The associations of depressive symptoms and perceived stress with arterial health in adolescents

This is a self-archived version of an original article. This version may differ from the original in pagination and typographic details. Author(s): Title: Year: Version: Copyright: Rights: Rights url: Please cite the original version: CC BY 4.0 https://creativecommons.org/licenses/by/4.0/ The associations of depressive symptoms and perceived stress with arterial health in adolescents © 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. Published version Toivonen, Emmi; Lee, Earric; Leppänen, Marja H.; Laitinen, Tomi; Kähönen, Mika; Lakka, Timo A.; Haapala, Eero A. Toivonen, E., Lee, E., Leppänen, M. H., Laitinen, T., Kähönen, M., Lakka, T. A., & Haapala, E. A. (2024). The associations of depressive symptoms and perceived stress with arterial health in adolescents. Physiological Reports, 12(6), Article e15986. https://doi.org/10.14814/phy2.15986 2024 Physiological Reports. 2024;12:e15986. | 1 of 10 https://doi.org/10.14814/phy2.15986 wileyonlinelibrary.com/journal/phy2 Received: 22 December 2023 | Revised: 6 March 2024 | Accepted: 14 March 2024 DOI: 10.14814/phy2.15986 ORIGINAL ARTICLE The associations of depressive symptoms and perceived stress with arterial health in adolescents EmmiToivonen1 | EarricLee1,2,3 | Marja H.Leppänen4 | TomiLaitinen5 | MikaKähönen6 | Timo A.Lakka4,5,7 | Eero A.Haapala1,4 1Faculty of Sports and Health Sciences, University of Jyväskylä, Jyväskylä, Finland 2Institut de Cardiologie de Montréal, Montréal, QC, Canada 3École de kinésiologie et des sciences de l’activité physique, Université de Montréal, Montréal, QC, Canada 4Institute of Biomedicine, University of Eastern Finland, Kuopio Campus, Kuopio, Finland 5Department of Clinical Physiology and Nuclear Imaging, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland 6Department of Clinical Physiology, Tampere University Hospital and Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland 7Foundation for Research in Health Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. Correspondence Eero A. Haapala, Sport & Exercise Medicine, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. Email: eero[email protected]i Funding information Opetusja Kulttuuriministeriö (Ministry of Education and Culture, Finland); Sosiaalija Terveysministeriö (Socialoch Hälsovårdsministeriet); Kela (Kansaneläkelaitos); Suomen Kulttuurirahasto (SKR); Lastentautien Tutkimussäätiö (Foundation for Pediatric Research); Diabetestutkimussäätiö (The Diabetes Research Foundation); Sydäntutkimussäätiö (Finnish Foundation for Cardiovascular Research); Juho Vainion Säätiö (Reppy Institute); Paavo Nurmen Säätiö (Paavo Nurmi Foundation) Abstract Cardiovascular and mental diseases are among the most important global health problems, but little is known on the associations between mental and arterial health in adolescents. Therefore, we investigated the associations of arterial health with depressive symptoms and perceived stress in adolescents. A total of 277 adolescents, 151 boys, 126 girls, aged 15–17 years participated in the study. Depressive symptoms were assessed using the Beck Depression Inventory and perceived stress by the Cohen Perceived Stress Scale. Arterial health was assessed by measures from carotid ultrasonography (carotid intimamedia thickness, Young's Elastic Modulus, carotid artery distensibility, stiffness index), impedance cardiography (pulse wave velocity, cardioankle vascular index), and pulse contour analysis (reflection index, stiffness index). The data were analyzed using linear regression models adjusted for age and sex. Depressive symptoms or perceived stress were not associated with indices of arterial health in the whole study group (β = −0.08 to 0.09, p > 0.05), in boys (β = −0.13 to 0.10, p > 0.05) or in girls (standardized regression coefficient β = −0.16 to 0.08, p > 0.05). We found no associations of depressive symptoms and perceived stress with arterial health in adolescents. These observations suggest that the association between mental and arterial health problems develop in later life. KEYWORDS adolescent, arterial stiffness, cardiovascular risk factors, depression, perceived stress 2 of 10 | TOIVONEN etal. 1 | INTRODUCTION Cardiovascular diseases (CVD) have a significant influence on morbidity and mortality. Global prevalence of CVD and cardiovascular mortality has also increased substantially during the past two decades (Roth etal.,2021). The pathophysiological origins of CVD, including arterial stiffening and atherosclerotic lesion formation characterized by fractures in elastin, collagen overproduction, and accumulation of lipids and fibrous tissue to the artery wall, could begin as early as adolescence (Agbaje,2023; Flore etal.,2015; Vlachopoulos etal.,2010). During this period, mental health problems affect about 13% of adolescents globally (Polanczyk etal.,2015), with depression being the main reason for mental illbeing (Whiteford etal.,2013). Adolescents are more vulnerable to stress, and stressors have a greater impact on brain function on adolescence compared to adulthood (Eiland & Romeo,2013; Pervanidou & Chrousos,2012). However, little is known about the associations of depression and stress with cardiovascular risk in adolescence, although it has been found in adulthood (Hare etal.,2014; Kivimaki & Steptoe,2018; Park et al., 2023). Identifying potential risk factors and preventing CVD early in life will lower its associated burden on individuals, public healthcare systems, and the economy (Laslett etal.,2012; Leal etal.,2006). Greater depressive symptoms have previously been associated with a higher pulse wave velocity (PWV) (Dietz & Matthews,2011) and a lower anklebrachial index (ABI) in adolescents (Tonhajzerova etal.,2022). However, conflicting reports exist. Some previous studies have reported weak and statistically insignificant associations of depressive symptoms with brachialanklePWV and cardioankle vascular index (CAVI) (Tonhajzerova etal.,2022), carotid intimamedia thickness (cIMT), carotid artery distensibility, carotid artery compliance, and carotid artery elastic modulus (Gross etal.,2018) in adolescents. Most of these previous studies have investigated the associations between depressive symptoms and arterial health, and only one study explored the role of perceived stress as a risk factor for impaired arterial health (Olive etal.,2020). The authors reported an insignificant association between perceived stress and PWV. With the exception of the work performed by Gross etal.(2018), the aforementioned studies assessed arterial health with only a small number of indices and did not consider pubertal status as a covariate. The pathophysiological mechanisms that may explain depressionand stressinduced changes in arterial stiffness and atherosclerosis leading to impaired arterial health include increased lowgrade inflammation, decreased heart rate variability (HRV), elevated sympathoadrenal and hypothalamic–pituitary–adrenal axis (HPAaxis) activity, and endothelial dysfunction (Nemeroff & GoldschmidtClermont,2012). Furthermore, increased cortisol concentration could also contribute to arterial stiffening which may lead to hypertension (Connell etal.,1987; Esler etal.,2008; Kelly etal.,1998; Pirpiris etal.,1993; Ushakov etal.,2016) and endothelial dysfunction (Black & Garbutt, 2002; GarcíaBueno etal.,2008; Toda & NakanishiToda,2011). Associations between mental and arterial health and the underlying pathophysiology may differ between boys and girls due to the different rate of maturation between sexes (Abreu & Kaiser, 2016; Brix et al., 2018), as pubertal development affects hormonal system and adipose tissue growth (Bergeron etal.,2015; Dunkel,2009). These associations have yet to be thoroughly investigated separately for both sexes. The associations between mental and arterial health in adolescents have yet to be fully elucidated. By improving our understanding in the domain, we may be able to detect early signs of possible cardiovascular risk in adolescence due to mental illbeing, which could have important implications for adulthood. Therefore, we explored the associations of depressive symptoms and perceived stress with several indices of arterial health including systolic blood pressure, cIMT, Young's Elastic Modulus, carotid artery distensibility, and stiffness index assessed by a carotid ultrasound, PWV and CAVI assessed using impedance cardiography, and stiffness index and reflection index assessed using pulse contour analyses to attain a more comprehensive perspective. 2 | METHODS The present crosssectional study is based on the 8year followup data from The Physical Activity and Nutrition in Children (PANIC) study. It is a controlled lifestyle intervention study in a population sample of children from the city of Kuopio, Finland (Eloranta etal.,2011). The Research Ethics Committee of the Hospital District of Northern Savo approved the study protocol in 2006 (Statement 69/2006) and in 2015 (Statement 422/2015). All adolescents and their parents gave written informed consent. The PANIC Study has been carried out in accordance with the principles of the Declaration of Helsinki as revised in 2008. The study was registered at Clini caltr ials. gov (NCT01803776). 736 children aged 6–8 years from primary schools of Kuopio were invited to participate in the baseline examination between 2007 and 2009. Inclusion criteria for participation were apparently healthy boy or girl, 6–9 years of age at baseline, living in the city of Kuopio, Finland. The exclusion criteria included any physical disability that could hamper participation in the intervention or no time 2051817x, 2024, 6, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15986 by University Of Jyväskylä Library, Wiley Online Library on [07/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 3 of 10 TOIVONEN etal. or motivation to attend the study. A total of 512 children, who represented 70% of those invited, participated in the baseline examinations. 8year followup examinations were performed between 2016 and 2017, and a total of 277 (N) adolescents (151 boys and 126 girls) aged 15–17 attended. We performed the main statistical analyses using the largest number of participants available for each analysis, and the number of participants in the main analyses varied from 206 to 265 (108–141 in boys, 98–125 in girls) due to missing data. In the complete case analyses, there was a total of 101 boys and 87 girls with complete data on all variables of interest. 2.1 | Assessment on arterial health Systolic (SBP) and diastolic blood pressure (DBP) were measured from the right arm using the Heine Gamma G7® aneroid sphygmomanometer (Heine Optotechnik) to the accuracy of 2 mm Hg. The measurement protocol included a 5 min seated resting period followed by three measurements with 2 min intervals in between. The average of all three values was used for both SBP and DBP. For the assessment of cIMT and elasticity of the left common carotid artery, carotid ultrasound imaging was performed utilizing the Acuson Sequoia 512 Ultrasound Mainframe® (Acuson, Mountain View, CA, USA) with a 14.0 MHz linear array transducer using a standardized protocol (Raitakari et al., 2003). The sonographers analyzed the ultrasound scans offline from the digitally stored images. Three measurements of the far wall at enddiastole were taken to derive maximal cIMT. To assess carotid artery elasticity, the diameter of the common carotid artery at enddiastole and endsystole was measured at least twice. In addition, the sonographer measured systolic (SBP) and DBP from the brachial artery just before and directly after the ultrasound scans. The means of the enddiastolic and endsystolic diameters as well as SBP and DBP values were used to calculate arterial elasticity indices. Carotid artery distensibility (CAD) was calculated as: Young's Elastic Modulus as: and Stiffness Index (SI) as: These measurements and analyses were performed at Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital by trained sonographers (Raitakari etal.,2003). Pulse wave velocity (PWV) was measured by impedance cardiography using the Circmon® 419 B202 impedance cardiography device (JR Medical Ltd, Saku Vald, 420 Estonia), using previously documented methods (Koivistoinen etal.,2007). Cardioankle vascular index (CAVI) was measured by recording the distance from the level of the aortic valve brachial level to the ankle and the time delay between the closing of the aortic valve to the detected change in arterial pressure wave at the set point. Details have been published elsewhere (Yambe etal.,2004). Arterial stiffness index (SIpca) and reflection index (RIpca) were assessed by pulse contour analysis using noninvasive finger photoplethysmography with the PulseTrace PCA2 device (MicroMedical, Gillingham, Kent, United Kingdom) as has been described previously (Veijalainen etal.,2011, 2013). SI was assessed in a supine position prior to the exercise test in a test laboratory at stable room temperature (20–22°C) after a 15min rest. SI was calculated by dividing body height by time between the first (systolic) peak and the second (diastolic) peak of the pulse contour and was expressed in meters per second. All the pulse contour data were visually evaluated, and the data were excluded from the analysis if an extra peak could be seen between the systolic and diastolic peak, or if the device had measured the indexes incorrectly or if the same child had considerable differences in the pulse contour values (Veijalainen etal.,2011). Reflection index was calculated as the percentage of the height of the second peak from the height of the first peak (Veijalainen etal.,2011). 2.2 | Assessment of depressive symptoms and perceived stress Depressive symptoms were assessed by the Beck's Depression Inventory that measures characteristic attitudes and symptoms of depression. It contains 21 selfreportable questions from scale 0 to 3, with a maximum possible point total of 63 (Beck et al., 1961). Beck's Depression Inventory is a suitable tool for assessing depressive symptoms in adolescents (Bennet etal.,1997; Stockings etal.,2015). Perceived stress was assessed by the Cohen Perceived Stress Scale (Cohen etal.,1983). The Finnish version (PSS10) contains 10 questions from scale 0 to 4, for a maximum of 40 points. The Cohen Perceived Stress Scale is effective in detecting perceived stress in adolescents (White,2014). In both of these scales, higher scores indicate greater difficulties in mental health. (systolic −diastolic diameter ) ÷diastolic diameter (SBP −DBP) ( [SBP −DBP]×diastolic diameter ) ([ systolic −diastolic diameter ] ÷IMT ) ln (SBP ÷DBP) [ (systolic −diastolic diameter)÷diastolic diameter ] 2051817x, 2024, 6, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15986 by University Of Jyväskylä Library, Wiley Online Library on [07/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 4 of 10 | TOIVONEN etal. 2.3 | Other assessments Body weight was measured using a calibrated InBody 720® bioelectrical impedance device (Biospace, Seoul, South Korea). Height was measured using a wallmounted stadiometer without shoes (Leppänen etal.,2019). BMI was calculated by dividing body weight (kg) by height (m) squared, and BMISDS was obtained using Finnish references (Saari et al., 2011). Visceral adipose tissue was measured using the Lunar® dualenergy xray absorptiometry device (GE Medical Systems, Madison, Wisconsin, USA) (Lakka etal.,2020). A research physician assessed pubertal status using the 5stage scale described by Tanner (Marshall & Tanner,1969, 1970). We used breast development in girls and testicular volume in boys to assess pubertal status. Parental education was categorized based on either ongoing or completed education of mothers and fathers (vocational school or less, polytechnic, or university degree) (Eloranta et al., 2011). Household income was categorized as ≤30,000, 30,001– 60,000 and >60,000 €/year (Eloranta etal.,2011). The highest level of education and household income reported by either parent were used in the analyses. 2.4 | Statistical analyses All data analyses were performed using the SPSS Statistics software, version 28.0 (IBM Corporation, Armonk, NY, USA). Differences in characteristics between boys and TABLE 1 Characteristics of participants. Boys (n = 109–151) Girls (n = 99–126)p for difference Age (years) 15.85 (0.46) (151) 15.75 (0.39) (126) 0.064 Weight (kg) 65.8 (15.1) (151) 57.9 (9.1) (125)<0.001 Height (cm) 176.6 (7.4) (151) 165.7 (5.8) (125)<0.001 BMISDS −0.14 (1.11) (151) 0.05 (0.89) (125) 0.115 Visceral adipose tissue (g) 209.3 (337.5) (138) 121.3 (149.4) (124)0.003 Pubertal status** 3 13.4 (17) 3.5 (4)<0.001 4 61.4 (78) 53.5 (61) 5 25.2 (32) 43.0 (49) Household income (€/y)** ≤30,000 10.9 (14) 7.9 (8) 0.102 30,001–60,000 18.8 (24) 29.8 (34) >60,000 70.3 (90) 63.2 (72) Parental education** Vocational school 13.8 (18) 14.5 (17)0.012 Polytechnic 32.3 (42) 49.6 (58) University 53.8 (70) 35.9 (42) Beck's Depression Inventory score* (0 to 63) 1.0 (1.0–2.5) (137) 2.0 (0.0–7.0) (121)<0.001 Cohen Perceived Stress Scale score (0 to 40) 11.0 (5.5) (141) 15.1 (5.7) (125)<0.001 Systolic blood pressure (mmHg) 115.7 (10.9) (151) 110.4 (9.1) (124)<0.001 Carotid intimamedia thickness (mm) 0.45 (0.06) (140) 0.43 (0.05) (125)0.002 Young's elastic modulus* 169.5 (138.6–206.8) (140) 145.6 (125.3–184.8) (125)<0.001 Carotid artery distensibility (%/10 mmHg) 2.68 (0.71) (140) 2.90 (0.70) (125)0.013 Carotid artery stiffness index 4.42 (1.16) (140) 4.14 (0.93) (100)0.029 Pulse wave velocity (m/s)* 5.65 (5.38–6.10) (117) 5.73 (5.46–6.10) (104) 0.381 Cardioankle vascular index * 6.05 (5.38–7.18) (109) 6.35 (5.60–7.10) (99) 0.240 Reflection index from pulse contour analysis (%) 58.1 (14.7) (132) 46.9 (12.9) (100)<0.001 Stiffness index from pulse contour analysis (m/s)* 5.7 (5.4–6.1) (132) 5.2 (4.9–5.4) (100)<0.001 Note: The data are means (standard deviations), *medians (interquartile ranges) or **percentages. The pvalues are from the ttest for continuous variables with normal distributions, the Mann Whitney Utest for continuous variables with skewed distributions and the chisquared test for categorical variables. Abbreviations: BMI, body mass index; BMISDS, body mass index standard deviation score; pvalues for statistically significant differences (p < 0.05) are in bold. 2051817x, 2024, 6, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15986 by University Of Jyväskylä Library, Wiley Online Library on [07/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 5 of 10 TOIVONEN etal. girls were investigated using the ttest for normally distributed continuous variables, the Mann–Whitney Utest for continuous variables with skewed distributions and the chisquared test for categorical variables. The associations of depressive symptoms and perceived stress with cardiovascular risk factors were investigated using the multivariate linear regression analysis. All the analyses were performed for the whole study group adjusted for age and sex, and also separately for boys and girls adjusted for age. The data were further adjusted for pubertal status, BMISDS, visceral adipose tissue, household income or parental education, which were entered into the models separately. We performed the analyses using the highest number of participants in each analysis. We also performed sensitivity analyses using complete sets of data for all variables of interest. pvalues lower than 0.05 were considered statistically significant. 3 | RESULTS 3.1 | Characteristics of participants Boys were taller and heavier and had more visceral adipose tissue than girls (Table1). Boys also had less advanced pubertal stage and had higher SBP, cIMT, YEM, SI, RIpca and SIpca and lower CAD than girls. 3.2 | Associations of depressive symptoms and perceived stress with indices of arterial health Depressive symptoms or perceived stress were not associated with measures of arterial health after adjustment for age and sex (Tables2 and 3). Further adjustments had no effect on the magnitude of these associations. The associations of depressive symptoms and perceived stress with indices of arterial health among participants with complete data on all variables of interest are presented in supplementary material and TablesS1 and S2. 4 | DISCUSSION We found no associations of depressive symptoms and perceived stress with measures of arterial health in adolescent boys and girls. These observations suggest that depressive symptoms and perceived stress are not cardiovascular risk factors in a general population of Finnish adolescents. TABLE 2 Associations of depressive symptoms with measures of arterial health. All (n = 206–257) Boys (n = 108–137) Girls (n = 98–121) β (95% CI) Beta pvalue β (95% CI) Beta pvalue β (95% CI) Beta pvalue Systolic blood pressure (mmHg) −0.04 (−0.09;- 0.02) −0.08 0.217 0.00 (−0.05;0.05) −0.01 0.931 −0.10 (−0.22;0.02) −0.16 0.095 Carotid intimamedia thickness (mm) −0.19 (−10.22;9.83) 0.00 0.970 2.85 (−5.71;11.41) 0.06 0.511 −5.50 (−26.71;15.71) −0.05 0.608 Young's elastic modulus 0.00 (−0.01;0.01) 0.00 0.944 0.00 (−0.01;0.01) −0.02 0.860 0.000 (−0.02;0.02) 0.00 0.985 Carotid artery distensibility (%/10 mmHg) −0.12 (−0.94;0.70) −0.02 0.771 0.12 (−0.64;0.88) 0.03 0.749 −0.39 (−1.91;1.14) −0.05 0.618 Carotid artery stiffness index 0.07 (−0.48;0.61) 0.02 0.813 −0.07 (−0.53;0.40) −0.03 0.770 0.34 (−0.81;1.50) 0.05 0.558 Pulse wave velocity (m/s) 0.15 (−0.91;1.20) 0.02 0.782 0.37 (−0.59;1.34) 0.07 0.446 −0.18 (−2.19;1.83) −0.02 0.859 Cardioankle vascular index −0.11 (−0.54;0.31) −0.04 0.596 0.12 (−0.54;0.30) −0.06 0.568 −0.08 (−0.82;0.65) −0.02 0.826 Reflection index from pulse contour analysis (%) 0.00 (−0.05;0.04) −0.02 0.821 0.02 (−0.02;0.06) 0.10 0.259 −0.06 (−0.16;0.04) −0.12 0.232 Stiffness index from pulse contour analysis (m/s) −0.52 (−1,66;0.62) −0.07 0.370 −0.76 (−1.18;0.24) −0.13 0.133 −0.09 (−2.64;2.46) −0.01 0.945 Note: Data are unstandardized regression coefficients and their 95% confidence intervals (β), standardized regression coefficients (Beta) and pvalues from linear regression models adjusted for age and sex in all participants and for age in sexstratified analyses. 2051817x, 2024, 6, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15986 by University Of Jyväskylä Library, Wiley Online Library on [07/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License 6 of 10 | TOIVONEN etal. Some previous studies have shown an inverse association between depressive symptoms and arterial health indices in adolescents (Belem da Silva et al., 2019; Dietz & Matthews, 2011; Tonhajzerova et al., 2022), which is contrary to the present findings. One explanation for this inconsistency may be that these earlier studies included participants with more severe depressive symptoms (Belem da Silva etal.,2019; Dietz & Matthews,2011; Tonhajzerova etal.,2022), whereas our study sample consisted of generally healthy adolescents. Moreover, Belem da Silva etal.(2019) used a longitudinal approach with a duration of 3 or 7 years using a relatively larger population (n = 4336 with complete mental health data). As such, there is a likelihood that a relatively longer sustenance of chronic depressive symptoms could negatively affect arterial health. We found no statistically significant association between depressive symptoms and several indices of arterial health. Our observations on the weak associations between depressive symptoms and arterial health are partially in line with the results by Tonhajzerova etal.(2022), who found no relationship between depressive symptoms to PWV and CAVI. However, higher depressive symptoms were shown to be associated with lower, albeit normal ABI, indicating poorer arterial health. While the reason for the stronger association between depressive symptoms and ABI compared to that of PWV and CAVI is unclear, the evidence suggests that ABI is a useful measure for detecting peripheral arterial problems. Low values of ABI could also be caused by reduced physical activity or autonomic dysregulation that are typical with severely depressed (Nemeroff & GoldschmidtClermont, 2012; Parsons etal.,2016) and, therefore, be more sensitive to depressive symptoms than PWV and CAVI. Moreover, the aforementioned study (Tonhajzerova etal.,2022) did not account for important covariates such as sex and height. ABI has been shown to be sensitive to variations in age, sex, height, and measurement order than PWV and/or CAVI (Aboyans etal.,2012). In line with the only other available study on the association of perceived stress and PWV in adolescents (Olive etal.,2020), we only found rather weak associations between perceived stress PWV, and other indices of arterial health. These findings in adolescents differ from those reported in adults, suggesting that increased perceived stress may lead to increased arterial stiffness (Logan etal.,2012, 2020; Mauss etal.,2021). Although the evidence remains somewhat inconclusive, adultbased studies seem to suggest that perceived stress may indeed have an effect on arterial stiffness (Bugajska etal.,2008; Wiernik etal.,2016). Nevertheless, there may be a few possible reasons for the insignificant results between mental and arterial health in our study. Impaired arterial health may require a longer, and more severe exposure to depressive symptoms and perceived stress in order for it to be reflected. The relatively healthy mental and physical (Randrianarisoa etal.,2015; The European Society TABLE 3 Associations of perceived stress with measures of arterial health. All (n = 206–265) Boys (n = 109–141) Girls (n = 99–125) β (95% CI) Beta pvalue β (95% CI) Beta pvalue β (95% CI) Beta pvalue Systolic blood pressure (mmHg) −0.04 (−0.11;0.02) −0.08 0.194 −0.04 (−0.13;0.04) −0.09 0.305 −0.05 (−0.16;0.07) −0.07 0.427 Carotid intimamedia thickness (mm) 4.06 (−7.85;15.98) 0.04 0.503 2.32 (−12.51;17.15) 0.03 0.757 7.14 (−12.14:27.43) 0.06 0.487 Young's elastic modulus 0.00 (−0.02;0.01) −0.01 0.868 −0.01 (−0.03;0.01) −0.06 0.510 0.01 (−0.02;0.03) 0.05 0.551 Carotid artery distensibility (%/10 mmHg) 0.09 (−0.87;1.06) 0.01 0.848 0.38 (−0.93;1.69) 0.05 0.567 −0.24 (−1.69;1.21) −0.03 0.748 Carotid artery stiffness index −0.04 (−0.68;0.61) −0.01 0.916 −0.15 (−0.95;0.66) −0.03 0.718 0.16 (−0.94;1.27) 0.03 0.768 Pulse wave velocity (m/s) 0.20 (−1.00;1.39) 0.02 0.738 0.78 (−0.80;2.37) 0.09 0.330 −0.49 (−2.14;1.35) −0.05 0.600 Cardioankle vascular index −0.14 (−0.61;0.33) −0.04 0.559 −0.05 (−0.73;0.63) −0.02 0.881 −0.21 (−0.89;0.47) −0.06 0.543 Reflection index from pulse contour analysis (%) 0.04 (−0.02;0.09) 0.09 0.195 0.03 (−0.03;0.10) 0.09 0.317 0.04 (−0.05;0.13) 0.08 0.410 Stiffness index from pulse contour analysis (m/s) −0.76 (−2.16;0.64) −0.08 0.285 −0.83 (−2.56;0.91) −0.08 0.348 −0.63 (−3.06;1.80) −0.05 0.607 Note: Data are unstandardized regression coefficients and their 95% confidence intervals (β), standardized regression coefficients (Beta) and pvalues from linear regression models adjusted for age and sex in all participants and for age in sexstratified analyses. 2051817x, 2024, 6, Downloaded from https://physoc.onlinelibrary.wiley.com/doi/10.14814/phy2.15986 by University Of Jyväskylä Library, Wiley Online Library on [07/04/2024]. See the Terms and Conditions (https://onlinelibrary.wiley.com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License | 7 of 10 TOIVONEN etal. of Hypertension (ESH) and of the European Society of Cardiology (ESC),2013; Salonen & Salonen,1993) characteristics of our participants may also have contributed additionally to that. As such, caution must be paid when comparing the present results to other similar populations with a greater prevalence of depression or perceived stress. Adolescence is a challenging period of life, as various physiological systems undergo perturbations and modifications. For instance, cIMT increases during maturation and with increasing age (Doyon etal.,2013; Jourdan etal.,2005; Randrianarisoa etal.,2015; Torkar etal.,2020). As such, increased cIMT might not solely reflect atherosclerotic or pathological changes, but maturationrelated changes as well. The strengths of the present study include a comprehensive, reproducible and valid assessment of arterial health. We used wellvalidated instruments for depression symptoms and perceived stress (Stockings et al., 2015; White, 2014), and accounted for several potential confounding factors. However, our study included a sample of relatively healthy adolescents with low levels of depressive symptoms and perceived stress, decreasing the generalisability of our results to adolescents with clinical mental disorders. Thus, low levels of depressive symptoms and perceived stress may reduce the magnitude of the associations between mental and arterial health in our study population. Moreover, a crosssectional design precludes causal interpretations. In conclusion, depressive symptoms and perceived stress were not associated with indices of arterial health in adolescents. Therefore, it remains uncertain whether depressive symptoms or perceived stress increase cardiovascular risk already in adolescence. More studies investigating whether depressive symptoms and perceived stress are related to cardiovascular stress responses in adolescents are needed. More crucially, the longitudinal relationship between arterial health, and depressive symptoms and perceived stress in a similar population group are warranted. This will provide further insight as to whether these associations would carry on into ones' early adulthood. AUTHOR CONTRIBUTIONS Conceptualization: Emmi Toivonen, Earric Lee, Eero A. Haapala; Methodology: Marja H. Leppänen, Mika Kähönen, Tomi Laitinen, Timo A. Lakka, Eero A. Haapala; Formal analysis and investigation: Emmi Toivonen; Writingoriginal draft preparation: Emmi Toivonen; Writingreview and editing: Earric Lee, Marja H. Leppänen, Tomi Laitinen, Mika Kähönen, Timo A. Lakka, Eero A. Haapala; Funding acquisition: Timo A. Lakka, Eero A. Haapala; Resources: Tomi Laitinen, Mika Kähönen, Timo A. Lakka; Supervision: Timo A. Lakka, Eero A. Haapala. All authors approved the final version of the manuscript. AKNOWLEDGEMENTS The PANIC study has been supported financially by grants from the Research Council of Finland, Ministry of Education and Culture of Finland, Ministry of Social Affairs and Health of Finland, Research Committee of the Kuopio University Hospital Catchment Area (State Research Funding), Finnish Innovation Fund Sitra, Social Insurance Institution of Finland, Finnish Cultural Foundation, Foundation for Pediatric Research, Diabetes Research Foundation in Finland, Finnish Foundation for Cardiovascular Research, Juho Vainio Foundation, Paavo Nurmi Foundation, Yrjö Jahnsson Foundation, and the city of Kuopio. CONFLICT OF INTEREST STATEMENT The authors declare they have no competing interests. DATA AVAILABILITY STATEMENT The data are not publicly available due to research ethical reasons and because the owner of the data is the University of Eastern Finland and not the research group. However, the corresponding author can provide further information on the PANIC study and the PANIC data on a reasonable request. ETHICS STATEMENT The Research Ethics Committee of the Hospital District of Northern Savo approved the study protocol in 2006 (Statement 69/2006) and in 2015 (Statement 422/2015). All adolescents and their parents gave written informed consent. The PANIC Study has been carried out in accordance with the principles of the Declaration of Helsinki as revised in 2008. ORCID Earric Lee https://orcid.org/0000-0003-3490-4262 Eero A. Haapala https://orcid. org/0000-0001-5096-851X REFERENCES Aboyans, V., Criqui, M. H., Abraham, P., Allison, M. A., Creager, M. A., Diehm, C., Fowkes, F. G. A., Hiatt, W. R., Jönsson, B., Lacroix, P., Marin, B., McDermott, M. 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