Journal of Cachexia, Sarcopenia and Muscle最新文献_第5页

Comment on ‘Prediabetes is an independent risk factor for sarcopenia in older men, but not in older women: the Bunkyo Health Study’ by Kaga et al. Kaga等人对“糖尿病前期是老年男性少肌症的独立危险因素，但不是老年女性：Bunkyo健康研究”的评论。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-12 DOI: 10.1002/jcsm.13293

Shanhu Qiu, Xue Cai, Zilin Sun, Tongzhi Wu

We read, with great interest, the recent article by Kaga et al., in which prediabetes was reported to be associated with sarcopenia in older men but not in older women based on the cross-sectional analysis using the baseline data from the Bunkyo Health Study.¹ This finding indicates that sarcopenia could have occurred prior to the onset of diabetes, particularly in older men, and highlights the need of conducting screening-oriented strategy for sarcopenia prevention in the aging population. However, in this article, several issues are worthy of discussion.

First, as indicated in the Methods part, the authors performed separate analyses by sex for the association of glycaemic status with sarcopenia. They found that after multivariate adjustment, prediabetes was associated with higher odds for sarcopenia compared with normoglycaemia (odds ratio [OR] 2.08, 95% confidence interval [CI]: 1.03 to 4.20) in men but not in women (OR 1.04, 95% CI: 0.61 to 1.76). However, when combining older men and women together, results from the fixed meta-analytical approach showed that prediabetes might not be significantly associated with higher odds of sarcopenia (OR 1.33, 95% CI: 0.87 to 2.03, P for heterogeneity = 0.12). Moreover, the interaction effect between men and women was not significant (P = 0.12), based on the test for interaction,² suggesting that sex may not mediate the association of prediabetes with sarcopenia. A possible explanation for this inconsistent outcome between men and women, as shown by Kaga et al.,¹ might be attributable to the difference in the sample sizes of male and female participants and hence the statistical power. However, as already noted by the authors in their Methods part that there existed considerable differences in body composition, muscle strength, or physical function in the aging population, it is therefore appropriate and reasonable to perform sex-stratified analyses. As a result, future studies with larger sample sizes are required to confirm the present findings regarding the association of prediabetes with sarcopenia between sex in the aging population.

Second, employing oral glucose tolerance test and haemoglobin A1c (HbA1c) to ascertain prediabetes diagnostic criteria by the Japan Diabetes Society is a strength of this article. However, there exists controversies regarding the cut-off points of fasting blood glucose and HbA1c for defining prediabetes. For example, the American Diabetes Association recommends a fasting blood glucose at 5.6–6.9 mmol/L to diagnose prediabetes, while the World Health Organization suggests 6.1–6.9 mmol/L; the American Diabetes Association recommends a HbA1c at 5.7–6.4% (39–47 mmol/mol) to diagnose prediabetes, while the International Expert Committee advocates 6.0–6.4% (42–47 mmol/mol).³ It is therefore of interest to know whether the study outcomes a

我们阅读,怀着极大的兴趣,最近的文章Kaga et al .,前驱糖尿病的报道与sarcopenia在老年男性而不是基于横断面分析老年妇女使用基线数据Bunkyo卫生Study.1这个发现表明sarcopenia可能发生糖尿病的发病之前,尤其是老年男性,凸显了需要进行screening-oriented老龄化sarcopenia预防策略。然而，在本文中，有几个问题值得讨论。首先，如方法部分所述，作者按性别分别分析了血糖状态与肌肉减少症的关系。他们发现，在多因素调整后，与血糖正常者相比，糖尿病前期男性发生肌肉减少症的几率更高(比值比[OR] 2.08, 95%可信区间[CI]: 1.03至4.20)，而女性没有(比值比[OR] 1.04, 95%可信区间[CI]: 0.61至1.76)。然而，当将老年男性和女性结合在一起时，固定荟萃分析方法的结果显示，前驱糖尿病可能与肌肉减少症的高几率没有显著相关性(OR 1.33, 95% CI: 0.87至2.03,P为异质性= 0.12)。此外，根据相互作用的检验，男性和女性之间的相互作用效应不显著(P = 0.12)， 2表明性别可能不会介导糖尿病前期与肌肉减少症的关联。正如Kaga等人所表明的，男性和女性之间结果不一致的一个可能的解释是，男性和女性参与者的样本量不同，因此统计能力不同。然而，正如作者在他们的方法部分已经指出的那样，老龄人口在身体组成、肌肉力量或身体功能方面存在相当大的差异，因此进行性别分层分析是适当和合理的。因此，未来需要更大样本量的研究来证实目前的研究结果，即糖尿病前期与老年人群中性别之间肌肉减少症的关系。其次，日本糖尿病学会采用口服糖耐量试验和血红蛋白A1c (HbA1c)确定糖尿病前期诊断标准是本文的优势。然而，对于空腹血糖和糖化血红蛋白的临界值定义前驱糖尿病存在争议。例如，美国糖尿病协会建议空腹血糖在5.6-6.9 mmol/L来诊断前驱糖尿病，而世界卫生组织建议为6.1-6.9 mmol/L;美国糖尿病协会推荐HbA1c在5.7-6.4% (39-47 mmol/mol)诊断前驱糖尿病，而国际专家委员会推荐6.0-6.4% (42-47 mmol/mol)因此，了解研究结果是否受到不同的前驱糖尿病诊断标准的影响是很有意义的。第三，根据空腹血糖和2小时血糖，可以将前驱糖尿病分为不同的表型，包括分离性空腹血糖受损(IFG)，分离性糖耐量受损(IGT)，或两者兼而有之。虽然人们普遍认为IFG和IGT都表现出胰岛素抵抗和β细胞功能障碍，但它们在潜在的病理生理上存在很大差异，并且代谢异常也有明显不同例如，IFG的特征是严重的肝脏胰岛素抵抗，但没有明确的证据表明骨骼肌(外周)胰岛素敏感性受损，而IGT的特征是明显的骨骼肌胰岛素抵抗，但只有中度的肝脏胰岛素抵抗。鉴于这些，并考虑到以生活方式为基础的2型糖尿病预防的益处可能受到糖尿病前期表型的影响，因此进一步研究糖尿病前期表型与肌肉减少症的关系是很有趣的。最后，前驱糖尿病是一种中间血糖状态，在自然史中可发展为糖尿病，维持为前驱糖尿病，或退化为正常血糖。先前的研究表明，前驱糖尿病的进展可能会增加心血管疾病的风险和全因死亡率，而前驱糖尿病的消退可能会带来健康益处，包括降低糖尿病或心血管疾病的风险虽然本研究的横断面设计可能无法解决糖尿病前期状态改变是否会影响肌少症的发展，但未来采用前瞻性队列设计的研究可能会受益于关注这一问题，因为它可能为实施有效的预防老年糖尿病前期人群肌少症的方法提供一些线索。作者声明他们没有利益冲突。

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引用次数: 0

Prognostic impact of cachexia by multi-assessment in older adults with heart failure: FRAGILE-HF cohort study 多重评估对老年心力衰竭患者恶病质预后的影响：FRAGILE-HF队列研究。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13291

Emi Maekawa, Takumi Noda, Daichi Maeda, Masashi Yamashita, Shota Uchida, Nobuaki Hamazaki, Kohei Nozaki, Hiroshi Saito, Kazuya Saito, Yuki Ogasahara, Masaaki Konishi, Takeshi Kitai, Kentaro Iwata, Kentaro Jujo, Hiroshi Wada, Takatoshi Kasai, Hirofumi Nagamatsu, Tetsuya Ozawa, Katsuya Izawa, Shuhei Yamamoto, Naoki Aizawa, Ryusuke Yonezawa, Kazuhiro Oka, Junya Ako, Shin-ichi Momomura, Nobuyuki Kagiyama, Yuya Matsue, Kentaro Kamiya

Background

Cachexia substantially impacts the prognosis of patients with heart failure (HF); however, there is no standard method for cachexia diagnosis. This study aimed to investigate the association of Evans's criteria, consisting of multiple assessments, with the prognosis of HF in older adults.

Methods

This study is a secondary analysis of the data from the FRAGILE-HF study, a prospective multicentre cohort study that enrolled consecutive hospitalized patients aged ≥65 years with HF. Patients were divided into two groups: the cachexia and non-cachexia groups. Cachexia was defined according to Evans's criteria by assessing weight loss, muscle weakness, fatigue, anorexia, a decreased fat-free mass index and an abnormal biochemical profile. The primary outcome was all-cause mortality, as assessed in the survival analysis.

Results

Cachexia was present in 35.5% of the 1306 enrolled patients (median age [inter-quartile range], 81 [74–86] years; 57.0% male); 59.6%, 73.2%, 15.6%, 71.0%, 44.9% and 64.6% had weight loss, decreased muscle strength, a low fat-free mass index, abnormal biochemistry, anorexia and fatigue, respectively. All-cause mortality occurred in 270 patients (21.0%) over 2 years. The cachexia group (hazard ratio [HR], 1.494; 95% confidence interval [CI], 1.173–1.903; P = 0.001) had a higher mortality risk than the non-cachexia group after adjusting for the severity of HF. Cardiovascular and non-cardiovascular deaths occurred in 148 (11.3%) and 122 patients (9.3%), respectively. The adjusted HRs for cachexia in cardiovascular mortality and non-cardiovascular mortality were 1.456 (95% CI, 1.048–2.023; P = 0.025) and 1.561 (95% CI, 1.086–2.243; P = 0.017), respectively. Among the cachexia diagnostic criteria, decreased muscle strength (HR, 1.514; 95% CI, 1.095–2.093; P = 0.012) and low fat-free mass index (HR, 1.424; 95% CI, 1.052–1.926; P = 0.022) were significantly associated with high all-cause mortality, but there was no significant association between weight loss alone (HR, 1.147; 95% CI, 0.895–1.471; P = 0.277) and all-cause mortality.

Conclusions

Cachexia evaluated by multi-assessment was present in one third of older adults with HF and was associated with a worse prognosis. A multimodal assessment of cachexia may be helpful for risk stratification in older patients with HF.

背景：恶病质严重影响心力衰竭（HF）患者的预后；然而，目前尚无标准的恶病质诊断方法。本研究旨在调查Evans标准（包括多项评估）与老年人HF预后的关系。方法：本研究是对FRAGILE-HF研究数据的二次分析，FRAGILE-HF研究是一项前瞻性多中心队列研究，纳入了年龄≥65岁的HF连续住院患者。患者分为两组：恶病质组和非恶病质对照组。根据Evans的标准，通过评估体重减轻、肌肉无力、疲劳、厌食、无脂肪质量指数下降和异常生化特征来定义恶病质。主要结果是生存分析中评估的全因死亡率。结果：1306名入选患者中有35.5%存在恶病质（中位年龄[四分位间距]，81[74-86]岁；57.0%为男性）；59.6%、73.2%、15.6%、71.0%、44.9%和64.6%的患者出现体重减轻、肌肉力量下降、无脂肪质量指数低、生物化学异常、厌食和疲劳。2年内270名患者（21.0%）发生全因死亡率。恶病质组（危险比[HR]，1.494；95%置信区间[CI]，1.173-1.903；P=0.001）在校正HF的严重程度后，其死亡率高于非恶病质对照组。心血管和非心血管死亡分别发生在148例（11.3%）和122例（9.3%）患者中。恶病质在心血管死亡率和非心血管死亡率中的校正HR分别为1.456（95%CI，1.048-2.023；P=0.025）和1.561（95%CI：1.086-2.243；P=0.017）。在恶病质诊断标准中，肌肉力量下降（HR，1.514；95%可信区间，1.095-2.093；P=0.012）和低脂肪游离质量指数（HR，1.424；95%置信区间，1.052-1.926；P=0.022）与高全因死亡率显著相关，但单独的体重减轻（HR，1.147；95%CI，0.895-1.471；P=0.0277）与全因死亡率之间没有显著关联。结论：通过多种评估评估的恶病质在三分之一的老年HF患者中存在，并且与更差的预后相关。恶病质的多模式评估可能有助于老年HF患者的风险分层。

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引用次数: 1

Corrigendum to I.S. Sinam et al. J of Cachexia, Sarcopenia and Muscle, 13, 3122–3136. DOI: 10.1002/jcsm.13100 I.S.Sinam等人的勘误表。恶病质，肌肉萎缩和肌肉杂志，133122-1336。DOI:10.1002/jcsm.13100。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13295

In the original full paper,¹ Figure 2D, we have inadvertently uploaded an incorrect figure. We came across this error during the process of data archiving. However, the correction did not affect the quantification (Figure 2D) and therefore, the original interpretation of data and conclusions remain same. Corrected data are identified in red arrow below.

Representative image of MYOG of C2C12 myotubes transfected with shPdk4 or shControl and treated with or without dexamethasone (DEX) (100 μM) for 24 h. Quantification represents the levels of the MYOG + ve cell. n = 4; number of image capture sites 20 from each group. **P < 0.01; ***P < 0.001; ****P < 0.0001. Tukey's multiple comparisons test was used for the analysed.

在原全文1 Figure 2D中，我们不小心上传了一个错误的图。我们在数据存档的过程中遇到了这个错误。然而，校正不影响量化(图2D)，因此，对数据和结论的原始解释保持不变。更正后的数据如下红色箭头所示。用shPdk4或shControl转染C2C12肌管，用或不加100 μM地塞米松(DEX)处理24 h后MYOG的代表性图像。定量表示MYOG + ve细胞的水平。n = 4;图像捕获站点数量，每组20个。* * P & lt;0.01;* * * P & lt;0.001;* * * * P & lt;0.0001. 采用Tukey多重比较检验进行分析。

引用次数: 0

Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates 短期停用不会影响吸收后或餐后肌肉蛋白质分解率。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13284

George F. Pavis, Doaa R. Abdelrahman, Andrew J. Murton, Benjamin T. Wall, Francis B. Stephens, Marlou L. Dirks

Background

The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2 days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions.

Methods

Twenty-three healthy, male participants (age: 22 ± 1 year; height: 179 ± 1 cm; body mass: 73.4 ± 1.5 kg; body mass index 22.8 ± 0.5 kg·m⁻²) took part in this randomized, controlled study. After 48 h of unilateral knee immobilization, primed continuous intravenous l-[¹⁵N]-phenylalanine and l-[ring-²H₅]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5 mg·kg body mass⁻¹·h⁻¹ amino acid infusion; FED). Bilateral m. vastus lateralis biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout.

Results

Amino acid infusion rapidly increased plasma phenylalanine (59 ± 9%), leucine (76 ± 5%), isoleucine (109 ± 7%) and valine (42 ± 4%) concentrations in FED only (all P < 0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8 ± 2.2 mU·L⁻¹ at 15 min in FED only (P < 0.001) and were 60% greater in FED than FAST (P < 0.01). Immobilization did not influence FBR in either FAST (CON: 0.150 ± 0.018; IMM: 0.143 ± 0.017%·h⁻¹) or FED (CON: 0.134 ± 0.012; IMM: 0.160 ± 0.018%·h⁻¹; all effects P > 0.05). However, immobilization decreased FSR (P < 0.05) in both FAST (0.071 ± 0.004 vs. 0.086 ± 0.007%·h⁻¹; IMM vs CON, respectively) and FED (0.066 ± 0.016 vs. 0.119 ± 0.016%·h⁻¹; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (P < 0.05) and to a greater extent in FED (CON: −0.012 ± 0.025; IMM: −0.095 ± 0.023%·h⁻¹; P < 0.05) than FAST (CON: −0.064 ± 0.020; IMM: −0.072 ± 0.017%·h⁻¹).

Conclusions

We conclude that merely 2 days of leg immobilization does not modulate postabsorptive and s

背景：吸收后和餐后肌肉蛋白质部分合成率（FSR）的下降并不能定量解释无并发症的短期废用期间的肌肉萎缩，而废用期间肌肉萎缩率最高。我们试图确定在吸收后和模拟餐后条件下，单侧膝关节固定2天是否会影响混合肌肉蛋白质分解率（FBR）。方法：23名健康男性参与者（年龄：22±1岁；身高：179±1cm；体重：73.4±1.5kg；体重指数：22.8±0.5kg·m-2）参加本随机对照研究。单侧膝关节固定48小时后，在吸收后（生理盐水输注；FAST）或模拟餐后状态（67.5 mg/kg体重-1·h-1氨基酸输注；FED）下，分别使用引发的连续静脉注射l-[15N]-苯丙氨酸和l-[环-2 H5]-苯丙氨酸来平行测定FBR和FSR。全程收集对照（CON）和固定（IMM）腿的双侧股外侧肌活检和动脉化静脉血样。结果：氨基酸输注使血浆苯丙氨酸（59±9%）、亮氨酸（76±5%）、异亮氨酸（109±7%）和缬氨酸（42±4%）浓度在单纯FED（P-1）或FED（CON:0.134±0.012；IMM:0.160±0.018%·h-1；所有效应P>0.05）中迅速升高，固定化降低了FSR（P-1；IMM与CON分别）和FED（0.066±0.016与0.119±0.016%·h-1；IMM和CON分别降低）。因此，固定化降低了净肌肉蛋白质平衡（P-1；P-1）。结论：我们得出结论，仅仅2天的腿部固定化并不能调节吸收后和模拟餐后肌肉蛋白质分解率。相反，在这些条件下，与短暂的实验废用相关的肌肉负性肌肉蛋白质平衡几乎完全是由基础肌肉蛋白质合成率降低和对氨基酸给药的合成代谢抵抗所驱动的。

{"title":"Short-term disuse does not affect postabsorptive or postprandial muscle protein fractional breakdown rates","authors":"George F. Pavis, Doaa R. Abdelrahman, Andrew J. Murton, Benjamin T. Wall, Francis B. Stephens, Marlou L. Dirks","doi":"10.1002/jcsm.13284","DOIUrl":"10.1002/jcsm.13284","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The decline in postabsorptive and postprandial muscle protein fractional synthesis rates (FSR) does not quantitatively account for muscle atrophy during uncomplicated, short-term disuse, when atrophy rates are the highest. We sought to determine whether 2 days of unilateral knee immobilization affects mixed muscle protein fractional breakdown rates (FBR) during postabsorptive and simulated postprandial conditions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Twenty-three healthy, male participants (age: 22 ± 1 year; height: 179 ± 1 cm; body mass: 73.4 ± 1.5 kg; body mass index 22.8 ± 0.5 kg·m<sup>−2</sup>) took part in this randomized, controlled study. After 48 h of unilateral knee immobilization, primed continuous intravenous <span>l</span>-[<sup>15</sup>N]-phenylalanine and <span>l</span>-[<i>ring</i>-<sup>2</sup>H<sub>5</sub>]-phenylalanine infusions were used for parallel determinations of FBR and FSR, respectively, in a postabsorptive (saline infusion; FAST) or simulated postprandial state (67.5 mg·kg body mass<sup>−1</sup>·h<sup>−1</sup> amino acid infusion; FED). Bilateral <i>m. vastus lateralis</i> biopsies from the control (CON) and immobilized (IMM) legs, and arterialized-venous blood samples, were collected throughout.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Amino acid infusion rapidly increased plasma phenylalanine (59 ± 9%), leucine (76 ± 5%), isoleucine (109 ± 7%) and valine (42 ± 4%) concentrations in FED only (all <i>P</i> < 0.001), which was sustained for the remainder of infusion. Serum insulin concentrations peaked at 21.8 ± 2.2 mU·L<sup>−1</sup> at 15 min in FED only (<i>P</i> < 0.001) and were 60% greater in FED than FAST (<i>P</i> < 0.01). Immobilization did not influence FBR in either FAST (CON: 0.150 ± 0.018; IMM: 0.143 ± 0.017%·h<sup>−1</sup>) or FED (CON: 0.134 ± 0.012; IMM: 0.160 ± 0.018%·h<sup>−1</sup>; all effects <i>P</i> > 0.05). However, immobilization decreased FSR (<i>P</i> < 0.05) in both FAST (0.071 ± 0.004 vs. 0.086 ± 0.007%·h<sup>−1</sup>; IMM vs CON, respectively) and FED (0.066 ± 0.016 vs. 0.119 ± 0.016%·h<sup>−1</sup>; IMM vs CON, respectively). Consequently, immobilization decreased net muscle protein balance (<i>P</i> < 0.05) and to a greater extent in FED (CON: −0.012 ± 0.025; IMM: −0.095 ± 0.023%·h<sup>−1</sup>; <i>P</i> < 0.05) than FAST (CON: −0.064 ± 0.020; IMM: −0.072 ± 0.017%·h<sup>−1</sup>).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>We conclude that merely 2 days of leg immobilization does not modulate postabsorptive and s","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 5","pages":"2064-2075"},"PeriodicalIF":8.9,"publicationDate":"2023-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9773108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Development and applicability of modified weight loss grading system in cancer: a real-world cohort study 癌症改良减肥分级系统的发展和适用性：一项现实世界的队列研究。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13287

Hailun Xie, Guotian Ruan, Lishuang Wei, Heyang Zhang, Yizhong Ge, Shiqi Lin, Mengmeng Song, Qi Zhang, Xi Zhang, Ziwen Wang, Chenan Liu, Jinyu Shi, Xiaoyue Liu, Ming Yang, Xin Zheng, Yue Chen, Xiaowei Zhang, Li Deng, Hanping Shi

Background

The original weight loss grading system (WLGS) was developed in western population, which did not perform effectively in cancer patients from China. This study aimed to develop and validate the modified WLGS (mWLGS) in the prognostic assessment of cancer patients in China.

Methods

A prospective multicentre real-world cohort study involving 16 842 patients diagnosed with cancer was conducted. Cox regression was used to calculate the hazard ratios for overall survival. Logistic linear regression was used to assess the odds ratio for 90-day outcomes.

Results

We calculated survival risks for the 25 mWLGS groups and clustered the approximate survival risks. Finally, we revised the prognostic grading system for mWLGS to include five grades of 0–4. Compared with the original WLGS, the mWLGS had a better prognostic differentiation effect in predicting the prognosis of patients with cancer. The survival rate gradually deteriorated with increasing grade of mWLGS, with the survival rate of grade 0 decreasing from 76.4% to 48.2% for grade 4 (76.4 vs. 72.8 vs. 66.1 vs. 57.0 vs. 48.2%, respectively). The mWLGS provides effective prognostic stratification for most site-specific cancers, especially lung and gastrointestinal cancers. High-grade mWLGS is independently associated with an increased risk of poor quality of life and adverse 90-day outcomes. Multivariate Cox regression analysis showed that the mWLGS was an independent prognostic factor for cancer patients in the validation cohorts.

Conclusions

Compared with the original WLGS, the mWLGS can better stratify the prognosis of cancer patients. mWLGS is a useful tool for predicting survival, 90-day outcomes, and quality of life in patients with cancer. These analyses may provide new insights into the application of WLGS in cancer patients in China.

背景：最初的体重减轻分级系统（WLGS）是在西方人群中开发的，但在中国癌症患者中效果不佳。本研究旨在开发和验证改良WLGS（mWLGS）在中国癌症患者预后评估中的作用。Cox回归用于计算总生存率的危险比。Logistic线性回归用于评估90天结果的比值比。结果：我们计算了25 mWLGS组的生存风险，并对近似生存风险进行了聚类。最后，我们修订了mWLGS的预后分级系统，将0-4分为五个等级。与原始WLGS相比，mWLGS在预测癌症患者预后方面具有更好的预后分化效果。生存率随着mWLGS分级的增加而逐渐恶化，0级的生存率从76.4%降至4级的48.2%（分别为76.4对72.8对66.1对57.0对48.2%）。mWLGS为大多数位点特异性癌症，特别是肺癌和胃肠道癌症提供了有效的预后分层。高级别mWLGS与生活质量差和90天不良结果的风险增加独立相关。多因素Cox回归分析表明，mWLGS是验证队列中癌症患者的独立预后因素。结论：与原WLGS相比，mWLGS能更好地对癌症患者的预后进行分层。mWLGS是预测癌症患者生存率、90天预后和生活质量的有用工具。这些分析可能为WLGS在中国癌症患者中的应用提供新的见解。

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引用次数: 0

Association of intrinsic capacity with incidence and mortality of cardiovascular disease: Prospective study in UK Biobank 内在能力与心血管疾病发病率和死亡率的关系：英国生物银行的前瞻性研究。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-07-11 DOI: 10.1002/jcsm.13283

Robinson Ramírez-Vélez, Maria Iriarte-Fernández, Guzman Santafé, Armando Malanda, John R. Beard, Antonio Garcia-Hermoso, Mikel Izquierdo

Background

The World Health Organization proposed the concept of intrinsic capacity (IC; the composite of all the physical and mental capacities of the individual) as central for healthy ageing. However, little research has investigated the interaction and joint associations of IC with cardiovascular disease (CVD) incidence and CVD mortality in middle- and older-aged adults.

Methods

Using data from 443 130 UK Biobank participants, we analysed seven biomarkers capturing the level of functioning of five domains of IC to calculate a total IC score (ranging from 0 [better IC] to +4 points [poor IC]). Associations between IC score and incidence of six long-term CVD conditions (hypertension, stroke/transient ischaemic attack stroke, peripheral vascular disease, atrial fibrillation/flutter, coronary artery disease and heart failure), and grouped mortality from these conditions were estimated using Cox proportional models, with a 1-year landmark analysis to triangulate the findings.

Results

Over 10.6 years of follow-up, CVD morbidity grouped (n = 384 380 participants for the final analytic sample) was associated with IC scores (0 to +4): mean hazard ratio (HR) [95% confidence interval, CI] 1.11 [1.08–1.14], 1.20 [1.16–1.24], 1.29 [1.23–1.36] and 1.56 [1.45–1.59] in men (C-index = 0.68), and 1.17 [1.13–1.20], 1.30 [1.26–1.36], 1.52 [1.45–1.59] and 1.78 [1.67–1.89] in women (C-index = 0.70). In regard to mortality, our results indicated that the higher IC score (+4 points) was associated with a significant increase in subsequent CVD mortality (mean HR [95% CI]: 2.10 [1.81–2.43] in men [C-index = 0.75] and 2.29 [1.85–2.84] in women [C-index = 0.78]). Results of all sensitivity analyses by full sample, sex and age categories were largely consistent independent of major confounding factors (P < 0.001).

Conclusions

IC deficit score is a powerful predictor of functional trajectories and vulnerabilities of the individual in relation to CVD incidence and premature death. Monitoring an individual's IC score may provide an early-warning system to initiate preventive efforts.

背景：世界卫生组织提出了内在能力（IC；个人所有身体和心理能力的组合）的概念，作为健康老龄化的核心。然而，很少有研究调查IC与中老年人心血管疾病（CVD）发病率和CVD死亡率的相互作用和联合关系。方法：使用443 130名英国生物银行参与者的数据，我们分析了七种生物标志物，这些生物标志物捕捉了IC五个领域的功能水平，以计算IC总分（从0分[较好的IC]到+4分[较差的IC]）。使用Cox比例模型估计IC评分与六种长期CVD疾病（高血压、中风/短暂性缺血性发作中风、外周血管疾病、心房颤动/扑动、冠状动脉疾病和心力衰竭）的发病率以及这些疾病的分组死亡率之间的关联，并进行1年里程碑分析以三角测量结果。结果：在10.6年的随访中，心血管疾病发病率分组（最终分析样本中的384 380名参与者）与IC评分（0至+4）相关：男性的平均危险比（HR）[95%置信区间，CI]1.11[1.08-1.14]，1.20[1.16-1.24]，1.29[1.23-1.36]和1.56[1.45-1.59]（C指数=0.68），1.17[1.13-1.20]，1.30[1.26-1.36]，1.52[1.45-1.59]和1.78[1.67-1.89]（C指数=0.70）。关于死亡率，我们的结果表明，较高的IC评分（+4分）与随后CVD死亡率的显著增加有关（平均HR[95%CI]：男性2.10[1.81-2.43][C指数=0.75]和女性2.29[1.85-2.84][C指数=0.78]），性别和年龄类别在很大程度上是一致的，独立于主要的混杂因素（P结论：IC缺陷评分是一个强有力的预测因素，可以预测与心血管疾病发病率和过早死亡相关的个体的功能轨迹和脆弱性。监测个体的IC评分可以提供一个预警系统来启动预防工作。

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引用次数: 0

Iron deficiency is related to lower muscle mass in community-dwelling individuals and impairs myoblast proliferation 铁缺乏与社区居民的低肌肉质量和损害成肌细胞增殖有关

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-06-30 DOI: 10.1002/jcsm.13277

Joanna Sophia J. Vinke, Alan R. Gorter, Michele F. Eisenga, Wendy A. Dam, Peter van der Meer, Jacob van den Born, Stephan J.L. Bakker, Martijn F. Hoes, Martin H. de Borst

Background

Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population-based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes.

Methods

In a population-based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24-h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5-bromo-2′-deoxy-uridine ELISA assay. Myocyte differentiation was assessed using Myh7-stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence-activated cell sorting. RNA sequencing (RNAseq) was used to identify ID-related gene and pathway enrichment in myoblasts and myocytes.

Results

Participants in the lowest age- and sex-specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25–2.10, P < 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03–1.75, P = 0.03) had a significantly higher risk of being in the lowest age- and sex-specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs-CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine-induced ID reduced myoblast proliferation rate (P-trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (−52%, P < 0.001) and tended to reduce mitochondrial oxygen consumption capacity (−28%, P = 0.10). Deferoxamine induced gene expression of cellular atrophy markers Trim63 (+20%, P = 0.002) and Fbxo32 (+27%, P = 0.048), which was reversed by ferric citrate (−31%, P = 0.04 and −26%, P = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in gly

背景:肌肉量减少与生活质量下降、发病率和过早死亡风险增加有关。铁对于能量代谢、核苷酸合成和许多酶促反应等细胞过程至关重要。由于铁缺乏(ID)对肌肉质量和功能的影响在很大程度上是未知的，我们的目的是在一个基于大量人群的队列中评估ID和肌肉质量之间的关系，并随后研究ID对培养的骨骼肌母细胞和分化肌细胞的影响。方法在8592名成人人群队列中，通过血浆铁蛋白和转铁蛋白饱和度评估铁状态，并通过24小时尿肌酐排泄率(CER)评估肌肉质量。采用多变量logistic回归评估铁蛋白和转铁蛋白饱和度与CER的关系。此外，小鼠C2C12骨骼肌母细胞和分化的肌细胞分别受到含或不含柠檬酸铁的去铁胺的影响。用5-溴-2 ' -脱氧尿苷ELISA法测定成肌细胞增殖。使用myh7染色评估肌细胞分化。采用海马线粒体通量分析评估心肌细胞能量代谢、耗氧量和细胞外酸化率，采用荧光活化细胞分选评估细胞凋亡率。采用RNA测序(RNAseq)技术鉴定成肌细胞和肌细胞中id相关基因及其富集途径。结果血浆铁蛋白最低年龄和性别五分位数的参与者(OR vs中五分位数1.62,95% CI 1.25-2.10, P <0.001)或转铁蛋白饱和度(or 1.34, 95% CI 1.03-1.75, P = 0.03)处于最低年龄和性别特异性五分位数的CER风险显著较高，与体重指数、估计GFR、血红蛋白、hs-CRP、尿尿素排泄、饮酒和吸烟状况无关。在C2C12成肌细胞中，去铁胺诱导的ID降低了成肌细胞的增殖率(P-trend <0.001)，但不影响分化。在肌细胞中，去铁胺降低了肌红蛋白的表达(- 52%，P <0.001)，并有降低线粒体耗氧能力的趋势(- 28%，P = 0.10)。去铁胺诱导细胞萎缩标志物Trim63 (+20%， P = 0.002)和Fbxo32 (+27%， P = 0.048)的基因表达，柠檬酸铁(- 31%，P = 0.04和- 26%，P = 0.004)逆转了这一作用。RNAseq表明，在成肌细胞和肌细胞中，ID主要影响糖酵解能量代谢、细胞周期调控和细胞凋亡相关基因;与柠檬酸铁共处理逆转了这些作用。结论:在常住人群中，ID与较低的肌肉质量有关，与血红蛋白水平和潜在的混杂因素无关。ID损害成肌细胞增殖和有氧糖酵解能力，并诱导肌细胞萎缩和凋亡的标志物。这些发现表明，ID会导致肌肉质量的减少。

{"title":"Iron deficiency is related to lower muscle mass in community-dwelling individuals and impairs myoblast proliferation","authors":"Joanna Sophia J. Vinke, Alan R. Gorter, Michele F. Eisenga, Wendy A. Dam, Peter van der Meer, Jacob van den Born, Stephan J.L. Bakker, Martijn F. Hoes, Martin H. de Borst","doi":"10.1002/jcsm.13277","DOIUrl":"https://doi.org/10.1002/jcsm.13277","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population-based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In a population-based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24-h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5-bromo-2′-deoxy-uridine ELISA assay. Myocyte differentiation was assessed using Myh7-stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence-activated cell sorting. RNA sequencing (RNAseq) was used to identify ID-related gene and pathway enrichment in myoblasts and myocytes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Participants in the lowest age- and sex-specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25–2.10, <i>P</i> < 0.001) or transferrin saturation (OR 1.34, 95% CI 1.03–1.75, <i>P</i> = 0.03) had a significantly higher risk of being in the lowest age- and sex-specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs-CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine-induced ID reduced myoblast proliferation rate (<i>P</i>-trend <0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (−52%, <i>P</i> < 0.001) and tended to reduce mitochondrial oxygen consumption capacity (−28%, <i>P</i> = 0.10). Deferoxamine induced gene expression of cellular atrophy markers <i>Trim63</i> (+20%, <i>P</i> = 0.002) and <i>Fbxo32</i> (+27%, <i>P</i> = 0.048), which was reversed by ferric citrate (−31%, <i>P</i> = 0.04 and −26%, <i>P</i> = 0.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in gly","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":"14 4","pages":"1865-1879"},"PeriodicalIF":8.9,"publicationDate":"2023-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13277","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"6111097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Hand grip strength in patients with advanced cancer: A prospective study 晚期癌症患者的握力:一项前瞻性研究

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-06-15 DOI: 10.1002/jcsm.13248

Sara Hadzibegovic, Jan Porthun, Alessia Lena, Pia Weinl?nder, Laura C. Lück, Sophia K. Potthoff, Lukas R?snick, Ann-Kathrin Fr?hlich, Luisa Valentina Ramer, Frederike Sonntag, Ursula Wilkenshoff, Johann Ahn, Ulrich Keller, Lars Bullinger, Amir A. Mahabadi, Matthias Totzeck, Tienush Rassaf, Stephan von Haehling, Andrew J.S. Coats, Stefan D. Anker, Eric J. Roeland, Ulf Landmesser, Markus S. Anker

Background

Hand grip strength (HGS) is a widely used functional test for the assessment of strength and functional status in patients with cancer, in particular with cancer cachexia. The aim was to prospectively evaluate the prognostic value of HGS in patients with mostly advanced cancer with and without cachexia and to establish reference values for a European-based population.

Methods

In this prospective study, 333 patients with cancer (85% stage III/IV) and 65 healthy controls of similar age and sex were enrolled. None of the study participants had significant cardiovascular disease or active infection at baseline. Repetitive HGS assessment was performed using a hand dynamometer to measure the maximal HGS (kilograms). Presence of cancer cachexia was defined when patients had ≥5% weight loss within 6 months or when body mass index was <20.0 kg/m² with ≥2% weight loss (Fearon's criteria). Cox proportional hazard analyses were performed to assess the relationship of maximal HGS to all-cause mortality and to determine cut-offs for HGS with the best predictive power. We also assessed associations with additional relevant clinical and functional outcome measures at baseline, including anthropometric measures, physical function (Karnofsky Performance Status and Eastern Cooperative of Oncology Group), physical activity (4-m gait speed test and 6-min walk test), patient-reported outcomes (EQ-5D-5L and Visual Analogue Scale appetite/pain) and nutrition status (Mini Nutritional Assessment).

Results

The mean age was 60 ± 14 years; 163 (51%) were female, and 148 (44%) had cachexia at baseline. Patients with cancer showed 18% lower HGS than healthy controls (31.2 ± 11.9 vs. 37.9 ± 11.6 kg, P < 0.001). Patients with cancer cachexia had 16% lower HGS than those without cachexia (28.3 ± 10.1 vs. 33.6 ± 12.3 kg, P < 0.001). Patients with cancer were followed for a mean of 17 months (range 6–50), and 182 (55%) patients died during follow-up (2-year mortality rate 53%) (95% confidence interval 48–59%). Reduced maximal HGS was associated with increased mortality (per −5 kg; hazard ratio [HR] 1.19; 1.10–1.28; P < 0.0001; independently of age, sex, cancer stage, cancer entity and presence of cachexia). HGS was also a predictor of mortality in patients with cachexia (per −5 kg; HR 1.20; 1.08–1.33; P = 0.001) and without cachexia (per −5 kg; HR 1.18; 1.04–1.34; P = 0.010). The cut-off for maximal HGS with the best predictive power for poor survival was <25.1 kg for females (sensitivity 54%, specificity 63%)

手掌握力(Hand grip strength, HGS)是一项广泛应用于评估癌症患者，特别是癌症恶病质患者力量和功能状态的功能测试。目的是前瞻性评估HGS在伴有或不伴有恶病质的晚期癌症患者中的预后价值，并为欧洲人群建立参考值。方法在这项前瞻性研究中，纳入了333例癌症患者(85%为III/IV期)和65名年龄和性别相似的健康对照。研究参与者在基线时没有明显的心血管疾病或活动性感染。使用手测力仪进行重复HGS评估，以测量最大HGS(公斤)。当患者在6个月内体重减轻≥5%或体重指数为20.0 kg/m2且体重减轻≥2% (Fearon标准)时，确定存在癌症恶病质。采用Cox比例风险分析来评估最大HGS与全因死亡率的关系，并确定具有最佳预测能力的HGS截断值。我们还在基线时评估了与其他相关临床和功能结果测量的关联，包括人体测量、身体功能(Karnofsky Performance Status和Eastern Cooperative of Oncology Group)、身体活动(4米步速测试和6分钟步行测试)、患者报告的结果(EQ-5D-5L和视觉模拟量表食欲/疼痛)和营养状况(Mini营养评估)。结果患者平均年龄60±14岁;163例(51%)为女性，148例(44%)基线时患有恶病质。癌症患者的HGS比健康对照组低18%(31.2±11.9 vs 37.9±11.6 kg, P <0.001)。癌症恶病质患者的HGS比无恶病质患者低16%(28.3±10.1比33.6±12.3 kg, P <0.001)。癌症患者平均随访17个月(6-50个月)，182例(55%)患者在随访期间死亡(2年死亡率53%)(95%置信区间48-59%)。最大HGS降低与死亡率增加相关(每- 5 kg;风险比[HR] 1.19;1.10 - -1.28;P & lt;0.0001;独立于年龄，性别，癌症分期，癌症实体和恶病质的存在)。HGS也是恶病质患者死亡率的预测因子(每- 5 kg;人力资源1.20;1.08 - -1.33;P = 0.001)且无恶病质(每- 5 kg;人力资源1.18;1.04 - -1.34;p = 0.010)。女性最大HGS的最佳预测能力为25.1 kg(敏感性54%，特异性63%)，男性为40.2 kg(敏感性69%，特异性68%)。结论在大多数晚期癌症患者中，最大HGS降低与全因死亡率升高、整体功能状态下降和身体机能下降有关。在有和没有癌症恶病质的患者中也发现了类似的结果。

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引用次数: 3

Comment on ‘Causal linkage of tobacco smoking with ageing: Mendelian randomization analysis towards telomere attrition and sarcopenia’ by Park et al. 对Park等人的“吸烟与衰老的因果关系:端粒磨损和肌肉减少症的孟德尔随机化分析”的评论。

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-06-14 DOI: 10.1002/jcsm.13279

Mingchong Liu, Chensong Yang, Yutao Pan, Guixin Sun

As we all know, it has been proven that tobacco smoking is associated with many diseases, including sarcopenia.¹ However, tobacco smoking as a lifestyle always affects our bodies for a quite long time, which is a great challenge for researchers to conduct a randomized controlled trial to identify the causal roles of tobacco smoking in diseases. We therefore read the recent paper by Park et al. This is a well-designed Mendelian randomization (MR) study, using genome-wide association studies (GWASs), which may prove the evidence of causal associations of tobacco smoking with telomere attrition and sarcopenia. These findings suggested that ever being a regular smoker in life (smoking initiation) was causally associated with shorter leucocyte telomere length (LTL), lower appendicular lean mass index (ALM), slower walking pace, and lower time spent on moderate-to-vigorous physical activity (MVPA).²

However, in this study, the high sample overlapping rate in the two-sample mendelian randomization raised concern about the conclusion: the data sources in the study were from UK Biobank (N = 337 138, for aging and sarcopenia) and a GWAS meta-analysis study named GSCAN (N = 1.2 million, for tobacco smoking).³ We carefully read the raw study of the GSCAN, and unfortunately, in the 1.2 million samples, 383 613 were from UK Biobank. According to the calculation methods for the maximum estimated value for sample overlapping rate, the cohort of aging and sarcopenia (337 138 samples) may be fully overlapped with samples for smoking (383 613 samples), which means the maximum estimated sample overlapping rate might be 100%. It was the violation of the essential assumptions of two-sample MR. The bias caused by sample overlapping should not be ignored.⁴

Interestingly, the raw data provided by GSCAN contains a dataset without UK Biobank cohorts (https://conservancy.umn.edu/handle/11299/201564). Therefore, using the GSCAN data without UK Biobank, we tried to re-perform the MR study by Park et al. Briefly, the data including 848 460 individuals for exposure (tobacco smoking) were from the GSCAN data without UK Biobank individuals. For outcomes, similar to Park's study, we used the summary GWAS data of the UK Biobank from the IEU database.⁵ Except for handgrip strength, the phenotypes of other outcomes were as same as the previous study: including LTL (N = 472 174, datasets ID: ieu-b-4879), adjusted appendicular lean mass (N = 450 243, datasets ID: GCST90000025), walking pace (N = 459 915, datasets ID: ukb-b-4711), moderate to vigorous physical activity (N = 377 234, datasets ID: GCST006097). In the study by Park et al., handgrip strength was defined as the average value of two hands. Because we did not have access to the detailed UK Biobank data, our study's phenotypes of handgrip strength were d

众所周知，吸烟已被证明与许多疾病有关，其中就包括肌肉减少症然而，吸烟作为一种生活方式，在相当长的时间内都会对我们的身体产生影响，这对研究人员来说是一个很大的挑战，通过随机对照试验来确定吸烟在疾病中的因果作用。因此，我们阅读了Park等人最近发表的论文。这是一项设计良好的孟德尔随机化(MR)研究，使用全基因组关联研究(GWASs)，可能证明吸烟与端粒磨损和肌肉减少症之间存在因果关系的证据。这些发现表明，在生活中经常吸烟(开始吸烟)与较短的白细胞端粒长度(LTL)、较低的阑尾瘦质量指数(ALM)、较慢的步行速度和较低的中高强度体育活动(MVPA)时间有关。2然而，在本研究中，双样本孟德尔随机化中的高样本重叠率引起了对结论的关注:研究中的数据来源来自UK Biobank (N = 337138，用于衰老和肌肉减少症)和GWAS荟萃分析研究GSCAN (N = 120万，用于吸烟)我们仔细阅读了GSCAN的原始研究，不幸的是，在120万个样本中，有383 613个来自UK Biobank。根据样本重叠率最大估计值的计算方法，衰老和肌肉减少症队列(337 138个样本)可能与吸烟队列(383 613个样本)完全重叠，即样本重叠率的最大估计值可能为100%。这违反了双样本mr的基本假设，样本重叠引起的偏差不容忽视。有趣的是，GSCAN提供的原始数据包含一个没有UK Biobank队列的数据集(https://conservancy.umn.edu/handle/11299/201564)。因此，使用没有UK Biobank的GSCAN数据，我们试图重新执行Park等人的MR研究。简而言之，包括848460名暴露(吸烟)个体的数据来自GSCAN数据，不包括UK Biobank个体。对于结果，与Park的研究类似，我们使用了IEU数据库中UK Biobank的GWAS汇总数据除握力外，其他结果的表型与既往研究相同:包括LTL (N = 472 174，数据集ID: ieu-b-4879)、调整后的阑尾瘦质量(N = 450 243，数据集ID: GCST90000025)、步行速度(N = 459 915，数据集ID: ukb-b-4711)、中度至剧烈运动(N = 377 234，数据集ID: GCST006097)。在Park等人的研究中，将握力定义为两只手的平均值。由于我们无法获得详细的UK Biobank数据，我们的研究将握力的表型分为右手(N = 461089，数据集ID: ukb-b-10215)和左手(N = 461026，数据集ID: ukb-b-7478)。在没有UK Biobank的GSCAN数据的GWAS中，只有8个与吸烟开始相关的snp在P值的显著性水平上被发现<5E-8。因此，在P值<5E-6的显著性水平上进行另一次分析。为了满足MR的三个核心消耗，设置了5个严格的SNPs过滤步骤:步骤1，聚集SNPs(连锁不平衡(LD) r2 >0.01, kb = 500) 30643251;步骤2，排除与混杂因素相关的snp;步骤3，排除统一程序中的snp;步骤4，排除与结果相关的snp;第5步，通过MR-PRESSO排除具有潜在多效性的snp。主要MR分析采用随机效应反方差加权(IVW)分析、MR- egger回归和加权中位数检验。在我们的分析中，只证明了吸烟与LTL和步行速度之间的因果关系(图1)。经常吸烟可能与较低的LTL存在因果关系(IVW, P = 0.045;加权中位数，P = 0.008)和较慢的步行速度(IVW, P = 0.043;加权中位数，P = 0.017)。然而，Park等人在研究中发现的其他关联，包括吸烟与ALM和MVPA，没有得到证实。至于握力，两项研究都没有提供吸烟和握力之间的显著因果估计。此外，在主MR分析中没有发现显著的多效性效应(所有MR- egger截距P <0.05)，这支持了我们研究中的主要估计。总之，基于我们的研究和之前的研究，我们认为吸烟与LTL和步行速度之间的因果关系是可以被证明的。吸烟在ALM和MVPA中的因果作用可能需要进一步讨论。此外，我们倾向于认为吸烟和握力之间不存在因果关系。此外，根据欧洲老年人肌少症工作组(EWGSOP2)修订后的肌少症定义，低肌力是肌少症最可靠的衡量标准，肌少症可以通过肌肉数量或质量低来确诊，而低体能表现则被认为是衡量肌少症严重程度的标准结合我们和以往的研究，在肌肉减少症的特征中，只证明了肌肉减少症与步行速度之间的因果关系，而没有提供肌肉力量和数量的显著而坚实的证据。吸烟对肌肉减少症的因果关系有待进一步研究。作者宣称他们没有竞争利益。国家自然科学基金(批准/奖励号:81971169)浦东新区卫健委领军人才培养计划(批准号:PWR 12020-06)。

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引用次数: 1

Respiratory sarcopenia is a predictor of all-cause mortality in community-dwelling older adults—The Otassha Study 呼吸性肌肉减少症是社区居住老年人全因死亡率的预测因子——奥塔沙研究

IF 8.9 1区医学

Journal of Cachexia, Sarcopenia and Muscle

Pub Date : 2023-06-14 DOI: 10.1002/jcsm.13266

Takeshi Kera, Hisashi Kawai, Manami Ejiri, Kumiko Ito, Hirohiko Hirano, Yoshinori Fujiwara, Kazushige Ihara, Shuichi Obuchi

As individuals age, skeletal muscle mass and function, including lean body mass and grip strength, and respiratory muscle mass and strength, tend to decline.^{1, 2} The term ‘respiratory sarcopenia’ emerged during a discussion on sarcopenia. Respiratory sarcopenia should encompass respiratory muscle mass and strength or function to adhere to the original sarcopenia definition, which considers whole-body muscle mass, grip strength, and gait speed. However, the decreasing respiratory muscle mass associated with aging has not been adequately discussed. The concept may appear simple; however, defining respiratory sarcopenia has not been extensively explored.

Inspiratory and expiratory maximal mouth pressure measurement as direct evidence of respiratory muscle strength is simple; however, access to relevant measuring equipment is limited. Moreover, evaluating respiratory muscle mass is challenging, and the respiratory sarcopenia using low respiratory muscle mass cannot be virtually established. Therefore, we proposed defining respiratory sarcopenia using the peak expiratory flow rate (PEFR) as an alternative to directly measuring respiratory muscle strength.³ Subsequently, the Japanese Working Group of Respiratory Sarcopenia of the Japanese Association of Rehabilitation Nutrition (JARN) published criteria for respiratory sarcopenia, which was defined based on a decline in the maximal mouth pressure and respiratory muscle mass and the presence of whole-body-sarcopenia, as measured using skeletal muscle mass, strength, and physical performance.⁴ However, this definition has not been established due to a lack of consensus. Moreover, to the best of our knowledge, the future health-related outcomes of respiratory sarcopenia have never been evaluated. Therefore, this survey confirmed whether respiratory sarcopenia, defined using PEFR and the JARN criteria, is associated with future mortality among community-dwelling older adults.

We assessed respiratory sarcopenia-related mortality after a 5-year follow-up of 470 participants (185 men aged 75.2 ± 5.5 years and 285 women aged 74.2 ± 5.4 years) who participated in a comprehensive health checkup program called ‘The Otassha Study’ conducted in the Tokyo Metropolitan Institute for Geriatrics and Gerontology in 2015. Participants who underwent spirometry and sarcopenia assessment were included; however, patients with chronic obstructive pulmonary disease (COPD) were excluded.

An electronic spirometer (Autospiro AS-507, Minato, Osaka, Japan) was used to measure pulmonary function. The PEFR as a percentage of the predicted value (%PEFR), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in 1 s (FEV₁), VC as a percentage of the predicted value (%VC), FVC as a percentage of the predicted value (%FVC), lower limit of normal FVC (FVC_LLN), and FEV₁/FVC were assessed.

A

随着年龄的增长，骨骼肌的质量和功能，包括瘦体重和握力，以及呼吸肌的质量和力量，都趋于下降。1,2“呼吸性肌肉减少症”一词是在一次关于肌肉减少症的讨论中出现的。呼吸性肌肉减少症应包括呼吸肌肉质量和力量或功能，以坚持原始的肌肉减少症定义，考虑全身肌肉质量，握力和步态速度。然而，与衰老相关的呼吸肌质量下降尚未得到充分讨论。这个概念可能看起来很简单;然而，呼吸道肌肉减少症的定义尚未得到广泛探讨。吸气和呼气最大口压测量作为呼吸肌力量的直接证据是简单的;然而，获得相关的测量设备是有限的。此外，评估呼吸肌肉质量具有挑战性，使用低呼吸肌肉质量的呼吸肌肉减少症不能完全建立。因此，我们建议使用呼气流量峰值(PEFR)作为直接测量呼吸肌力量的替代方法来定义呼吸性肌肉减少症随后，日本康复营养协会(JARN)的日本呼吸性肌肉减少症工作组公布了呼吸性肌肉减少症的标准，该标准是根据最大口压和呼吸肌肉质量的下降以及全身肌肉减少症的存在来定义的，通过骨骼肌质量、力量和身体表现来测量然而，由于缺乏共识，这一定义尚未确立。此外，据我们所知，呼吸性肌肉减少症的未来健康相关结果从未被评估过。因此，这项调查证实了呼吸性肌肉减少症(PEFR和JARN标准定义)是否与社区居住老年人的未来死亡率有关。我们对470名参与者(185名男性，年龄75.2±5.5岁，285名女性，年龄74.2±5.4岁)进行了为期5年的随访，评估了呼吸肌减少症相关的死亡率，这些参与者参加了2015年在东京都老年医学研究所进行的一项名为“Otassha研究”的综合健康检查计划。接受肺活量测定和肌肉减少症评估的参与者被纳入;然而，慢性阻塞性肺疾病(COPD)患者被排除在外。使用电子肺活量计(Autospiro AS-507, Minato, Osaka, Japan)测量肺功能。评估PEFR占预测值的百分比(%PEFR)、肺活量(VC)、用力肺活量(FVC)、1s内用力呼气量(FEV1)、肺活量占预测值的百分比(%VC)、肺活量占预测值的百分比(%VC)、正常肺活量下限(FVCLLN)、FEV1/FVC。多频生物阻抗身体成分分析仪(InBody 720, InBody。使用Co.， Seoul, Korea)测量骨骼肌质量，并使用手动秒表确定5米路程中的步态速度，加减速区为3米。站立时使用斯梅德利式手测力仪测量握力。体重指数(BMI)计算为体重/身高2。根据亚洲肌肉减少症工作组(Asian Working Group for sarcopenia 2019.5)概述的标准对原发性肌肉减少症进行定义。在本研究中，呼吸道肌肉减少症的定义采用以下两种方法:(1)基于我们之前的研究的PEFR， (2) JARN标准。在第一种方法中，当PEFR低于临界值(男性4.40 L/s，女性3.21 L/s)时，定义PEFR呼吸性肌肉减少症根据JARN流程图，呼吸性肌肉减少症是用呼吸肌肉量和最大口压来定义的4;然而，我们没有测量呼吸肌质量，这很难测量，也没有测量最大口腔压力。因此，在第二种方法中，当患者同时患有肌肉减少症和低FVC时，诊断为根据JARN标准定义的呼吸性肌肉减少症。根据性别、年龄和身高，当FVC低于FVCLLN时，参与者被定义为患有JARN呼吸性肌肉减少症。我们将“确定的”和“可能的”呼吸性肌肉减少症定义为JARN呼吸性肌肉减少症。总体而言，61名(13.0%)和21名(4.5%)参与者分别被归类为PEFR和JARN呼吸性肌肉减少症，12名(2.6%)参与者被归类为两者兼有。在5年的随访中，470名参与者中有31人(6.6%)死亡。PEFR和JARN呼吸性肌肉减少症的5年死亡率分别为8例(13.1%)和5例(23.8%)。原发性肌肉减少症的死亡率为13(25.0%)(表1)。图1显示了原发性、JARN呼吸性和PEFR呼吸性肌肉减少症的累积死亡结果。采用Kaplan-Meier曲线和log-rank检验的生存分析显示，在5年随访期间，肌肉减少症和PEFR以及JARN、呼吸性肌肉减少症与死亡显著相关。骨骼肌减少症合并PEFR和JARN呼吸性骨骼肌减少症患者的生存时间比无原发性和呼吸性骨骼肌减少症患者短(log-rank检验，P <0.001, P = 0.020, P = 0.001)。采用Cox比例风险回归模型分析原发性、PEFR呼吸性和JARN呼吸性肌减少症与死亡的关系(表2)。在粗模型中，原发性肌减少症患者(风险比[HR]， 6.36;95%置信区间[CI]， 3.11-12.98;P & lt;0.001)， PEFR呼吸性肌肉减少症(HR, 2.51;95% ci, 1.12-5.62;P = 0.025)， JARN呼吸性肌肉减少症(HR, 4.52;95% ci, 1.74-11.78;P = 0.002)在5年随访期间死亡风险增加。在模型2(调整BMI和合并症)和模型3(调整生活方式和模型2中的所有变量)中，原始和JARN呼吸性肌肉减少症与死亡风险增加相关。然而，JARN呼吸性肌肉减少症的HR (HR, 3.95;95% ci, 1.50-10.39;P = 0.005)与原肌减少症的发生率接近(HR, 3.05;95% ci, 1.34-6.96;p = 0.008)。由于本研究和JARN提出的FVCLLN和PEFR的临界值可能不适合考虑未来的死亡率，因此我们改变了%FVC、PEFR和%PEFR的临界值，并观察模型3中死亡率的HR变化(图2)。PEFR(图2A)和%PEFR(图2B)在PEFR或%PEFR值较低时，用于定义呼吸性肌肉减少症的PEFR(图2A)和%PEFR(图2B)趋向于HR值为1.0。%PEFR临界值为76.1% ~ 81.2%，HR显著;然而，使用绝对PEFR的呼吸性肌肉减少症临界值的HR(女性比男性低1.19 L/s)在模型3的任何PEFR值中都不显著。对于%FVC, HR显著高于1.0;然而，它在%FVC值的低(73.6%)和高(127.0%)范围内几乎是恒定的(图2C)。Cook等人报道，低PEFR的社区居住成年人的死亡率高于先前报道的死亡率这一发现也与Fragoso等人7 Buchman等人8报道的死亡率与一些变量(包括肢体肌肉力量、呼吸肌力量和肺功能)之间的关系一致。呼吸肌力与死亡率的相关性高于肢体肌力。然而，他们可能包括COPD和其他呼吸系统综合征患者;因此，这是一个自然的结果。本研究中获得的死亡率HR与使用PEFR定义呼吸性肌肉减少症的研究相似，即使排除了COPD。然而，在调整协变量后，这种关系不显著。可能使用PEFR定义的呼吸性肌肉减少症与死亡率之间的关系较弱，或者定义PEFR的临界值不合适。这意味着，当死亡率被设定为未来与健康相关的结果时，我们之前研究中推荐的临界值是不合适的;因此，需要一个更合适的值。相比之下，JARN呼吸性肌肉减少症的死亡率HR是显著的，即使在调整协变量后也是如此。由于该HR与原发性肌少症的HR接近，且JARN呼吸性肌少症的定义中包含了原发性肌少症的概念，因此可能只是反映了肌少症。尽管FVC %的临界值波动，但死亡率保持不变，这与原始肌肉减少症的临界值接近。JARN呼吸性肌肉减

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