Women and heart disease: Female hormones protect against heart damage from body clock disruptions

The classic Hollywood portrayal of a man jolted awake at 5 a.m. with crushing chest pain from a heart attack contrasts againstthe more subtle symptoms of heaviness and fatiguein women who suffer cardiac events.

Now medical researchers working to understand that range of symptoms have found major differences in thehearts of male and female mice, and new insight into howthe body clockaffects the sexes differently.

The discovery could openthe door to a betterway 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 werecovered in hospital gowns, doctors and researchersviewed them as one andthe same.

That has proved misguided given that, for one thing,the hormone estrogen influenceshow women are affectedby heart disease, offering some protection before menopause.

Cardiovascular researcher TamiMartino focusseson thedifferences 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,Martinoa biomedical sciences professor at the University ofGuelphemployedmice with a genetic mutation in the cells that keep time, helping the body respond to light and dark signals.In humans, similar cellshelpour 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 shift workers

Thatgenetic "clock" mutation effectively mademale 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 fromcardiomyopathy,a disease of the heart muscle.The researchers found that, in female mice, the presence of estrogen seems to keepthe heart healthyeven whenthe sleep-wake cycle is disrupted.

Martino's experiments, published in the journalCardiovascular 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 muchthe heartmusclestruggled 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 acknowledgedthis week with aNobel 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 to an increasingly 24-hour lifestyle.

Our cellular clocks can be thrown out of synch travelling across time zones or doingshift 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 micefindings opennew 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 maleand female hearts, it presents the possibility of giving men and womenheart 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 femalesdiffer.

Scientists are looking at other ways heart health variesbetween men and women, said Tannenbaum.They've found sex differences in the progenitor, or precursor, stem cells thatrebuild heart muscles, for example.

Personalized medicine for men and women based on the science of sex differences is possible and already happening.- Dr.CaraTannenbaum

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 withdifferent dosesfor 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.