Women and heart disease: Fe­male

The Miracle - - Front Page - By:CBC’s Amina Za­far

For 1st time, sci­en­tists see how es­tro­gen pro­tects the fe­male heart dur­ing sleep-wake cy­cle

The clas­sic Hol­ly­wood por­trayal of a man jolted awake at 5 a.m. with crush­ing chest pain from a heart at­tack con­trasts against the more sub­tle symp­toms of heav­i­ness and fa­tigue in women who suf­fer car­diac events. Now med­i­cal re­searchers work­ing to un­der­stand that range of symp­toms have found ma­jor dif­fer­ences in the hearts of male and fe­male mice, and new in­sight into how the body clock af­fects the sexes dif­fer­ently. The dis­cov­ery could open the door to a bet­ter way of un­der­stand­ing heart disease. To move for­ward, sci­en­tists first had to take a step back to ex­am­ine how heart disease man­i­fests dif­fer­ently in men and women. His­tor­i­cally, though men and women vary in size, shape and more, once male and fe­male pa­tients were cov­ered in hos­pi­tal gowns, doc­tors and re­searchers viewed them as one and the same. That has proved mis­guided given that, for one thing, the hor­mone es­tro­gen in­flu­ences how women are af­fected by heart disease, of­fer­ing some pro­tec­tion be­fore menopause. Car­dio­vas­cu­lar re­searcher Tami Martino fo­cusses on the dif­fer­ences in how male and fe­male hearts re­spond to time-of-day sig­nals. It turns out that the cir­ca­dian clock, the body’s chief time­keeper, may of­fer fe­male hearts more pro­tec­tion against heart disease. In her study, Martino — a bio­med­i­cal sciences pro­fes­sor at the Univer­sity of Guelph — em­ployed mice with a ge­netic mu­ta­tion in the cells that keep time, help­ing the body re­spond to light and dark sig­nals. In hu­mans, sim­i­lar cells help our bod­ies to rev up af­ter we awaken and to rest at night. It is “the first time that any­body’s been able to look at how the fe­male heart is pro­tected and specif­i­cally how the cir­ca­dian mech­a­nism helps to pro­tect against that as well,” said Martino. Ro­dent d shift hif work­ers k That ge­netic “clock” mu­ta­tion ef­fec­tively made male and fe­male mice into the equiv­a­lent of shift work­ers. But only the ag­ing male mice showed cir­ca­dian sys­tems that were out of whack, which took a toll on their hearts. A healthy cir­ca­dian clock pro­tects the heart from car­diomy­opa­thy, a disease of the heart mus­cle. The re­searchers found that, in fe­male mice, the pres­ence of es­tro­gen seems to keep the heart healthy even when the sleep-wake cy­cle is dis­rupted. Martino’s ex­per­i­ments, pub­lished in the journal Car­dio­vas­cu­lar Re­search, also ex­am­ined the ef­fects of ovar­ian hor­mones in pro­tect­ing fe­male mice aged to the equiv­a­lent of 70 to 90 years in hu­mans. As soon as in­ves­ti­ga­tors re­moved ovaries from fe­male mice, the ro­dents de­vel­oped heart disease. The re­searchers mea­sured how much the heart mus­cle strug­gled to keep up with en­ergy de­mands, and found they fared worse. This work could be an im­por­tant step to­ward un­der­stand­ing how women’s bod­ies can cope with liv­ing much longer past menopause than gen­er­a­tions past, with­out the heart-pro­tect­ing ben­e­fits of es­tro­gen. Martino’s re­search builds on work ac­knowl­edged this week with a No­bel Prize in Phys­i­ol­ogy or Medicine. The Swedish academy hon­oured three U.S.-born sci­en­tists for their “dis­cov­er­ies of molec­u­lar mech­a­nisms con­trol­ling the cir­ca­dian rhythm” in fruit fly mod­els. This area of re­search is help­ing to shed light into how we can adapt p to an in­creas­ingly g y 24- hour life­style. Our cel­lu­lar clocks can be thrown out of synch trav­el­ling across time zones or do­ing shift work, for ex­am­ple. Now sci­en­tists are in­ves­ti­gat­ing what hap­pens when we burn the can­dle at both ends be­cause of “social jet lag” — hec­tic sched­ules that lead peo­ple to sleep in on week­ends af­ter go­ing too hard all week. For Martino and her col­leagues, the mice find­ings open new av­enues to ex­plore. “The idea is now if women are go­ing to be de­vel­op­ing heart disease, why is this hap­pen­ing? Why were they pro­tected ear­lier on? Why do they lose that pro­tec­tion? Be­cause now if you take away the hor­mones as they get older, they’re go­ing to be sus­cep­ti­ble to social jet lag. They’re go­ing to be sus­cep­ti­ble to sleep dis­or­ders.” Cul­ture change com­ing If body clocks re­spond dif­fer­ently in male and fe­male hearts, it presents the pos­si­bil­ity of giv­ing men and women heart med­i­ca­tions at dif­fer­ent times of day, she said. For Dr. Cara Tan­nen­baum, sci­en­tific direc­tor of the Cana­dian In­sti­tutes of Health Re­search’s Gen­der and Health, the find­ings are an ex­cit­ing con­fir­ma­tion of how males and fe­males dif­fer. Sci­en­tists are look­ing at other ways heart health varies be­tween men and women, said Tan­nen­baum. They’ve found sex dif­fer­ences in the pro­gen­i­tor, or pre­cur­sor, stem cells that re­build heart mus­cles, for ex­am­ple. Still, it will take “a bit of a cul­ture change,” for med­i­cal re­search to catch up on how treat­ment should dif­fer be­tween the sexes, said Tan­nen­baum. “We’re get­ting there.” One ex­am­ple: Health Canada warned that pre­scrip­tion sleep­ing pills con­tain­ing zolpi­derm, sold as Am­bien, should be pre­scribed with dif­fer­ent doses for men and women. “This ex­am­ple re­flects the con­cept that per­son­al­ized medicine for men and women based on the sci­ence of sex dif­fer­ences is pos­si­ble and al­ready hap­pen­ing,” Tan­nen­baum said.

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