scieee Open visual document viewer

Associations of cardiorespiratory fitness, physical activity, and BMI with arterial health in middle‐aged men and women

Haapala, Eero,Lee, E., Laukkanen, J. A.

Full text

This is a sel -a chi ed e sion o an o iginal a icle. This e sion may di e om he o iginal in pagina ion and ypog aphic de ails. Au ho (s): Ti le: Yea : Ve sion: Copy igh : Righ s: Righ s u l: Please ci e he o iginal e sion: CC BY 4.0 h ps://c ea i ecommons.o g/licenses/by/4.0/ Associa ions o ca dio espi a o y i ness, physical ac i i y, and BMI wi h a e ial heal h in middle‐aged men and women © 2020 The Au ho s. Physiological Repo s published by Wiley Pe iodicals, Inc. on behal o The Physiological Socie y and he Ame ican Physiological Socie y Published e sion Haapala, Ee o; Lee, E., Laukkanen, J. A. Haapala, E., & Lee, E. (2020). Associa ions o ca dio espi a o y i ness, physical ac i i y, and BMI wi h a e ial heal h in middle‐aged men and women. Physiological Repo s, 8(10), A icle e14438. h ps://doi.o g/10.14814/phy2.14438 2020 Physiological Repo s. 2020;8:e14438. | 1 o 10 h ps://doi.o g/10.14814/phy2.14438 wileyonlinelib a y.com/jou nal/phy2 1 | INTRODUCTION A e ial s i ness is an independen isk ac o o ca - dio ascula diseases (Vlachopoulos, Aznaou idis, & S e anadis,2010); which a e s ill he leading cause o mo bid- i y and p ema u e mo ali y wo ldwide (Global s a us epo on noncommunicable diseases:, 2014,2015). S i ening o a - e ial wall dec eases compliance and dis ensibili y o a e ies in esponse o p essu e changes and inc eases pulse p essu e. This may lead o pa hophysiological le en icula hype o- phy, and an inc eased isk o hype ension, ischemic hea dis- ease, and hea ailu e (Zieman, Meleno sky, & Kass,2005). DOI: 10.14814/phy2.14438 ORIGINAL RESEARCH Associa ions o ca dio espi a o y i ness, physical ac i i y, and BMI wi h a e ial heal h in middle-aged men and women Ee o A.Haapala1,2 | Ea icLee1 | Ja i A.Laukkanen1,3,4 This is an open access a icle unde he e ms o he C ea i e Commons A ibu ion License, which pe mi s use, dis ibu ion and ep oduc ion in any medium, p o ided he o iginal wo k is p ope ly ci ed. © 2020 The Au ho s. Physiological Repo s published by Wiley Pe iodicals, Inc. on behal o The Physiological Socie y and he Ame ican Physiological Socie y. 1Facul y o Spo and Heal h Sciences, Uni e si y o Jy äskylä, Jy äskylä, Finland 2Physiology, Ins i u e o Biomedicine, School o Medicine, Uni e si y o Eas e n Finland, Kuopio, Finland 3Depa men o In e nal Medicine, Cen al Finland Heal hca e Dis ic , Jy äskylä, Finland 4Ins i u e o Public Heal h and Clinical Nu i ion, Uni e si y o Eas e n Finland, Kuopio, Finland Co espondence Ee o A. Haapala, Spo s & Exe cise Medicine, Facul y o Spo and Heal h Sciences, Uni e si y o Jy äskylä, PO Box 35, FI-40014 Uni e si y o Jy äskylä, Jy äskylä, Finland. Email: [email p o ec ed]. Abs ac We in es iga ed he associa ions o ca dio espi a o y i ness (CRF), physical ac i i y (PA) wi h ega d o ae obic and esis ance aining, and body mass index (BMI) wi h pulse wa e eloci y (PWV) and augmen a ion index (AIx) in middle-aged adul s wi h a leas one ca dio ascula isk ac o . A o al o 84 (46 men and 38 women) pa icipa ed in he s udy. Ca dio espi a o y i ness was measu ed using a maximal g aded exe cise es on a cycle e gome e and was de ined as maximal powe ou pu (Wmax) no malized o body weigh -0.35. Pa icipa ion in ae obic and esis ance ain- ing was assessed by a de ailed ques ionnai e and BMI was calcula ed as weigh (kg)/ [heigh (m2)]. Pulse wa e eloci y and AIx we e measu ed using an applana ion o- nome y be o e (p e), immedia ely a e (pos ), and a e 10min (pos 10) o maximal exe cise es . Ca dio espi a o y i ness, PA, o BMI was no associa ed wi h PWV o AIx. Pulse wa e eloci y dec eased signi ican ly om p e o pos 10 among hose in he highes hi d o CRF (mean di e ence=−0.793m/s, 95% CI=−1.494 o −0.091, p=.023) and in no mal weigh pa icipan s (p=.084 o ime*g oup in e ac ion mean di e ence=−0.781m/s, 95% CI=−1.496 o −0.066, p=.029), bu no among hose in he o he hi ds o CRF o o e weigh o obese pa icipan s. Pa icipan s who had egula esis ance aining had con inuously highe AIx om p e o pos 10 han hose who had no egula esis ance aining (mean di e ence=−1.98, 95% CI=−4.02 o 0.069, p=.058). In conclusion, exe cise may dec ease PWV and AIx. Ou esul s sugges ha posi i e a e ial esponses o exe cise could be sligh ly imp o ed in i and no mal weigh indi iduals. KEYWORDS A e ial s i ness, Exe cise, Fi ness, Obesi y 2 o 10 | HAAPALA e AL. A e ial s i ness de elops h ough complica ed cellula and molecula p ocesses leading o ayed and b oken elas in, and inc eases wha is o en uno ganized and dys unc ional colla- gen ibe con en in he a e y wall (Zieman e al.,2005). While a e ial s i ness inc eases na u ally wi h in- c easing age (McEnie y, Yasmin, Qasem, Wilkinson, & Cockc o , 2005), i has been sugges ed ha low ca dio- espi a o y i ness, lack o physical ac i i y, obesi y, and being o e weigh leads o ea ly ascula aging and p ema- u e inc eases in a e ial s i ness (Nilsson,2008). Highe ca dio espi a o y i ness has been in e sely associa ed wi h lowe a e ial s i ness in child en (Veijalainen e al., 2016), adolescen s and young adul s (Bo eham e al.,2004; Haapala, Laukkanen, Takken, Kujala, & Finni,2018), and middle-aged and olde adul s (Vai ke icius e  al., 1993). P e ious s udies in adul s ha e in es iga ed he associa ions o measu es o ca dio espi a o y i ness scaled by body weigh (BW); ye simple a io scaling by BW has been ound o be physiologically and s a is ically inapp op ia e me hod o emo e he e ec o body size on ca dio espi a o y i - ness (K achle e  al., 2015; Tanne , 1949; Welsman & A ms ong,2019). The e o e, use o a io s anda d scaling may ha e obscu ed ou unde s anding on he ole o ca dio- espi a o y i ness in he de elopmen o a e ial s i ening. Physical ac i i y and pa icula ly igo ous in ensi y physi- cal ac i i y has been in e sely associa ed wi h a e ial s i ness in c oss-sec ional (Endes e al., 2016) and longi udinal s udies ( Laa e al.,2011). Exe cise in e en ions ha e also p o ided some e idence ha egula ae obic exe cise (Asho , La a, Sie o, Celis-Mo ales, & Ma he s,2014; Li e al.,2015), bu no esis- ance exe cise (Miyachi,2013), may dec ease a e ial s i ness, bu he posi i e e ec o ae obic exe cise aining on a e ial s i ness has no been con i med in all s udies (Mon e o, Roche, & Ma inez-Rod iguez,2014). Fu he mo e, s udies on he ole o ca dio espi a o y i ness, body mass index (BMI), o blood p essu e in he e ec s o acu e maximal exe cise on a e ial s i - ness and a e ial dila a ion capaci y emain somewha limi ed. The ole o ca dio espi a o y i ness, exe cise aining, and weigh s a us in a e ial s i ness and a e ial one is s ill lim- i ed and inconsis en . The e o e, he aim o his s udy was o in es iga e he ole o ca dio espi a o y i ness no malized o BW using allome y and a io s anda d, endu ance and esis- ance exe cise, BMI, and blood p essu e wi h a e ial s i ness and a e ial one. We also s udied he associa ions o ca dio- espi a o y i ness, endu ance and esis ance exe cise, and BMI wi h blood p essu e. Finally, we in es iga ed he ole o ca dio espi a o y i ness, endu ance and esis ance exe cise, BMI, and blood p essu e on changes in a e ial s i ness and a e ial dila a ion one in esponse o a maximal g aded ex- e cise es . We hypo hesized ha ca dio espi a o y i ness, endu ance exe cise aining, and o e weigh and obesi y, and ele a ed blood p essu e a e associa ed wi h poo e a e ial heal h in adul s wi h a leas one ca dio ascula isk ac o . 2 | METHODS 2.1 | Pa icipan s A o al o 102 pa icipan s we e ec ui ed om he ci y o Jy äskylä, Cen al Finland egion, h ough he local ou -o -hospi al heal h ca e cen e . The s udy g oup con- sis ed o asymp oma ic pa icipan s (no ca dio ascula symp oms) wi h a leas one ca dio ascula isk ac o , such as a his o y o smoking, dyslipidemia, hype ension, obesi y, diabe es, o amily his o y o co ona y hea dis- ease. All pa icipan s wi h diagnosed ca dio ascula dis- eases we e excluded. P io o pa icipa ion in he s udy, all pa icipan s we e in o med abou he esea ch pu - poses and measu emen p ocedu es and we e sc eened by a ca diac specialis . A o al o 84 (46 men and 38 women) had he comple e da a used in hese analyses. The esea ch p o ocol and s udy design we e app o ed by he ins i u ional e iew boa d o he Cen al Finland Hospi al Dis ic e hical commi ee, Jy äskylä, Finland (Dn o 5U/2016). All s udy pa icipan s p o ided w i - en in o med consen p io o he inclusion in he s udy. The s udy was pe o med as s a ed by he Decla a ion o Helsinki. 2.2 | Assessmen o ca dio espi a o y i ness A maximal exe cise es was conduc ed on an elec omag- ne ically b aked cycle e gome e (Mona k Exe cise AB, Sweden) u ilizing a g aded exe cise es p o ocol wi h con- inuous ECG eco dings (Ca dioSo so wa e V.1.84, GE Heal hca e, F eibu g, Ge many) o assess he le el o ae obic exe cise capaci y (Laukkanen e  al., 2018). The symp om- limi ed exe cise es was s a ed wi h 3-min wa m-up wi hou wo kload o each pa icipan and con inued wi h 20W in- c emen s applied e e y 1min un il oli ional exhaus ion. All exe cise es s we e supe ised by an expe ienced physician wi h he assis ance o a ained nu se. We de ined ca dio espi a o y i ness as he maximal powe ou pu (Wmax) de ined as he wo kload a he end o he ex- e cise es scaled by BW-1 and allome ically scaled Wmax by BW-0.35, because Wmax/BW-1 had a s ong in e se associa ion wi h BW (β=−0.587, 95% con idence in e al (CI)=−0.782 o −0.392, p<.001) indica ing ha a io scaling by BW-1 was no able o emo e he e ec o body size on ca dio espi a o y i ness. The e o e, allome ic scaling o Wmax was pe o med by log-linea eg ession models (Agbaje e  al., 2019). The scaling exponen o BM was 0.35 (95% CI=0.14 o 0.56). The powe unc ion a io emo ed he associa ions o Wmax wi h BW (β=−0.061, 95% CI=−0.317 o 0.195, p=.636) sugges ing he alidi y in scaling ca dio espi a o y i ness o body size. | 3 o 10 HAAPALA e AL. 2.3 | Assessmen o physical ac i i y We assessed ae obic and esis ance exe cise by a ques ion- nai e (Lakka e al., 2010). The pa icipan s illed in a ques- ionnai e whe he hey pa icipa ed in ae obic o esis ance exe cise. This is a de ailed quan i a i e ques ionnai e based on common physical ac i i ies and enables he assessmen o key componen s o physical ac i i y. Pa icipan s we e asked o eco d he equency (numbe o sessions pe week), a e age du a ion (hou s and minu es pe session), and in ensi y o hei physical ac i i y. Because o missing da a on he equency, a e age du a ion, and he in ensi y o physical ac i i y, we di ided pa icipan s as hose who pa icipa ed in ae obic o esis ance aining and hose who did no . 2.4 | Assessmen o a e ial s i ness and blood p essu e Pulse wa e eloci y (PWV) and augmen a ion index (AIx) as measu es o a e ial s i ness we e measu ed be o e, im- media ely a e , and 10min a e he maximal g aded exe - cise es by a single ained esea che (EL) using a PulsePen de ice (DiaTecne s. .l., Milan, I aly; www.pulse pen.com) which includes one onome e and an in eg a ed ECG uni (Lee e al.,2018, 2019). The measu emen o a e ial s i ness and a e ial dila a ion capaci y ollowed closely es ablished guidelines (Tomlinson,2012; Van Bo el e al.,2012). Pulse wa e eloci y was measu ed by eco ding ca o id and pe iphe al ( emo al) wa e o ms in apid succession a a sample a e o 1kHz, and de ined as he ansi dis ance be- ween he measu ing si es di ided by he ime delay be ween he dis al pulse and p oximal pulse wa e, using he ECG ace as e e ence. T ansi dis ances we e assessed by body su - ace measu emen s using a ape measu e om he sup as e - nal no ch o each pulse eco ding si e (ca o id and emo al). Di ec ca o id o emo al measu emen was adjus ed o 80% (common ca o id a e y–common emo al a e y×0.8) o he calcula ion o PWV as ecommended by cu en guide- lines. T ansi ime was de ined as he di e ence be ween he delay o he dis al pulse wa e o he R wa e belonging o he ECG qRs complex and he delay o he p oximal pulse wa e o he R wa e belonging o he ECG qRs complex. The pulse wa e delay was de e mined by calcula ing he ime elapsed om he peak o he R wa e and he “ oo ” o he p essu e pulse wa e. Augmen a ion index is ano he measu e ha has been used o desc ibe cen al a e ial s i ness bu AIx also e lec s pe iphe al a e ial one. Changes in AIx in esponse o ex- e cise may e lec a e ial dila a ion and opening o pe iph- e al a e ial ee. AIx was ob ained om he ca o id p essu e wa e o m analysis. AIx is a pa ame e which p o ides an indica ion o he con ibu ion o e lec ed wa es o he o al pulse p essu e and was de ined as he di e ence be ween he second and i s sys olic peak on a e ial pulse wa e o m and was exp essed as a pe cen age o cen al pulse p essu e ((AIx)=augmen ed p essu e/pulse p essu e×100). Supine b achial sys olic blood p essu e and dias olic blood p essu e we e ob ained using an oscillome ic Mic oli e BP A200 blood p essu e moni o (Mic oli e Co p., Taipei, Taiwan) o be e sensi i i y and accu acy. Two sequen ial eadings we e eco ded, and he mean alues we e used. Pa icipan s es ed in he supine posi ion o 10min be o e PWV was measu ed a baseline. Howe e , due o he na u e o he s udy, a e ial s i ness was measu ed immedia ely and 10min a e he exe cise es exposu e wi hou ha ing laid supine o 10min. The p essu e alues eco ded by onome y we e cali- b a ed o he blood p essu e alues ob ained a he b achial a e y; whe e hey we e assigned o he app op ia e pix- els and he alues o mean a e ial p essu e and all o he p essu e- ela ed pa ame e s we e e-es ablished. The alues deduced by he so wa e apply he es ablished concep ha he mean a e ial p essu e emains unchanged in he ac om he ao a o he pe iphe al a e ies. Mean a e ial p es- su e was calcula ed by he so wa e as dias olic blood p es- su e+1/3(sys olic blood p essu e–dias olic blood p essu e). 2.5 | S a is ical me hods S a is ical analyses we e pe o med by SPSS s a is ical so - wa e, e sion 23.0 (IBM co p. A monk, NY, USA). Basic cha ac e is ics be ween sexes we e compa ed using S uden 's es o no mally dis ibu ed con inuous a iables, he Mann–Whi ney U es o skewed con inuous a iables, o chi-squa ed es o ca ego ical a iables. The associa ions o ca dio espi a o y i ness and BMI wi h PWV, AIx, sys olic and dias olic blood p essu e, and mean a e ial p essu e we e in es iga ed using linea eg ession analyses adjus ed o age and sex. Linea eg ession analyses we e also used o in es i- ga e he associa ions o sys olic and dias olic blood p essu e, and mean a e ial p essu e wi h PWV and AIx. Di e ences in PWV and AIx be ween hose who egula ly engaged in ae obic o esis ance aining and hose who did no we e s udied wi h ANOVA adjus ed o age and sex. The associa- ions o ca dio espi a o y i ness, BMI, ae obic exe cise, and esis ance exe cise wi h PWV we e u he adjus ed o mean a e ial p essu e and hose wi h AIx o hea a e (Wilkinson e al.,2000) and mean a e ial p essu e. We s udied changes in PWV and AIx in esponse o a maximal g aded exe cise es and he ole o ca dio espi- a o y i ness, BMI, exe cise, and blood p essu e in hese changes using epea ed measu es ANOVA. In hese analyses, we used only Wmax/BW-0.35 as a measu e o ca dio espi a o y 4 o 10 | HAAPALA e AL. i ness because i e icien ly emo ed he e ec o body size on ca dio espi a o y i ness. We in es iga ed he ole o ca - dio espi a o y i ness as hi ds, weigh s a us (no mal weigh , o e weigh , obesi y), ae obic and esis ance exe cise (yes/ no; N o esis ance exe cise=82), blood p essu e (no mo- ensi e (sys olic blood p essu e<120mmHg and dias olic blood p essu e<80mmHg), high (sys olic blood p essu e 120–129mmHg and dias olic blood p essu e<80mmHg), s age 1 (sys olic blood p essu e 130–139mmHg o dias olic blood p essu e 80–89mmHg), s age 2 (sys olic blood p es- su e≥140mmHg o dias olic blood p essu e≥90mmHg) (Whel on e al., 2018)), and PWV a he p eassessmen as hi ds by s udying ime*g oup in e ac ions om p e o pos 10 assessmen s using epea ed measu e ANOVA. Di e ences in PWV and AIx om p e o pos 10 assessmen s be ween adul s in he hi ds o ca dio espi a o y i ness, be ween no - mal weigh , o e weigh , and obese adul s, be ween adul s in he ae obic o esis ance exe cise g oups, be ween adul s in he blood p essu e g oups, and be ween hose in he PWV hi ds we e in es iga ed using epea ed measu es ANOVA wi h Sidak co ec ion o mul iple compa isons. These da a we e u he adjus ed o age and sex. p<.05 was conside ed s a is ically signi ican . 3 | RESULTS 3.1 | Basic cha ac e is ics Men we e alle and hea ie , had highe blood p essu e, lowe AIx, and highe ca dio espi a o y i ness exp essed as Wmax/BW-0.35 and Wmax/BW-1 han women (Table1). Men also pa icipa ed in esis ance aining less equen ly han women. 3.2 | Associa ions o ca dio espi a o y i ness, physical ac i i y, and BMI wi h a e ial s i ness, a e ial dila a ion capaci y, and blood p essu e Ca dio espi a o y i ness exp essed as Wmax/BW-0.35 o Wmax/BW-1 we e no associa ed wi h PWV o AIx a e ad- jus men o age and sex (Table2). Fu he adjus men o mean a e ial p essu e o hea a e had no e ec on hese associa ions. Ne e heless, ca dio espi a o y i ness ex- p essed as Wmax/BW-1 was posi i ely associa ed wi h PWV in women (β=0.253, p=.145) bu in e sely associa ed wi h PWV in men (β=−0.256, p=.056; p=.019 o in e ac ion). All (n=84) Men (n=46) Women (n=38) p Age 53.1 (9.9) 53.3 (11.1) 52.9 (8.3) .849 Heigh 172.7 (9.1) 179.0 (6.5) 165.1 (5.0) <.001 Weigh 81.4 (15.7) 88.0 (13.3) 73.4 (14.8) <.001 Body mass index 27.2 (4.4) 27.5 (3.9) 26.9 (4.9) .564 Weigh s a us .502 No mal weigh (%) 31.0 28.3 34.2 P e alence o o e weigh (%) 46.4 52.2 39.5 P e alence o obesi y (%) 22.6 19.6 26.3 Sys olic blood p essu e 137.3 (15.6) 140.7 (14.0) 133.2 (16.7) .027 Dias olic blood p essu e 84.8 (10.3) 87.0 (10.7) 82.0 (9.3) .026 Mean a e ial p essu e 102.3 (11.4) 104.9 (11.1) 99.1 (11.0) .018 Ao ic pulse wa e eloci y 9.7 (2.1) 9.9 (2.0) 9.3 (2.0) .172 Ao ic augmen a ion index 10.9 (14.2) 6.3 (13.7) 16.6 (12.8) .001 Maximal powe ou pu (W) 229.9 (53.0) 261.6 (45.4) 191.6 (32.1) <.001 Maximal powe ou pu (W/kg o BW−0.35) 49.3 (10.2) 54.7 (9.2) 42.8 (6.9) <.001 Maximal powe ou pu (W/kg o BW−1) 2.9 (0.6) 3.0 (0.6) 2.7 (0.5) .008 Maximal hea a e achie ed in he exe cise es 173.5 (13.9) 176.0 (15.7) 170.5 (10.7) .961 Endu ance exe cise (%) 70.4 65.9 75.7 .338 Resis ance aining (%) 42.7 31.8 55.3 .032 Da a a e om he S uden 's es o con inuous a iables and chi-squa ed es o ca ego ical a iables and a e displayed as means (SD) o pe cen ages (%). p alues e e o s a is ical signi icance o di e ences be ween men and women. BW=body weigh . TABLE 1 Basic cha ac e is ics | 5 o 10 HAAPALA e AL. Fu he adjus men o mean a e ial p essu e a enua ed he associa ion be ween Wmax/BW-1 and PWV in men (β-0.121, p = .230). In addi ion, ca dio espi a o y i ness exp essed as Wmax/BW-1 was in e sely associa ed wi h dias olic blood p essu e a e adjus men o age and sex. Howe e , ca di- o espi a o y i ness was no associa ed wi h dias olic blood p essu e when i app op ia ely exp essed as Wmax/BW-0.35. Sex modi ied he associa ions o esis ance aining and PWV (p = .036 o sex in e ac ion), bu he di e ences be- ween women (9.8 s. 8.8 m/s, mean di e ence = 1.0 m/s, 95% CI=−0.279 o 2.281, p=.121) o men (9.3 s. 10.1m/s, mean di e ence = −0.820 m/s, 95% CI = −2.002 o 0.361, p=.161) who esis ance ained and hose who did no we e no s a is ically signi ican . Fu he adjus men o mean a e ial p essu e augmen ed he di e ences in men (9.2 s. 10.1m/s, mean di e ence=−0.864 m/s, 95% CI = −1.650 o −0.078, p=.032), bu i had no e ec on he di e ences in women (da a no shown). Pa icipan s who esis ance ained had highe AIx han hose who did no (14.9% s. 8.0%, mean di e ence 6.8%, 95% CI = 1.1 o 12.6, p = .020). This di e ence emained s a is ically signi ican a e u he adjus men o hea a e. The e we e no o he s a is ically signi ican di e ences be ween ae obic o esis ance aining g oups. Body mass index was no associa ed wi h PWV o AIx in men and women combined. Howe e , BMI was posi i ely associa ed wi h PWV in men (β= 0.264, p = .048) and in- e sely wi h PWV in women (β=−0.247, p=.121, p=.012 o in e ac ion). Fu he adjus men o mean a e ial p essu e s eng hened he associa ion in women (β=−0.317, p=.034) bu a enua ed i in men (β=−0.037, p=.730). Sys olic blood p essu e, dias olic blood p essu e, and mean a e ial p essu e we e di ec ly associa ed wi h PWV and AIx (Table2). 3.3 | E ec s o ca dio espi a o y i ness, ae obic and esis ance aining, and weigh s a us on changes in a e ial s i ness in esponse o a maximal g aded exe cise es Pulse wa e eloci y dec eased om p e- o pos - es (mean di e ence = −0.420 m/s, 95% CI = −0.893 o 0.052, p=.096) bu was highe a pos 10 han p eassessmen (mean di e ence (p e s. pos 10)=0.258m/s, 95% CI=−0.494 o 0.258, p=.043 o main e ec ). Ca dio espi a o y i ness exp essed as Wmax/BW-0.35 did no modi y he changes in PWV in esponse o exe cise (p = .196 o Wmax/BW-0.35* ime in e ac ion, Figu e 1a). Howe e , pa icipan s in he lowes hi d o Wmax/BW-0.35 had con inuously highe PWV om p e o pos 10 han hose in he second hi d (mean di e ence 1.3m/s, 95% CI=0.1 o 2.5, p=.022, p=.027 o he main e ec ). This di e - ence was no longe s a is ically signi ican a e u he ad- jus men o age and sex (p=.462). Fu he adjus men o TABLE 2 Associa ions o ca dio espi a o y i ness, exe cise, and body mass index wi h a e ial s i ness and dila a ion capaci y and blood p essu e. N=84 Ao ic pulse wa e eloci y Augmen a ion index Sys olic blood p essu e Dias olic blood p essu e Mean a e ial p essu e β (95% CI) pβ (95% CI) pβ (95% CI) pβ (95% CI) pβ (95% CI) p Maximal powe ou pu / BW−0.35 −0.047 (−0.309 o 0.216) .725 0.033 (−0.227 o 0.293) .799 0.049 (−0.213 o 0.311) .710 −0.031 (−0.302 o 0.239) .818 0.003 (−0.262 o 0.267) .982 Maximal powe ou pu / BW−1 −0.051 (−267 o 0.267) .639 0.023 (−0.191 o 0.237) .831 −0.082 (−0.294 o 0.133) .450 −0.223 (−0.440 o −0.005) .045 −0.172 (−0.387 o 0.042) .113 Body mass index 0.002 (−0.200 o 0.204) .986 0.007 (−0.193 o 0.208) .942 0.123 (−0.077 o 0.324) .224 0.325 (0.129 o 0.520) .001 0.253 (0.057 o 0.448) .012 Sys olic blood p essu e 0.494 (0.301 o 0.688) <.001 0.357 (0.152 o 0.563) .001 Dias olic blood p essu e 0.496 (0.311 o 0.682) <.001 0.414 (0.222 o 0.607) <.001 Mean a e ial p essu e 0.538 (0.352 o 0.352) <.001 0.424 (0.226 o 0.621) <.001 No e: The da a a e s anda dized eg ession coe icien s and hei 95% con idence in e als adjus ed o age and sex. BW=body weigh . 6 o 10 | HAAPALA e AL. mean a e ial p essu e s eng hened hese di e ences (p o he main e ec =0.043), bu he pos hoc compa isons we e no s a is ically signi ican . Addi ional analyses showed ha PWV dec eased signi ican ly om p e o pos 10 only in he highes hi d o Wmax/BW-0.35 (mean di e ence=−0.793m/s, 95% CI=−1.494 o −0.091, p=.023) a e adjus men o age and sex. Weigh s a us modi ied he e ec s o a maximal g aded exe cise es on PWV (p=.084 o in e ac ion, Figu e1b). Pulse wa e eloci y dec eased om p e o pos 10 assessmen (mean di e ence=−0.781m/s, 95% CI=−1.496 o −0.066, p=.029) only in no mal weigh pa icipan s (p=.034 o he main e ec ). The e we e no di e ences in PWV among no mal weigh , o e weigh , and obese pa icipan s (p=.914 o he main e ec ). Addi ional adjus men o mean a e ial p essu e had no e ec on hese esul s. Res ing blood p essu e did no modi y he exe cise esponse on PWV (p=.930 o in e ac ion, Figu e1c). No mo ensi e pa icipan s had lowe PWV om p e o pos 10 han hose a s age 1 (mean di e ence=−1.70, 95% CI=−3.42 o −0.11, p=.052) and s age 2 hype ension (mean di e ence=−2.79, 95% CI=−4.45 o −1.12, p<.001, p<.001 o main e ec ). P e-PWV modi ied he e ec o a maximal g aded exe - cise es on PWV (p=.003 o in e ac ion, Figu e1d). Pulse wa e eloci y dec eased only in highes hi d om p e o pos (mean di e ence=−1.2, 95% CI=−2.2 o −0.1, p=.026) and pos 10 (mean di e ence=−1.1, 95% CI=−1.9 o −0.4, p=.003). Pa icipan s who we e in he highes hi d o PWV a he p eassessmen had con inuously highe PWV om p e o pos 10 han hose he middle (mean di e ence=1.9, 95% CI=1.1 o 2.7, p=.003) and he lowes hi d (mean di e - ence=3.4, 95% CI=2.6 o 4.2, p<.001, p<.001 o main e ec ). Fu he adjus men s had no e ec on hese esul s. Ae obic endu ance aining o esis ance aining did no modi y PWV esponses o exe cise. The e we e no s a is i- cally signi ican di e ences in PWV be ween hose who ex- e cised egula ly and hose who did no . 3.4 | E ec s o ca dio espi a o y i ness, ae obic and esis ance aining, and weigh s a us on changes in a e ial one in esponse o a maximal g aded exe cise es AIx dec eased linea ly om p e o pos 10 (mean di e ence p e s. pos =−9.2%, 95% CI=−13.7 o −4.7, p<.001; pos s. pos 10=−8.0%, 95% CI=−12.6 o 3.5, p<.001 o main e ec ). Weigh s a us pa ly modi ied he e ec o a maxi- mal g aded exe cise es on AIx (p= .062 o in e ac ion, FIGURE 1 Changes in ao ic pulse wa e eloci y (PWV) om p e- o pos - and pos 10-exe cise assessmen s among adul s in he hi ds o ca dio espi a o y i ness exp essed as maximal powe ou pu (Wa s) scaled by body weigh in kilog ams0.35 (N o he lowes , middle, and he highes hi d we e 29, 28, and 27, espec i ely) (a), no mal weigh (N=26), o e weigh (N=39), and obese (N=19) adul s (b), adul s wi h no mal blood p essu e (N=9), wi h ele a ed blood p essu e (N=11), wi h s age 1 hype ension (N=28), and s age 2 hype ension (N=36) (c), and adul s in he hi ds o PWV (N o he lowes , middle, and he highes hi d we e 29, 29, and 26, espec i ely) (d). Da a a e mean and 95% con idence in e al. * deno es s a is ically signi ican (p<.05) change in PWV P e Pos Pos 10 7 8 9 10 11 12 Ao ic PWV Lowes hi dMiddle hi dHighes hi d Ca dio espi a o y i ness (Wmax/BM –0.35 ) * P ePos Pos 10 7 8 9 10 11 Ao ic PWV No mal weigh O e weigh Obesi y Weigh s a us * P e Pos Pos 10 4 6 8 10 12 Ao ic PWV No mal Ele a ed S age 1 hype ension S age 2 hype ension Blood p essu e P e Pos Pos 10 6 8 10 12 14 Ao ic PWV Lowes hi dMiddle hi dHighes hi d Pulse wa e eloci y * * ab cd | 7 o 10 HAAPALA e AL. Figu e2a). In no mal weigh pa icipan s, AIx a pos 10 was lowe han in p e (mean di e ence=−20.5, 95% CI=−27.2 o −13.8, p < .001) and pos (mean di e ence = −15.7, 95% CI=−22.8 o −8.6, p<.001) (p<.001 o he main e ec ). In o e weigh pa icipan s, AIx a pos (mean di - e ence=−10.6, 95% CI=−17.9 o −3.2, p=.003) and pos 10 (mean di e ence=−16.3, 95% CI=−23.0 o −9.6, p<.001, p<.001 o main e ec ) we e lowe han p e-ex- e cise AIx. Simila ly, in obese pa icipan s pos (mean di - e ence=−12.5, 95% CI=−21.2 o −3.9, p=.004) and pos 10 (mean di e ence=−14.8, 95% CI=−23.5 o −6.2, p = .001, p < .001 o main e ec ) AIx we e lowe han p e-exe cise AIx. Fu he adjus men o hea a e had no e ec on hese esul s. Resis ance aining modi ied he esponse o AIx o a maximal g aded exe cise es (p=.026 o ime*g oup in- e ac ion, Figu e2b) and he dec ease in AIx was la ge in pa icipan s wi h egula esis ance aining. AIx dec eased om p e o pos (mean di e ence=−11.6, 95% CI=−18.8 o −4.4, p = .001) and pos 10 (mean di e ence = −22.6, 95% CI = −29.1 o −16.1, p < .001) in pa icipan s who had egula esis ance aining. AIx a pos was also highe han a pos 10 (mean di e ence = 11.0, 95% CI = 3.4 o 18.5, p=.002). Among hose who had no egula aining AIx a p e was highe han a pos (mean di e ence=7.5, 95% CI=−1.8 o 13.2, p=.006) and pos 10 (mean di e - ence=−12.9, 95% CI=7.9 o 18.0, p<.001). Fu he mo e, pa icipan s who had egula esis ance aining had con inu- ously highe AIx om p e o pos 10 han hose who had no egula esis ance aining (p=.058 o he main e ec , mean di e ence =−1.98, 95% CI= −4.02 o 0.069, p = .058). This di e ence s eng hened a e adjus men o age and sex (p=.037). Fu he adjus men o hea a e had no e ec on hese di e ences. Ae obic endu ance aining did no modi y AIx esponses o exe cise. Wmax/BW-0.35, blood p essu e, o PWV did no modi y he esponse o AIx o a maximal g aded exe cise es and he e we e no di e ences in AIx be ween he hi ds o Wmax/BW- 0.35, blood p essu e g oups, o hi ds o PWV. The esul s on he associa ions o blood p essu e wi h AIx emained simila when no mo ensi e and ele a ed g oups we e combined. 4 | DISCUSSION The mos consis en inding in ou s udy was ha a highe sys olic blood p essu e, dias olic p essu e, and mean a e- ial p essu e we e s ongly associa ed wi h highe PWV and AIx. We ound no associa ion o ca dio espi a o y i ness o he le el o exe cise aining wi h a e ial s i ness o a e ial one in middle-aged subjec s wi h ca dio ascula isk ac o s. Ne e heless, we obse ed an in e se associa ion be ween ca dio espi a o y i ness exp essed as Wmax/BW-1 and dias- olic blood p essu e. Howe e , his associa ion a enua ed when ca dio espi a o y i ness was app op ia ely no malized o BM using allome y and exp essed as Wmax/BW-0.35. We also obse ed ha a highe BMI was ela ed o highe dias- olic blood p essu e and mean a e ial p essu e. Fu he mo e, PWV dec eased among pa icipan s wi h highe i ness le el and no mal body weigh in esponse o a maximal g aded exe cise wi h inc easing wo kloads. Finally, we obse ed a sligh ly augmen ed AIx esponse o a maximal g aded ex- e cise es in no mal weigh compa ed o obese pa icipan s. In con as wi h he esul s o some p e ious s udies show- ing an in e se associa ion be ween ca dio espi a o y i ness and a e ial s i ness in child en (Veijalainen e al.,2016), adolescen s and young adul s (Bo eham e  al., 2004; Haapala e  al., 2018), and olde adul s (Vai ke icius e  al., 1993), we ound no ela ionship o ca dio espi a- o y i ness o a e ial s i ness and a e ial one. Howe e , ou esul s ag ee wi h indings showing weak associa ion be ween ca dio espi a o y i ness and a e ial s i ness in young and middle-aged adul s while showing an in e se associa ion in olde adul s (Vai ke icius e al.,1993). One eason o weak associa ions be ween ca dio espi a o y i - ness and a e ial s i ness may be ha ou s udy popula ion had no diagnosed ca dio ascula diseases, which may lead o a e ial s i ening o endo helial dys unc ion. The e o e, FIGURE 2 Changes in augmen a ion index (AIx) om p e- o pos - and pos 10- exe cise assessmen s among (a), no mal weigh (N=26), o e weigh (N=39), and obese (N=19) adul s, and (b), adul s wi h (N=35) and wi hou (N=47) egula esis ance aining. Da a a e mean and 95% con idence in e al. *(p<.05), ** (p<.01), and *** (p<.001) deno es s a is ically signi ican change in AIx P e Pos Pos 10 –20 –10 0 10 20 30 Ao ic AIx No mal weigh O e weigh Obesi y Weigh s a us *** ** *** *** *** ** P ePos Pos 10 – 20 – 10 0 10 20 30 Ao ic AIx No esis ance ainining Resis ance aining Resis ance aining ** *** ** ** *** ab 8 o 10 | HAAPALA e AL. i is possible ha he associa ions o ca dio espi a o y i - ness and exe cise wi h a e ial heal h a e s onge in in- di iduals wi h mo e ad anced ch onic diseases (G een, Spence, Halliwill, Cable, & Thijssen,2011). Fu he mo e, p e ious s udies ha e also sugges ed ha ela i ely highe exe cise load is equi ed o imp o e ascula unc ions in asymp oma ic heal hy adul s (G een e al.,2011). Ano he eason may be ha ou s udy sample was qui e homogenous and he e we e no enough a ia ion and he e o e s udies in la ge samples a e needed. Fu he mo e, as expec ed, we obse ed ha ca dio espi a o y i ness exp essed as Wmax/ BW-1 was in e sely associa ed wi h dias olic blood p es- su e. Howe e , his associa ion was no longe seen when he e ec o body size on ca dio espi a o y i ness was app op ia ely con olled using allome y. This obse a ion sugges s ha he associa ion be ween ca dio espi a o y i - ness and dias olic blood p essu e was la gely explained by di e ences in body size and composi ion. We ound ha egula ae obic endu ance exe cise was no associa ed wi h a e ial s i ness. P e ious s udies ha e shown ha ae obic exe cise aining can imp o e ascula unc ions (G een e al.,2011; Thijssen e al.,2010). Howe e , ae obic exe cise aining has been ound o ha e only limi ed e ec s o exe cise aining on a e ial s i ness in obese (Mon e o, Robe s, & Vine ,2014) o p ehype ensi e o hype ensi e adul s (Mon e o, Roche, e al., 2014). The e o e, i is possible ha he e ec s o ae obic exe cise aining on a e ial s i ness equi e subs an ial educ ion also in o he ca diome abolic isk ac o s (Mon e o, Roche, e al., 2014). Ano he explana- ion o hese con as ing indings may be ha we used a ough dicho omy assessmen me hod o sepa a e hose who ha e a his o y o egula ae obic exe cise. Second, ou me hodology o egula physical ac i i y was no de ailed enough o assess in ensi y o exe cise. I is possible ha he epo ed egula ae obic exe cise may ha e been o oo low in in ensi y and/ o du a ion o cause bene icial e ec s on a e ial s i ness in his popula ion wi h ca dio ascula isk ac o s. Indeed, shea s ess agains he a e y wall has been shown o be an impo - an ac o o imp o ing ascula unc ion (G een e al.,2011). While he e is e idence showing ha s eng h aining has none o inc easing e ec s on a e ial s i ness (Miyachi,2013), we ound some e idence on he dimo phic associa ions acco ding o gende be ween s eng h aining g oups in PWV showing ha women who esis ance ained had s i e a e ies han hose who did no ained while opposi e was obse ed in men, al hough hese di e ences did no each s a is ical sig- ni icance. The eason o hese opposing associa ions is no well unde s ood. Menopause has been ound o ampli y a e- ial s i ening (Takahashi e al.,2005), and i is possible ha women who p e e ed esis ance aining we e al eady meno- pausal and hey we e encou aged o egula ly pa icipa e in a esis ance aining p og am. Howe e , possible sex-di e - ences in hese associa ions wa an s u he s udies. We obse ed ha BMI was ela ed o dias olic blood p es- su e and mean a e ial p essu e, bu no wi h a e ial s i ness. Fu he mo e, in line wi h p e ious s udies (Sa a e al.,2018) blood p essu e was s ongly and di ec ly associa ed wi h PWV and AIx. Inc eased blood p essu e has been ound o dec ease elas ic po en ial o a e y wall by causing excessi e collagen p oduc ion (Zieman e al.,2005), and change as- cula smoo h muscle cell ac ion, he eby (Sa a e al.,2018) inc easing a e ial s i ness. In addi ion, inc eased a e ial s i ness may pa ly explain ele a ed blood p essu e (Sa a e al.,2018). A g aded exe cise wi h inc easing wo kload had a small o e all e ec on PWV. Howe e , we ound ha hose pa - icipan s wi h he highes ca dio espi a o y i ness, no mal weigh , and hose wi h he highes PWV demons a ed a sligh dec ease in PWV in esponse o a maximal g aded ex- e cise es . We also ound a sligh dec ease in PWV in obese pa icipan s om p e o pos , bu PWV e u ned o p e le els wi hin 10min. These esul s may imply ha indi iduals wi h highe ca dio espi a o y i ness and no mal weigh can be e egula e ascula unc ion and blood conduc ance o ma ch pe iphe al oxygen equi emen s. P e ious s udies ha e shown ha seden a y indi iduals ha e blun ed ni ic oxide-depen- den asodila a ion ha can be p e en ed by exe cise (Black, G een, & Cable,2008). Fu he mo e, obesi y has been associa ed wi h impai ed ni ic oxide-dependen asodila a ion (Higashi, Sasaki, Nakagawa, & Ma suu a,2001) sugges ing ha obese adul s could no inc ease a e ial dila a ion in a simila manne o no mal weigh adul s, which is an essen ial ascula adap- ion o inc easing exe cise wo kload. These obse a ions a e pa ly suppo ed by ou indings showing ha only no mal weigh pa icipan s exhibi ed a consis en dec ease AIx in esponse o a maximal g aded exe cise es . We also ound ha al hough hose who esis ance ained had highe AIx p eassessmen , he AIx dec eased o he same le el a e a maximal g aded exe cise es han in o he pa icipan s. A plausible explana ion o dec eased AIx in esponse o a maximal g aded exe cise es is exe cise-induced ni ic ox- ide-dependen pe iphe al asodila ion (G een e  al., 2011). The eason o highe AIx in esis ance aining pa icipan s may be ha esis ance aining induced peaks in blood p es- su e may ha e inc ease ascula smoo h muscle one (Sa a e al.,2018). The s eng hs o his s udy include a measu emen o ca dio espi a o y i ness using a maximal exe cise es and alid and ep oducible measu es o a e ial s i ness. We no only in es iga ed c oss-sec ional associa ions o ca dio- espi a o y i ness, BMI, exe cise aining, and blood p es- su e wi h a e ial s i ness bu also hei ole in he e ec s o a maximal g aded exe cise es , which is commonly used in clinical p ac ice, allowing us o cap u e mo e comp e- hensi e pic u e o de e minan s o a e ial heal h. We also