停經後女性的骨骼肌氧合度與心肌灌流：休閒身體活動與活動劑量的影響

Abstract

研究背景：停經後女性罹患心血管疾病的機率較停經前增加，是造成失能與死亡的主要因素之一。缺乏身體活動與運動耐力差為罹患心血管疾病的危險因子之一，已有研究指出影響其運動耐力的主要原因，與周邊的血流不足或肌肉代謝異常有關。停經後女性的休閒身體活動多屬不足，目前實證支持增加身體活動量可有效預防心血管疾病。然而休閒身體活動量對於心血管危險因子或心肌灌流的影響，則較少劑量反應的相關研究。 研究目的：本研究針對停經後女性，目的如下：（一）評估休閒身體活動量與運動耐力，探討休閒身體活動對於心肌灌流功能與骨骼肌氧合度的影響；（二）評估骨骼肌氧合度對於運動耐力、心肌灌流與心臟功能的影響；（三）評估不同劑量的運動訓練（中、高運動量）對於心血管危險因子與骨骼肌氧合度的作用。 研究方法：本研究分兩階段，第一階段採橫向性的分析，共有67位無心血管疾病症狀與診斷的停經後女性，依其每週休閒身體活動量分組，比較兩組的心血管危險因子、運動耐力與骨骼肌氧合度反應、以及心肌灌流與功能，分析身體活動與各參數的相關性；並探討骨骼肌氧合度與運動耐力、心肌灌流與心臟功能的相關性。第二階段採縱向式介入研究，以不同劑量的運動訓練（中、高運動量），評估對於心血管危險因子、運動耐力與周邊骨骼肌氧合度反應的效果。第一階段的測量參數包括：基本資料、體重與身體組成、血液生化參數、休息心電圖、鉈-201運動式單光子閃爍攝影、最大運動測試相關參數、與利用近紅外線光譜檢查肌肉氧合能力，依2007年女性心血管疾病實証醫學指引中的危險分級評估未來發生心血管疾病的危險性；以休閒身體活動量的中位數將受試者分為低活動量組（36位，平均每週休閒身體活動量為0 MET-hr/week）與高活動量組（31位，平均每週休閒身體活動量為27.2 ± 24.6 MET-hr/week）。第二階段37位停經後女性參與，將願意接受運動者以隨機分為中運動量（每週運動三次，每次50分鐘，11位）與高運動量（每週運動四次，每次50分鐘，11位），其餘為控制組（維持身體活動量不變，15位）。運動介入方式為三個月的有氧與阻力合併訓練，所有受試者研究期間的飲食與用藥習慣維持不變。本研究以SPSS 13.0（SPSS Inc., Chicago, Illinois）套裝軟體做統計分析，利用t檢定法或卡方檢定比較第一階段橫向研究中不同休閒身體活動量組各參數的差異，並做相關性分析統計。第二階段研究中，不同運動訓練量的效果，以重複測量變異數分析（repeated measure ANOVA）或是共變數分析（analysis of covariance, ANCOVA）檢定各組測量參數的差異。 結果：低活動量組與高活動量組的基本資料與共病症相似，低活動量組的總膽固醇（208.8 ± 32.6 vs 190.2 ± 34.7 mg/dL, p=0.034）與C反應蛋白（0.33 ± 0.43 vs 0.13 ± 0.19 mg/dL, p=0.042）明顯較高，最大攝氧量較低（19.0 ± 2.8 vs 21.6 ± 4.0 ml/kg/min, p=0.001），骨骼肌去氧血紅素改變量較少（2.3 ± 1.2 vs 3.1 ± 1.5 ×10-4μM, p=0.011）、復氧期去氧血紅素回復到1/2改變量所需時間較長（61.2 ± 57.9 vs 33.1 ± 25.5 seconds, p=0.017），兩組的心肌灌流影像相似，低活動量組與高活動量組分別有17%與12%的受試者為可逆缺損型的心肌影像，運動後左心室攝出率較休息時下降的人數比例分別為50%與29%，低活動量組有較多比例的受試者未來有罹患心血管疾病的危險性（61% vs 32%, p=0.027）。休閒身體活動量與心血管危險因子、運動耐力、運動時的心血管反應與骨骼肌去氧血紅素改變量皆有顯著相關；而骨骼肌去氧血紅素改變量則與最大攝氧量（r=0.303）以及鉈-201肺/心吸收比值（r= -0.301）具有相關性。控制組、中運動量與高運動量組的休閒身體活動量的改變各為：-4.1 ± 8.7、17.0 ± 7.4、30.5 ± 14.4 MET-hr/week，兩組運動組的活動量改變與能量消耗改變皆明顯高於控制組（p<0.005），兩組比較則無差異，運動訓練的順應性為95.8 ± 9.3%與85.9 ± 19.1%。運動訓練的效果主要可以降低腰圍，增加運動耐力，且骨骼肌擷氧能力有增加的傾向，控制組則無上述的改變。運動訓練對於運動時的心率反應作用，包括降低休息心率、改善心率恢復與增加運動時的心率收縮壓乘積變化量，皆傾向支持較高運動量的訓練。 結論：在無心血管疾病症狀與診斷的停經後女性，休閒身體活動量越高，心血管疾病危險因子越低，且運動耐力與骨骼肌擷氧能力越佳，心臟功能亦較佳。每週大於三次的運動訓練可以有效改善心血管疾病危險因子，運動耐力與運動時的心血管反應，並有增加骨骼肌擷氧能力的趨勢。

Background and Purpose. Cardiovascular disease (CVD) remains the major cause of disability and mortality in postmenopausal women, and previous studies have demonstrated physical inactivity and exercise intolerance are the major risk factors. This study aimed to evaluate (1) leisure physical activity (LPA) and its effects on myocardial perfusion and skeletal muscle oxygenation; (2) the effects of skeletal muscle oxygenation on exercise performance, myocardial perfusion, and cardiac function; (3) the dose-response relationship of varying amounts of exercise on the CVD risk and skeletal muscle oxygenation in asymptomatic postmenopausal women without CVD. Methods. Sixty-seven postmenopausal women were recruited and divided into physical inactive (PIA, n=36, 68.4 years, LPA 0 MET-hour/week) and physical active (PA, n=31, 59.3 years, LPA 27.2 ± 24.6 MET-hour/week) groups according to their self-reported LPA. Outcome measurements included clinical characteristics, ECG-gated 201Tl SPECT scanning at stress and rest, cardiopulmonary exercise testing and simuteneously measurement of skeletal muscle oxygenation by near infrared spectroscopy, and CVD risks classification. The eligible participants for the follow-up study were then divided into controls (n=15, 57.8 years, usual physical activity level) and exercise group. The exercise group was randomized into moderate (n=11, 54.7 years, 3 sessions/week) and high amount (n=11, 58.7 years, 4 sessions/week) exercise training. The effects of exercise dose-response on CVD risks, cardiopulmonary fitness, and exercising skeletal muscle oxygenation were assessed. In the cross-sectional analysis, group comparisons were performed using independent sample t test or Chi-square test. Pearson or Spearson’s correlation was used in correlation analysis. Analysis of the effects of exercise between groups was performed by repeated measure ANOVA or ANCOVA with post hoc analysis. Results. The PIA group and PA were similar in clinical characteristics and comorbidities. Significantly higher total cholesterol (208.8 ± 32.6 vs. 190.2 ± 34.7 mg/dL) and C-reactive protein (0.33 ± 0.43 vs 0.13 ± 0.19 mg/dL), lower peak VO2 (19.0 ± 2.8 vs. 21.6 ± 4.0 ml/kg/min), lower skeletal muscle deoxy-hemoglobin change during exercise (2.3 ± 1.2 vs. 3.1 ± 1.5 ×10-4 μM) and slower recovery to baseline of deoxy-hemoglobin (61.2 ± 57.9 vs. 33.1 ± 25.5 seconds) were noted in the PIA group (all p<0.05). Myocardial perfusion image with reversible defect was 17 % and 12% in the PIA and PA group, respectively. More women in the PIA group tended to have a worsening in LVEF by exercise than in the PA group (50% vs. 29%, p=0.133). More PIA women were categorized as “at risk” of having CVD (61% vs. 32%, p=0.027). The muscle deoxy-hemoglobin change during exercise was correlated significantly with peak VO2 (r=0.303) and lung-to-heart ratio (r=-0.301). In the follow-up study, LPA changes during the study period were -4.1 ± 8.7, 17.0 ± 7.4, and 30.5 ± 14.4 MET-hour/week in the control, moderate, and high amount exercise groups. Waist circumference, cardiopulmonary fitness, and hemodynamic response adapted to exercise significantly improved after exercise training in the moderate and high exercise groups, while the improvements were not noted in the control group. A trend of increased muscle deoxy-hemoglobin change during exercise was noted in both exercise groups. Conclusion. Postmenopausal women with higher LPA levels had lower CVD risk, better cardiopulmonary fitness and muscle oxygen extraction, and tended to have preserved cardiac function. Exercise training of more than 3 sessions weekly improved CVD risk, cardiopulmonary fitness, and hemodynamic response adapted to exercise. A trend of improved ability of muscle oxygen extraction was noted after exercise training.