fall groups included 7, 36, and 151 subjects, respectively; the high and low risk groups included 43 and 151 subjects, respectively. Logistic regression analysis was performed with risk of falls as the dependent variable, and factors that showed a significant difference in the comparison of the high and low risk groups as independent variables. In this analysis, toe grip strength and diastolic blood pressure were identified as independent risk factors for a fall. CONCLUSIONS: Toe grip strength is an independent risk factor for falls, and improvement of toe grip strength might prevent falls.

施設入居高齢者の転倒リスクと認知機能を調査し、身体機能ならびに足趾把持筋力との関連について検討した。軽費老人ホームに入居している高齢者26名(52足)を対象とした。転倒リスクに対する多変量解析で、転倒リスクを従属変数、ハイリスク群と正常群2群の比較において有意差を示した因子を独立変数としたロジスティック回帰分析を行い、足趾把持筋力が独立した危険因子として抽出された。実際の転倒経験について、転倒経験群が6名、ニアミス経験群が4名、非経験群が16名であった。転倒群・ニアミス経験群のFall Risk Index、足趾把持筋力は非転倒群よりも有意に低い値を示し、10回椅子立ち上がりテスト(SS-10)、Time up and go、5m歩行速度は非転倒群よりも有意に長かった。転倒に対する多変量解析では、5m歩行速度が独立した危険因子として抽出された。

Fall Risk Index(FRI)を用いて高齢者の転倒スコアを調査し、足趾把持筋力との関連を検討することを目的とした。65歳以上の高齢者41名(82足)、平均年齢71.7±4.8歳を対象とした。対象者のFRIを評価し、足趾把持筋力を測定した。FRIのCutoff値でハイリスク群(10以上)と正常群(9以下)に分類して、足趾把持筋力と実際の転倒状況を比較した。足趾把持筋力は左右2回ずつ測定し、それぞれ良い値の左右の平均値とした。また体重の影響を補正するため体重比足趾把持筋力を算出した。転倒状況は本人への聞き取り調査を行った。FRIのハイリスク群(14名)は10.4±0.8、正常群(27名)は5.7±1.9であった。ハイリスク群の足趾把持筋力は、正常群よりも有意に低値であった(5.2±2.4kg vs.9.5±3.9kg、p<0.01)。また、実際の転倒経験は、ハイリスク群が正常群より有意に高値であった(転倒経験/ニア転倒経験/非転倒:6/8/0名vs.0/12/15名、p<0.01)。高齢者のFRIハイリスク群は、足趾把持筋力が低値であった。すなわち、高齢者の転倒には足趾把持筋力が関連することが示された。(著者抄録)

一般大学生5名(男子4名、女子1名)を対象とし、足趾保持筋力トレーニング+足趾運動巧緻性トレーニングの実施前後で身体機能の比較検討を行った。トレーニングの内容は「タオルギャザー」「足を平行に開いたムカデ歩き」「ゴルフボールのゴロゴロ&キャッチ&リリース」「足趾ジャンケン体操」で、身体機能の評価項目は「足アーチ高率」「足趾把持筋力」「足趾柔軟性」「足趾運動巧緻性」「閉眼片足立ち時間」「Time Up and Go(TUG)」「5 Chair Stands」「10m最大歩行」「最大1歩幅」とした。検討の結果、トレーニングによって「TUG」と「5 Chair Stands」の有意な改善が認められた。

Purpose: Maintenance and enhancement of vascular endothelial function contribute to the prevention of cardiovascular disease and prolong a healthy life expectancy. Given the reversible nature of vascular endothelial function, interventions to improve this function might prevent arteriosclerosis. Accordingly, we studied the effects of a 6-month static stretching intervention on vascular endothelial function (reactive hyperaemia peripheral arterial tonometry index: RH-PAT index) and arterial stiffness (brachial-ankle pulse wave velocity: baPWV) and investigated the reversibility of these effects after a 6-month detraining period following intervention completion. Methods: The study evaluated 22 healthy, non-smoking, premenopausal women aged &gt;= 40 years. Subjects were randomly assigned to the full-intervention (n=11; mean age: 48.6 +/- 2.8 years) or a half-intervention that included a control period (n=11; mean age: 46.9 +/- 3.6 years). Results: Body flexibility and vascular endothelial function improved significantly after 3 months of static stretching. In addition to these improvements, arterial stiffness improved significantly after a 6-month intervention. However, after a 6-month detraining period, vascular endothelial function, flexibility, and arterial stiffness all returned to preintervention conditions, demonstrating the reversibility of the obtained effects. Conclusion: A 3-month static stretching intervention was found to improve vascular endothelial function, and an additional 3-month intervention also improved arterial stiffness. However, these effects were reversed by detraining.

【目的】減量成功の女性肥満患者に対しインスリン抵抗性改善に寄与する体組成因子の同定を目的とした。【方法】6ヵ月間の食事、運動療法、認知行動療法による行動介入プログラムで介入前体重より5%以上減量した肥満女性81名(平均年齢39.0±9.1歳、BMI 33.4±4.4kg/m2)を対象にした。介入前後に二重エネルギーX線吸収測定法(DXA)により体組成を評価し、骨格筋量の変化を検討した。インスリン抵抗性としてHOMA-IRを測定した。その後、減量時のHOMA-IRの変化に対する身体組成の影響につき検討した。【結果】体重変化率は-10.4±4.7%、HOMA-IR変化率は-20.1±39.3%と有意な改善が見られた。体組成変化率では、総脂肪量は-18.9±9.6%と有意に減少、総除脂肪量も-2.7±4.4%の有意な減少が見られたが、その変化量は脂肪量に比べ有意に低値であった(P<0.01)。各々の体重補正値では、体脂肪率は-9.8±7.4%と有意な減少に対し、総除脂肪率では8.8±7.3%と有意な増加が見られた。さらに、HOMA-IR変化率を従属変数とする重回帰分析では、総除脂肪率が独立変数として抽出された(β=-0.320、R2=0.091、P<0.01)【結論】女性肥満に対するインスリン抵抗性改善には体重、BMI、脂肪量減少だけでなく総除脂肪率の維持増加が重要であると考えられた。(著者抄録)

Background: Irisin is a myokine implicated in lipid and glucose metabolism. The objective of this study is to examine the effect of a body weight reduction on the serum irisin level and physical indicators in obese Japanese patients without diabetes. Methods: The subjects were 22 patients (male/female, 5/17; age, 46.1 +/- 16.0 years; body mass index [BMI], 36.9 +/- 5.0 kg/m(2)) who completed a 6-month body weight reduction program at our clinic. The program included diet, exercise therapy and cognitive behavioral therapy. Blood parameters, body composition, exercise tolerance, homeostasis model assessment of insulin resistance (HOMA-IR), and serum irisin were determined before and after intervention, and relationships among changes in these data were examined. Results: There were significant decreases in body weight and BMI after the intervention. Irisin before the intervention was significantly positively correlated with HOMA-IR (r=0.434, P&lt;0.05). The mean irisin level showed no significant change after the intervention in all participants. However, improvements in % body fat, subcutaneous fat area, triglycerides, and fasting glucose were significantly greater in patients with an increase in irisin compared to those with a decrease in irisin after the intervention. Patients with an increase in irisin also had significantly lower fasting insulin (9.7 +/- 4.8 vs. 16.4 +/- 8.2, P&lt;0.05) and HOMA-IR (2.2 +/- 1.1 vs. 3.7 +/- 1.6, P&lt;0.05) after the intervention, compared to patients with a decrease in irisin. Conclusion: Body weight reduction did not alter irisin levels. However, irisin may play important roles in fat and glucose metabolism and insulin resistance, and the effects of body weight reduction on irisin kinetics may be a key for obesity treatment.

Approximately, 70 % of acute myocardial infarctions are known to develop from mild atherosclerotic lesions. Therefore, it is important to evaluate mild coronary plaques to prevent acute coronary syndrome (ACS). The aim of the present study was to investigate the effects of exercise-based cardiac rehabilitation (CR) on mild coronary atherosclerosis in non-culprit lesions in patients with ACS. Forty-one men with ACS who underwent emergency percutaneous coronary interventions and completed a 6-month follow-up were divided into CR and non-CR groups. Quantitative coronary angiography (QCA) was performed using the automatic edge detection program. The target lesion was a mild stenotic segment (10-50 % stenosis) at the distal site of the culprit lesion, and the segment to be analyzed was determined at a segment length ranging from 10 to 15 mm. The plaque area was significantly decreased in the CR group after 6 months, but was significantly increased in the non-CR group (P &lt; 0.05). The low-density lipoprotein (LDL) cholesterol, LDL/high-density lipoprotein (HDL) ratio and high-sensitivity C-reactive protein (Hs-CRP) levels were significantly reduced in both groups (P &lt; 0.01). Peak VO2 in the CR group was significantly increased (P &lt; 0.01). Changes in the plaque area correlated with those in Hs-CRP in both groups, while that association with those in HDL-C was observed in only CR group. Stepwise regression analysis revealed the decrease in Hs-CRP as an independent predictor of plaque area regression in the CR group. CR prevented the progression of mild coronary atherosclerosis in patients with ACS.