超重及肥胖2型糖尿病患者血浆脂蛋白相关磷脂酶A2水平与颈动脉内膜中层厚度的相关性研究

［摘要］　目的　探讨超重及肥胖2型糖尿病（T2DM）患者血浆脂蛋白相关磷脂酶A₂（Lp-PLA₂）水平及其与颈动脉内膜中层厚度（IMT）的相关性。方法　选择2018-01～2018-08桂林医学院附属医院收治的T2DM患者95例,根据体质量指数（BMI）将其分为单纯T2DM组（BMI<24 kg/m²）56例和超重及肥胖T2DM组（BMI≥24 kg/m²）39例。比较两组空腹血糖（FBG）、总胆固醇（TC）、三酰甘油（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、空腹胰岛素（FINS）、胰岛素抵抗指数（IRI）、糖化血红蛋白（HbA1c）、颈动脉IMT和Lp-PLA₂。分析Lp-PLA₂与颈动脉IMT的相关性。结果　与单纯T2DM组相比,超重及肥胖T2DM组的FINS、IRI、TC、LDL-C、Lp-PLA₂及颈动脉IMT水平较高,HDL-C水平较低,差异有统计学意义（P<0.05）。两组FBG、HbA1c、TG比较差异无统计学意义（P>0.05）。T2DM患者血浆Lp-PLA₂水平与颈动脉IMT水平呈正相关（r=0.388,P=0.000）。单纯T2DM组和超重及肥胖T2DM组血浆Lp-PLA₂水平与颈动脉IMT水平均呈正相关（r=0.292,P=0.029;r=0.470,P=0.003）。多元线性回归分析结果显示,较高水平的BMI、LDL-C及Lp-PLA₂是影响颈动脉IMT增厚的主要危险因素（P<0.05）。结论　超重及肥胖T2DM患者的血浆Lp-PLA₂水平较高,且Lp-PLA₂水平与颈动脉IMT呈正相关,检测该指标可能有利于临床医师及早发现、干预糖尿病大血管病变的发生。     

Ketone body kineticsin vivo using simultaneous administration of acetoacetate and 3-hydroxybutyrate labelled with stable isotopes

Summary Isotope dilution studies of ketone body (KB) turnover have usually been performed using a single¹⁴C tracer and the so called ‘combined KB specific activity’. By definition, this approach does not allow to evaluate the individual kinetics of acetoacetate (AcAc) and 3-hydroxybutyrate (R-BHB) which is feasible only using the separate administration of¹⁴C tracer AcAc and R-BHB. In the present study we followed a different approach using the simultaneous administrationin vivo of [1,2,¹³C₂] AcAc and m [1,2,3,4¹³C₄] R-BHB which allows to evaluate the individual kinetics of the two KB in the some study, thus minimizing the magnitude of blood sampling and the potential changes in the metabolic conditions of each subject. The four isotopic¹³C/¹²C KB ratios of AcAc and R-BHB tracer and tracee blood concentrations along with the fluorimetric measurement of¹²C concentrations were determined in each blood sample. Using compartmental analysis following single dose bolus injection the production rate of KB was 206 ± 57 μmol/min/1.73 m² (mean ± SD). The turnover rate of KB using noncompartmental analysis, during continuous infusion in a separate study was 294 ± 41. The plasma clearance rates of AcAc and R-BHB were 1966 ± 502 and 1443 ± ml/min/1.73 m², respectively. The mean residence time was 17 ± 3 min and the total distribution volume 20 ± 9.7 1/m². We conclude that: (1) stable isotope tracer infusion allows the contemporaryin vivo administration of the two KB and the simultaneous assessment of individual AcAc and R-BHB kinetics; (2) the estimated compartmental and noncompartmental parameters of KB turnover were similar to those observed in normal overnight fasting subjects following separate radioactive tracer injections. This study was partially supported by CNR grant n^o 840084904 and by a grant from theMinistero della Pubblica Istruzione, Rome, Italy.     

氮气洗入/洗出法测定急性肺损伤患者肺复张容积的研究

  目的 探讨氮气洗入/洗出法测急性肺损伤(ALI)患者肺复张容积的准确性及可行性。方法 将15例有创机械通气的ALI患者纳入本研究,根据ARDSnet法和跨肺压法滴定2种呼气末正压(PEEP) 水平,分别通气30 min,记录各PEEP水平下潮气量(Vt)、气道平台压等呼吸力学及血流动力学指标,并利用氮气洗入/洗出法测2种PEEP水平的呼气末肺容积(EELV),根据公式推算氮气洗入/洗出法测的肺复张容积,同时根据低流速压力-容积(P-V)曲线法获得肺复张容积,比较2种方法获得的肺复张容积的相关性及一致性。结果 (1)ARDSnet法滴定的PEEP为（7±2） cm H₂O（1 cm H₂O=0.098 kPa）,气道峰压为（23±5） cm H₂O,气道平台压为(17±4） cm H₂O;跨肺压法滴定的PEEP为（14±5 )cm H₂O,气道峰压为（28±6） cm H₂O,气道平台压为（22±6） cm H₂O,2种方法比较差异有统计学意义(P<0.05)。(2) 低流速P-V曲线法测的肺复张容积为100（-25~185）ml,氮气洗入/洗出法测的肺复张容积为180（-19~255）ml,两者具有较好的相关性,R²=0.755,P<0.0001,且测量误差为46（8~80）ml。结论 氮气洗入/洗出法可测定ALI患者的肺复张容积。        

ω-3鱼油脂肪乳剂对重症急性胰腺炎患者炎症免疫与器官功能的影响

  目的 探讨静脉应用ω-3鱼油脂肪乳剂对重症急性胰腺炎（SAP）患者炎症反应、免疫功能及器官功能的影响。方法 临床确诊为SAP患者随机分为常规治疗组(A组)和常规+鱼油治疗组(B组),A组常规治疗（抗感染、抑酶、胃肠减压、通便导泻及器官功能支持等）;B组：按A组的常规治疗后静脉滴注10%ω-3鱼油脂肪乳剂0.2 g·kg^-1·d^-1,连续应用14 d。观察治疗前、治疗后7天、治疗后14天C反应蛋白（CRP）、TG、TC、T细胞亚群（CD⁺₄、CD⁺₈）水平及补体C₃、补体C₄水平;测腹内压（膀胱压）,记录急性生理与慢性健康评估Ⅱ（APACHEⅡ）、达到液体负平衡时间、肠内营养时间、住ICU时间及28 d病死率。结果 53例SAP患者入选本研究,其中6例因肾衰竭行床旁血液净化治疗,2例自行退出,最后45例纳入本研究。B组（22例）患者治疗后14天CD⁺₄ T细胞、CD⁺₄/CD⁺₈、补体C₃改善明显优于A组（23例）;B组治疗后7天、14天CRP、腹内压、APACHEⅡ评分较A组下降更明显;B组患者开始液体负平衡时间［(3.55±0.86) d］明显短于A组［（4.61±1.12）d］,开始肠内营养时间［（3.86±1.17）d］明显早于A组［（5.30±1.61）d］,住ICU时间［(11.36±3.13)d比（14.96±4.0）d］、28 d病死率（4.5%比4.4%）2组差异无统计学意义（P>0.05）。结论 SAP患者静脉应用鱼油脂肪乳剂可减轻炎性反应,改善免疫功能,并可早期达到液体负平衡管理及恢复肠道功能,为SAP提供新的、有效的治疗手段。     

基于智能穿戴设备探讨睡眠时长与高血压关系的真实世界研究

目的 基于智能穿戴设备测量睡眠时长与家庭血压,明确睡眠时长与高血压的关联性。方法 本研究数据资料来自由中国医疗保健国际交流促进会发起的“血压健康研究”,由中国人民解放军总医院执行。本研究采用在线招募方式,招募来自全国34个省、自治区、直辖市的受试者。根据纳入与排除标准,2021年12月至2023年1月共纳入1706例既往无高血压病史的成年受试者,采用华为智能血压手表测量睡眠数据及家庭血压数据,通过填写电子问卷收集受试者人口学资料和病史等信息。按照基线时血压测量数值将受试者分为高血压组[收缩压(SBP)≥135mmHg(1mmHg=0.133kPa),和(或)舒张压(DBP)≥85mmHg,n=851]和非高血压组(SBP＜135mmHg,且DBP＜85mmHg,n=855)。采用SPSS 26.0统计软件进行数据分析。根据数据类型,分别采用t检验或χ²检验进行组间比较。采用多因素logistic回归分析睡眠时长与高血压之间的横断面关系。结果 1706例受试者中男性1519例(89.04%),女性187例(10.96%);年龄(44.87±11.52)岁;体质量指数(BMI)为(24.99±3.33)kg/m²;睡眠时长(7.35±1.10)h;收缩压(125.97±11.75)mmHg,舒张压(84.66±8.45)mmHg;心率(77.43±9.63)次/min。在不同睡眠时长(≥9h、7~<9h、5~<7h、<5h)受试者中,高血压患病率比较(45.26%、48.16%、52.63%和67.65%),差异有统计学意义(P=0.046)。随着睡眠时长缩短,高血压患病率有增高趋势。未校正混杂因素的多因素logistic回归分析结果显示,与睡眠时长7~<9h组比较,睡眠时长≥9h组(OR=0.890,95%CI 0.583~1.358;P=0.589)及睡眠时长5~<7h组(OR=1.196,95%CI 0.974~1.469;P=0.088)高血压风险无统计学差异;睡眠时长<5h组(OR=2.250,95%CI 1.086~4.665;P=0.029)的受试者高血压风险增加。校正了所有可获取混杂因素(年龄、性别、BMI、高盐饮食习惯、吸烟/饮酒史、呼吸睡眠暂停综合征史、糖尿病史、慢性肾脏病史等)后,与睡眠时长7~<9h组的受试者比较,睡眠时长≥9h组(OR=0.952,95%CI 0.606~1.495;P=0.831)及睡眠时长5~<7h组(OR=1.056,95%CI 0.848~1.315;P=0.625)高血压风险无统计学差异;睡眠时长<5h组(OR=2.238,95%CI 1.026~4.884;P=0.043)受试者的高血压风险依然增加。结论 睡眠时长过长及睡眠时长轻度不足与高血压风险无显著关联,睡眠时长过短与高血压风险增加显著关联。     

Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity, sexual dysfunction, increase body fat, weight gain and the development of cardiac disease. Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors. Methods Fifty-six self referred men without diabetes mellitus, hypertension, or cardiovascular disease (ages 52.3 ± 7.8 years) were randomly selected from a large cohort. Baseline weight, body fat composition, fasting glucose, hemoglobin A1c and fasting lipid levels, as well as free and total testosterone levels were assessed. All patients were assessed and followed 6–18 months after initiation of the program. The program consisted of a low glycemic load balanced nutrition diet, a recommended structured daily exercise program of 30–60 minutes, as well as once to twice weekly intramuscular testosterone injections (113.0 ± 27.8 mg). Results At follow up, weight was reduced from 233.9 ± 30.0 pounds (lbs) to 221.3 ± 25.1 lbs (P < 0.001), BMI was reduced from 33.2 ± 3.3 kg/m² to 31.3 ± 2.8 kg/m² (P < 0.0001). Total body fat was 27.1% ± 5.2% vs. 34.3% ± 5.7% at baseline (P < 0.0001). Fasting glucose was reduced from 95.3 ± 14.4 mg/dL to 87.5 ± 12.6 mg/dL (P < 0.0001). Total cholesterol was reduced from 195.4 ± 33.0 mg/dL to 172.7 ± 35.0 mg/dL (P < 0.005). No clinically significant adverse events were recorded. Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted. The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.     

正常范围内CD4+ T细胞水平对2型糖尿病患者胰岛素抵抗的影响

［摘要］　目的　探讨正常范围内CD4⁺ T细胞水平对2型糖尿病（T2DM）患者胰岛素抵抗的影响。方法　招募2021年9月至2022年6月徐州医科大学附属医院收治的T2DM患者269例,依据正常范围内的CD4⁺ T细胞水平将其分为4组：A组58例,414～670个/μl;B组78例,671～927个/μl;C组74例,928～1 183个/μl;D组59例,1 184～1 440个/μl。对研究对象的干扰素-γ（INF-γ）、白细胞介素-17(IL-17)、总胆固醇（TC）、甘油三酯（TG）、C反应蛋白（CRP）等指标进行检测。行口服葡萄糖耐量试验（OGTT）及胰岛素释放试验,计算稳态模型胰岛β细胞分泌指数（HOMA-β）,胰岛素抵抗指数（HOMA-IR）和Matsuda指数评估胰岛素敏感性IS（ISI_M）,分析各指标间的关联性。结果　四组CRP、INF-γ、IL-17、糖化血红蛋白（HbA_1c）、空腹血糖（FPG）、HOMA-IR、ISI_M比较差异有统计学意义（P<0.05),且CRP、INF-γ、IL-17、HbA_1c、FPG、HOMA-IR与CD4⁺ T细胞水平呈正关联,ISI_M与CD4⁺ T细胞水平呈负关联。Spearman秩相关性分析结果显示,HOMA-IR与CD4⁺ T细胞、CRP、HbA_1c、FBG、IL-17、INF-γ呈显著正相关（P<0.05）,与ISI_M呈显著负相关（P<0.05）。多元线性回归分析结果显示,CD4⁺ T细胞、FBG、IL-17、INF-γ水平与HOMA-IR水平呈正关联（P<0.05）。控制FPG及其他混杂因素（CRP、HbA_1c、IL-17、INF-γ）后,偏相关分析结果显示,HOMA-IR与CD4⁺ T细胞呈正相关（r=0.343,P<0.05）。结论　在CD4⁺ T细胞正常水平范围内,T2DM患者的CD4⁺ T细胞水平越高,其胰岛素抵抗越重,外周组织对胰岛素的敏感性也更低。     

放射性125I粒子植入治疗非小细胞肺癌近期疗效的多因素分析

  目的 探讨影响放射性¹²⁵I粒子植入治疗非小细胞肺癌（NSCLC）近期疗效的因素。方法 141例原发性NSCLC患者实施CT引导下放射性¹²⁵I粒子植入治疗,其中26例单纯粒子植入,115例粒子植入联合化疗。所有患者术后6个月行胸部CT检查,根据肿瘤大小变化进行疗效评估,并分析影响近期疗效的相关因素。结果 （1）粒子植入后完全缓解37例,部分缓解93例,有效率92.2%。（2）单因素分析显示：肿瘤分型（F=5.162,P=0.023）、覆盖100%肿瘤瘤体剂量（D₁₀₀）（F=100.713,P=0.000）、治疗模式（F=16.205,P=0.000）对局部疗效有影响。单因素logistic回归分析显示：D₁₀₀、治疗模式、肿瘤分型均为影响局部疗效的独立因素。（3）单因素分析显示：肿瘤分型（χ²=7.313,P=0.007）、D₁₀₀（χ²=71.6,P=0.000）、治疗模式（χ²=20.5, P=0.000）均为影响晚期NSCLC粒子植入治疗效果的重要因素。所有患者治疗期间均未发生相关严重并发症,且与近期疗效无明显相关（P>0.05）。结论 CT引导下放射性¹²⁵I粒子植入治疗NSCLC是一种安全、有效的治疗方法,D₁₀₀为影响近期疗效最主要的因素。     

Effect of anti-CD11b (αM-MAC-1) and anti-CD54 (ICAM-1) monoclonal antibodies on indomethacin induced chronic ileitis in rats

Leukocyte emigration from blood to sites of inflammation involves sequential interaction of specific adhesion molecules expressed by both leukocytes and endothelial cells. The central steps in leukocyte-endothelial adhesive interactions are leukocyte rolling, sticking, and transmigration. This study investigated the effect of monoclonal antibodies against CD54 (ICAM-1) and CD11b (α^M-chain of MAC-1) on intestinal inflammation. Anti-CD54 and anti-CD11b were tested in rats with indomethacin-induced chronic ileitis. Macroscopic changes were assessed by a modified version of the Wallace et al. score. Leukocyte rolling and sticking were investigated by intravital microscopy. Results show that indomethacin administration led to a chronic inflammatory response characterized by significant increase (P<0.05) in rolling (from 5.41±2.87 to 32.41±15.03 100 μm^–1 s^–1) and sticking (from 0.16±0.18 to 9.11±5.3 100 μm^–1 s^–1) leukocytes. After antibody treatment only the anti-CD11b group showed significant (P<0.05) reduction in rolling (from 32.41±15.03 to 6.6±2.7 100 μm^–1 s^–1) and sticking (from 9.11±5.3 to 0.07±0.09 100 μm^–1 s^–1) leukocytes. This was also the case for macroscopic changes. Indomethacin led to a rise in the Wallace score from 0 to 4.29±0.76 points (P<0.05) and anti-CD11b to a reduction from 4.29±0.76 to 1.29±1.11 points (P<0.05). Anti-CD54 and combined anti-CD11b/CD54 administration was not followed by significant changes. Therefore we suggest that leukocyte-based CD11b but not endothelial-based CD54 contributes most to leukocyte adhesion in the setting of indomethacin-induced ileitis in rats. Accepted: 7 September 1999     

肥胖与前庭神经鞘瘤患者术后并发症及二次手术的关联性研究

［摘要］　目的　探讨肥胖与前庭神经鞘瘤（VS）患者术后并发症及二次手术的关联性。方法　回顾性分析2013年6月至2023年6月于新疆医科大学第一附属医院接受乙状窦后入路手术治疗的377例VS患者的临床及影像学资料。根据体质量指数（BMI）将患者分为肥胖组（BMI≥28 kg/m²,91例）和非肥胖组（BMI<28 kg/m²,286例）。比较两组临床资料及术后并发症发生率和二次手术率,采用多因素logistic回归分析探讨BMI对术后脑脊液漏及二次手术的影响。结果　与非肥胖组相比,肥胖组性别为男性,以及合并糖尿病、高血压的人数比例更大,差异有统计学意义（P<0.05）。两组年龄、住院时间、手术侧别、肿瘤性质、肿瘤体积分级、手术时间比较差异无统计学意义（P>0.05）。肥胖组术后脑脊液漏发生率及二次手术率高于非肥胖组,差异有统计学意义（P<0.05）。两组颅内出血、切口感染、颅内感染、深静脉血栓及其他术后并发症发生率比较差异无统计学意义（P>0.05）。经调整年龄、性别、肿瘤体积分级、肿瘤性质后,多因素logistic回归分析结果显示,较高的BMI水平是患者发生术后脑脊液漏［OR(95%CI)=1.168（1.051～1.299）,P=0.004］及二次手术［OR(95%CI)=1.160（1.053～1.277）,P=0.003］的危险因素。结论　肥胖与VS患者术后脑脊液漏和二次手术密切相关,且BMI增高是VS患者术后脑脊液漏和二次手术的危险因素。     

Comparison of the Seattle Heart Failure Model and Cardiopulmonary Exercise Capacity for Prediction of Death in Patients With Chronic Ischemic Heart Failure and Intracoronary Progenitor Cell Application

Background:

Despite many therapeutic advances, the prognosis of patients with chronic heart failure (CHF) remains poor. Therefore, reliable identification of high‐risk patients with poor prognosis is of utmost importance. Cardiopulmonary exercise testing (CPET) provides important prognostic information by peak O₂ uptake (peak VO₂), maximal oxygen pulse (O₂ Pmax), O₂ uptake efficiency slope (OUES), and VE/VCO₂ slope (VE/VCO₂). A different approach for prognostic assessment is the Seattle Heart Failure Model (SHFM), which is based on clinical data and calculates the estimated annual mortality.

Hypothesis:

Comparison of the prognostic value of the Seattle Heart Failure Score and cardiopulmonary excercis testing in patients with chronic heart failure.

Methods:

One hundred fifty‐seven patients with ischemic heart failure and recent intracoronary progenitor cell application were analyzed for mortality during a follow‐up of 4 years. CPET (peak VO₂, O₂ Pmax, OUES, VE/VCO₂) was performed in all patients at baseline. The SHFM score was calculated for every patient, with data obtained at the time of CPET.

Results:

During follow‐up, 24 patients died (15.2%). Nonsurvivors had significantly worse initial CPET results and a higher SHFM score compared to survivors. Receiver operating characteristics curve analysis of sensitivity and specificity revealed the largest area under the curve value for the SHFM score, followed by VE/VCO₂ slope. Kaplan Meier analysis using cutoff points of SHFM and VE/VCO₂ slope with highest sensitivity and specificity resulted in significant discrimination of survivors and nonsurvivors. By multivariate analysis, only the SHFM score persisted as independent predictor of mortality in these patients.

Conclusions:

These data indicate superior prognostic power of the SHFM score compared to CPET in patients with chronic ischemic heart failure. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

Ventilatory response to exercise improves risk stratification in patients with chronic heart failure and intermediate functional capacity

Background Peak oxygen consumption (VO₂) has an important prognostic role in chronic heart failure (CHF), but its discriminatory power is limited in patients with intermediate exercise capacity (peak VO₂ between 10-18 mL/kg/min). Thus, supplementary exertional indexes are greatly needed. Methods Six hundred patients with CHF with left ventricular ejection fraction (LVEF) ≤40% who performed a symptom-limited cardiopulmonary exercise testing were screened and followed up for 780 ± 450 days. Results Eighty-seven patients had major cardiac events (77 cardiac deaths and 10 urgent heart transplantations). Multivariate analysis revealed the rate of increase of minute ventilation per unit of increase of carbon dioxide production (VE/VCO₂ slope) (χ², 79.3, P < .0001), LVEF (χ², 24.6, P < .0001), and peak VO₂ (χ², 9.4, P < .0001) as independent and additional predictors of major cardiac events. VE/VCO₂ slope was the strongest independent predictor of outcome (χ², 20.9, P = .0001) in patients with intermediate peak VO₂ (n = 403), and the best cutoff value was 35 (χ², 25.8; relative risk = 3.2, 95% CI 2.0-5.1, P < .0001). Total mortality rate was 30% in patients with VE/VCO₂ slope ≥35 (n = 103, 26%) and 10% in those with VE/VCO₂ slope <35 (n = 300, 74%) (P < .0001). Patients with VE/VCO₂ slope ≥35 had a similar total mortality rate to those with peak VO₂ ≤10 mL/kg/min (30% vs 37%, P not significant). Conclusions A rational and pragmatic risk stratification process with symptom-limited cardiopulmonary exercise testing in CHF should include both peak VO₂ and VE/VCO₂ slope, the latter index effectively predicting outcome in almost one fourth of patients with intermediate exercise capacity. (Am Heart J 2002;143:418-26.)     

O Impacto da Aptidão Cardiorrespiratória no Paradoxo da Obesidade em Insuficiência Cardíaca com Fração de Ejeção Reduzida

Background:Higher body mass index (BMI) has been associated with improved outcomes in heart failure with reduced ejection fraction. This finding has led to the concept of the obesity paradox.Objective:To investigate the impact of exercise tolerance and cardiorespiratory capacity on the obesity paradox.Methods:Outpatients with symptomatic heart failure and left ventricular ejection fraction (LVEF) ≤ 40%, followed up in our center, prospectively underwent baseline comprehensive evaluation including clinical, laboratorial, electrocardiographic, echocardiographic, and cardiopulmonary exercise testing parameters. The study population was divided according to BMI (< 25, 25 – 29.9, and ≥ 30 kg/m²). All patients were followed for 60 months. The combined endpoint was defined as cardiac death, urgent heart transplantation, or need for mechanical circulatory support. P value < 0.05 was considered significant.Results:In the 282 enrolled patients (75% male, 54 ± 12 years, BMI 27 ± 4 kg/m², LVEF 27% ± 7%), the composite endpoint occurred in 24.4% during follow-up. Patients with higher BMI were older, and they had higher LVEF and serum sodium levels, as well as lower ventilatory efficiency (VE/VCO₂) slope. VE/VCO₂ and peak oxygen consumption (pVO₂) were strong predictors of prognosis (p < 0.001). In univariable Cox regression analysis, higher BMI was associated with better outcomes (HR 0.940, CI 0.886 – 0.998, p 0.042). However, after adjusting for either VE/VCO₂ slope or pVO₂, the protective role of BMI disappeared. Survival benefit of BMI was not evident when patients were grouped according to cardiorespiratory fitness class (VE/VCO₂, cut-off value 35, and pVO₂, cut-off value 14 mL/kg/min).Conclusion:These results suggest that cardiorespiratory fitness outweighs the relationship between BMI and survival in patients with heart failure.     

B-type natriuretic peptide kinetics and cardiopulmonary exercise testing in heart failure

BackgroundIn patients with chronic heart failure (CHF), B-type natriuretic peptide (BNP) is related to peak oxygen consumption (peak VO₂) and the relationship between minute ventilation and carbon dioxide production (VE/VCO₂ slope). However, the exercise response depends on the mode of exercise. This study sought to compare peak treadmill and bicycle exercise responses with respect to their relationship with BNP and to assess whether BNP measured at rest or during exercise could identify patients with greater functional impairment and ventilatory inefficiency.MethodsTwenty-three patients with mild-to-moderate stable systolic CHF (age 72 ± 8 years, left ventricular ejection fraction 32 ± 7%) underwent treadmill and bicycle cardiopulmonary exercise testing within 5 (interquartile range 3–7) days. BNP was measured at rest and at peak exercise.ResultsBNP at rest was an independent multivariate predictor of both peak VO₂ and the VE/VCO₂ slope for both exercise modes. However, the proportion of variance explained univariately and multivariately was ≤ 0.55, indicating that BNP did not strongly explain the variation of peak VO₂ and the VE/VCO₂ slope. The exercise-induced rise in circulating BNP did not differ between the test modes [treadmill: 50 (24–89) pg/ml vs. bicycle: 46 (15–100) pg/ml; p = 0.73]. BNP levels at peak exercise were strongly related to resting values, but did not provide additional information on peak VO₂ or the VE/VCO₂ slope.ConclusionsIn typical CHF patients, BNP measured at rest or at peak exercise does not strongly predict peak VO₂ or the VE/VCO₂ slope regardless of the exercise mode, and is therefore not a sufficiently accurate surrogate for cardiopulmonary exercise testing.     

The Lowest VE/VCO2 Ratio During Exercise as a Predictor of Outcomes in Patients With Heart Failure

BackgroundThe lowest minute ventilation (VE) and carbon dioxide production (VCO₂) ratio during exercise has been suggested to be the most stable and reproducible marker of ventilatory efficiency in patients with heart failure (HF). However, the prognostic power of this index is unknown.Methods and ResultsA total of 847 HF patients underwent cardiopulmonary exercise testing (CPX) and were followed for 3 years. The associations between the lowest VE/VCO₂ ratio, maximal oxygen uptake (peak VO₂), the VE/VCO₂ slope, and major events (death or transplantation) were evaluated using proportional hazards analysis; adequacy of the predictive models was assessed using Akaike information criterion (AIC) weights. There were 147 major adverse events. In multivariate analysis, the lowest VE/VCO₂ ratio (higher ratio associated with greater risk) was similar to the VE/VCO₂ slope in predicting risk (hazard ratios [HR] per unit increment 2.0, 95% CI 1.1–3.4, and 2.2, 95% CI 1.3–3.7, respectively; P < .01), followed by peak VO₂ (HR 1.6, 95% CI 1.1–2.4, P = .01). Patients exhibiting abnormalities for all 3 responses had an 11.6-fold higher risk. The AIC weight for the 3 variables combined (0.94) was higher than any single response or any combination of 2. The model including all 3 responses remained the most powerful after adjustment for β-blocker use, type of HF, and after applying different cut points for high risk.ConclusionsThe lowest VE/VCO₂ ratio adds to the prognostic power of conventional CPX responses in HF.     

Development of a cardiopulmonary exercise prognostic score for optimizing risk stratification in heart failure: the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE) study

BackgroundCardiopulmonary exercise testing (CPET) provides powerful information on risk of death in heart failure (HF). We sought to define the relative and additive contribution of the 3 landmark (CPET) prognostic markers—peak oxygen consumption (VO₂), minute ventilation/carbon dioxide production (VE/VCO₂) slope, and exercise periodic breathing (EPB)—to the overall risk of cardiac death and to develop a prognostic score for optimizing risk stratification in HF patients.Methods and ResultsA total of 695 stable HF patients (average LVEF: 25 ± 8%) underwent a symptom-limited CPET maximum test after familiarization and were prospectively tracked for cardiac mortality. At multivariable Cox analysis EPB emerged as the strongest prognosticator. Using a statistical bootstrap technique (5000 data resamplings), point estimates, and 95% confidence intervals were obtained. Thirty-two configurations were adopted to classify patients into a given cell, according to EPB presence or absence and values of the 2 other covariates. Configurations without EPB and with VE/VCO₂ slope ≤30 were not significantly different from 0 (reference value). Statistical power of configurations increased with higher VE/VCO₂ slope and lower peak VO₂. This prompted us to formulate a score including EPB as a discriminating variable, the (P)e(R)i(O)dic (B)reathing during (E)xercise (PROBE), which ranges between -1 and 1, with zero as reference configuration, that would help to optimize the prognostic accuracy of CPET-derived variables. The greatest PROBE score impact was provided by EPB, followed by VE/VCO₂ slope, whereas peak VO₂ added minimal prognostic power.ConclusionsEPB with an elevated VE/VCO₂ slope leads to the highest and most precise PROBE score, whereas no additional risk information emerges when EPB is present with a peak VO₂ ≤10 mL O₂·kg^?1·min^?1. PROBE score appears to provide a step forward for optimizing CPET use in HF prognostic definition.     

The minute ventilation/carbon dioxide production slope is prognostically superior to the oxygen uptake efficiency slope

BackgroundVentilatory efficiency, commonly assessed by the minute ventilation (VE)-carbon dioxide production (VCO₂) slope, has proven to be a strong prognostic marker in the heart failure (HF) population. Recently, the oxygen uptake efficiency slope (OUES) has demonstrated prognostic value, but additional comparisons to established cardiopulmonary exercise test (CPET) variables are required.Methods and ResultsA total of 341 subjects were diagnosed with HF participated in this analysis. The VE/VCO₂ slope and the OUES were calculated using 50% (VE/VCO₂ slope₅₀ or OUES₅₀) and 100% (VE/VCO₂ slope₁₀₀ or OUES₁₀₀) of the exercise data. Peak oxygen consumption (VO₂) was also determined. There were 47 major cardiac-related events during the 3-year tracking period. Receiver operating characteristic (ROC) curve analysis demonstrated the classification schemes for both VE/VCO₂ slope and OUES calculations as well as peak VO₂ were statistically significant (all areas under the ROC curve: ≥0.74, P < .001). Area under the ROC curve for the VE/VCO₂ slope₁₀₀ was, however, significantly greater than OUES₅₀, OUES₁₀₀, and peak VO₂ (P < .05).ConclusionsAlthough the OUES was a significant predictor of mortality, the VE/VCO₂ slope maintained optimal prognostic value. An elevated VE/VCO₂ slope may be the single best indicator of increased risk for adverse events.     

Exercise oscillatory breathing and NT-proBNP levels in stable heart failure provide the strongest prediction of cardiac outcome when combining biomarkers with cardiopulmonary exercise testing

BackgroundN-Terminal pro–brain natriuretic peptide (NT-proBNP) and cardiopulmonary exercise testing (CPET)–derived variables are gold standards for assessing prognosis in heart failure (HF) patients. We sought to refine cardiac events prediction by performing a combined analysis of NT-proBNP with markers of exercise ventilatory efficiency.Methods and ResultsA total of 260 stable HF patients underwent measurements of plasma NT-proBNP levels before, at peak exercise, and at 1-minute CPET recovery phase along with peak oxygen uptake (VO₂), ventilation to CO₂ production (VE/VCO₂) slope, and exercise periodic breathing (EPB) determinations. After a median follow-up period of 20.6 months, there were 54 cardiac-related deaths. Univariate analysis including NT-proBNP at rest, at peak exercise, and at 1 minute recovery, peak VO₂, VE/VCO₂ slope, and EPB showed NT-proBNP to be the strongest independent predictor with equivalent performance for rest, peak, and recovery levels. Thus, only NT-proBNP at rest was considered (Harrel C 0.783, 95% confidence interval [CI] 0.722–0.844) with VE/VCO₂ slope (Harrel C 0.720, 95% CI 0.646–0.794), EPB (Harrel C 0.685, 95% CI 0.619–0.751), and peak VO₂ (Harrel C 0.618, 95% CI 0.533–0.704). With bivariate stepwise analyses, NT-proBNP along with EPB emerged as the strongest prognosticators (Harrel C 0.800, 95% CI 0.737–0.862).ConclusionsIn the refinement for robust outcome predictors in HF patients, NT-proBNP levels together with EPB led to the most powerful definition. VE/VCO₂ slope and peak VO₂ did not provide any prognostic adjunct. A biomarker/CPET approach seems very promising to warrant the continuous implementation in the prognostic work-up of HF patients.     

A flattening oxygen consumption trajectory phenotypes disease severity and poor prognosis in patients with heart failure with reduced,mid‐range,and preserved ejection fraction

Background

In heart failure (HF), a flattening oxygen consumption (VO₂) trajectory during cardiopulmonary exercise test (CPET) reflects an acutely compromised cardiac output. We hypothesized that a flattening VO₂ trajectory is helpful in phenotyping disease severity and prognosis in HF with either reduced (HFrEF), mid‐range (HFmrEF), or preserved (HFpEF) ejection fraction.

Methods and results

Overall, 319 HF patients (198 HFrEF, 80 HFmrEF, and 41 HFpEF) underwent CPET. A flattening VO₂ trajectory was tracked and defined as an inflection of VO₂ linearity as a function of work rate with a second slope downward inflection >35% extent of the first one. Peak VO₂, the minute ventilation/carbon dioxide production (VE/VCO₂) slope, and the presence of exercise oscillatory ventilation (EOV) were also determined. Pulmonary artery systolic pressure (PASP) and tricuspid annular plane systolic excursion (TAPSE) were measured by echocardiography. A flattening VO₂ occurred in 92 patients (28.8%). PASP and TAPSE at rest were significantly higher and lower (P < 0.001), respectively. The primary outcome was the combination of all‐cause death, heart transplantation and left ventricular assist device implantation. The secondary outcome was the primary outcome plus hospitalization for cardiac reasons. In the multivariate model including peak VO₂, VE/VCO₂ slope, EOV and VO₂ trajectory, a flattening VO₂ trajectory and EOV were retained in the regression for primary (X² = 35.78, and 36.36, respectively; P < 0.001) and secondary (X² = 12.45 and 47.91, respectively; P < 0.001) outcomes.

Conclusions

Results point to a flattening VO₂ trajectory as a likely new and strong predictor of events in HF with any ejection fraction. Given the relation of right‐sided cardiac dysfunction to pulmonary hypertension, this oxygen pattern might suggest a real‐time decrease in pulmonary blood flow to the left heart.

     

Comparison of ventilatory expired gas parameters used to predict hospitalization in patients with heart failure

Background Several ventilatory expired gas measures obtained during exercise testing demonstrate prognostic value in the heart failure (HF) population. Comparison of prognostic efficacy between pertinent measures is sparse. Methods The ability of various expressions of peak oxygen consumption (VO₂), the relationship between minute ventilation (VE) and carbon dioxide production (VCO₂), and the partial pressure of end-tidal carbon dioxide (P_ETCO₂) were assessed to determine which measure(s) best predicted cardiac-related hospitalization over a 1-year period in subjects diagnosed with HF. Results Univariate Cox regression analysis found that several expressions of peak VO₂, VE-VCO₂ relationship, and P_ETCO₂ were significant predictors of hospitalization. Multivariate Cox regression analysis revealed that the VE/VCO₂ slope significantly predicted hospitalization (χ² = 29.1, P < .00001). Peak VO₂ and P_ETCO₂ did not provide additional predictive value. Conclusions The prognostic superiority of the VE/VCO₂ slope over peak VO₂ may be a result of the latter measure's partial dependence on subject effort and skeletal muscle function. (Am Heart J 2002;143:427-32.)