In follow-up to our recent state-of-the-art review on running published in the November 2015 issue of Mayo Clinic Proceedings, 1 we have additional data regarding the relationship of high-dose running with prognosis. Clearly, observational studies have recently reported that leisure-time running provides mortality benefits. However, the dose-response relationship between running and mortality has been increasingly debated, specifically whether more running is better or worse

Blair, Steven

Lavie, Carl

Lee, Duck-Chul

Sui, Xuemei

In follow-up to our recent state-of-the-art review on running published in the November 2015 issue of Mayo Clinic Proceedings, 1 we have additional data regarding the relationship of high-dose running with prognosis. Clearly, observational studies have recently reported that leisure-time running provides mortality benefits. However, the dose-response relationship between running and mortality has been increasingly debated, specifically whether more running is better or worse.This accepted Letter to Editor was published as 70. Lee DC, Lavie CJ, Sui X, Blair SN. Running and mortality: Is more actually worse? Mayo Clin Proc. 2016;91(4):534-541. Doi: 10.1016/j.mayocp.2016.01.013. Posted with permission.</p

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LETTERS TO THE EDITORRunning and Mortality: IsMore Actually Worse?To the Editor: In follow-up to ourrecent state-of-the-art review on runningpublished in theNovember2015 issueofMayo Clinic Proceedings,1 we have addi-tional data regarding the relationship ofhigh-dose running with prognosis.Clearly, observational studies have re-cently reported that leisure-time runningprovides mortality benefits. However,the dose-response relationship betweenrunning and mortality has been increas-ingly debated, specifically whether morerunning is better or worse.The Copenhagen City Heart Study(CCHS) indicated a reverse J-shaped as-sociation between weekly jogging timeor frequency and all-cause mortality,suggesting loss of mortality benefitswith higher doses of jogging at 2.5hours or more per week or 4 times ormore per week in a relatively healthycohort (N¼5048).2 Similarly, ourrecent analysis of running and cause-specific mortality suggested a reverseJ-shaped association, specifically on cor-onary heart disease mortality, unlikeother causes of death.3 Data from theNational Runners’ and Walkers’ HealthStudies (NRWHS) of 2377 heart attacksurvivors also indicated a reverseJ-shaped association of running orwalking with all-cause and cardio-vascular disease (CVD) mortality,with loss of benefit at high exercisedoses.4 Both the CCHS and NRWHShave limitations. The CCHS had rela-tively small numbers of deaths andused sedentary nonjoggersdie, withoutincluding active nonjoggers who areactive in other types of physical activityexcept joggingdas the reference groupin their analysis. This factor, in turn,may contribute to greater mortalitybenefits in joggers. The NRWHS hadno nonrunning inactive control groupbut used inadequate exercisers (<1.07metabolic equivalent task [MET]eh/d)as the reference group in their analyses.534In our large study of running andmortality from the Aerobics Center Lon-gitudinal Study (ACLS) in 55,137 par-ticipants (13,016 runners [24%] and3413 deaths [6%]),5 we found differentresults. Specifically, we found signifi-cantly lower all-cause and CVD mortal-ity risks even in the highest quintiles ofrunning doses compared with norunning, although mortality benefitstrended slightly less at the highestquintiles.Current Study. In the current study,the large sample size from the ACLSallowed us to further investigatewhether “more is better or worse”regarding running andmortality. Partic-ipants in the highest quintiles ofrunning doses were additionally classi-fied into 3 tertiles of running time, dis-tance, frequency, and total amount.Detailed information on the studydesign and the assessment of runninghas been described previously.5 Wefound that the mortality benefits werenot significant in the highest tertiles ofrunning compared with no running(P.05) (Figure), similar to the findingsof the other major running studiesmentioned previously. However,although there was apparent loss ofbenefit in the highest-dose runners,partly due to the smaller numbers andwider confidence intervals (CIs), therewas no increase in mortality but rather adeclining trend in benefit in all-causeand CVD mortality, even at the high-est dose compared with nonrunners.Therefore, there may be no remarkableincrease in mortality risk comparedwith nonrunners no matter how muchone runs, although there also may be nomortality benefits in excessive running.Another interesting and importantquestion focuses on the effects of highdoses of running compared with lowdoses of running. (Low-dose runninggenerally provided the most favorablemortality benefits in all 3 of the previ-ously discussed studies.) In the CCHS,considering both duration and speedwww.mayoclinicproceedings.org n ª 2016 Maof jogging, the authors found that themoderate and strenuous joggers whojogged more or at a faster speed (4times/wk or 2.5 h/wk at <7 mphor any running at7mph) (to convertto kph, multiply by 1.6) had 3-foldand 9-fold significantly increased risksof mortality, respectively, comparedwith light joggers, who jogged less ata slower speed (<2.5 h/wk at 7mph). However, their analyses in-cluded very small numbers of deathsin the light (n¼7), moderate (n¼8),and strenuous (n¼2) joggers. TheNRWHS also reported similar resultsusing total amount of running/walking based on both duration andspeed. Cardiovascular disease mortal-ity increased 2-fold in the group withthe highest amount of running/walking (7.2 MET-h/d) comparedwith the group with the lower amount(3.6-7.2 MET-h/d), with a hazard ratio(HR) (95% CI) of 1.97 (1.00-3.67)(P¼.05), based on 13 deaths in thehighest running/walking group.We conducted similar analyses andfound different results, indicating nosignificant differences in all-cause mor-tality (HR, 1.27; 95% CI, 0.89-1.81;P¼.19) and CVD mortality (HR, 1.66;95% CI, 0.87-3.16; P¼.12) in the high-est (2944 MET-min/wk, which isequal to 7 MET-h/d) compared withthe lowest (<506 MET-min/wk, whichis equal to <1.2 MET-h/d) amounts ofrunning, although HRs were greater inthose at the highest exercise levels.Similar results were observed in bothmen and women, with HRs (95% CIs)of 1.21 (0.84-1.75) and 1.84 (0.95-3.54) for all-cause and CVD mortality,respectively, in men and 3.07 (0.79-11.91) for all-cause mortality in women(there were no CVD deaths in womenrunning the highest running amount).Similar results were also found in youngand old individuals (<50 vs50 years)with HRs (95%CIs) of 1.57 (0.98-2.51)and 2.01 (0.81-5.02) for all-cause andCVD mortality, respectively, in youngindividuals and 0.93 (0.52-1.64) andMayo Clin Proc. n April 2016;91(4):534-541yo Foundation for Medical Education and Research1.000.70(0.58-0.85) 0.67(0.55-0.80) 0.67(0.55-0.82)0.71(0.58-0.86) 0.74(0.52-1.04)0.58(0.40-0.83)0.97(0.73-1.27)0 <51 51-80 81-119Running time (min/wk)120-175 176-209 210-269 ≥2701.01.000.45(0.31-0.66) 0.52(0.37-0.73)0.60(0.42-0.84) 0.53(0.37-0.75)0.64(0.34-1.19)0.48(0.25-0.92)0.88(0.54-1.42)0.50.20 <51 51-80 81-119Running time (min/wk)120-175 176-209 210-269 ≥2701.000.66(0.54-0.80)0.76(0.63-0.91)0.65(0.54-0.78)0.68(0.55-0.83) 0.75(0.54-1.05)0.71(0.52-0.97)0.86(0.63-1.17)Hazard ratio (95% CI) of all-cause mortalityHazard ratio (95% CI) of CVD mortality0 <6 6-8 9-12Running distance (miles/wk)13-19 20-23 24-30 ≥311.01.000.46(0.31-0.66) 0.58(0.41-0.83) 0.50(0.36-0.70)0.60(0.41-0.86) 0.54(0.28-1.05)0.69(0.41-1.17)0.66(0.37-1.20)0.50.30 <6 6-8 9-12Running distance (miles/wk)13-19 20-23 24-30 ≥311.000.65(0.51-0.84) 0.68(0.56-0.82) 0.67(0.56-0.80)0.71(0.60-0.84) 0.73(0.57-0.93)0.87(0.65-1.15)0 1-2 3 4Running frequency (times/wk)5 6 ≥71.01.000.53(0.33-0.83)0.39(0.25-0.59)0.53(0.38-0.73) 0.53(0.38-0.73)0.72(0.48-1.07)0.88(0.55-1.41)0.50.30 1-2 3 4 5 6Running frequency (times/wk)≥71.000.67(0.55-0.81) 0.71(0.59-0.85) 0.72(0.60-0.87)0.66(0.54-0.80) 0.70(0.49-0.99)0.67(0.46-0.96 )0.88(0.65-1.19)1.00.50.31.00.50.31.00.50.31.00.50.3 0 <506 506-812813-1199Total amount of running (MET-min/wk)1200-18391840-22492250-2943≥2944Nonrunners Q1 Q2 Q3 Q4 Q5-T1 Q5-T2 Q5-T3Total amount of running (MET-min/wk)1.01.000.48(0.33-0.68) 0.51(0.36-0.73)0.61(0.43-0.85) 0.52(0.36-0.74)0.64(0.34-1.19) 0.50(0.25-1.01)0.80(0.47-1.36)0.50.2 0 <506Nonrunners Q1 Q2 Q3 Q4 Q5-T1 Q5-T2 Q5-T3506-812813-11991200-18391840-22492250-2943≥2944FIGURE. Hazard ratios of all-cause and cardiovascular disease (CVD)mortality by weekly running time, distance, frequency, and total amount.Participants were classified into 8 groups: nonrunners and 5 quintiles of each running dose (Q1 to Q5) with the last quintile (Q5) additionallycategorized into 3 tertiles (Q5-T1,Q5-T2, andQ5-T3) using largermarkers (7 groups for running frequency because of limited numbers in7times/wk). All hazard ratios were adjusted for baseline age (years), sex, examination year, smoking status (never, former, or current), alcoholconsumption (heavy drinker or not), other physical activities except running (0, 1-499, or500 metabolic equivalent task minutes per week[MET-min/wk]), and parental CVD (yes or no). The number of participants (number of all-cause deaths)were 42,121 (2857), 2710 (110), 2584(116), 2505 (103), 2647 (112), 850 (33), 822 (30), and898 (52) in the corresponding8 running timegroups fromnonrunners toQ5-T3; 42,121(2857), 2626 (105), 2473 (120), 2961 (123), 2218 (92), 885 (36), 1027 (40), and 826 (40) in running distance; 42,121 (2857), 2757 (62), 3076(105), 2817 (131), 2500 (143), 1215 (66), and 651 (49) in running frequency; and 42,121 (2857), 2609 (109), 2598 (122), 2558 (116), 2626(105), 863 (31), 886 (30), and 876 (43) in total running amount. The number of participants (number of CVD deaths) were 40,319 (1055),2628 (28), 2501 (33), 2435 (33), 2567 (32), 827 (10), 801 (9), and 863 (17) in the corresponding 8 running time groups from nonrunners toQ5-T3; 40,319 (1055), 2550 (29), 2386 (33), 2874 (36), 2156 (30), 858 (9), 1001 (14), and 797 (11) in running distance; 40,319 (1055), 2714(19), 2993 (22), 2725 (39), 2396 (39), 1174 (25), and 620 (18) in running frequency; and 40,319 (1055), 2531 (31), 2508 (32), 2477 (35), 2553(32), 842 (10), 864 (8), and 847 (14) in total running amount. The bars indicate 95% CIs, and hazard ratios appear next to the bars.LETTERS TO THE EDITOR1.19 (0.47-3.02) for all-cause and CVDmortality, respectively, in old individ-uals. Moreover, slow and fast runners(<6.7 vs 6.7 mph, using medianspeed) had similar results, with HRsMayo Clin Proc. n April 2016;91(4):534-541www.mayoclinicproceedings.org(95% CIs) of 1.54 (0.79-2.99) and1.24 (0.37-4.18) for all-cause andCVD mortality, respectively, in slowrunners and 1.41 (0.87-2.28) and 2.47(0.98-6.21) for all-cause and CVDmortality, respectively, in fast runners.Therefore, our findings from a consider-ably larger number of runners anddeaths suggest again that there may beno substantially increased mortality535MAYO CLINIC PROCEEDINGSrisk associated with a higher amountof running, even compared with alower amount of running (which pro-vided the maximal mortality bene-fits), although it is still possible thatmore may be worse. Therefore,further exploration is clearly war-ranted to investigate whether thereis an optimum upper limit of runningbeyond which additional runningproduces adverse health effects.Conclusion. People run not only toimprove health but also for competi-tion, fitness, weight management, stressrelief, socialization, or fun. As a popularand convenient leisure-time physicalactivity, running provides numerousadditional health benefits, includinglower risks of obesity, hypertension,dyslipidemia, type 2 diabetes, stroke,osteoarthritis, and certain cancers.1Many studies, including ours, supportthat a small amount of running, evenbelow the current minimum guidelines(<75 min/wk), can substantially reducemortality risk and extend life. Despitethe study limitations, our results clearlysuggest that regarding running andmortality, “more is not better,” and ourhighest runners (still only in the low tomid 30 miles per week range) had atrend of loss of benefit; nevertheless,these highest runners still had trends oflower mortality than did nonrunnersand only a nonsignificant trend ofhigher mortality than did the lower-dose runners (P.05). Therefore, untilwe have more compelling evidence onrunning doses andmortality, we shouldemphasize that “even a little is great”rather than debating whether “more isbetter or worse” from a public healthperspective.Acknowledgments. We thank theCooper Clinic physicians and techni-cians for collecting the baseline dataand the staff at the Cooper Institutefor data entry and data management.The content of this report is solelythe responsibility of the authors and536does not necessarily represent the offi-cial views of the National Institutes ofHealth.Duck-chul Lee, PhDIowa State UniversityAmesCarl J. Lavie, MDOchsner Clinical School-The University ofQueensland School of MedicineNew Orleans, LAXuemei Sui, MD, PhD, MPHSteven N. Blair, PEDUniversity of South CarolinaColumbiaGrant Support: This study was support by grantsAG06945, HL62508, and DK088195 from theNational Institutes of Health.1. Lavie CJ, Lee D, Sui X, et al. Effects of runningon chronic diseases and cardiovascular and all-cause mortality. Mayo Clin Proc. 2015;90(11):1541-1552.2. Schnohr P, O’Keefe JH, Marott JL, Lange P,Jensen GB. Dose of jogging and long-term mortality:the Copenhagen City Heart Study. J Am Coll Cardiol.2015;65(5):411-419.3. Lee D, Lavie CJ, Vedanthan R. Optimal doseof running for longevity: is more better orworse? [editorial]. J Am Coll Cardiol. 2015;65(5):420-422.4. Williams PT, Thompson PD. Increased cardiovascu-lar disease mortality associated with excessive exer-cise in heart attack survivors. Mayo Clin Proc. 2014;89:1187-1194.5. Lee D, Pate RR, Lavie CJ, Sui X, Church TS,Blair SN. Leisure-time running reduces all-cause and cardiovascular mortality risk [pub-lished correction appears in J Am Coll Cardiol.2014;64(14):1537]. J Am Coll Cardiol. 2014;64(5):472-481.http://dx.doi.org/10.1016/j.mayocp.2016.01.013Factors AffectingBurnout in PhysiciansTo the Editor: I appreciated theinsightful data presented by Shana-felt et al1 in their article in theDecember 2015 issue of Mayo ClinicProceedings, and I share the con-cerns about burnout rates amongphysicians in the United States.Although burnout is undoubtedly amultifactorial issue, one wondersabout the role of recent federalmandates.Speaking as an endocrinologistwho is engaged in the care of patientsdaily, a major source of stress stemsfrom the implementation of electronicmedical records (EMRs), the pressurefrom the federally mandated Mean-ingful Use programs that provide in-centives to physicians who meet theimplementation criteria, and thefinancial penalties imposed on thosewho do not.2 Although the goalsmay be beneficentdie, to track andshare clinical conditions and to usethe information to engage patientsand their familiesdthe reality is thatthe currently employed EMR often re-sults in needlessly complicated tasksfor the physician with questionableclinical benefit to the patient. Inaddition, clinical notes have becomemuch lengthier because of requiredinformation and verbiage, withoutcontaining more relevant data thathave utility for the reader. PhysicianEMR training requires hours tocomplete, while familiarizationwith the system requires monthsof use. In addition, each upgradeof existing systems to meet thenext stage of Meaningful Use iscostly. Indeed, some senior physi-cians in our health care practicegroup have opted to retire earlyrather than be burdened by the“forced” complicated digitization ofpatient records.Another issue relevant to physi-cians concerns obtaining supplies forMedicare patients. No longer is a pre-scription for glucometer strips for aninsulin-dependent diabetic patientsufficient; health care professionalsnow need to justify why a patientneeds to test more than 3 times aday and must periodically completepaperwork attesting to this need.Clinics are asked by some suppliersto keep a copy of patient glucoselogs over a 6-month period. For pa-tients requiring diabetic shoes, Medi-care does not consider a podiatrist’sMayo Clin Proc. n April 2016;91(4):534-541www.mayoclinicproceedings.org

Running and Mortality: Is More Actually Worse?

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Running and Mortality: Is More Actually Worse?

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