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Beijing Da Xue Xue Bao Yi Xue Ban.
2020 Feb 18; 52(1): 152–157.
Chinese.
doi:
10.19723/j.issn.1671-167X.2020.01.024
PMCID:
PMC7439077
PMID:
32071479
心肺适能对动脉粥样硬化性心血管疾病高危患者的保护作用
Protective effect of cardiopulmonary fitness on patients with high risk of atherosclerotic cardiovascular disease
任 川
北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
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任 川
吴 晓月
北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
Find articles by
吴 晓月
赵 威
北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China 北京大学第三医院体检中心,北京 100191, Physical Examination Center, Peking University Third Hospital, Beijing 100191, China
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赵 威
陶 立元
北京大学第三医院临床流行病学研究中心,北京 100191, Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
Find articles by
陶 立元
刘 萍
北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China
Find articles by
刘 萍
高 炜
北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China 北京大学第三医院心内科,北京大学第三医院血管医学研究所,国家卫生健康委员会心血管分子生物学与调节肽重点实验室,分子心血管学教育部重点实验室,心血管受体研究北京市重点实验室,北京 100191, Department of Cardiology, Peking University Third Hospital; Institute of Vascular Medicine of Peking University Third Hospital; Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides of National Health Commission; Key Laboratory of Molecular Cardiovascular Science of Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing 100191, China 北京大学第三医院体检中心,北京 100191, Physical Examination Center, Peking University Third Hospital, Beijing 100191, China 北京大学第三医院临床流行病学研究中心,北京 100191, Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing 100191, China
2. 结果
2.1. 一般资料
研究共纳入544例患者,其中506例患者完成随访,失访率6.9%。根据ASCVD总体风险评估分为低危250例,中危93例,高危163例。对研究对象随访至2019年2月,中位随访时间为19个月(9~28个月), 共有51例(10.1%)患者在随访期内发生ASCVD事件,其中心肌梗死、不稳定心绞痛、冠脉血运重建治疗者 33例,缺血性脑卒中、短暂脑缺血发作、颈动脉血运重建者18例。出现ASCVD事件的患者作为ASCVD组( n =51),其余患者作为非ASCVD组( n =455)。
2.2. ASCVD组与非ASCVD组的基线特征比较
与非ASCVD组相比,ASCVD组患者年龄,合并高血压病史比例,钙离子拮抗剂、他汀类降血脂药物及阿司匹林应用比例显著高于非ASCVD组( P 均<0.05),HDL-C显著低于非ASCVD组( P <0.05)。两组间性别、BMI、高脂血症、糖尿病病史、血清TC、TG、LDL-C、FBG、全血HbAlc水平、β-受体阻滞剂、血管紧张素转换酶抑制剂/血管紧张素Ⅱ受体拮抗剂应用比例差异无统计学意义,见 表1 。
1
ASCVD组和非ASCVD组的基线资料
General information of ASCVD group and non ASCVD group
| Items | Non ASCVD group( n =455) | ASCVD group( n =51) | P |
| BMI, body mass index; TC, total cholesterol; LDL-C, low density lipoprotein cholesterol; HDL-C, high density lipoprotein cholesterol; TG, trigly-ceride; FBG, fasting blood glucose; HbAlc, glycosylated hemoglobin; ACEI/ARB, angiotensin converting enzyme inhibitors/angiotensin Ⅱ receptor antagonists; ASCVD, atherosclerotic cardiovascular disease; VO 2 peak, peak oxygen uptake. | |||
| Age/years, x ± s | 56.0±13.1 | 63.7±9.2 | <0.001 |
| Gender | 0.084 | ||
| Male, n (%) | 224(49.2) | 32(62.7) | |
| Female, n (%) | 231(50.8) | 19(37.3) | |
| BMI/(kg/m 2 ), x ± s | 25.3±3.8 | 26.2±3.0 | 0.105 |
| Medical History | |||
| Hypertension, n (%) | 189(41.5) | 30(58.8) | 0.023 |
| Hyperlipidemia, n (%) | 196(43.1) | 25(49.0) | 0.473 |
| Diabetes, n (%) | 82(18.0) | 13(25.5) | 0.215 |
| Smoking, n (%) | 118(25.9) | 17(33.3) | 0.287 |
| Laboratory tests | |||
| TC/(mmol/L), x ± s | 4.71±0.97 | 4.43±1.18 | 0.058 |
| LDL-C/(mmol/L), M (IQR) | 1.88(1.01) | 2.13(0.71) | 0.616 |
| HDL-C/(mmol/L), M (IQR) | 1.16(0.20) | 1.05(0.22) | 0.011 |
| TG/(mmol/L), x ± s | 2.53±1.02 | 2.31±1.04 | 0.163 |
| FBG/(mmol/L), M (IQR) | 5.5(0.7) | 5.7(0.8) | 0.805 |
| HbAlc, n (%) | 5.9(0.6) | 6.1(0.8) | 0.433 |
| Medication | |||
| ACEI/ARB, n (%) | 73(16.0) | 13(25.4) | 0.204 |
| β-blockers, n (%) | 54(11.9) | 8(15.7) | 0.456 |
| Calcium channel blockers, n (%) | 82(18.0) | 16(31.4) | 0.026 |
| Statins, n (%) | 103(22.6) | 23(45.1) | 0.001 |
| Aspirin, n (%) | 60(13.2) | 19(37.3) | <0.001 |
| Cardiopulmonary exercise testing | |||
| VO 2 peak/[mL/(kg·min)], M (ITR) | 19.1(3.2) | 16.3(3.6) | <0.001 |
| Positive result, n (%) | 30(6.6) | 4(7.8) | 0.189 |
2.3. ASCVD组与非ASCVD组VO 2 peak与ASCVD事件发生的相关性
ASCVD组VO 2 peak显著低于非ASCVD组( P <0.01, 表1 )。以是否发生ASCVD事件为因变量,以VO 2 peak及ASCVD危险分层为自变量,校正了性别因素,进行Logistic回归分析,结果提示VO 2 peak[ OR 0.893(95% CI :0.831~0.959), P =0.002]及ASCVD危险分层[ OR 1.428(95% CI :1.028~1.878), P =0.031]与ASCVD事件发生均独立相关。VO 2 peak每升高1 mL/(kg·min),ASCVD事件发生风险降低11%。
2.4. ASCVD不同危险程度患者中VO 2 peak水平与ASCVD事件发生的相关性
依据患者VO 2 peak的三分位数[14.4 mL/(kg·min), 23.0 mL/(kg·min)]将患者分为低、中、高VO 2 peak组。
在ASCVD危险分层高危的患者中,高VO 2 peak组为44例,中VO 2 peak组61例,低VO 2 peak组58 例。ASCVD组阿司匹林应用比例显著高于非ASCVD 组,VO 2 peak显著低于非ASCVD组( P 均<0.05),见 表2 。以是否发生ASCVD事件为因变量,校正了性别、年龄、BMI、TC、钙拮抗剂、他汀类降血脂药物和阿司匹林应用情况后,进行Logistic回归分析,结果提示中水平VO 2 peak[ OR 0.210(95% CI :0.054~0.814), P =0.024)及高水平VO 2 peak [ OR 0.146(95% CI :0.025~0.870), P =0.035]患者中ASCVD事件的发生均显著下降,见 图1 。
2
ASCVD危险分层高危和中、低危患者中ASCVD组和非ASCVD组的基线资料
General information of ASCVD group and non ASCVD group in ASCVD low /moderate risk and high risk populations
| Items | Low /moderate risk | High risk | ||||
|
Non ASCVD group
( n =313) |
ASCVD group
( n =30) |
P |
Non ASCVD group
( n =142) |
ASCVD group
( n =21) |
P | |
| Abbreviations as in Table 1 . | ||||||
| Age/years, x ± s | 55.3±13.6 | 65.1±9.1 | <0.001 | 57.6±11.6 | 61.8±9.2 | 0.117 |
| Gender | 0.152 | 0.479 | ||||
| Male, n (%) | 145(46.3) | 18(60.0) | 79(55.6) | 14(66.7) | ||
| Female, n (%) | 168(53.7) | 12(40.0) | 63(44.4) | 7(33.3) | ||
| BMI, kg/m 2 | 24.8±3.5 | 26.2±2.8 | 0.039 | 26.6±4.0 | 26.3±3.4 | 0.740 |
| Medical History | ||||||
| Hypertension, n (%) | 93(29.7) | 14(46.7) | 0.056 | 96(67.7) | 16(76.2) | 0.630 |
| Hyperlipidemia, n (%) | 121(38.6) | 12(40.0) | 0.885 | 75(52.8) | 13(61.9) | 0.585 |
| Diabetes, n (%) | 6(1.9) | 2(6.7) | 0.100 | 76(53.5) | 11(52.4) | 0.737 |
| Smoking, n (%) | 60(19.2) | 8(26.7) | 0.325 | 58(40.8) | 9(42.9) | 0.993 |
| Laboratory tests | ||||||
| TC/(mmol/L), x ± s | 4.66±0.90 | 4.16±1.04 | 0.005 | 4.84±1.09 | 4.83±1.29 | 0.957 |
| LDL-C/(mmol/L), M (IQR) | 1.75(1.02) | 1.74(1.22) | 0.637 | 2.26(0.77) | 2.46(0.74) | 0.186 |
| HDL-C/(mmol/L), M (IQR) | 1.20(0.19) | 1.11(0.20) | 0.084 | 1.02(0.20) | 0.90(0.33) | 0.326 |
| TG/(mmol/L), x ± s | 2.41±0.97 | 2.06±0.80 | 0.052 | 2.80±1.07 | 2.66±1.24 | 0.588 |
| FBG/(mmol/L), M (IQR) | 5.4(0.5) | 5.6(0.3) | 0.735 | 6.4(1.6) | 6.2(1.6) | 0.341 |
| HbAlc, n (%) | 5.7(0.3) | 5.7(0.5) | 0.575 | 6.5(1.5) | 6.6(1.3) | 0.961 |
| Medication | ||||||
| ACEI/ARB, n (%) | 41(13.1) | 5(16.7) | 0.584 | 32(22.5) | 8(38.1) | 0.122 |
| β-blockers, n (%) | 32(10.2) | 3(10.0) | 0.969 | 22(15.5) | 5(23.8) | 0.397 |
| Calcium channel blockers, n (%) | 45(14.4) | 9(30.0) | 0.025 | 37(26.1) | 7(33.3) | 0.575 |
| Statins, n (%) | 70(22.3) | 14(46.7) | 0.004 | 33(23.2) | 9(42.9) | 0.052 |
| Aspirin, n (%) | 43(13.7) | 10(33.3) | 0.005 | 17(12.0) | 9(42.9) | 0.001 |
| Cardiopulmonary exercise testing | ||||||
| VO 2 peak, mL/(kg·min), M (ITR) | 19.4(3.1) | 16.1(4.4) | 0.006 | 18.8(2.8) | 16.3(1.7) | 0.014 |
| Positive result, n (%) | 16(5.1) | 2(6.7) | 0.340 | 14(9.9) | 2(9.5) | 0.242 |
在ASCVD危险分层高危和中、低危患者中,不同水平的VO 2 peak与ASCVD事件相关性的Logistic回归
Logistic regression analysis of ASCVD events by categories of VO 2 peak in ASCVD low /moderate risk and high risk populations
Model is adjusted for age, gender, BMI, TC, calcium channel blockers use, statin use, aspirin use. VO 2 peak, peak oxygen uptake; ASCVD, arteriosclerotic cardiovascular disease; BMI, body mass index; TC, total cholesterol; OR , odds ratio.
在ASCVD危险分层中、低危的患者中,高VO 2 peak组为127例,中VO 2 peak组107例,低VO 2 peak组109例。ASCVD组TC、VO 2 peak显著低于非ASCVD组,年龄、BMI、钙拮抗剂、他汀类降血脂药物、阿司匹林应用比例显著高于非ASCVD组( P 均<0.05),见 表2 。以是否发生ASCVD事件为因变量,校正了性别、年龄、BMI、TC、钙拮抗剂、他汀类降血脂药物和阿司匹林应用情况后,进行Logistic回归分析,结果提示中水平VO 2 peak[ OR 0.533(95% CI :0.179~1.582), P =0.257]及高水平VO 2 peak [ OR 0.770(95% CI : 0.236~2.513), P =0.665]患者中ASCVD事件的发生并未见显著下降,见 图1 。
3. 讨论
本研究发现高VO 2 peak与ASCVD事件的发生呈负相关关系,并且独立于传统ASCVD危险因素。进一步在 ASCVD危险分层高危和中、低危的患者中分别探讨了高VO 2 peak对ASCVD事件发生的保护作用,结果发现ASCVD高危的患者中VO 2 peak越高,发生ASCVD的风险越低,中水平VO 2 peak发生ASCVD风险可降低79%,高水平VO 2 peak发生ASCVD的风险可降低85%,但在ASCVD危险分层中低危的患者中这种保护作用并不显著。
既往的数十年间,如何降低人群ASCVD事件的发生一直是研究关注的问题,可干预的因素更是其中的焦点,但既往研究多针对如何减少危险因素的存在,如糖尿病、高血压、高脂血症、吸烟、肥胖等。近年来,心肺适能这一具有保护作用且可通过干预提高的因素也逐渐引起了大家的关注。既往研究提示,低心肺适能是心血管事件发生、心血管疾病死亡和全因死亡的独立预测因子 [ 6 , 7 ] ,而高心肺适能可延缓动脉粥样硬化进展 [ 8 ] ,这种保护作用在所有性别 [ 9 ] 和种族 [ 10 ] 间均存在。VO 2 peak是心肺适能的经典指标,本研究再次证实了高VO 2 peak对ASCVD事件的发生具有保护作用,VO 2 peak每升高1 mL/(kg·min),ASCVD事件发生风险降低11%,并且这种保护作用是独立于传统危险因素的。
虽然基于种族、基因等因素,每个个体所能达到的最大心肺适能不尽相同,但对于未患ASCVD的人群,实际心肺适能更多地取决于患者的运动习惯、营养状况等,是可以通过精准科学的运动和营养干预获得提高的。本研究结果显示在ASCVD高危人群中心肺适能的保护作用更为突出。ASCVD高危往往意味着合并了多种危险因素,同时还存在内皮功能障碍、氧化应激异常等,而通过科学的运动锻炼提高心肺适能不仅仅改善这一类人群丛集出现的ASCVD传统危险因素 [ 11 ] ,还可增加心肌等张机械性和代谢性功能,增加电稳定性;降低血纤维蛋白原活性,减少血小板聚集;并可改善或修复内皮功能,延缓动脉粥样硬化斑块的形成,这可称之为运动锻炼治疗的“多效性”。本研究结果提示,在临床实践中对ASCVD高危人群除了应干预传统危险因素外,还应重视对心肺适能这一保护因素的提高,增加其获益。既往研究提示,健康人群高心肺适能与远期全因死亡率降低有关 [ 12 ] ,本研究ASCVD中低危患者高心肺适能的保护作用并不显著,可能与本研究的样本量较小,随访时间较短有关,中、低危风险的患者可能需要更长时间的干预方可收效。
本研究通过心肺运动试验准确测定了心肺适能的“金指标”VO 2 peak。既往研究中常常用问卷调查日常体力活动 [ 6 ] ,通过运动平板 [ 12 ] 或20 m往返跑 [ 13 ] 推测个体的心肺适能,但实际上这些方式估测的心肺适能与实际存在一定差异,心肺适能最准确的测定方法是进行症状限制性心肺运动试验,通过吸入的氧气直接测定VO 2 peak。既往研究 [ 14 , 15 ] 曾比较日常体力活动和心肺适能与冠心病发生风险的相关性,Williams等 [ 14 ] 的研究表明心肺适能降低所致心血管疾病风险是体力活动减少所致风险的2倍,而Ekblom-Bak等 [ 15 ] 的研究结果也表明心肺适能对风险评估的价值更大。此外,无气体分析的运动负荷试验可能会高估患者的心肺适能 [ 16 ] ,因而通过心肺运动试验对心肺适能进行准确评估更为合理。
本研究因患者入选过程中对于无临床症状的ASCVD患者无法做到完全排除,可能对结果造成一定影响。同时入选患者均为临床就诊的患者,ASCVD事件的发生率相对较高,此结论可能不适用于一般健康人群。此外,本研究样本量略小,随访时间较短,可能会影响心肺适能对ASCVD中低危患者保护作用的评估。
Funding Statement
“立信扬帆”科研基金（BJUHFCSOARF201801-11）; 首都临床特色应用研究与成果推广基金（Z151100004015047）; 国家自然科学基金（81601968）
Supported by the CS Optimizing Antithrombotic Research Fund(BJUHFCSOARF201801-11); Capital Clinical Application Research and Promotion Projects of Beijing Municipal Science and Technology Commission(Z151100004015047); National Natural Science Foundation of China(81601968)
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Articles from
Journal of Peking University (Health Sciences)
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