leven etal BMC Pubic Heath (2020) 202726, pe/do.org/0.1185/12889-02008715-4 BMC Public Health The association between physical activity ® with incident obesity, coronary heart SS disease, diabetes and hypertension in adults: a systematic review of longitudinal studies published after 2012 Laura Cleven", Janina Krell-Roesch"”, Claudio R, Nigg'? and Alexander Woll! Abstract Background: A growing body of studies that investigated the longitudinal association between physical activity (PA) and the outcome of incident obesity, coronary heart disease (CHD), diabetes and hypertension has become available in recent years. Thus, the purpose of this systematic review was to provide an update on the association between PA and onset of obesity, CHD, diabetes and hypertension in individuals aged >18 years who were free of the respective conditions at baseline Methods: We systematically searched OVID, Pubmed, and Web of Science databases for pertinent literature published between January of 2012 and February of 2019, To ensure that conclusions are based on high quality evidence, we only included longitudinal studies conducted in samples of 2500 participants and with 25 years of follow-up. Result: The search yielded 8929 records of which 26 were included in this review. Three studies were conducted fon the outcome of incident obesity, eight on incident CHD, nine on incident diabetes, four on incident hypertension, one on the outcome of both diabetes and hypertension, and one on the outcome of CHD, diabetes and hypertension. Overall, there was an association between PA and lower risk of incident obesity, CHD and diabetes, but not hypertension. Higher levels or amount of PA were associated with a reduced risk of new onset of the respective diseases in 20 studies (77%). Whereas four studies reported an elevated risk of incidence of diseases with lower PA levels (15%). PA was not associated with incidence of diseases in two studies (8%). (Continued on nest page) = conespondence: buacievenskiveds "inaiut of Sports and Spon Soence, KafstuheIstute of Technology rl, Gemma Full of author informatio salable atthe en ofthe aricle € The Aso) 2900 Open Aes The ae ned unde a Cee Commons Arun 4 ston er ‘tm ess eatin dbion ar epoca ma oot rs) OMe licence, ues inated there iv 3 ced et te motel Fm ere yur ended ue ox parted by Say regulon o xn te pee yo wl Ped a ‘data mace avalatle mths atc, ures otherwise stata 2 cre new the dataleven etal BMC Pubic Heath (2020) 202726, Page 2 of 15 (Contrved rom previous pag Conclusion: Higher levels of PA are likely associated with a lower risk of becoming obese, develop CHD or diabetes, These findings replicate and strengthen conclusions from earlier reviews underlining the importance of promoting PA in adults, The associations between PA and incident hypertension were less consistent. More research, particularly using prospective cohort designs in large population-based samples, is needed to further Untangle the association between PA and incident hypertension. ‘Trail registration: CRD42019124474 (PROSPERO Protocol registration), Date of registration in PROSPERO 27 February 2019. Keywords: Physical activity, Obesity, Coronary heart disease, Diabetes, Hypertension, Adults, Longitudinal study, Cohort study Background ‘The World Health Organization identified non- communicable diseases (NCDs), such as diabetes melli- tus or cardiovascular diseases to be a major threat to economies and societies [1]. NCDs are implicated in 73% of all global deaths in 2017, with 28.8 million deaths attributed to risk factors like high blood pressure, high blood glucose, or high body mass index (BMI) [2]. Fur- thermore, NCDs are forecasted to account for 81% of all slobal deaths in 2040 [3]. NCDs usually develop over a long time period and may be impacted by an individual's health behaviors [4] AAs such, many NCDs may be preventable by decreasing ‘metabolic risk factors such as hypertension, overweight and obesity, or hyperglycemia, as well as by decreasing. behavioral risk factors like tobacco or alcohol use, an unhealthy diet, and physical inactivity [1,5]. ‘A growing body of research suggests that high levels of physical activity (PA) may have a protective effect on vari- ‘ous health conditions including but not limited to over- ‘weight and obesity [6], coronary heart disease (CHD) [7, 8}, type 2 diabetes melitus (9, 10), hypertension [L1, 12), and hyperglycemia [13, 14]. In addition, several longitu- dlinal studies have become available that examine the asso- ciation between PA and new onset of NCDs [15-20]. The current systematic review presents an update of a previously published review by our group (20), that exam- ined the long-term effects of PA on type 2 diabetes melli- tus, CHD, overweight/obesity and dementia by including studies published before 2012. Given the high significance of this topic and since we expected a substantial amount of relevant studies published after 2012, we provide an up- dated review of longitudinal studies on the association be- tween PA and incident obesity, CHD, diabetes and hypertension over the past 7 years. Hypertension has been added to the current review as it is widely regarded as a major risk factor for several NCDs [21] Methods ‘This review was conducted in accordance with the Pre- ferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guideline [22]. The protocol ‘was registered in the PROSPERO register of systematic reviews (CRD42019124474). Search strategy Pertinent articles published between January of 2012 and February of 2019 were searched in electronic databases (PubMed, Web of Science and EMBASE by OVID) by applying a combination of one or more of the following search terms: “longitudinal and/or long-term’; “physical activity/exercise’; “adult”; “overweight and/or obesity’, “coronary heart disease and/or coronary artery disease andlor ischemic disease”, “diabetes mellitus and/or dia betes type 2, “hypertension and/or blood pressure”. Both titles and abstracts were searched. After identifica- tion of studies, their bibliographies were searched manu- ally to identify additional relevant studies. ‘Study inclusion & exclusion criteria ‘We defined the following inclusion criteria for this sys- tematic review: (1) Longitudinal, ie. prospective cohort study designs (2) Studies reporting the association be- tween PA and new onset of obesity, CHD, type 2 dia- betes mellitus and/or hypertension; (3) Studies providing information on the assessment of PA (predictor vari- able). PA could be leisure-time/habitual PA, work- related PA, transportation related PA, organized and unorganized PA, etc; (4) Only studies with 25 years of follow-up were included to allow for a meaningful con- 18 years, that were free of the diseases of interest at baseline; (6) Studies with more than 500 par- ticipants were included, to improve the probability to capture a substantial amount of incidence cases: and (7) articles written in English. Excluded from this review were (1) studies investigat- ing the effect of a specific PA intervention, as well as (2) clinical trials, cross-sectional studies, systematic reviews, and meta-analyses.leven etal BMC Pubic Heath (2020) 202726, Page 3 of 15 Records identified through database searching, (n = 8922) Additional records identified through other sources I Records after duplicates removed Records excluded 2 (n=4754) | (n=4415) i aa ¥ Records screened Records excluded + (n= 339) (n= 218) Full-text articles assessed Full-text articles excluded, for eligibility | GRRE | with reasons* (n=121) (n=95) l Included (n= 26) Studies included in qualitative synthesis Fig 1 Flow Chat (modified based on (22), = main reasons for exclusion ef studies (n fsigns n= 6 folowup time <5 years: n= 20 other PRin= 10 other td 35 other outcomes of interest = 24 other definition of Screening & data extraction All pertinent studies detected after searching the elec- tronic databases were imported to a reference man- ager software (Citavi 6) and duplicates were removed. The study selection process was divided into three phases. Two independent reviewers (LC & JKR) screened the titles of the articles, followed by the ab- stracts, and finally the full-texts based on the inclu- sion criteria. All studies meeting the eligibility criteria were included in this review. Disagreement was re- solved by consensus or by consulting a third author (CN). The following information was extracted by one reviewer (LC): first author's name, publication year, study design, study setting, sample size, follow-up time, participant characteristics (eg. age, sex, BMI) at baseline, assessment and type of PA (eg. type, dur- ation, intensity), assessment and type of outcomes of interest (ie. obesity, CHD, diabetes and hypertension), and main results/ findings of the stady (eg. hazard ratios, relative risk). Extracted data were verified by another author (JKR). Quality assessment and risk of bias The quality of included studies was evaluated independ- ently by two authors (LC & JKR) using the 22-item Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement version 4 [23]. Simi- larly, potential risk of bias of each study included in this systematic review was assessed through the Tool to As- sess Risk of Bias in Cohort Studies [24] by the same au- thors (LC & JKR). Any discrepancies between the two reviewers were resolved by discussion or by consulting a third reviewer (CN).leven etal BMC Pubic Heath (2020) 202726, Results Overall, we identified 8929 articles, of which 8903 articles were excluded as they did not meet the inclusion criteria as described above. The reader is referred to Fig. 1 for a flow chart summarizing the search process and number of studies at each step. Twenty-six studies were included in this review with a combined N of 1,145,298 participants, and follow-up times ranging between 5 and 34years ‘Three articles examined the association between PA and. incident obesity [25-27], eight studies examined the asso- ciation between PA and incident CHD [28-35], nine stud- ies examined the association between PA and incident diabetes [36~44], and four studies examined the associ- ation between PA and incident hypertension [45~48}. In addition, one study reported the association between both PA and diabetes as well as PA and hypertension [49], and another study reported the association between PA and. CHD, diabetes, and hypertension [50]. ‘Association between PA and obesity "The studies included in this review showed an overall as- sociation between higher PA and lower risk of incident ‘obesity. Two out of three studies reported a reduced risk ‘of becoming obese for individuals with high PA levels as compared to low PA (25, 27]. One study showed an Page 4 of 15 clevated risk (142%) of becoming obese for persons who ‘were physically inactive [26]. The characteristics of the included studies are summarized in Table 1. ‘Association between PA and CHD ‘Overall, there was an association between higher levels or amount of PA and a decreased risk of incident CHD. Seven ‘out of nine studies reported a reduced risk of new onset of ‘CHD with increasing PA levels as compared to low or no PA [28, 32-35], whereas one study revealed an association between PA and decreased CHD risk only for vigorous in- tensity PA [29]. One study did not find a significant associ- ation for occupational PA and CHD risk [50]. Two out of nine studies examined the impact of change in PA levels ‘over time as predictor variable and failed to detect a signifi ‘ant association with incident CHD (31, 33) Please refer to ‘Table 2 for a summary of studies on PA and incident CHD. ‘Association between PA and diabetes ‘The studies included in this review provide evidence of an association between increasing PA levels and a decreased risk of incident diabetes. Nine out of 11 studies reported a gradual inverse association between Increasing PA levels with up to high/vigorous-inten- sity and a decreased risk of incident diabetes (36-39, Table 1 Overview of longitudinal studies on the association between PA and the outcome of obesity (BMI230ka/m?) athor Coury Chaactersucs Followup ime reditor vale Physical Outcome Wain results actly of incre Beletal UK ___N=3670, 73¥omale, lOyeats Baseline Seifreparteddursion of Wcident OR [5 Cif low level PA as 2014 (25) Whitehall 555¢60year 1997-1999. VPA th) besty reference su Follow-up: 2002 i ep ae a ono s ‘High ee PA 64 440851 Invemedte: 156-425 oe High 427-2056 High evel PA 068 [045,088] mer yeas Montgomerie Australia N= 1521, 506% Set ceported, sore Incident AR [95% CI Association between etal. 2014) make age 4462 Baseline 1999-2008, frequency xtime per obesly physical inact & incident ba Teaayeas follow up: 2008. seston x tery boesiy 2006, 2008-2010 Inge: «100 sedentary 42 (103, 195] p=00%0 100-1600 low etiv: 1600-2200 moderate, > 3200 hgh Pavey etal Ausra W=273S women, 12yeats So reported, Change OR [95% Cif increasing cumulative go1a 2 746 (006-285) Baglin: scone (MET mink) inBMl PA wth very low acy as years 2 pwn Yevlow e250 cy nie — : rans to obesity: 073 10 Low (250 to < 500) awipeos Active (00 t0 < 1000) Sry active > 1000 (OR [95% CH, vey high cumulative PA wath very low acti 2s reference “Teaston to obesity 052 030, 092}, p<.05, ‘Abbreviation: 6 Body Nass index. cconence nena hour, MET metab equals mp mines, VPA hades Cigoreu PIySCT ac, ‘umber of partipants, OF eas aap vai, Pa phys acy, A late isk SD Standard devaen, wh weak "Medel ase for age, 0 thi" Model ajsted fr ape, sex none conten dabetes, sta, chon obstructive pulmonary sas, carovascat Bees an mental heh" Mosel ested fo eacatonal evel sta of eidenes, rane of children occupation wok te walling, wrk Rey Ibbor smoking stun onal consumption energy ste dicing, ol conacepve al se, numberof cro conetons‘leven etal BMC Pubic Heath (2020) 202726, Page 5 of 15 Table 2 Overview of longitudinal studies on the association between PAA and the outcome of CHD aor Coumy ——— Chaacersties Folin Predict variable Physical Outcome of Nain esas uptime _sctity intrest, Tromisick USA Nawes—_V=97230 wornen 366 20yeas selfrepored LIPA Incident CH HI [DS% Cl of CHD event etal Health Study 46 yea Baseline: (METH, n quinties)—_(ponfotal MU fatal for total LTPA": Gola pa Nis) wr -< oo = <1: 10 erence) ~ 1-59-0286 (058, 1.08) Follow -1-59 - 6-149: 066 (052, 084) uP?) 4g 1-209 15-299: 048 (036, 083} 20 - 230-053 [04l, 070) Sima, nceasing META wk were associated with a decreased rok of nedent (CHD when loking at moderate ntersty PA ooh, 235 wel as looking at Vigorous intent PA ony Delaney USA, Multe 95656, 47496 male, 613. Syears Selfreported PA (total Incident CAC AR 95H CN of PA ane etal” Ethnic Study of 99yeas BMI 28354 Baseline mira otal MET-minvd) incident CAC (01309 Atherosclerosis Agim 2000 — oy + Vigorous activity 097 (034,100) p= 0088 Follow No association between op intentional sedentary, 2005 MPA and condoning PA 2 and indent CAC, Feraro tay, MONICA, Median Selfreponed OPA score incident CHD fist HR 95% CI of fist CHD etal PAMELA, SEM yeas 1-5 teres cutoffs at 25, acute coronary event (tal or noma by (2018 20} (QE 3125), SpPA index in/k event a5 Mi acute OPA group’ 129. ofMPAorVPA based on coronary 159) METS of ast) Symctome or LONE 66.06, 2591 coronary Basle ication) Intermediate: 1989 easeaeeston) eftence) es High: 118 1072, 1941 Folow - Poor HR (56 CH of fist HD vp: 2008 event Catal r norfata by Irxermediae: 1-149 . MPR oF 1-74 VPAOF S0PA grou 1-149 MPA plus VPA Poot 10 eterence) Intermediate: 081 (050, 13a Recommended 2150, Recommended: 058 (030, MPR or> 75 VPA cr mal 2 ISDMPA plus VPA Jeffers UK Bish Medan Selfrepored usual PA Incident CHD Fst HR [05% I of Fit CHD tal Rejonal Heart years yeas core) fata or nonfat MI event fatal or nonfatal by (ota (Sty Baseline events D9 Code PA group ogg active 2) ‘410-414, (D- 10 2000 - Occasional 6-5) (Code 21423, 1252) - None: 1.0 (ference) regio ~ Lane 6-81 Occasion 052 (034, ans} Moderate 0-12) Light 047 (230,074) Moderately vigorous (13 Moderate: 051 (032, 082] a Moderately vigorous and Vigorous & 21) vigorous: 044 128,065), ‘Change in PA p=0008 (09562000) ‘Nays inactive HR (9596 C1 of ist HD‘leven etal BMC Pubic Heath (2020) 202726, Page 6 of 15 Table 2 Overview of longitudinal studies on the association between PA and the outcome of CHD (Continued) ‘abot Comiy Owaneests oe foe — Sansa aaron ay ‘change in PA group" became ae “ays rae 10 tacts Aoys ache dec mci 87 | a ‘3 says sene 07053 i eats Nether, NaSSO mec 9067 yun. Step PA ete CH tT Phan eof Sr Nin foo eileen ears estan Reber iS fora.) Susy Fr ar oo eos 20 Feesanens Tl: 10 lee Serie tenes ezngenta| a asain Tere 20788 052 "Shaws ** faeedan tee Teen 76305 ieee pe omer 98 ies told pea Tertiles 3: 126.7 (2970) — Sewanee eesen Derm e104, Stale, Sane Seep TPA et CHO fal HRS Cl of MO Pa Sa apn Maderaeesyen” Tee “een oo (2012) 33] City Heart jentary (ME ICD-8 Code = Women | Men say _ ADO Cede en 2 25135 YE Modes Code a10-414, 1097. 1831 138) goo D0 cle aang au 2008 Change in PA categories (096, 1311 ene ies a 2-3 egos “gran al oo fase ee oy

150mintnk Strengthening aces was, Say scat ah Igner kof dene cabetes compted wh blog ctv ipooled 022 (023,033). ning Nersay ort 38413 Tyee SalieeponedLIPA cident abetes Rak fates decrees ea Tenet th ae se repre vated with PAY RRS Cl] Women (2017) (37) Health Study) information ane ‘through medical Men: con PA, 47% 1984-1986 record) oa Weston Love 10 elrence Follow-up: - High ‘Medium: 081 (0165, 1.00) | 19951957 0 (6,088 = Hate 076 161,095 | 065, (031,088 pe 6011p e001 radvaliverseasocaten Seon enc, ton, inersy and ek of nce (abcess, Graal iene association beeen eer, ensty ad wakof ldent cabetes: ‘ertemales fteund 9 urpean Medan 123 Sateponed PAPA, ncdent abetes—_ Aone evel ference in PA a counts yeas LA (eg between nacive it Ho PCM : modesty racine) ek Study) shacaml associated with a 13% relative fassine: — - Moderately acne tection nk of elent 13t Clbetes nes 2 5 7 and bk Folawup: Moderately ate ete adleven etal BMC Pubic Heath (2020) 202726, Page 9 of 15 Table 3 Overview of longitudinal studies on the association between PA and the outcome of diabetes (Continued) aor County Characesics Folowup Predictor variable Physical Outcome oftnerest in vests time aatvty 3525 women) 2007 ave Tedoction ip ferates 093 ras, asap? Increased rk of incident ddabetes associated wih ower levels of PA evident across BM saa in bor sees, withthe ‘exception of obese women fens UK Na3012 Medan. Selteponed PA cident pe 2 dabts if dates deemed th aa mene ary Gatreporinduded "Px Doseraponce aac (2012) [38 years, oad after validation through HR [95% Cl) Baseline: Occasional Wea) = None: 1.0 (reference) 12 19 ~ ocean 054 031,094 Folowap 2005 - Mode = vat 034 a, 065 Modesty vonois Morte 033 (017 065 ors = modesty vga 022 preaen Vigorous 026 (013,058 Poot Tang pat et nee imeraybh a sce wi owe kf ete Koloweou Gee Aca N=1485 49% Dyers Seltepored PACMETariv lent dates Moder nest PA sac ca Suh ae “ (resulta wih once not fone — ‘Stic seeped) Sabet On oem 2001-2002 yy = 150-330 Very tow: 1.0 (reference) folowun, - Modete=331-1484 101 07741, 181 201-2012 High 21404 Moderate: 0.47 (0.24, 0.93] th 104105818 edna Meiko e168 Medan 44 Seroponed PA scent ype 2 dabetes Pats wi else Ceara Cy medun’s—poson yes ccueronl Kiar trl Geasued so Act Meme fod Gora v9 Dooce” jeoston SST Een of AMPA) reat tng tesa kot et Sty) Sesaraary Saising TN mesicaton) atten 0 15 59 C110, males, - 1.92) a5 compared to reference sjoup & 120 Mer erik p= 00087 Faw: 21-59 Noasociaon between a ‘ccopatonl and Wal PA and cee eee diabetes risk se MO 4-2 no Mehig Sweden —«-N=1448 yeas Salteponed TPA cet dabetes IPAs ascidian oa women Semed ik nicer Basan, - Aosta w LA cor) Hal Dyes Saselne dfabetes HR 95% CI! Some PA at est -Noncteseacte:10 tenes Falowup Rega emrse -Non bes hace 173 tone 3h, wie "013 13RD pagar tig nd ce Obese ave: 243 EME pete sons aston om obese rate: 1.7 ieae na Shietal Cina SYA Medan 54 Setrepned PAMET vel nent bets Ge Tot PAs asacted wih eos ta menses uric ‘eee teduced tn eet abet S3yea Hi (959% CI for MET eve?leven etal BMC Pubic Heath (2020) 202726, Page 10 of 15 Table 3 Overview of longitudinal studies on the association between PA and the outcome of dabetes (Continued) Tathor County Characerisis Follow-up Predictor vale: Physical Outcome of nest Mun esas time aatvity Basaine—_-Q1<43 (0 eterence) PING gp 43-85 2-088 (072,099) Followup: 0365-89 02-072 (061,085 2004-2008 Q 7 Syosset 0489-121 (ct 066 (055,078 sz 121 (05-065 (054,077 wallams & USA N=48116 Median 62. Saltvepoted PAMETIvd Incident dlabetes Greater MET is associated Thompson yeas an with loner 1k of ieient 2012 601 a abet HR 95% CT Baseline: - Moderate Running: 0879 (83,0929) 1986-1999 gorau Waking: 0877 (082,093) Followup: Other vigorous: 088 095, 2006 007) ther moderate: 0968 [0908 02) Other ight 099 (0736, 1.12 “Rbbrevator: BP Cl confidence tel dy or FA azar, OW ierqure ange LTP eur ne physical acy, WET metabo equalent min ‘inutes MVPA moderate to grou physical ath, number of peripats,OP8 accupatonal phys acvky, OF od a, PA physica acy, relive ‘ek wreck Hod! putes for ge uation alcool frequency inthe pst? weeks sking, Hood pressure medication ise, prealentcrdowcur aise, BML PA suman scare: b Mode acre fr sty ctr educton, smoking tts aleael consumption energy ike MY Mode! aust fo age ron © ‘Modal dusted forage sex url try of abies hypertension, Pyreccetrlemtn cing sat education, pyle weit euler, ‘ahorence to the Medtarancan det astng ghcose, ile" Model ated fr Sex age eacaton lve, mara satus, cent making acelntake {ox energy nak, parent ston of dabetes seeping HOU, leure/woding NET mink" Meda aghsted for Baseline covarstes 9e, education, smakNg, Consumption of leo lyre, hypertension, parental NStoy of dabetes (lates on" Model sted fr age 3 ere, energy wake SmiN kobel consumption, education lve occupation, meame lee hypertension, fly Hstry af abet" Medel astd or baseline age ge age, ex ae, ‘ducation smeling, aks of ed mea ut kao preening Cx at bse reduction of incident hypertension by 6% for each 10 metabolic equivalent of task hours per week increment of leisure time PA [58]. However, another meta-analysis detected an inverse association for recreational PA and, incident hypertension but not for occupational PA [59] OF note, the causes of hypertension are multifactorial and the way they interact and ultimately contribute to the development of hypertension is unclear. Thus, po- tential__mechanisms for prevention of hypertension through PA also remain unclear. Some studies included in this review also reported find ings stratified by sex and body weight. For example, one study observed a gradual inverse association between fre- quency, duration and intensity of PA and risk of incident diabetes in males, but only a gradual inverse association, between frequency and intensity of PA and risk of incident diabetes in females [37]. Additionally, another study re- ported that, while overall PA irrespective of body weight ‘was not associated with the outcome of incident hyperten- sion, obese males with high PA had a significantly lower risk of hypertension than obese males with low PA [47] ‘The quality of included studies was independently assessed by two reviewers and was rated as moderate to good, with scores ranging between 16 and 22 (total range: 0-22). This is not surprising since we only cluded studies. published in or after 2012 that may already have followed quality guidelines on reporting, findings of observational studies such as STROBE: [23]. ‘The potential risk of bias was rated moderate to poor and there were several concerns that warrant brief dis- ‘cussion: 1) All studies included in this review assessed PA through self-reported questionnaires which may be prone to recall bias. However, given the large sample sizes and since the baseline measurements of PA of many studies took place several years or even decades ago, objective measurement of PA might not have been feasible. There is good reason to believe that more longi- tudinal studies using novel objective techniques such as accelerometry (eg. [60, 61)) will become available in the near future. 2) The studies differed regarding the assess- ment of the outcomes of interest, e.g, some studies ob- jectively measured blood glucose levels or blood. pressure (eg. [47, 45]) whereas others relied on self- reported information by the study participants and/or medical chart review (eg. [40, 48]. 3) The studies dif- fered in terms of adjustment for potential confounders and mediators which makes a comparison of findings between studies difficult. 4) Five studies were conducted only among males (30, 31, 38, 40, 44] and five studies ‘were conducted only among females (28, 41, 43, 46, 48} We did not investigate potential mechanisms under- lying the associations between PA and incident obesi‘leven etal BMC Pubic Heath (2020) 202726, Page 11 of 15 Table 4 Overview of longitudinal studies on the associat between PA and the outcome of hypertension far Coury Chaocersses Falowup Fedor veable —Oucome ot Mom resus time Physi scree Gian Win Nased—_ W=TRS5D yeas __Safrepored PA __nedenk Aon baween PA a nee a” Heh uy women hypertension hypertension vats by age (ovale for Gaia eal cohen yea icRaa. Beene: METH or gos epotce — acton¢ ON) 2 arc quits ae in NS Fatowune Toho R95 Cones or PA GS ak 20 compared to 2250-01 19 efrerc 2 .00 (O91 111) g3 10509 14; 101 (oor, 1125 05 087 078 0971 ‘Age 51-60-01 19 (ference; 02 094 [088 100; 03 094 fo, 109),04 091, (085,097 05 036 1080, 092) = Age2 6107 10 (ference OP 103 [097, 109; 03 098 (083, 103), 04 099 (093,105; 05 095 90 1.01) etal Chins N=1008, Median A? Setreponed PA Incident ‘No signlcant association between PA 2015) 65} 3548019 years : hypertension and risk of hypertension HR [95% Cl yeas 63456 en rales Baseline: = Occasional Occasional 0.74 (040,138) 208 Followups: - Everydoy Frequent 096 051, 183) ae Everyday: 10 (ference) Medina Meco (Mexico =154), Medan 118 Seepored PA Incident Paricpants with < 1 MET-minfv ffs etal iy Diabetes median 45, —_years, (cccupational esure, hypertension ure (137 (9596107, 175, p=0015) ola a Susyh (108 39-52) total acttyn MET- measured by of ocupational MVPA tH 1.52.17, years 45% Sasng | invck of WPA) sty team) 1.971 p= 0001) had increased sk of roles oy Fnypetenson as compated to reference croup (2 1200 MET)” Followus: = 2= 1-509 No asocaton was obsened between 1995-1994, total PA and hypertension. 12519543 =¢00-11999 2008-2008 = 4=2 1200 Pavey etal Australa N=N1285 Baseline: Selfveported PA Ccautence of OR (858 I] for hypertension decined (2013) 46) thustalan women, mean 1998 er mirven) hypertension with increasing PA volume decline Longitudinal age 485 years (seeped) Sight ofeater in MPA than MPA group 2 Follow — None ey aa Stuty oF ee PAS UPR . os a eee rae 7 i pe as eee a oo ee oe — Cte eee es oe eee oo See etal Trendelag Health 427% males gg, Total hypertension LTPA total score": RR [95% Cl) ee sec, Tone anny = oa Folowus: = Medium ~ Low 1 Weerence)leven etal BMC Pubic Heath (2020) 202726, Page 12 of 15 Table 4 Overview of longitudinal studies on the association between PA and the outcome of hypertension (Continued) athor Coury Choncersis Follow — Predict verable Outcome of Main esas time Prysealactty interest. 995.1957 High ‘Machine 096 (992,105) | 0961090, 1.08] Frequency (per wh) High: 096 090, 1011 | 097 (080,103) p=0138|p=0276 None . Frequency of PA associated with reduced : kof hypertension only in males Ae FR 087 (078 Ose) 23 (Obese eres with high PA have ewer feof hypertension (1.16 (079,170) a ‘than obese males with ow PA (RR 150 127,177, Intensity (bese females with low PA have : increased sk of hypertension (RR 1.5 = 135, 177), vellams & USA N=a3893 — Medan62 Sefteported PA Incident heater META i associ with lover Tompson yes a hypertension rsko incident hypertension HR [95% Ct 012) 0) : fasetne: —- ight funing: 0958 (094, 097) PPE Moderate Wiaking: 0928 (0899, 0957) Followeun: ——Vigorout other vigorous 098 (097, 095) 2008 (other moderate: 0997 [0976 1018) ther light: 0885 073, 1006) “breton: Ccondence eal dd, hour haa aon 1 equal ange TPA tena physical avy, MET metabo aquaent an ‘ints MPA maderate pyle acy, VPA moderate ovigerous pica acy, Vmumber of patants NA not avssbep value Pa phys cy, [tele rok Se standard ec wk week "Model estes for 92, gender an folow-up te; ® Model adjusted for sextime, age education lve, maa status, curent smoking alcohol intake, ‘ot ery nak, seep hours sure working NETuiinik «Mod! ajstd for sdedemographi ge education mara stats, oe of residence), behavior [mating seo nd iting cronecontions covariates," Nodel ste or ag, marl ats education, smoling. kona frequency It 2 ‘reek Bl PA suman scae* Mal adjusted for sctne age age age) sex nc, ean arcing rake led ea, lea preening CHD diabetes and CHD. However, it has previously been pos- ‘ulated that there are acute and chronic effects of PA on. insulin resistance, which may account for improvements in insulin action and decreased blood glucose levels as @ response to engagement in PA [62]. Additionally, PA im- pacts energy balance by increasing total energy expend- iture, which in tur causes an energy deficit and may lead to lower body weight [63]. Stimulating responses in adipose and body tissues by PA may also influence total ‘energy balance and body composition [63]. Furthermore, studies suggest that regular PA increases capillaization and may reverse endothelial alterations, which is @ major risk factor for CHD [64]. ‘The strengths of this review are the rigorous search, and selection strategy following published guidelines and, conducted by two reviewers. Also, both quality and po- tential risk of bias were assessed by two authors inde- pendently. We deliberately focused on studies published after January of 2012 in order to provide an update of a systematic review previously published by our group 20]. In addition, even though unintentional, our review included studies from various countries such as Sweden, Norway, UK, Greece, Mexico, China, Australia, Italy, US, the Netherlands, Germany, France, Spain and Denmark which may add to the generalizability of our observa- tions. The major limitations of this review pertain to the relatively small number of included studies. This may be due to the fact that we only included studies with large sample size (N= 500) and relatively long follow-up time of 25years. However, we believe that these criteria en- sure validity of our conclusions and a higher probability of generalizability of the study findings. In addition, a large body of research on PA and overweight/obesity published after 2012 focused on change in BMI or body ‘weight over time. We opted to not include these studies in our review as we chose our outcome of interest to be incident obesity, and information on change in BMI or body weight over time is thus not sufficient. For in- stance, a person could be underweight at baseline and fan increase in BMI or weight might actualy reflect pro- gression to a healthier body constitution. At the same time, we also acknowledge that particularly obesity and.leven etal BMC Pubic Heath (2020) 202726, hypertension are conditions for which individuals can take action to improve, ie a person develops incident obesity but may be able to decrease body weight in order to progress back to overweight or normal weight. Fur- thermore, our search terms may have been too narrow for not comprehensive enough and there may be pub- lished studies that we were not able to identify. How- ever, in order to compensate for this potential shortcoming, we also manually searched bibliographies of included studies. Finally, the studies differed with regard to the depth of investigating PA variables. As such, PA was only one of many predictors in some studies (eg. [36, 42]) and thus only one finding re- lated to PA and the outcome of interest was reported. Whereas in other studies, the association between various PA parameters (eg. type, intensity, frequency, duration) and the outcome of interest was examined, (eg. [30, 471). “More research to untangle the association and poten tial underlying mechanisms between PA and the out- come of incident overweight, CHD, diabetes and hypertension is needed, preferably using prospective co- hort studies with large sample sizes, long, follow-up and. objective measurement of both predictor variable (ic. PA) and the outcomes of interest. In addition, meta- analytic approaches to address research questions per- taining the association between PA and various health outcomes are warranted. Conclusion Overall, this systematic review replicates, updates, and, extends the growing body of research on the associations between PA and incident obesity, CHD and diabetes. No clear association between PA and reduced risk for hypertension was detected. This review emphasises the contribution of PA in the prevention of various chronic diseases, Reducing the risk of new onset of NCDs and. thereby reducing the economic burden on health sys- tems is of high importance to societies worldwide. Re- gional and global action plans and preventive strategies (eg. [651) should highlight the beneficial impact of regu- lar PA and support national governments in the imple- mentation of concrete actions towards achieving a higher engagement in PA among individuals across all ages. Abbreviations fe Body mars Index CHD: Coronary het aso: NCD Non ‘communicable dieses PA Physalacivy PRIMA rele Reporting lems fr Sjtemaie Reviews and Meta rae Acknowledgements Nocopphabi Page 13 of 15 ‘Author’ conteibutions Cet conducted te erature setch, and exact and interpet ata LC wrote he fst ao the manuscript MR, CN and AW revsed he ‘manuscipt Al authors ead and approved the fal manuscript ending (Creche funting by the Garman Academic change Sewice DAD or 2a visting prfesorhip at KT ‘Availabilty of data and materials Al daa generated or ana crng ths sty a nce in he published orice Ethics approval and consent to partkipate Not appabe Consent fr publication notapplcable Competing interests Aras dare no conics of inerestpralning to this anu ‘urthordetais "inst of Sons ae Spent Scenes, Kah ie of Technoiogy, teats, GemanyTransatonl Neuoscence ane Aging Labora, Mayo Cine, Scone, AZ, USK, “resent aderoes Insti of Spot Sere Uns of Ber Be, Sten Received: 29 May 2019 Accepted: 15 Apt 2020 Published online: 19 May 2020 References 1 Wel Heth Organization, Global tats report on nercomancable ‘deine 014 Geneva Wel Hh Cxgantaton, 2014 2 The Lancet GBD 2017 ape wa, arc 2016921683. ex l0roreso10-725838587, 3. 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Clin Cham. 208 (699-107, pe. og/10137nche 201727203 Whoo ER Wale Une A Phys acy nthe revi et vstent of coer ay dose Am Heat Ao. 2018 pie certo teiianar 17007725 65, Moh Ce hee Euopeanzaton of phys acy promason- 2 ‘ecuncionaaproach Heth Ply. 2019128317 26 p//star/0 ‘oie reathpa 201801008 © Publisher's Note Springs Rate resins ns ith regard to jrsicsorl cams in pubis! maps and rt sional sins Page 15 of 15 ead o submit your research? Choose BMC an benef om: + fast, convenient one submission + thorugh peer review eagerness researhes nyo ld 1 apd pbletion on acceptance + sport forreceah ts, nung large and amples types + eld Open cess whe estes wie olabeatn ard ees catons ‘rnin sy for your ear: ove 100M wba ews per ye BMC AG research lan progres. earn more iomedcentacon/ainsons