PracticeUpdate: Cardiology

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Excess CV risk in women linked to very low
coronary flow reserve, not obstructive disease
Excess cardiovascular risk in
women relative to men with
stable ischaemic heart disease
symptoms, who were referred
for coronary angiography, has
been shown to be associated
with severely impaired
coronary flow reserve, not
obstructive disease.
This conclusion was based on results of a 3-year, single-centre observational
study led by Viviany R. Taqueti, MD, MPH, of Brigham and Women’s Hospital,
Boston, Massachusetts.
Over the last 3 decades, case fatality rates for cardiovascular disease in the US
have been higher for women than for men, yet obstructive coronary artery disease is
less prevalent in women, leading to an unexplained “coronary artery disease paradox”
for women and heart disease.
As Dr Taqueti explained, “While luminal coronary angiography may be the
gold standard for diagnosing obstructive coronary artery disease – and remains a
cornerstone of care in patients with cardiovascular disease – it is not used to evaluate
how well the coronary arteries can respond to and accommodate normal stress (as
captured by coronary blood flow reserve) and often misses diffuse atherosclerosis
and small-vessel disease because technique resolution is limited.
And yet, growing data suggest that diffuse atherosclerosis and small-vessel disease
may contribute to adverse cardiovascular events including acute coronary syndromes,
heart failure, and death due to cardiovascular disease from plaque erosion, impaired
coronary vasoreactivity, and microvascular dysfunction.
Coronary flow reserve, as assessed noninvasively using stress testing with positron
emission tomography, provides a combined physiologic measure of large- and small-
vessel coronary artery disease and myocardial ischaemia. Coronary flow reserve
assessment also identifies patients at risk of cardiovascular events, independent of
traditional measures of stress-induced ischaemia and left ventricular ejection fraction.
Coronary flow reserve has not been measured routinely in clinical practice.
Hypothesising that some of the excess risk in women may be attributable to
impaired coronary flow reserve rather than visible plaque, Dr Taqueti and colleagues
sought to investigate the impact of sex, coronary flow reserve, and the severity of
angiographic coronary artery disease on adverse cardiovascular events.
They followed 329 consecutive patients (43% women) referred for invasive coronary
angiography after stress testing with positron emission tomographic myocardial
perfusion and with preserved left ventricular ejection fraction for a median of
3 years for a composite endpoint of major adverse cardiovascular events, including
cardiovascular death and hospitalisation for nonfatal myocardial infarction or heart
failure.
When stratified by sex and coronary flow reserve, only women with severely
impaired coronary flow reserve demonstrated significantly increased adjusted risk
of cardiovascular disease events (P < 0.0001, P for interaction 0.04). Interestingly,
the differential effect of sex on outcomes was amplified in patients with very low
coronary flow reserve (<1.6), in whom more men than women harboured multivessel
obstructive coronary artery disease and underwent surgical revascularisation, possibly
mitigating their risk.
Thus, though symptomatic high-risk women demonstrated a significantly lower
burden of obstructive coronary artery disease relative to men, they were not protected
from cardiovascular disease events. Dr Taqueti noted, “The excess cardiovascular risk
in women was independently associated with impaired coronary flow reserve, which
may have represented a hidden biological risk, and a phenotype less amenable to
revascularisation, a treatment strategy fundamentally targeted at opening or bypassing
obstructive plaques”.
Dr Taqueti stated, “Our results suggest that current therapies, possibly in a sex-
specific manner, are insufficient to restore coronary vascular function. A clearer
understanding of the relationship between microvascular dysfunction and conditions
comorbid with coronary artery disease, including insulin resistance and heart failure,
may guide development of novel systemic therapies to harness the benefit of more
‘complete revascularisation’ in a manner not defined by anatomy alone.”
She added, “Coronary flow reserve may represent an important biomarker of risk
not only for prospective studies evaluating the role of ischaemia and revascularisation,
but also as a target of emerging anti-inflammatory, lipid-lowering, and neurohormonal-
modulating agents (for example, inhibitors of interleukin-1, PCSK9, neprilysin,
and the sodium/glucose cotransporter 2) on cardiovascular outcomes, especially in
women.”
Recognising important limitations of
the observational nature of these data,
this hypothesis-generating work may
help to explain the observed gap between
cardiovascular disease events and a diagnosis
of coronary artery disease in women relative
to men by quantifying the hidden risk of
ischaemic heart disease in this population.
Dr Taqueti added, “These findings suggest
that low coronary flow reserve may represent
a novel target for cardiovascular disease risk
reduction, especially in patients without
traditional obstructive coronary artery
disease. Fully closing the ‘gender gap’ in
ischaemic heart disease will likely require
more than equitable application of current
guidelines. We need to think creatively
about the biological contributions
underlying what may be a surprisingly
common phenotype with a disproportionate
impact on women’s cardiovascular health.”
Fully closing the ‘gender gap’ in
ischaemic heart disease will
likely require more than
equitable application of current
guidelines. We need to think
creatively about the biological
contributions underlying what
may be a surprisingly common
phenotype with a
disproportionate impact on
women’s cardiovascular health.
CARDIOLOGY
CONFERENCES 2017
JANUARY
26–27 January 2017 | Barcelona, Spain
Eurovalve Congress 2017
MARCH
24–27 February 2017 | Hong Kong
CardioRhythm 2017
17–19 March 2017 | Washington, USA
American College Of Cardiology 66th Annual Scientific
Sessions & Expo 2017
JUNE
28–30 June 2017 | Hamilton, New Zealand
CSANZ New Zealand Annual Scientific Meeting 2017
JULY
6–8 July 2017 | Singapore
Asian Pacific Society of Cardiology Congress 2017
AUGUST
8–10 August 2017 | Perth, Australia
Australia & New Zealand Endovascular Therapies
Meeting 2017
© 2016 AHA
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