Actress and writer Carrie Fisher, who died earlier this week after suffering a cardiac event on a flight, was not only an entertainment icon, but also a prominent mental health advocate. Fisher was well known for being outspoken about her experiences with drug and alcohol addiction and bipolar disorder, which she was diagnosed with in her early twenties, and she frequently wrote about them in articles and her best-selling 2008 memoir Wishful Drinking (Simon & Schuster). Her voice countered the stigma surrounding psychiatric disorders and helped support others with similar struggles—sometimes directly.

In an advice column she wrote for The Guardian just last month Fisher offered guidance to a young adult with bipolar disorder. In it, she explains that she initially rejected the bipolar disorder diagnosis she received at the age of 24, only accepting it at age 28, “when I overdosed and finally got sober. Only then was I able to see nothing else could explain away my behavior.” She emphasized the importance of connecting with others who have the disorder, adding, “We have been given a challenging illness, and there is no other option than to meet those challenges.”

Some have conjectured that Fisher’s earlier substance abuse and struggles with her weight may have contributed to her death, with medical doctors weighing in about the cardiovascular dangers of cocaine in particular. Though these hypotheses are speculative, one possibility that has been overlooked is the influence of her bipolar disorder, which has been linked in several studies to cardiovascular disease and mortality.

This association “has been confirmed in representative and population-wide studies and approximates a two-fold increased risk—that is, persons with bipolar disorder are about twice as likely to develop or die from cardiovascular disease than would otherwise be expected,” says Jess Fiedorowicz, an associate professor of psychiatry, internal medicine and epidemiology at the University of Iowa, who published a study on this topic in 2009 in Psychosomatic Medicine. “Importantly, the onset of cardiovascular disease occurs very prematurely among people with bipolar disorder, up to 17 years earlier than in the general population,” adds Benjamin Goldstein, a child and adolescent psychiatrist at the University of Toronto, who published a related study in 2015 in Circulation.

The possible factors underlying the connection are numerous and often overlapping. “Negative lifestyle behaviors, including suboptimal nutrition, being sedentary, cigarette smoking, and excessive use of alcohol and substances are more common among people with bipolar disorder,” says Goldstein. “The distress of the mood symptoms of mania and depression that define bipolar disorder, and the life stress that occurs as a consequence of symptoms, further adds to cardiovascular risk.”

Additionally, individuals with bipolar disorder are less likely to be screened for cardiovascular disease risk factors. “Even when these risk factors are identified, they are less likely to be prescribed the appropriate treatments, and patients may be less likely to consistently adhere to them” when they are prescribed the right medications, notes Fiedorowicz. In addition, many of the medications used to treat bipolar disorder may cause adverse effects “such as weight gain, increases in triglycerides, diabetes mellitus and even sudden cardiac death due to arrhythmia,” he says. Another potential influence is bipolar disorder’s effect on the hypothalamic-pituitary-adrenal axis and the autonomic nervous system, which are activated both by acute stress and by bipolar mood states.

The magnitude of the elevated heart disease risk in people with bipolar disorder, however, exceeds the effects of traditional cardiovascular risk factors, suggesting the possibility of shared causes between the two diseases. “For example, episodes of mania and depression have been linked with increased levels of inflammation, which in turn is known to increase the risk of heart disease,” explains Goldstein. “There is also evidence of problems with the function and structure of blood vessels among people with bipolar disorder, and this occurs in the brain as well as the body.” He and colleagues are currently exploring the role of tiny “microvessels” in these processes.

Future research should focus on exploring these and other possible mechanisms, as well as interventional studies regarding targeted cardiovascular risk reduction strategies that would “take into consideration barriers to optimal heart health that are unique to people with bipolar disorder,” Goldstein says. On the treatment front, there is also a “need to disseminate the types of health care delivery models that can provide integrated psychiatric and other medical care to those with bipolar and related disorders,” Fiedorowicz adds.

While Fisher fit the bill for at least several of these risk factors at different points in her life, there is no definitive way to know whether her bipolar disorder or addiction history contributed to her death. It is clear, though, that an invaluable advocate for mental health has been lost. In that November column in The Guardian, she told the advice-seeker, “Think of [your diagnosis] as an opportunity to be heroic… an emotional survival. An opportunity to be a good example to others who might share our disorder.” She certainly accomplished that in her own life.