Women have advantage with some types of CHF
Women have advantage with some types of CHF
Observers intrigued, but more research needed
A study from the University of North Carolina in Chapel Hill reports that under some specific conditions, women with severe heart failure had better survival than men with similar disease.
Kirkwood F. Adams Jr., MD, and his team re-examined FIRST data (Flolan International Randomized Survival Trial) to compare the outcomes of men and women who had either NYHA Class III B or IV heart failure.
Difference in non-ischemic disease
In the study group, men were more likely to be white and have developed their CHF after suffering ischemic heart disease. But when comparing only the patients who developed CHF from non-ischemic causes, men had three times the relative risk of death than women. The researchers did not find statistically significant difference in risk between the sexes in ischemic-based CHF.
The original study, FIRST, assembled 471 patients to test the drug. (The FIRST trial was stopped early because of higher mortality among subjects taking the drug.)
The patients had these characteristics of end-stage heart failure:
severe left-ventricular ejection fraction of 18 +/- 4.9%; standard drug therapy regimen including a loop diuretic, digitalis, and ACE inhibitor for at least a month; cardiac index of less than 2.2 L • min-1 • m2; pulmonary wedge pressure greater than 15 mmHg (unless on intravenous vasoactive drugs).Patients also received non-invasive tests, which included a six-minute walk test. Parti-cipants were then assigned to one of four primary CHF causes: ischemic, hypertensive, idiopathic, or other.
The patients were randomized to the drug or standard CHF care and followed up with clinical visits after two weeks and one month, then returned monthly. Home health visits were also used to make sure patients were seen at least twice a month.
In addition to gender of the patient, the original study was designed with these CHF characteristics as patient variables:
age;race;
height, weight, body surface area, and body mass;
geographic location by continent;
primary cause of CHF;
NYHA functional class;
use of dobutamine at baseline;
diabetes history;
CHF duration;
atrial fibrillation;
serum sodium;
serum creatinine;
cardiac index;
pulmonary artery wedge pressure;
right atrial pressure;
systolic blood pressure;
mean pulmonary artery pressure;
heart rate;
left-ventricular ejection fraction;
six-minute walk test results;
group randomization.
Women won in the survival comparisons after many statistical adjustments.
Adams’ team corrected for CHF variables in many different ways, but women still had increased survival in cases of non-ischemic heart disease. The trend of men having about twice the risk of death held whether the team adjusted for the long list of baseline characteristics, those that were found to be independent predictors of survival, or omitted results on the walk test.
Some observers say they find the study and results interesting.
"It’s a confirmatory finding," says Amparo C. Villablanca, MD, director of the Women’s Cardiovascular Health Program and clinic at the University of California, Davis, School of Medicine. The Framingham Heart Study has made similar findings, she says, so the concept that women may have a survival advantage in some types of heart failure is not new.
The study is helpful, she says, because it hints at how the cause of the heart failure can make a difference in patient survival.
Villablanca says a caveat of the study was the results of the formal interaction testing. When the researchers tested the relationship between the cause of heart failure and the association of gender with outcome, the result was not statistically significant. But when they performed a stratified analysis based on whether ischemic or non-ischemic disease caused the heart failure, the result was statistically significant. "It really depended on how they looked at it."
Villablanca adds the study is interesting because it showed fewer patients died overall who had ischemic-based CHF, compared to patients who had non-ischemic disease.
It’s important to remember the study was only reporting on a subset of all the people with heart failure, Villablanca says, considering the majority of heart failure cases occur as a result of ischemic heart disease.
And another consideration is that women who infarct usually go on to do worse than men who have a myocardial infarction, says Marjorie Stanek, MD, director of the Women’s Heart program at Albert Einstein Medical Center in Philadelphia.
Both Villablanca and Stanek say it also would have been interesting to know if any of the female subjects were on hormone replacement therapy. But both say it’s a good continuation of looking at how heart disease affects women.
Interesting details of the study
The FIRST trial used a six-minute walk test to help assess the extent of the subject’s heart failure. Overall, women could not walk as far during that time as men could, although women had a better chance for survival. The difference in performance can be attributed to several different facets of the patients, say Stanek and Villablanca.
First, overall, women in the study were older than the men. With age could have come comorbidities or just age-related symptoms that could have kept women from walking as far as men.
Also, men may tend to push a little harder during exercise, says Stanek, who is also the director at Einstein’s cardiac stress lab.
The walk test was not the sole determinant of severity of disease, adds Villablanca, noting the original study looked at factors such as use of Dobutamine at the onset of the research.
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