Prof Carl Pepine, UF Health Shands Hospital, Gainesville Florida, USA

Carl Pepine, Professor of Medicine, UF Health Shands Hospital, Gainesville Florida, USA, talks to Cardio Debate about the problem of ischaemic heart disease in women and the “WISE” programme (Women’s Ischaemic Syndrome Evaluation).

WISE in an acronym for the Women’s Ischemic Syndrome Evaluation, which grew out of an initiative in our country to address the problem that more women have ischaemic heart disease, more women die of ischeamic heart disease and more women have what’s called ‘normal coronary angiograms’ than men, yet there were no reasonable explanations for those findings.

So in 1996 we were funded to begin a series of projects called the WISE programme.

This was a consecutive case cohort of almost 1000 women recruited from four different sites in the United States. These women all had symptoms and signs of stable ischameic heart disease, and then had to be referred for a coronary angiogram.

We then did various testing routines at the centres and followed the patients, initially for five years, and the more recently we did a 10-year follow up.

And what we found was that among the women who had signs and symptoms of ischaemia, two thirds of the women had no obstructive coronary artery disease, which is in distinct contrast to what you would expect in a comparable cohort of men, where 80-90 per cent of the men would have severe obstructive disease.

Furthermore, we learned that these women had adverse outcomes, and it clearly was not a benign syndrome. The adverse outcomes consisted of an increase in hospitalisation. Most of those hospitalisations were for heart failure, they of course also had myocardial infarctions and strokes in follow-up. But we were surprised at the increase in hospitalisation for heart failure because these women had normal systolic left ventricular function at their baseline coronary angiography.

So when we retrospectively looked at their left ventricular and diastolic blood pressure we found that it was elevated, it was 16. And we also found that in a sample of patients who were hospitalised for these heart failure admissions, that the left ventricular ejection faction was presumed. So this we believe then is a harbinger of heart failure with preserved ejection fraction, which we’re seeing now with increased frequencies, particularly in older women.

So those findings were reported initially, and then as I said extended to a 10-year follow-up. And we basically saw again increasing frequencies of those adverse outcomes.

Multiple studies, much larger and also extending to men, have replicated those findings. Additionally we found that the women who had testing for endothelial dysfunction and testing for coronary microvascular dysfunction had an alarming increase in the adverse outcomes. So it turned out that those two findings were predictors of those two outcomes.

What are the key points?
It’s important to evaluate these women. The evaluation shouldn’t stop with the finding of the so-called ‘normal’ angiogram – that’s because the outcome is clearly not benign.

And the additional evaluation should consist of additional testing for coronary vascular problems such as endothelial dysfunction and microvascular dysfunction.