More non-cardiac death explains higher rate of post-PCI mortality in females

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Rajiv Gulati

According to a new study, the higher rate of all-cause mortality after percutaneous coronary intervention (PCI) in females relates to an excess of non-cardiac death. Furthermore, the study shows that the causes of non-cardiac death in women after PCI are different from those of men.

Claire E Raphael (Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA) and others report in Circulation: Cardiovascular Interventions that the reason why women have higher long-term mortality after PCI compared with men “has been uncertain”. They note that the potential reasons may relate to the fact that women, generally, are older and have greater comorbidity when they undergo PCI than when men do or may relate to “undefined sex-specific factors”.

Additionally, the authors observe, previous studies reviewing sex differences after PCI focused on all-cause mortality rather than cause-specific mortality. “Cause-specific mortality represents a more useful synthesis of baseline risk factors than all-cause mortality because it enables separation of the influence of cardiac and non-cardiac death,” they comment.

Thus, they performed a single-centre study “using rigorously ascertained cause-specific mortality” to evaluate long-term trends in causes of death in women compared with men after PCI, examine the effect of baseline risk on final cause of death to determine whether there is a sex-specific biological factor, and determine specific causes of death in women and men.

Using data from the Mayo Clinic PCI registry, the authors reviewed data from 16,280 men and 6,847 women who underwent PCI between 1991 and 2012. They found that in an unadjusted analysis, all-cause mortality was significantly higher in women and this excess was because of non-cardiac deaths. Similar to findings of previous studies, Raphael et al found that across three time periods (1991–1997, 1998–2005, and 2006–2012) “there was a temporal shift from predominantly cardiac death to predominantly non-cardiac death in both sexes”.  They add that this shift may “in part” be related to the increased use of secondary prevention measures that has been observed in both sexes.

After adjusting for age and comorbidities, the shift from predominantly cardiac death to non-cardiac death remained. However, in this adjusted analysis, the incidence non-cardiac death was no longer higher in women. There was also no significant difference in the incidence in cardiac death between men and women.

In the contemporary era (2006–2012), the cumulative five-year incidence of myocardial infarction/sudden cardiac death was similar in men and women. However, Raphael et al note “nominally more women died of heart failure”. They add that, in terms of non-cardiac death, women were more likely to die of chronic diseases while men more were likely to die of cancer. The authors observe: “After adjustment for age and baseline comorbidities, there was no difference in heart failure or chronic disease deaths between the sexes; however, the higher rates of cancer in males compared with females remained.”

Acknowledging that the differences in causes of non-cardiac death between men and women after PCI “likely result from differences in baseline risk in women and men”, Raphael et al comment that they “do suggest sex-specific differences in long-term healthcare needs after PCI”.

“Although women had higher unadjusted rates of all-cause mortality compared with men, this is because of an excess of non-cardiac than cardiac deaths with no evidence of a sex-specific biological factor,” the authors conclude.

Study author Rajiv Gulati (Department of Cardiovascular Diseases, Mayo Clinic, Rochester, USA) told Cardiovascular News that why women who undergo PCI tend to be older and have more comorbidity than men who undergo PCI is “not really known”. However, he says that possible explanations include coronary artery disease beginning later or becoming severe/symptomatic later in women; women not coming to medical attention or not being referred for invasive studies, until later than men. Regarding the fact that non-cardiac death was behind the increased mortality in women, Gulati comments: “By virtue of an older age at presentation, more non-cardiac comorbidities would have been accumulated thereby increasing the risk for non-cardiac death.  We have to remember the issue of competing risks – everyone has to die of something. “

In terms of preventing non-cardiac death in both men and women, he says that the focus should still be preventative cardiac deaths. “While cardiac death risk has declined, there are continued opportunities for improvement. These might include strategies to increase uptake and use of secondary preventative medications that already have proven prognostic benefit, use of newer therapies in lipid and heart-failure management, and pursuit of completeness of revascularisation. Stressing improved lifestyle measures such as tobacco avoidance, improved diet and levels of activity will likely also have an effect at reducing non-cardiac deaths (certain cancers) as well as cardiac deaths,” Gulati observes.

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