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Lack of sex-specific differences in the associations between the dimensions of great vessels and exercise performance in amateur cyclists

  • Michał J. Pytka ,

    Roles Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft

    mjpytka@gmail.com

    Affiliations Department of Cardiology – Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland, University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland, Doctoral School, Poznan University of Medical Sciences, Poznan, Poland

  • Remigiusz A. Domin,

    Roles Investigation, Writing – review & editing

    Affiliations University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland, Doctoral School, Poznan University of Medical Sciences, Poznan, Poland, Department of Endocrinology, Metabolism and Internal Medicine, Poznan University of Medical Sciences, Poznań, Poland

  • Mikołaj S. Żołyński,

    Roles Investigation

    Affiliations Department of Cardiology – Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland, University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland

  • Jan Niziński,

    Roles Funding acquisition, Investigation

    Affiliation University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland

  • Tomasz Krauze,

    Roles Project administration, Resources, Software

    Affiliations Department of Cardiology – Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland, University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland

  • Barbara Więckowska,

    Roles Formal analysis

    Affiliation Department of Computer Science and Statistics, Poznan University of Medical Sciences, Poznań, Poland

  • Andrzej Wykrętowicz,

    Roles Formal analysis, Supervision

    Affiliation Department of Cardiology – Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland

  • Przemysław Guzik

    Roles Conceptualization, Data curation, Formal analysis, Funding acquisition, Methodology, Supervision, Writing – review & editing

    Affiliations Department of Cardiology – Intensive Therapy, Poznan University of Medical Sciences, Poznań, Poland, University Centre for Sports and Medical Studies, Poznan University of Medical Sciences, Poznań, Poland

Abstract

Background

Endurance training enhances exercise capacity and triggers cardiovascular adaptations in both males and females. We investigated the relationship between the dimensions of great vessels and exercise capacity in amateur cyclists while considering sex differences.

Methods

Using resting transthoracic echocardiography, we measured the dimensions of the main pulmonary artery (PA), aorta, and inferior vena cava (IVC) in 190 participants, who subsequently underwent a cardiopulmonary exercise test (CPET) until exhaustion.

Results

The mean age of study participants was 30 years. Males (71%) exhibited a larger aortic annulus (approximately 3.5 mm, p<0.0001) and PA diameter (2.4 mm, p<0.0001) than females. No significant sex differences were found in expiratory or inspiratory IVC diameters. Males achieved greater peak exercise capacity, including workload, O2 consumption (VO2), and O2 pulse. Aortic and PA dimensions showed strong correlations with energy expenditure, workload, VO2, and O2 pulse. However, these correlations weakened when analyzed separately by sex. Multivariate linear regression revealed associations between CPET results, vessels size, and sex, with sex differences observed only in the intercepts—not in interactions between sex and vessels size. Despite males having better CPET results and larger vessels, the relationships between peak exercise capacity parameters and vessel dimensions were similar in both sexes.

Conclusion

Larger vessel dimensions (of the aorta, PA, and IVC) were associated with greater peak exercise capacity in amateur cyclists, with no significant sex differences in these associations.

Introduction

Various tissues and organs increase their demand for O2 and fuel during exercise [1, 2]. Energy production in the working muscles requires a constant supply of fuel and O2 and effective removal of heat and CO2. Simultaneously, various metabolites, including CO2, lactate, H+ ions, and adenosine, are produced during muscular exertion. These substances must be efficiently transported from the working muscles to other organs for processing. For example, CO2 is exhaled via the lungs, while lactate is utilized for gluconeogenesis in the liver or kidneys. Additionally, less active muscles can use lactate as a fuel source through the Cori cycle, which converts lactate into pyruvate for subsequent use in the Krebs cycle to produce ATP. The respiratory and cardiovascular systems adapt to match the demand for O2 delivery and increase the capacity to transport exercise metabolites. As a result, pulmonary ventilation, blood pumped by the heart and transported through the vessels increase [25].

Endurance exercise (including both training and physical work) causes the adaptation of many organs and systems to allow them to perform better. The heart of an athlete provides a classic example of such exercise-induced organ adaptation [1, 6]. The pulmonary and musculoskeletal systems also undergo exercise-induced remodeling, although the exact patterns of this process are not well understood [1, 79]. Many factors, including the type (endurance, power, mixed, and/or skill), volume, intensity, and duration of exercise; genetic predisposition; age; and sex, may contribute to such changes [6, 10].

An athlete’s heart is larger than that of a non-athlete, with thicker walls and dilated chambers, leading to increased myocardial mass. This translates into improved cardiac function, allowing highly trained individuals to achieve a greater cardiac output with a lower heart rate (HR) [1]. During exercise, cardiac output can increase up to 8-fold, reaching 40 L/min, compared to the resting 5 L/min [1]. Blood flow to muscles increases significantly (up to a 30-fold increase in elite athletes), while e.g. the digestive system receives less perfusion [11]. Exercise also benefits the vascular system by reducing arterial wall thickness and increasing lumen diameter, leading to decreased vascular resistance in muscle arteries during exercise [1].

Both males and females experience the effects of endurance exercise, which lead to adaptation of cells, tissues and organs. However, there are variations due to differences in body size and composition; sex hormones; genetics; and environmental factors like diet, lifestyle, training time, pregnancies, and stress [12]. Females generally have smaller cardiac chambers and mass and smaller aortic diameters than men. These anatomical differences might influence how the heart responds to exercise in males and females [12, 13], however research in this topic is lacking.

Despite extensive research on the cardiovascular system, a crucial gap remains in our understanding of how the dimensions of great vessels relate to exercise capacity in males and females This study examined a group of amateur cyclists with varying exercise levels to assess the relationship between dimensions of the aorta, main pulmonary artery (PA), and inferior vena cava (IVC) with exercise capacity. We further investigated whether these associations existed separately in males and females and if these associations differed by sex. This research is exploratory, and no hypothesis regarding sex differences was formulated. Consequently, we aim to establish associations rather than causality.

Materials and methods

Bioethical issues

This paper presents results of a project that was approved by the Bioethics Committee of Poznan University of Medical Sciences (decision 693/20). The study was conducted according to the Declaration of Helsinki [14]. All data were treated confidentially and anonymized for storage and analysis. The data were collected, stored, and analyzed in the REDCap data capture tools hosted at Poznan University of Medical Sciences [15].

Study group recruitment

We enrolled 215 consecutive adult volunteers who claimed to be recreationally physically active and cycled regularly for a cross-sectional, observational study with a single timepoint assessment. The recruitment took place between December 1st 2020, and April 30th 2023. Details of all participants have already been published [16]. The enrolment included consecutive volunteers who responded to the recruitment call who wanted to participate in a study to evaluate their cardiovascular function by electrocardiogram (ECG), echocardiography (ECHO), and CPET. All participants took part voluntarily and were informed about the study and the fact that they could abandon the study at any time. Written informed consent was collected from all volunteers.

For this substudy, we selected participants with complete data from CPET and ECHO measurements concerning great vessel dimensions. Therefore, 190 subjects were analyzed. The inclusion criteria were being recreationally physically active and cycling regularly for at least 1 h per week to ensure the participation of a wide variety of amateur cyclists. Individuals with chronic diseases or who were taking medications were excluded from the study. Allowed substances included vitamin D, dietary supplements, and oral contraceptives for women.

Health status

Physicians performed a comprehensive pre-participation screening, including a detailed medical and family history, physical examination, and blood pressure measurement. A resting 12-lead ECG was performed to detect abnormalities such as arrhythmias, conduction problems, signs of left ventricle (LV) or right ventricle (RV) hypertrophy, pre-excitation syndromes, or channelopathies. In addition, resting transthoracic ECHO assessed cardiac structure and function to exclude clinically significant abnormalities such as moderate to severe valve stenosis or regurgitation (e.g., mitral regurgitation or aortic stenosis). Six individuals were excluded due to LV hypertrophy or moderate mitral or tricuspid regurgitation.

Anthropometric measurements and physical activity assessment

Body height and weight were measured to calculate body mass index (BMI). To assess physical activity, we used the International Physical Activity Questionnaire (IPAQ) [17], as well as additional questions regarding basic characteristics of training (cycling sessions per week and hours of cycling training per session and per week). MET-min (metabolic equivalent of task–minutes) were calculated according to IPAQ interpretation guidelines [17]. The MET-min is a parameter showing the volume of exercise undertaken by a participant.

Spirometry

Participants underwent baseline resting spirometry (Vyntus CPX, Vyaire Medical, IL, USA) after resting in a sitting position for at least 5 min. The measured values included forced expiratory volume in 1 s (FEV1). Maximal voluntary ventilation was calculated using the formula FEV1 × 40 and defined the limit of breathing reserve for CPET [18]. The test was performed until five results met the criteria for adequate quality [18, 19], and the mean results from the three best repetitions were used for analysis.

Cardiopulmonary exercise test

CPET was performed on a cycle ergometer (Excalibur Sport 2, Lode, Groningen, The Netherlands) using a CPET system (Vyntus CPX, Vyaire Medical, IL, USA). HR was recorded using a chest-strap HR monitor (Polar H10, Polar, Kempele, Finland). The tidal volume and content of O2 and CO2 in the inhaled and exhaled air were measured using the breath-by-breath method.

The CPET was executed according to the Association for Respiratory Technology & Physiology guidelines [18] using an individualized incremental ramp protocol tailored to the participants’ current physical performance. Additionally, we took into consideration the IPAQ result–MET-min and IPAQ category. For participants in the lower physical activity category we aimed for the peak load after 10 minutes of exercise to reach 2.5–3.5 W/kg, for the moderate physical activity category– 3.5–4.5 W/kg and for the high physical activity category– 4.5–5.5 W/kg. The resting phase lasted 2 minutes, the warmup phase (pedaling with no additional load) lasted 2 minutes. The main phase of the test (incremental ramp protocol) aimed to last 8−12 min [18, 20] and was terminated at the will of the participant at peak effort. The participants were encouraged to exert maximal effort; they could increase cadence, muscle strain, or both. During peak exercise, all participants reached at least 8 points in the modified Borg scale, the median RER was 1.24 (RER > 1.15 defines high effort), and all reached >90% of predicted maximal heart rate and/or maximal VO2. During the recovery phase, monitoring continued for at least 10 min while the participant was seated.

The recorded parameters, which were used for further analysis, included:

  • HR: heart rate;
  • VO2: the volume of O2 consumed per min;
  • O2 pulse: the ratio of VO2 to HR;
  • VCO2: the volume of CO2 produced per min;
  • VE: minute ventilation;
  • RER: respiratory exchange ratio; and
  • EE: energy expenditure.

EE, expressed as kcal per min, was calculated using the Weir formula for indirect calorimetry [21]:

The recorded time points included averaged breath-by-breath values from the last 15 s of the rest and peak exercise phases, the latter of which usually occurred before the end of the cycling.

Echocardiography

Echocardiography was performed in all participants according to the American Society of Echocardiography guidelines [22]. Experienced cardiologists used a 3.5-MHz transducer on a Vivid E95 or E9 ECHO machine from General Electric Healthcare Technologies (Chicago, IL, USA). The IVC was measured in the subcostal view approximately 1 cm before the entrance to the right atrium. The IVC expiratory and inspiratory diameters were obtained using the M-mode while the patient was breathing deeply. In the parasternal long axis view, the following diameters of the aorta were measured: aortic annulus diameter, aortic sinus of Valsalva diameter, and aortic sinotubular junction (STJ) diameter. From the suprasternal view, we quantified the diameter of the arch of the aorta. The diameter of the abdominal aorta was measured in the longitudinal plane, in the subcostal view focused on the proximal abdominal aorta. Finally, in the parasternal short axis view, focused on the PA, the diameters of the PA and of the left pulmonary artery (LPA) and right pulmonary artery (RPA) (1 cm after their takeoff) were measured. Most measurements of arteries were taken using the leading-to-leading method. The aortic annulus and IVC dimensions were measured using the trailing-to-leading approach.

The echocardiographic data (images and cine loops) were analyzed using TOMTEC Imaging Systems (TOMTEC-ARENA Build No. 544347, TOMTEC Imaging Systems GmbH, Unterschleissheim, Germany, distributed by Phillips, Amsterdam, The Netherlands).

An example of echocardiographic measurements is presented in Fig 1.

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Fig 1. An example of echocardiographic measurements for the study.

A–measurements of the aorta in the parasternal long axis (aortic annulus, sinus of Valsalva and sinotubular junction diameters). B–measurement of the arch of the aorta in the suprasternal view. C–measurement of the diameter of the main pulmonary artery and the left and right pulmonary arteries in the modified parasternal short axis with focus on the main pulmonary artery. D–measurement of the inferior vena cava during inspiration and expiration–measured in M-mode.

https://doi.org/10.1371/journal.pone.0313165.g001

Statistical analysis

QQ-plots and the D’Agostino–Pearson test were used to test the normality of the data distributions [23]. The mean ± standard deviation (SD) summarizes data with a normal distribution, while the median and difference between the 75th and 25th percentiles (interquartile range) describe data that are not normally distributed. Depending on the data distribution, comparisons between the sexes were made using either the parametric Student’s t-test or the non-parametric Mann–Whitney test. Associations between the dimensions of great vessels and peak exercise performance parameters from CPET, as well as the influence of sex, were preliminarily examined using Pearson correlation (all these parameters were normally distributed). Multivariate linear regression models analyzed the effects of vascular dimensions (x) and sex and the interactions of these parameters (x × sex) on exercise capacity parameters (HR, VO2, VO2·kg−1, VCO2, VE, load, O2 pulse, and RER). Within these models, the estimate for x represents the direct association between a peak CPET parameter and a specific great vessel dimension. The sex estimate (0 = female, 1 = male) indicates the presence of sex differences in peak CPET parameters; a significant estimate indicates significant sex differences in the dependence of CPET on vessel dimensions. The interaction term x × sex reflects whether the association between specific vessel dimensions and peak CPET parameters differs between male and female cyclists. This approach essentially compares two separate regressions for each sex: the sex effect compares the intercepts, while the x × sex interaction compares the slopes of these regressions. As our primary aim was to determine whether the slopes of the relationships between exercise capacity and the dimensions of great vessels differed between males and females, we focused on reporting only the p-value for the interaction term between vessels size and sex. In all analyses, only p-values <0.05 were considered significant. JMP® Pro 17.0.0 (622753) (JMP Statistical Software, Cary, NC, USA) was used for statistical analyses.

Results

Study group characteristics

Table 1 summarizes the characteristics of the 190 participants (134 males, 71%; 56 females, 29%). Males were taller (by 13 cm) and heavier (by 19.2 kg) than females, with a BMI 3.1 kg·m−2 higher. However, median age and measures of exercise volume (e.g., hours per week and intensity) were similar between the sexes. The mean value of MET minutes per week was 4225. The IPAQ classified most participants (56%) as very active, 34% moderately active, and 10% less active. Cycling was the main sport activity for all participants, and the median number of cycling sessions per week was 4. The median cycling training time was 3.5 hours/week, with a minimum of 2 hours per week (only 22 participants, 11%). Other sports activities undertaken in the study group included running (40%), gym (25%), swimming (19%), team sports (9%), and others (31%).

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Table 1. Clinical characteristics of studied male and female amateur cyclists and their peak cardio-pulmonary exercise test results.

https://doi.org/10.1371/journal.pone.0313165.t001

Echocardiography

Table 1 summarizes the echocardiographic measurements of the aorta, PA, and IVC. Males had larger aortic diameters than females at the annulus, sinus of Valsalva, STJ, aortic arch, and proximal abdominal aorta. The diameter of the PA was 2.4 mm larger in males, and the diameters of the LPA and RPA were 1.8 and 1.7 mm larger, respectively. The diameter of the IVC was 20.8 mm during expiration and 10.3 mm during inspiration and was similar in males and females. The absolute and relative increases in IVC diameter during expiration were similar in males and females (10.5 vs. 10.6 mm and 51.1% vs. 50.6%, respectively).

Cardiopulmonary exercise test

The data from CPET at rest and during peak exercise are presented in Table 1. During peak exercise, the HR increased by 225%, from 82 to 184 bpm, and was comparable between males and females. Males achieved higher peak load (343 vs. 229 W), as well as load per unit body mass (4.31 vs. 3.72 W·kg−1). For all participants, breathing frequency increased by 325%, reaching 51 breaths per min at peak exercise, and the peak VE was 144 L·min−1. O2 pulse was higher in males and reached 20.7 mL·beat−1 (334% increase) compared to 14.0 mL·beat−1 (326% increase) in females. The peak RER was 1.24, indicating very high effort by the participants. The data are available in the supporting information–S1 Table.

Associations between the dimensions of great vessels and exercise capacity

The diameter of the aorta, particularly at the levels of the annulus, the sinuses of Valsalva, and the proximal abdominal segment below the diaphragm, as well as of the LPA, showed significant positive correlations of moderate strength with peak EE, workload, O2 pulse, VCO2, VO2, and VE. Interestingly, peak HR showed a weak negative correlation with the same dimensions. The IVC showed weak or nonsignificant correlations with the same exercise capacity parameters, with the exception of O2 pulse. All correlations were generally weaker when analyzed separately for males and females. Fig 2 illustrates some of the strongest correlations observed, focusing on the aortic annulus and selected peak CPET parameters.

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Fig 2. Correlations between aortic annulus diameter and peak exercise capacity parameters from CPET.

The red dots and shaded ellipses represent females, the blue dots and shades represent males. Abbreviations: O2 pulse—the ratio of VO2 to HR; VE–minute ventilation; VO2 –the volume of consumed O2.

https://doi.org/10.1371/journal.pone.0313165.g002

In Table 2, we present the results of the Pearson correlation coefficient analysis for associations between the dimensions of great vessels and exercise capacity. Generally, stronger correlations were found in the whole study group, and weaker correlations were found in the subgroups for each sex. The strongest recorded correlations were moderate (r≥0.4) and were found between dimensions of the aorta and of the PA and peak EE, load, O2 pulse, VCO2, and VO2, as well as between dimensions of the aorta and VE.

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Table 2. Pearson correlation coefficient for associations between the dimensions of great vessels and exercise capacity parameters in the study group and in sex-subgroups.

https://doi.org/10.1371/journal.pone.0313165.t002

In the whole study group, larger aortic dimensions were correlated with higher peak EE, load, O2 pulse, VCO2, VO2, and VO2·kg−1 and with lower peak HR. Specifically, the strongest correlations included aortic annulus diameter with: EE (r = 0.56, p<0.0001), O2 pulse (r = 0.56, p<0.0001), VCO2 (r = 0.55, p<0.0001), and VO2 (r = 0.55, p<0.0001); aortic sinus of Valsalva diameter with O2 pulse (r = 0.56, p<0.0001); proximal abdominal aorta diameter with O2 pulse (r = 0.55, p<0.0001); and LPA with O2pulse (r = 0.55, p<0.0001). Larger dimensions of the thoracic aorta were correlated with higher O2 pulse and lower HR in males. Proximal abdominal aorta diameter was larger in cyclists (both males and females) who achieved higher peak EE, load, O2 pulse, VO2 and RER. The abdominal aorta was additionally correlated with higher VCO2 in males and with higher VE in females.

Larger dimensions of the PA and its branches were correlated with higher EE, load, O2 pulse, VCO2, VE, VO2, and VO2·kg−1 and with lower HR in all cyclists. For males, the correlations were significant between the diameters of the PA, LPA, and RPA and EE, HR, O2 pulse, VCO2, VO2, and VO2·kg−1, as well as between the diameters of the RPA and LPA and RER. In females, fewer correlations were found: between PA diameter and EE, O2 pulse, VCO2, VE, VO2; LPA diameter and EE, VO2, O2 pulse and VE; RPA diameter and EE, HR, O2 pulse, RER, VO2, VO2·kg−1 and VE.

The IVC expiratory and inspiratory diameters were correlated with higher EE, load, O2 pulse, VCO2, and VO2·kg−1 in males. In females, only the IVC expiratory diameter was associated with higher EE, O2 pulse, VE, and VO2 and lower HR.

Sex-specific associations between peak CPET parameters and resting dimensions of great vessels

Tables 3 and 4 summarize the potential influence of the dimensions of great vessels, sex, and their interaction on peak CPET parameters. The estimate for each vessel dimension (x) represents its direct effect on peak CPET. The estimate for sex (0 = female, 1 = male) indicates sex differences in peak CPET. Significant interaction terms (x × sex) indicate that the relationship between a vessel dimension and peak CPET differs between males and females. However, no interactions were statistically significant, indicating that these relationships were comparable in both sexes. Therefore, the final regressions (Table 4) included only vessel dimension (x) and sex as independent variables, without interaction terms.

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Table 3. Table 3 shows the p-values for the interaction terms between resting large vessel dimensions and sex in their influence on peak CPET parameters.

As none of these interaction terms were statistically significant and influenced the linear regression models, the estimates for vessel dimensions and sex are omitted from this table for clarity. The final regression models without interaction terms are shown in Table 4. Data presented for N = 190 (134 males, 56 females).

https://doi.org/10.1371/journal.pone.0313165.t003

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Table 4. Associations between peak CPET parameters with resting dimensions of the great vessels and sex.

Data presented for N = 190 (134 males, 56 females).

https://doi.org/10.1371/journal.pone.0313165.t004

Significant associations were found between both peak HR and O2 pulse and aortic, PA, and IVC dimensions. In contrast, fewer associations were observed between RER or VE and vascular dimensions. Males and females showed significant differences in the relationships between peak CPET parameters and vessel dimensions. This can be attributed to both higher peak CPET values and larger sizes of great vessel in males than females. Consistently, the correlations between CPET parameters and vessel dimensions were stronger and parallel in males (Fig 3). Notably, the interactions between vessel dimensions and sex did not affect the associations between these variables and CPET results. Taken together, these results suggest that sex differences exist in the baseline values (intercepts) of the relationships between CPET and vessel dimensions but not in the overall trends (slopes) of these associations.

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Fig 3. An example of graphic presentation of associations between main pulmonary artery diameter and peak exercise capacity parameters (load, VO2, O2pulse and VCO2).

Red dots and shades indicate females, blue dots and shades represents males. Abbreviations: O2pulse—the ratio of VO2 to HR; VE–minute ventilation; VO2 –the volume of consumed O2.

https://doi.org/10.1371/journal.pone.0313165.g003

Discussion

Larger major vessel dimensions, particularly of the aorta and PA, were associated with greater peak exercise capacity in amateur cyclists, regardless of their sex. The strongest correlations were observed between aortic and PA dimensions and peak O2 pulse, VO2, VCO2, VE, and EE. However, these correlations were moderate at best. IVC dimensions showed weak or nonsignificant correlations with peak CPET parameters. When these correlations were analyzed separately for males and females, weaker or nonsignificant associations were found. Linear regression models with interactions showed that male cyclists had larger dimensions of the aorta and PA, and their peak exercise capacity was generally greater than that of females—this was reflected by the intercepts of the regression lines. However, the slopes of the regression lines indicating the strength of the association between CPET parameters and vessel diameter did not differ significantly between the sexes—this was demonstrated by nonsignificant effects of the interactions between vessel dimensions and sex.

Changes in the vascular system due to exercise

The vascular system transports nutrients and O2 to working muscle cells and removes various substances like CO2, lactates, excessive H+, and heat from them [2426]. Repeated endurance training involves hours of exercise during which blood flow (including cardiac output and venous return) increases through all arteries and veins to meet the increased metabolic demands of the muscles. Over time, endurance training increases total blood volume by 20–25% in trained individuals and up to 50% in elite athletes. This increase is primarily due to direct increases in red blood cell mass and plasma volume [5].

During exercise, the aorta and arteries must efficiently deliver this increased blood volume to the working muscles. Meanwhile, deoxygenated blood returns from the muscles through the veins, including the IVC, to the right side of the heart, which pumps it through the PA to the lungs for essential gas exchange (O2 uptake and CO2 removal) and heat dissipation.

Repeated endurance exercise leads to vascular adaptations, which are particularly evident in the microvasculature of trained muscle groups [27]. Muscle capillarization may serve as a limiting factor for exercise performance [28]. Training elevates the number of capillaries per muscle fiber by 10–20% within several weeks in untrained individuals, with a slower rate of increase in well-trained athletes [28]. Not only capillary density, but also capillary positioning may be influential [28]. However, research linking muscle capillarization and exercise performance is lacking [28].

Endurance training also triggers arterial remodeling. Increased circulating blood volume and altered shear stress and transmural pressure lead to a decrease in arterial wall thickness and an increase in lumen diameter [1, 29]. These widened arteries result in reduced vascular resistance, effectively priming the muscles for an increase in blood supply during exercise [1]. The dimensions of the aorta [13, 3035], PA [36, 37], and IVC [38, 39] are reported to be larger in training athletes than in sedentary controls. Similarly to other studies, we demonstrated that healthy amateur cyclists with greater exercise capacity had larger aortic diameters [13, 3035]. However, less is known about the PA and IVC and about possible sex differences.

Arteries of athletes

Repeated exercise improves vascular plasticity and increases the body’s ability to respond to physical activity [29]. Endurance training activates endothelial nitric oxide synthase, leading to the production of nitric oxide, which dilates both arteries and veins [9]. As a result, the large arteries that supply and drain frequently used muscles are enlarged [29, 40]. For example, wheelchair-using athletes have larger aortas, subclavian arteries, and carotid arteries but a smaller IVC and abdominal aortas than controls. In rowers, the brachial artery is disproportionately enlarged [29, 40]. In our study, cyclists with greater exercise capacity had not only a wider thoracic aorta but also a wider abdominal aorta, which supplies blood to the leg muscles used during cycling. This finding was consistent in both male and female cyclists with superior peak CPET results.

Aortic dimensions of athletes

Athletes have larger diameters of the aortic root than controls [13, 3035]. However, most of them do not exceed the 99th percentile for males and females (40 and 38 mm, respectively) [30, 31, 33, 35]. Athletes have an aortic diameter that is 3.2 mm larger at the level of the sinuses of Valsalva and an aortic valve annulus that is 1.6 mm larger compared to nonathletic controls [31]. No progression of aortic root enlargement in athletes is observed if the values are less than the 99th percentile [30]. However, if the values are greater and aortic root dilatation is present, it is most probably pathologic and likely to progress [31]. Differences due to athletic discipline and aortic root size have been reported [32, 41]. Athletes who train in sports with a higher dynamic component have a larger aortic root [32]. The diameter of the aortic root is larger in males than in females [3133]. Similarly, we found that all aortic diameter measurements (annulus, sinus Valsalva, STJ, arch, and abdominal) were greater in males than in females.

Arterial dimensions and exercise capacity

According to Radegran et al., common femoral artery diameter was correlated with peak VO2 during exercise on an ergometer (r = 0.91) [42]. Also, Rasica et al. report a strong correlation between resting superficial femoral artery diameter and peak VO2, which may represent a key adaptation for active muscles perfusion [27]. Vanhees et al. reported that a 16-week training program (which included 48 h of cycling, jogging, and calisthenics) increased VO2; however, it decreased resting brachial artery diameter and mean blood flow velocity in the brachial artery and had no effect on aortic diameter or cardiac output [43]. These results can be explained by the fact that the total training time was short, which could account for the lack of changes in aortic diameter. The decreased brachial artery diameter can be explained by the training program, which heavily favored lower-body workouts (83% of the training time). Another study found that after a 3-month exercise program (indoor cycling 2 or 3 times per week) healthy females had increased diameters of the infrarenal aorta, thoracic aorta, and brachial artery. No differences were reported in aortic root or carotid artery diameters [44]. A positive correlation was found between the absolute change in peak workload and the absolute change in the diameter of the ascending aorta (r = 0.42) [44]. Factors associated with aortic size at the sinuses of Valsalva included sex, height, sport type (rowing), and elite competitor status (rowing participation in world championships or Olympics or marathon time under 2 h and 45 min) [34]. We report that increased aortic dimensions in amateur cyclists were associated with better exercise performance during CPET in both males and females.

Adaptation of the great vessels to exercise and heat redistribution

Heat is a byproduct of metabolism, energy production and energy use in muscles, at rest and during exercise. Heat must be redistributed to other organs, mainly the skin and lungs, to dissipate it from the body to prevent hyperthermia. Increased blood flow through working muscles prevents heat accumulation [45]. Similar physiological responses to exercise are typical of fever. A rise in body temperature during fever is accompanied by skin vessel dilation and increased HR, cardiac output, and ventilation [46]. Repeated exercise does not change the amount of heat produced per exercise bout, but during each bout of exercise the heat accumulation is lower [45]. This is due to increased blood flow through working muscles and an increased release of heat into the blood [45]. The physiology of exercise during heat stress has been studied, but little is known about the mechanisms of vascular adaptation under these conditions or whether greater heat production contributes to long-term vascular remodeling in endurance athletes [4, 5, 47].

In our study, amateur cyclists with larger diameters of the aorta, PA, and IVC had a greater peak exercise capacity and a higher EE. One report suggests that humans have a larger aortic diameter (a surrogate measure for cardiac output), reflecting higher EE, than apes [48]. In a group of patients with abdominal aortic aneurysm, resting EE was higher than in controls [49]. Otherwise, the link between aortic dimensions and EE has not been studied.

Better exercise performance improves heat loss capacity (activation of cutaneous vasodilation and increased blood flow at a lower core temperature, reduction in the internal temperature threshold for the onset of sweating, and increased sweat rate) [4, 5, 50]. One proposed mechanism is that exercise leads to hypervolemia, an increase in total body water volume. This means that a greater volume of interstitial fluid is available for cardiac output and is distributed to working muscles and other organs, including the skin and sweat glands. Increased exercise intensity also increases the total loss of Na+ and Cl ions via sweat [50, 51]. Increased skin perfusion and a greater amount of water available for evaporation through the skin facilitates more efficient heat loss [4, 5, 52]. This training-induced, prolonged hypervolemia may be responsible for the adaptation of great vessels, ultimately leading to improved exercise performance.

The inferior vena cava during exercise

The maximal expiratory IVC diameter is usually between 15 and 25 mm and is larger in males than in females [38, 53]. However, in patients under 60 years old, sex differences are nonsignificant [38]. Our findings are similar: no differences between males and females in IVC diameter during expiration (20.6 vs. 21.0 mm, respectively) or inspiration (10.2 vs. 10.5 mm, respectively) were found.

Larger expiratory IVC diameters have been reported in trained athletes [38, 39]. Furthermore, IVC diameter correlates with exercise capacity parameters such as VO2 [54]. We found correlations between expiratory IVC and peak exercise capacity parameters (HR, VO2, O2 pulse, and load). This suggests that IVC size can be influenced by endurance training. It is possible that a larger IVC diameter means the individual has a larger reservoir of circulating blood and therefore is better prepared for sustaining longer bouts of exercise. This observation is supported by the clinical measurement of IVC diameter to assess patient volemic status. For example, the IVC diameter is related to percent weight loss after football practice [55]. Patients with hypervolemia have a larger IVC; similarly, athletes with better exercise performance, and therefore a larger volemic reservoir, have a larger IVC.

Pulmonary arteries during exercise

Athletes have larger PA dimensions than non-athletes, as well as a greater pulmonary vascular reserve, which is essential for accommodating the significantly increased blood flow that occurs during exercise [36, 37]. Athletes with higher pulmonary blood flow tend to have higher peak VO2 [36]. Chung et al. reported correlations between dimensions of the PA and aorta (as measured using computed tomography) and exercise capacity (as measured by a 6-min walk test) [56]. We used a more accessible method to measure the dimensions of the PA, namely, transthoracic ECHO. We also used CPET to measure exercise capacity in more detail than provided by the 6-min walk test.

Our results showed that larger dimensions of the main PA, LPA, and RPA were positively correlated with exercise capacity. These associations were observed in both males and females. To date, no studies have specifically analyzed the relationship between PA diameter and exercise capacity using CPET.

Study limitations

This study was cross-sectional and lacked a control group of sedentary people. During recruitment, we enrolled more males than females (149 vs. 60), mainly due to the consecutive enrollment process. For a various reasons, a higher proportion of adult males are regular cyclists, and our male-female ratio reflects amateur cyclists’ demographics. However, not all echocardiographic measurements were possible for each participant. Thus, complete datasets with the results of CPET and the dimensions of the great vessels were analyzed for 190 subjects (134 males, 56 females). Furthermore, the inclusion criterion for our study was amateur cycling for at least 1 hour per week to include individuals with a large variety of exercise training levels. This allowed us to observe CPET results and associations with echocardiographic parameters in a wide range of exercise levels. However, this resulted in recruiting volunteers with varying exercise levels, who undertook various sports activities. Future studies should include a more homogenous group of highly trained individuals to assess better the impact of exercise training on the dimensions of great vessels. Our results showed more significant associations between the dimensions of great vessels and CPET parameters in males than in females. However, this observation may have been influenced by the unbalanced distribution of the data. If we had included more women, we assume that similar trends would have been found in their exercise capacity. Additionally, it should be noted that although our study’s protocol selection and customization adhered to established guidelines [18, 20], different test protocols can influence peak power achieved during the test. Many studies show minor differences between protocols terminated due to exhaustion, regardless of the test duration or power increments between stages [5759] Some studies report no differences between test protocols [60]. Finally, it is important to recognize that our study group consisted of volunteers of European descent. Therefore, our results cannot be extrapolated to the general population.

Conclusion

Males had larger dimensions of the thoracic and proximal abdominal aorta and of the PA and its branches. However, there were no sex differences in the dimensions of the IVC. We observed associations between the dimensions of great vessels and higher exercise capacity parameters (particularly VO2, O2 pulse, load, and peak EE). These associations were present in both sexes and had comparable directions. The differences in these associations were due to the differing intercepts, which resulted from the observation that males generally have larger vessel dimensions, body size and greater exercise capacity than females. This finding indicates that the direction of changes in the vascular system in exercising males and females is similar and there are no sex-specific changes in this regard. Future studies should determine these findings’ clinical and practical applicability, for example, in health-related screening purposes or tailoring training protocols.

Supporting information

References

  1. 1. Hellsten Y, Nyberg M. Cardiovascular Adaptations to Exercise Training. 1st ed. In: Terjung R, editor. Comprehensive Physiology. 1st ed. Wiley; 2015. pp. 1–32.
  2. 2. Qiu Y, Fernández-García B, Lehmann HI, Li G, Kroemer G, López-Otín C, et al. Exercise sustains the hallmarks of health. J Sport Health Sci. 2023;12: 8–35. pmid:36374766
  3. 3. Hargreaves M, Spriet LL. Skeletal muscle energy metabolism during exercise. Nat Metab. 2020;2: 817–828. pmid:32747792
  4. 4. Périard JD, Eijsvogels TMH, Daanen HAM. Exercise under heat stress: thermoregulation, hydration, performance implications, and mitigation strategies. Physiological Reviews. 2021;101: 1873–1979. pmid:33829868
  5. 5. Périard JD, Travers GJS, Racinais S, Sawka MN. Cardiovascular adaptations supporting human exercise-heat acclimation. Autonomic Neuroscience. 2016;196: 52–62. pmid:26905458
  6. 6. Haykowsky MJ, Samuel TJ, Nelson MD, La Gerche A. Athlete’s Heart: Is the Morganroth Hypothesis Obsolete? Heart, Lung and Circulation. 2018;27: 1037–1041. pmid:29773412
  7. 7. Peters CM, Dempsey JA, Hopkins SR, Sheel AW. Is the Lung Built for Exercise? Advances and Unresolved Questions. Medicine & Science in Sports & Exercise. 2023;55: 2143. pmid:37443459
  8. 8. Smith JAB, Murach KA, Dyar KA, Zierath JR. Exercise metabolism and adaptation in skeletal muscle. Nat Rev Mol Cell Biol. 2023;24: 607–632. pmid:37225892
  9. 9. Green DJ, Hopman MTE, Padilla J, Laughlin MH, Thijssen DHJ. Vascular Adaptation to Exercise in Humans: Role of Hemodynamic Stimuli. Physiol Rev. 2017;97: 495–528. pmid:28151424
  10. 10. La Gerche A, Wasfy MM, Brosnan MJ, Claessen G, Fatkin D, Heidbuchel H, et al. The Athlete’s Heart—Challenges and Controversies: JACC Focus Seminar 4/4. Journal of the American College of Cardiology. 2022;80: 1346–1362. pmid:36075838
  11. 11. Joyner MJ, Casey DP. Regulation of Increased Blood Flow (Hyperemia) to Muscles During Exercise: A Hierarchy of Competing Physiological Needs. Physiological Reviews. 2015;95: 549–601. pmid:25834232
  12. 12. Colombo CSSS, Finocchiaro G. The Female Athlete’s Heart: Facts and Fallacies. Curr Treat Options Cardio Med. 2018;20: 101. pmid:30390143
  13. 13. Flanagan H, Cooper R, George KP, Augustine DX, Malhotra A, Paton MF, et al. The athlete’s heart: insights from echocardiography. Echo Res Pract. 2023;10: 15. pmid:37848973
  14. 14. Sawicka-Gutaj N, Gruszczyński D, Guzik P, Mostowska A, Walkowiak J. Publication ethics of human studies in the light of the Declaration of Helsinki–a mini-review. Journal of Medical Science. 2022;91: e700–e700.
  15. 15. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—A metadata-driven methodology and workflow process for providing translational research informatics support. Journal of Biomedical Informatics. 2009;42: 377–381. pmid:18929686
  16. 16. Pytka MJ, Domin RA, Żołyński MS, Niziński J, Krauze T, Wykrętowicz A, et al. Sex differences in the associations between right heart structure and peak exercise capacity parameters in amateur cyclists. Front Physiol. 2024;15: 1427101. pmid:39135708
  17. 17. Hagströmer M, Oja P, Sjöström M. The International Physical Activity Questionnaire (IPAQ): a study of concurrent and construct validity. Public Health Nutr. 2006;9: 755–762. pmid:16925881
  18. 18. Pritchard A, Burns P, Correia J, Jamieson P, Moxon P, Purvis J, et al. ARTP statement on cardiopulmonary exercise testing 2021. BMJ Open Resp Res. 2021;8: e001121. pmid:34782330
  19. 19. Cooper BG, Hull JH, Lloyd JK. ARTP statement on pulmonary function testing. BMJ Open Resp Res. 2020;7: e000664. pmid:32631928
  20. 20. Sietsema KE, Sue DY, Stringer WW, Ward SA. Wasserman & Whipp’s principles of exercise testing and interpretation. 2021.
  21. 21. Weir JB de V. New methods for calculating metabolic rate with special reference to protein metabolism. The Journal of Physiology. 1949;109: 1–9. pmid:15394301
  22. 22. Mitchell C, Rahko PS, Blauwet LA, Canaday B, Finstuen JA, Foster MC, et al. Guidelines for Performing a Comprehensive Transthoracic Echocardiographic Examination in Adults: Recommendations from the American Society of Echocardiography. Journal of the American Society of Echocardiography. 2019;32: 1–64. pmid:30282592
  23. 23. Guzik P, Więckowska B. Data distribution analysis–a preliminary approach to quantitative data in biomedical research. Journal of Medical Science. 2023;92: e869–e869.
  24. 24. Fulghum K, Hill BG. Metabolic Mechanisms of Exercise-Induced Cardiac Remodeling. Front Cardiovasc Med. 2018;5: 127. pmid:30255026
  25. 25. Watkins BA, Smith BJ, Volpe SL, Shen C-L. Exerkines, Nutrition, and Systemic Metabolism. Nutrients. 2024;16: 410. pmid:38337694
  26. 26. Trangmar SJ, González-Alonso J. Heat, Hydration and the Human Brain, Heart and Skeletal Muscles. Sports Med. 2019;49: 69–85. pmid:30671905
  27. 27. Rasica L, Inglis EC, Iannetta D, Soares RN, Murias JM. Fitness Level‐ and Sex-Related Differences in Macrovascular and Microvascular Responses during Reactive Hyperemia. Medicine & Science in Sports & Exercise. 2022;54: 497. pmid:34652334
  28. 28. Hellsten Y, Gliemann L. Peripheral limitations for performance: Muscle capillarization. Scandinavian Journal of Medicine & Science in Sports. 2024;34: e14442. pmid:37770233
  29. 29. Green DJ, Spence A, Rowley N, Thijssen DHJ, Naylor LH. Vascular adaptation in athletes: is there an ‘athlete’s artery’? Experimental Physiology. 2012;97: 295–304. pmid:22179421
  30. 30. Gati S, Malhotra A, Sedgwick C, Papamichael N, Dhutia H, Sharma R, et al. Prevalence and progression of aortic root dilatation in highly trained young athletes. Heart. 2019; heartjnl-2018-314288. pmid:30910821
  31. 31. Iskandar A, Thompson PD. A Meta-Analysis of Aortic Root Size in Elite Athletes. Circulation. 2013;127: 791–798. pmid:23322885
  32. 32. Abulí M, Grazioli G, Sanz De La Garza M, Montserrat S, Vidal B, Doltra A, et al. Aortic root remodelling in competitive athletes. Eur J Prev Cardiolog. 2020;27: 1518–1526. pmid:31852302
  33. 33. Chatrath N, Bhatia R, Fyyaz S, Forster J, Marwaha S, Scrocco C, et al. The aortic root in young adults. European Heart Journal. 2023;44: ehad655.2021.
  34. 34. Churchill TW, Groezinger E, Kim JH, Loomer G, Guseh JS, Wasfy MM, et al. Association of Ascending Aortic Dilatation and Long-term Endurance Exercise Among Older Masters-Level Athletes. JAMA Cardiol. 2020;5: 522. pmid:32101252
  35. 35. Stephen Hedley J, Phelan D. Athletes and the Aorta: Normal Adaptations and the Diagnosis and Management of Pathology. Curr Treat Options Cardio Med. 2017;19: 88. pmid:28990148
  36. 36. La Gerche A, MacIsaac AI, Burns AT, Mooney DJ, Inder WJ, Voigt J-U, et al. Pulmonary transit of agitated contrast is associated with enhanced pulmonary vascular reserve and right ventricular function during exercise. Journal of Applied Physiology. 2010;109: 1307–1317. pmid:20724567
  37. 37. Domenech-Ximenos B, Garza MSL, Prat-González S, Sepúlveda-Martínez Á, Crispi F, Perea RJ, et al. Exercise-induced cardio-pulmonary remodelling in endurance athletes: Not only the heart adapts. Eur J Prev Cardiolog. 2020;27: 651–659. pmid:31423814
  38. 38. Franco ACC, Carneiro L dos S, Franco RSM, Góes AM de O. Influence of sex and age on inferior vena cava diameter and implications for the implantation of vena cava filters. J Vasc Bras. 21: e20210147. pmid:36407662
  39. 39. Goldhammer E, Mesnick N, Abinader EG, Sagiv M. Dilated Inferior Vena Cava: A Common Echocardiographic Finding in Highly Trained Elite Athletes. Journal of the American Society of Echocardiography. 1999;12: 988–993. pmid:10552361
  40. 40. Zeppilli P, Vannicelli R, Santini C, Russo A, Picani C, Pulmieri V, et al. Echocardiographic Size of Conductance Vessels in Athletes and Sedentary People. Int J Sports Med. 1995;16: 38–44. pmid:7713629
  41. 41. Pelliccia A, Di Paolo FM, Quattrini FM. Aortic Root Dilatation in Athletic Population. Progress in Cardiovascular Diseases. 2012;54: 432–437. pmid:22386294
  42. 42. Rådegran G, Saltin B. Human femoral artery diameter in relation to knee extensor muscle mass, peak blood flow, and oxygen uptake. American Journal of Physiology-Heart and Circulatory Physiology. 2000;278: H162–H167. pmid:10644595
  43. 43. Vanhees L, Hespel P, Van Hoof R, Fagard R, Amery A. Effect of Physical Training on Systemic and Brachial Artery Haemodynamics in Normal Men. Int J Sports Med. 1992;13: 145–151. pmid:1555904
  44. 44. Bjarnegård N, Hedman K, Länne T. Vascular Adaptation to Indoor Cycling Exercise in Premenopausal Women. Int J Sports Med. 2019;40: 245–252. pmid:30836390
  45. 45. Krustrup P, González‐Alonso J, Quistorff B, Bangsbo J. Muscle heat production and anaerobic energy turnover during repeated intense dynamic exercise in humans. The Journal of Physiology. 2001;536: 947–956. pmid:11691886
  46. 46. Balli S, Shumway KR, Sharan S. Physiology, Fever. StatPearls. Treasure Island (FL): StatPearls Publishing; 2024. http://www.ncbi.nlm.nih.gov/books/NBK562334/
  47. 47. Maunder E, Plews DJ, Wallis GA, Brick MJ, Leigh WB, Chang W-L, et al. Temperate performance and metabolic adaptations following endurance training performed under environmental heat stress. Physiological Reports. 2021;9: e14849. pmid:33977674
  48. 48. Ríos L, Sleeper MM, Danforth MD, Murphy HW, Kutinsky I, Rosas A, et al. The aorta in humans and African great apes, and cardiac output and metabolic levels in human evolution. Sci Rep. 2023;13: 6841. pmid:37100851
  49. 49. Delaney C, Miller M, Allan R, Spark J. The impact of abdominal aortic aneurysm on muscle mass and energy expenditure: A novel preliminary investigation. Vascular. 2015;23: 602–606. pmid:25575973
  50. 50. Baker LB. Physiology of sweat gland function: The roles of sweating and sweat composition in human health. Temperature (Austin). 2019;6: 211–259. pmid:31608304
  51. 51. Baker LB, De Chavez PJD, Ungaro CT, Sopeña BC, Nuccio RP, Reimel AJ, et al. Exercise intensity effects on total sweat electrolyte losses and regional vs. whole-body sweat [Na+], [Cl−], and [K+]. Eur J Appl Physiol. 2019;119: 361–375. pmid:30523403
  52. 52. Convertino VA. Blood Volume Response to Physical Activity and Inactivity. The American Journal of the Medical Sciences. 2007;334: 72–79. pmid:17630597
  53. 53. Rudski LG, Lai WW, Afilalo J, Hua L, Handschumacher MD, Chandrasekaran K, et al. Guidelines for the Echocardiographic Assessment of the Right Heart in Adults: A Report from the American Society of Echocardiography: Endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. Journal of the American Society of Echocardiography. 2010;23: 685–713. pmid:20620859
  54. 54. Churchill TW. The Impact of Exercise and Athletic Training on Vascular Structure and Function. Curr Treat Options Cardio Med. 2020;22: 59.
  55. 55. Waterbrook AL, Shah A, Jannicky E, Stolz U, Cohen RP, Gross A, et al. Sonographic Inferior Vena Cava Measurements to Assess Hydration Status in College Football Players During Preseason Camp. J of Ultrasound Medicine. 2015;34: 239–245. pmid:25614397
  56. 56. Chung KS, Kim YS, Kim SK, Kim HY, Lee SM, Seo JB, et al. Functional and Prognostic Implications of the Main Pulmonary Artery Diameter to Aorta Diameter Ratio from Chest Computed Tomography in Korean COPD Patients. PLoS One. 2016;11: e0154584. pmid:27152915
  57. 57. Drake JP, Finke A, Ferguson RA. Modelling human endurance: power laws vs critical power. Eur J Appl Physiol. 2024;124: 507–526. pmid:37563307
  58. 58. Luttikholt H, Jones AM. Effect of protocol on peak power output in continuous incremental cycle exercise tests. Eur J Appl Physiol. 2022;122: 757–768. pmid:34993576
  59. 59. Michalik K, Korta K, Danek N, Smolarek M, Zatoń M. Influence of Intensity RAMP Incremental Test on Peak Power, Post-Exercise Blood Lactate, and Heart Rate Recovery in Males: Cross-Over Study. Int J Environ Res Public Health. 2019;16: 3934. pmid:31623132
  60. 60. Mcnaughton L, Roberts S, Bentley D. The Relationship Among Peak Power Output, Lactate Threshold, and Short-Distance Cycling Performance: Effects of Incremental Exercise Test Design. Journal of strength and conditioning research / National Strength & Conditioning Association. 2006;20: 157–61. pmid:16506862