PracticeUpdate: Cardiology

CONFERENCE COVERAGE

AHA 2016

10

Excess CV risk in women linked to very low coronary flow reserve, not obstructive disease

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T his 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.”

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.

CARDIOLOGY CONFERENCES 2017

JANUARY 26–27 January 2017 | Barcelona, Spain Eurovalve Congress 2017 http://eurovalvecongress.com MARCH 24–27 February 2017 | Hong Kong CardioRhythm 2017 www.cardiorhythm.com

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.

17–19 March 2017 | Washington, USA American College Of Cardiology 66th Annual Scientific Sessions & Expo 2017 https://accscientificsession.acc.org JUNE 28–30 June 2017 | Hamilton, New Zealand CSANZ New Zealand Annual Scientific Meeting 2017 http://www.csanzasm.nz/

JULY 6–8 July 2017 | Singapore Asian Pacific Society of Cardiology Congress 2017 www.apsc2017.com

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.”

AUGUST 8–10 August 2017 | Perth, Australia Australia & New Zealand Endovascular Therapies Meeting 2017 www.anzet.com.au

© 2016 AHA

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