Table_2_Sex- and Age-Related Physiological Profiles for Brachial, Vertebral, Carotid, and Femoral Arteries Blood Flow Velocity Parameters During Growth and Aging (4–76 Years): Comparison With Clinical Cut-Off Levels.DOCX

Ultrasound-derived blood flow velocity (BFV) levels [e.g., peak systolic velocity (PSV)], intrabeat indexes (e.g., resistive), and intersegment ratios [e.g., internal/common carotid artery (ICA/CCA) PSV ratio] are assessed to describe cardiovascular physiology and health status (e.g., disease severity evaluation and/or risk stratification). In this respect, fixed cut-off values (disregard of age or sex) have been proposed to define “significant” vascular disease from BFV-derived data (parameters). However, the use of single fixed cut-off values has limitations. Accurate use of BFV-derived parameters requires knowing their physiological age-related profiles and the expected values for a specific subject. To our knowledge, there are no studies that have characterized BFV profiles in large populations taking into account: (i) data from different age-stages (as a continuous) and transitions (childhood–adolescence–adulthood), (ii) complementary parameters, (iii) data from different arteries, and (iv) potential sex- and hemibody-related differences. Furthermore, (v) there is little information regarding normative data [reference intervals (RIs)] for BFV indexes.
Aims: The aims of this study are the following: (a) to determine the need for age-, body side-, and sex-specific profiles for BFV levels and derived parameters (intrabeat indexes and intersegment ratios), and (b) to define RIs for BFV levels and parameters, obtained from CCA, ICA, external carotid, vertebral, femoral, and brachial arteries records.
Methods: A total of 3,619 subjects (3–90 years) were included; 1,152 were healthy (without cardiovascular disease and atheroma plaques) and non-exposed to cardiovascular risk factors. BFV data were acquired. The agreement between left and right data was analyzed (Concordance correlation, Bland–Altman). Mean and SD equations and age-related profiles were obtained for BFV levels and parameters (regression methods; fractional polynomials).
Results: Left and right body-side derived data were not always equivalent. The need for sex-specific RIs was dependent on the parameter and/or age considered. RIs were defined for each studied artery and parameter. Percentile curves were compared with recommended fixed cut-off points. The equations for sex, body-side, and age-specific BFV physiological profiles obtained in the large population (of children, adolescents, and adults) studied were included (spreadsheet formats), enabling to determine for a particular subject, the expected values and potential data deviations.

本研究通过评估超声衍生血流速度（blood flow velocity, BFV）水平[如收缩期峰值流速（peak systolic velocity, PSV）]、心动周期内指数（如阻力指数）及节段间比值[如颈内动脉/颈总动脉（internal/common carotid artery, ICA/CCA）PSV比值]，以描述心血管生理状态与健康状况，例如疾病严重程度评估及/或风险分层。就此而言，既往已有研究提出基于BFV衍生参数（指标）确定“显著性”血管疾病的固定截断值，且未考虑年龄或性别因素。然而，单一固定截断值的应用存在局限性。精准使用BFV衍生参数，需明确其生理年龄相关特征谱，以及特定受试者的预期参考值。据我们所知，目前尚无研究在大样本人群中对BFV特征谱进行系统性表征，且未涵盖以下维度：(i) 不同年龄阶段（以连续变量形式）及年龄过渡阶段（儿童期-青少年期-成年期）的数据；(ii) 互补衍生参数；(iii) 不同动脉的检测数据；(iv) 潜在的性别及半侧躯体相关差异。此外，(v) 目前关于BFV各项指数的正常参考数据[参考区间（reference intervals, RIs）]的相关信息仍较为匮乏。
研究目的：本研究旨在达成以下目标：(a) 明确BFV水平及其衍生参数（心动周期内指数与节段间比值）是否需要建立年龄、躯体侧别及性别特异性的特征谱；(b) 基于颈总动脉（common carotid artery, CCA）、颈内动脉（internal carotid artery, ICA）、颈外动脉、椎动脉、股动脉及肱动脉的检测数据，确定BFV水平与各参数的参考区间（RIs）。
研究方法：本研究共纳入3619名年龄介于3~90岁的受试者，其中1152名为健康个体（无心血管疾病及动脉粥样硬化斑块），且未暴露于心血管危险因素。研究人员采集了所有受试者的BFV数据，并分析了左右侧检测数据的一致性（采用一致性相关分析、Bland-Altman分析）。通过回归分析方法（分数多项式模型），推导得到BFV水平及各参数的均值与标准差方程，以及年龄相关特征谱。
研究结果：左右侧躯体的BFV衍生数据并非始终一致。建立性别特异性参考区间（RIs）的必要性取决于所分析的参数及/或受试者年龄。本研究为所有纳入分析的动脉及参数均确定了参考区间。将百分位曲线与推荐的固定截断值进行了对比。本研究还提供了基于大样本人群（儿童、青少年及成人）推导得到的性别、躯体侧别及年龄特异性BFV生理特征谱方程（以电子表格格式呈现），可用于确定特定受试者的预期参考值及潜在数据偏差。