The Lat­est Sci­ence And The (Re­as­sur­ing) Truth

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There’s no doubt run­ning changes your heart. Like all mus­cles, it adapts to the stress of any reg­u­lar en­durance ex­er­cise. Whether th­ese adap­ta­tions are good or bad has been de­bated for over a cen­tury. Re­cently, the oc­ca­sional tragic death at a ma­jor marathon and pe­ri­odic sen­sa­tion­al­ist head­lines have caused con­cern, but rest as­sured that in the cur­rent view of med­i­cal sci­ence the ob­vi­ous changes are, at worst, harm­less. Run­ner’s en­larged heart? That’s stronger mus­cle and big­ger cham­bers to pump more blood, not a sign of heart fail­ure. Low rest­ing heart rate? It’s not a sign of an ar­rhyth­mia (ir­reg­u­lar heart rhythm), as it is in non-run­ners; it’s just that each con­trac­tion pumps so much blood that the heart doesn’t need to beat as of­ten.

In re­cent decades, the de­bate about run­ning and car­diac risk has fo­cused on sud­den deaths at en­durance races. In 1977, Dr Paul Thomp­son a car­di­ol­o­gist and 2:28 marathoner, was run­ning San Fran­cisco’s Bay to Breakers 12K when one such death oc­curred. The tragedy sent Thomp­son on a life­long ca­reer path; he is now per­haps the world’s lead­ing author­ity on the car­diac con­se­quences of run­ning. In 1979, Thomp­son pub­lished re­search on 18 men and women who died dur­ing or im­me­di­ately af­ter run­ning, 13 of whom had heart dis­ease. ‘Su­pe­rior phys­i­cal fit­ness does not guar­an­tee pro­tec­tion against ex­er­cise deaths,’ he warned.

Such deaths were in­cred­i­bly rare in the 1970s, partly be­cause run­ning as a mass-par­tic­i­pa­tion sport was new. But as the global num­bers of marathon fin­ish­ers have grown ex­po­nen­tially, so, sadly, have the tragic deaths such as that of Cap­tain David Seath at last year’s London Marathon. Th­ese in­ci­dents gen­er­ate head­lines and pro­vide am­mu­ni­tion for those who ar­gue that run­ning is dan­ger­ous, but the truth is, when run­ners younger than 40 die dur­ing a race, it’s usu­ally due to an un­di­ag­nosed ge­netic heart ab­nor­mal­ity; when older par­tic­i­pants die, they usu­ally had pre-ex­ist­ing heart dis­ease. Some­times, there’s no ex­pla­na­tion. What­ever the cause, the heart’s elec­tri­cal sys­tem goes hay­wire, caus­ing an ar­rhyth­mia called ven­tric­u­lar fib­ril­la­tion, in which the heart stops pump­ing blood.

If that were the whole story, the case against run­ning would be eas­ily dis­missed. Yes, vig­or­ous ac­tiv­ity tem­po­rar­ily raises your risk of car­diac ar­rest. But reg­u­lar ex­er­cise has such a dra­matic ef­fect on other car­diac risk fac­tors such as blood pres­sure, obe­sity and choles­terol, that its pro­tec­tive ben­e­fits dur­ing your non-ex­er­cis­ing hours swamp any risks dur­ing ex­er­cise.

That’s not the whole story, though. Re­cently the dis­cus­sion has fo­cused less on sud­den deaths, and more on the pos­si­bil­ity that decades of run­ning can cause wear and tear on your heart. Ac­cord­ing to this the­ory, each marathon pushes your heart a lit­tle be­yond its lim­its, and over time all the vig­or­ous beat­ing leads to fi­bro­sis, or scar­ring. That fi­bro­sis, along with other dam­age, might lead to atrial fib­ril­la­tion (rapid and ir­reg­u­lar heart­beat). And the tur­bu­lent flow of blood through your coro­nary ar­ter­ies dur­ing run­ning might con­trib­ute to the for­ma­tion of artery- clog­ging plaques, rais­ing heart at­tack risk.

This means, in the­ory, that longterm run­ners should be less healthy and long-lived. It’s only now, four decades af­ter the first run­ning boom, that we have large num­bers of peo­ple en­ter­ing their re­tire­ment years hav­ing run for most of their adult lives. And their mor­tal­ity statis­tics re­veal that – well, in­ter­pret­ing those stats is what sci­en­tists have been ar­gu­ing about, the me­dia have been sen­sa­tion­al­is­ing, and non-run­ning col­leagues have been lec­tur­ing you about.

AT­TACK AND RE­SPONSE This de­bate erupted at the 2012 Amer­i­can Col­lege of Sports Medicine (ACSM) meet­ing in San Fran­cisco. Epi­demi­ol­o­gist Dr Duck- chul Lee pre­sented an anal­y­sis of more than 50,000 pa­tients who had vis­ited the Cooper Clinic in Texas be­tween 1971 and 2002, in­clud­ing 14,000 reg­u­lar run­ners. The good news: 15 years af­ter their ini­tial vis­its, the run­ners were 19 per cent less likely to have died than the non-run­ners. The bad news: those ben­e­fits ac­crued pri­mar­ily to those run­ning less than 20 miles per week. Those who ran more were sta­tis­ti­cally no bet­ter off than non-run­ners.

Shortly af­ter­wards, car­di­ol­o­gist Dr James O’keefe pub­lished a re­view in the Mayo Clinic Pro­ceed­ings, sum­maris­ing the po­ten­tial neg­a­tive car­diac ef­fects of too much run­ning: fi­bro­sis, cal­ci­fied ar­ter­ies, ar­rhyth­mias. It was a po­tent com­bi­na­tion-punch: O’keefe’s pa­per ex­plain­ing what could go wrong and Lee’s data seem­ingly pro­vid­ing ev­i­dence that it was hap­pen­ing. News out­lets around the world picked up the story, am­pli­fied on so­cial me­dia by a mix of fear and schaden­freude: ‘Yous­mu­grun­nersstill thinkyou’re­so­healthy,eh?’

Later in 2012, O’keefe and car­di­ol­o­gist Dr Carl J Lavie ar­gued in the jour­nal Heart that vig­or­ous ex­er­cise should be lim­ited to 30-50 min­utes a day. ‘In con­trast,’ they wrote, ‘run­ning too fast, too far and for too many years may speed one’s progress to­wards the fin­ish line of life.’ Again, this was cat­nip to head­line writ­ers. That pat­tern re­curred over the next few years: be­tween 2012 and 2015, O’keefe alone wrote more than a dozen aca­demic pub­li­ca­tions about the dan­gers of ex­ces­sive en­durance train­ing, mostly re­fer­ring to the ear­lier re­search. With rep­e­ti­tion, the head­lines be­came in­creas­ingly fa­mil­iar and the claims be­gan to feel like fact.

But the ev­i­dence was still very much in dis­pute. The next study to garner head­lines about the risks of run­ning, from re­searchers in Copen­hagen, drew con­clu­sions from just two deaths among ‘stren­u­ous’ run­ners – a sta­tis­ti­cally du­bi­ous claim that in­cited an avalanche of crit­i­cism. Lee’s data from 2012, though fre­quently cited as ev­i­dence of run­ning’s deadly po­ten­tial, still hadn’t gone through peer re­view to be pub­lished in an aca­demic jour­nal. In a 2013 re­sponse to O’keefe and Lavie’s Heart ed­i­to­rial, car­dio­vas­cu­lar re­searcher Dr Thomas We­ber pointed out a flaw in Lee’s sta­tis­ti­cal anal­y­sis: The re­searchers had ‘ad­justed’ the data to elim­i­nate dif­fer­ences in body mass in­dex, blood pres­sure and choles­terol lev­els – the risk fac­tors that run­ning would be ex­pected to lower. ‘ This

rep­re­sents a se­lec­tive in­ter­pre­ta­tion of the data, at the best,’ wrote We­ber.

We­ber high­lighted a ma­jor chal­lenge of this type of re­search: how do you com­pare groups of peo­ple with widely dif­fer­ing be­hav­iours and phys­i­cal char­ac­ter­is­tics? ‘Sta­tis­ti­cal ad­just­ment’ was used to cor­rect for th­ese dif­fer­ences in the Cooper Clinic sub­jects, in ef­fect al­low­ing them to com­pare groups as if every­one had the same age, smok­ing his­tory, etc. But this breaks down when the dif­fer­ences be­tween the groups are a di­rect con­se­quence of the be­hav­iour you’re study­ing. Com­par­ing death rates of smok­ers and non-smok­ers, you might find smok­ers have higher rates of lung cancer. But it would be wrong to ‘ sta­tis­ti­cally ad­just’ the re­sults to make the group’s rates of lung cancer equal, be­cause smok­ing causes lung cancer, which, in turn, raises death rates. The dif­fer­ence in lung cancer rates isn’t a fluke to be brushed aside; it’s the whole point! Sim­i­larly, run­ning is known to lower BMI, blood pres­sure and choles­terol lev­els, which low­ers heart dis­ease risk. By equal­is­ing th­ese pa­ram­e­ters, the re­searchers were in ef­fect say­ing: if you ig­nore the known health ben­e­fits of run­ning, run­ning has no health ben­e­fits.

Lee and his col­leagues fi­nally pub­lished their peer-re­viewed Cooper Clinic data in 2014, with no sta­tis­ti­cal ad­just­ment and a very dif­fer­ent mes­sage. In­stead of warn­ing about the dan­gers of run­ning more than 20 miles a week, they em­pha­sised the dra­matic re­duc­tion in risk of dy­ing from heart dis­ease from run­ning just five to 10 min­utes a day. Run­ning fur­ther they said, didn’t of­fer fur­ther ben­e­fits, but nei­ther did it make things worse.

Me­dia re­ac­tion was muted. ‘ The press loves the “ex­er­cise is bad” story,’ says Lavie. ‘ We wanted to em­pha­sise that even a lit­tle run­ning is good.’ Still, the de­bate was far from over. MORE OR LESS? On the first day of 2016’s ACSM con­fer­ence, the world’s lead­ing ex­perts gath­ered for a sym­po­sium called ‘Op­ti­mal Dose of Run­ning for Health: Is More Bet­ter or Worse?’. Lee, Lavie and Thomp­son were joined by Dr Paul Wil­liams, a bio­statis­ti­cian whose re­search on run­ners has been fol­low­ing 156,000 men and women since the early 1990s.

Lee em­pha­sised the ben­e­fits of just a lit­tle vig­or­ous ex­er­cise (five to 10 min­utes a day). He also said that even in the very top mileage sub­group of his sub­jects, there was no sta­tis­ti­cally sig­nif­i­cant in­crease in car­diac risk. ‘It doesn’t sup­port that more is worse,’ Lee said. ‘But more may not be bet­ter.’

Wil­liams ar­gued that more re­ally is bet­ter. His 156,000 sub­jects, many ini­tially re­cruited from Run­ner’s

World sub­scribers in the US, walk or run 156 mil­lion miles per year, giv­ing him masses of data. He has pub­lished 65 stud­ies on how run­ning af­fects con­di­tions rang­ing from di­a­betes to cataracts, Alzheimer’s and breast cancer. In nearly ev­ery case, not only does run­ning help, but more is bet­ter. For ex­am­ple, men run­ning at least 40 miles a week were 26 per cent less likely to de­velop coro­nary heart dis­ease than those run­ning 13. Why the ap­par­ent con­tra­dic­tion with Lee’s re­sults? Wil­liams per­mit­ted him­self a smile when the ques­tion was posed dur­ing the Q& A ses­sion. ‘At 156,000 sub­jects, we’re big­ger than they are,’ he said. ‘So I’ll stand be­hind our data.’

While that data is re­as­sur­ing for most run­ners, it doesn’t tell us much about those at the ex­tremes of the dis­tance curve. For them, we need to look at what changes and what po­ten­tial warn­ing signs ap­pear in their hearts af­ter decades of train­ing. Later at the con­fer­ence Lavie and Thomp­son of­fered the car­di­ol­o­gist’s per­spec­tive on th­ese changes.

The most well doc­u­mented risk is atrial fib­ril­la­tion, the most com­mon

of the ir­reg­u­lar or ab­nor­mal heart rhythms known as ar­rhyth­mias. Stud­ies have linked atrial fib­ril­la­tion to cu­mu­la­tive years of ex­er­cise. While the con­di­tion can raise stroke risk when com­bined with other risk fac­tors such as high blood pres­sure, it’s gen­er­ally more in­con­ve­nience than im­mi­nent threat. Not every­one agrees run­ning is a risk fac­tor – in Wil­liams’ data, those run­ning 39+ miles per week were least likely to re­port car­diac ar­rhyth­mias – but Thomp­son and many oth­ers are con­vinced it is.

More con­cern­ing is the pos­si­bil­ity that high doses of ex­er­cise cause ath­er­o­scle­ro­sis, as cal­cium- rich plaques ac­cu­mu­late in the ar­ter­ies lead­ing to your heart. This was di­ag­nosed in 1968 Bos­ton Marathon win­ner Amby Bur­foot (see I ♥ Run­ning, left). The re­sult­ing nar­rowed, stiff­ened ar­ter­ies can re­duce blood sup­ply to the heart, or a plaque can rup­ture, trig­ger­ing a heart-at­tack-in­duc­ing block­age. It’s pos­si­ble that the rush of blood through th­ese ar­ter­ies dur­ing ex­er­cise ac­cel­er­ates plaque for­ma­tion, or that ex­er­cise al­ters hor­mone lev­els as­so­ci­ated with plaques. It’s also pos­si­ble peo­ple who run most are dif­fer­ent in other ways, Lavie noted: ‘They may have ex­treme per­son­al­i­ties, so they’re al­ways men­tally stressed, sleep-de­prived and so on.’

Even less clear is whether plaques in marathon­ers’ ar­ter­ies pose the same risks as plaques in non-run­ners. Denser plaques ac­tu­ally lower heart dis­ease risk, Thomp­son said, and there’s mount­ing ev­i­dence that marathon­ers tend to have dense, sta­ble plaques that are much less likely to rup­ture and cause a block­age. Data pre­sented by re­searchers from var­i­ous London hos­pi­tals to the Euro­pean So­ci­ety of Car­di­ol­ogy in 2015 showed long-term run­ners had more highly cal­ci­fied ar­ter­ies if they clocked 35+ miles a week. But more than 70 per cent of plaques in male ath­letes were dense, sta­ble plaques, com­pared with just 30 per cent in non-ath­letes. ‘For me,’ says car­di­ol­o­gist Ahmed Merghani, who led the study, ‘what a plaque looks like is more im­por­tant than the pres­ence or ab­sence of ath­er­o­scle­ro­sis.’

Per­haps the most con­tro­ver­sial topic is fi­bro­sis, patches of scar tis­sue that may ac­cu­mu­late in the heart and could con­trib­ute to other con­di­tions, such as atrial fib­ril­la­tion. In 2011, UK re­searchers ex­am­ined the hearts of 12 vet­eran ath­letes who had been train­ing hard for an av­er­age of 43 years and had com­pleted an av­er­age of 178 marathons, 65 ul­tra marathons and four Iron­man triathlons each. Half of them showed signs of fi­bro­sis – ‘an un­ex­pect­edly high preva­lence’. In con­trast, last year, Ger­man sci­en­tists as­sem­bled 33 equally re­mark­able masters en­durance ath­letes, with an av­er­age age of 45 and in­clud­ing for­mer Olympians, a marathon cham­pion and Iron­man win­ners, and found no ev­i­dence of ex­er­ci­sein­duced fi­bro­sis. Thomp­son’s take: The phe­nom­e­non is prob­a­bly real, but very rare. THE HEART OF THE MAT­TER All this is pretty con­fus­ing. The hearts of long­time run­ners are dif­fer­ent, it seems, but the con­se­quences are un­clear. More clar­ity would come from a clin­i­cal trial in which peo­ple were as­signed to run var­i­ous weekly dis­tances for decades. ‘ But that’s im­pos­si­ble,’ says Lavie. And so we are stuck mak­ing our de­ci­sions with im­per­fect in­for­ma­tion.

Even with bet­ter in­for­ma­tion, we’d still be left to roll the dice, as we do in count­less de­ci­sions ev­ery day. What if it turned out that run­ning 40+ miles a week would ex­tend life by two years for 99 per cent of peo­ple, but shorten it by 10 years for the other one per cent? Would you carry on? Such de­ci­sions are deeply un­com­fort­able, which is why we avoid think­ing about them when we, say, take an an­tibi­otic or step out­side on a sunny day. That’s why, for Thomp­son, the fruits of the de­bate are ‘in­tel­lec­tu­ally in­ter­est­ing, clin­i­cally worth know­ing, but not worth wor­ry­ing about’.

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