Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps

Paul, Tracy K.; Sivanesan, Kaartiga; Schulman‐Marcus, Joshua

doi:10.1016/j.tcm.2016.08.002

Cited by 27 publications

(14 citation statements)

References 39 publications

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“…In the majority of these cases, chronic stable angina is caused by coronary microvascular dysfunction. This condition, previously known as cardiac syndrome X, is named microvascular angina, which often pertains to women with symptoms of chronic stable angina, normal or near-normal coronary arteries, and evidence of ischaemia during stress testing or during acetylcholine testing 13,14 . Increasing attention has been focused on the recognition of this condition, and microvascular angina might occur in up to 40% of patients with angina, depending on the studies [15][16][17] .…”

Section: Pathophysiologymentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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Chronic stable angina pectoris is the most prevalent symptomatic manifestation of ischaemic heart disease, and its management is a priority (BOX 1). Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revasculariza tion [1][2][3][4] . However, revascularization by either percutaneous coronary angioplasty or CABG surgery is indicated in patients who have significant artery steno sis (50% left main narrowing or proximal three-vessel disease) to reduce myocardial ischaemia and its adverse clinical manifestation. Antianginal agents are approved by documenting that they improve total exercise duration, together with a reduction in daily frequency of chronic stable angina compared with placebo and/or equivalence to an active comparator. Cardiovascular outcomes, although highly advocated, are not a pre requisite for regulatory approval. None of the antianginal drugs has been proved to reduce cardiovascular mortality or the rate of myocardial infarction. When patients are optimally treated, mortality for chronic stable angina is low, which might explain why all trials designed to improve prognosis have been negative. Guidelines recom mend a first-choice and a second-choice approach, based more on tradition and expert opinion, rather than evidence. This categorical approach has been questioned in the past couple of years 5-8 . Newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than is available for the traditional first-choice drugs. Equally, the often-needed combin ation of double or triple therapy is based on expert opinion and not related to the underlying pathophysio logy. What constitutes optimal antianginal treatment, therefore, varies considerably between countries, and the majority of doctors treat their patients according to their own preconceptions.A group of experts with experience and interest in chronic stable angina met at the University of Ferrara, Italy, to discuss an individualized approach to medical treatment of chronic stable angina, on the basis E X P E RT C O N S E N S U S D O C U M E N TA 'diamond' approach to personalized treatment of angina Abstract | In clinical guidelines, drugs for symptomatic angina are classified as being first choice (β-blockers, calcium-channel blockers, short-acting nitrates) or second choice (ivabradine, nicorandil, ranolazine, trimetazidine), with the recommendation to reserve second-choice medications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. No direct comparisons between first-choice and second-choice treatments have demonstrated the superiority of one group of drugs over the other. Meta-analyses show that all antianginal drugs have similar efficacy in reducing symptoms, but provide no evidence for improvement in survival. The newer, second-choice drugs have more evidence-based clinical data that are more contemporary than is available for tr...

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Section: Pathophysiologymentioning

confidence: 99%

A 'diamond' approach to personalized treatment of angina

et al. 2017

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“…Yet, women with angina and confirmed ischemia have increased mortality from IHD [63]. As discussed later on, the recent application of modern clinical diagnostic tools, such as cardiac computed tomography angiography (CCTA) and positron emission tomography (PET), is changing the paradigm of how disease is diagnosed [64, 65], broadening definitions of CAD and ischemia, respectively, to better reflect pathological phenotypes more prevalent in certain patients, especially women.…”

Section: Sex Differences In Clinical Presentation Diagnosis and Manamentioning

confidence: 99%

Sex Differences in the Coronary System

Taqueti

2018

Advances in Experimental Medicine and Biology

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Cardiovascular disease remains the leading cause of morbidity and mortality for both women and men. Emerging evidence supports that ischemic heart disease (IHD) may manifest differently in women and men, in ways ranging from the clinical presentation, diagnosis, and management of disease to the basic biology and biomechanics of cardiomyocyte function and the coronary circulation. Women consistently present with a higher burden of symptoms and comorbidities as compared with men and experience worse outcomes. These data have proved perplexing given the decreased likelihood of women to demonstrate obstructive coronary artery disease (CAD) on coronary angiography. Reported sex differences have long been influenced by the practice of defining heart disease primarily as obstructive CAD, but obstructive plaque is now recognized as neither necessary nor sufficient to explain symptoms of IHD, and it is no longer adequate to tailor diagnostic and treatment strategies only to this subset of patients. To date, women remain underrepresented in guideline-changing heart disease research and trials, creating important limitations in the evidence base for cardiovascular medicine. Smaller epicardial coronary arteries in women as compared to men, coupled with differences in shear stress and inflammatory mediators over the life span, may modify the development of CAD in susceptible patients into a diffuse pattern with more contribution from coronary vasomotor dysfunction than focal obstruction. Newer studies corroborate that symptomatic women are more likely than men to present with nonobstructive CAD and coronary microvascular dysfunction. When present, these processes increase cardiovascular risk in both women and men but may constitute an especially malignant phenotype in a subset of severely affected women, with implications for the management of not only CAD but also heart failure with preserved ejection fraction. This represents a state-of-the-art review of sex differences in the coronary system, with an eye toward how diverse pathophysiological processes may contribute to IHD phenotypes prevalent in women and men. Beyond providing women and men with equitable optimal care according to current paradigms, understanding the pathophysiology of IHD beyond a conventional focus on obstructive CAD is needed to address what is likely a combination of biological as well as environmental determinants of their prognosis.

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“…Recently, more and more attention has been devoted to the recognition of this condition and it is estimated that microvascular angina could occur in up to 40% or even more, depending on the study consulted [59-61]. This high percentage, however, includes patients with symptoms of angina with suspected ischaemia, but without a clear demonstration of it.…”

Section: Pathophysiology Of Anginamentioning

confidence: 99%

“…In the majority of patients, the underlying pathology is atherosclerotic narrowing of one or more epicardial coronary arteries, which limits coronary blood flow [5, 6]. Nevertheless, angina, in a limited proportion of patients, may occur in the absence of significant coronary artery disease (CAD) and obstructive lesions, or even in the presence of angiographically normal coronary arteries [7-9]. The underlying mechanisms of angina, in this subset of patients, are related to functional alterations of the coronary circulation at the level of the coronary microcirculation [10, 11].…”

Section: Introductionmentioning

confidence: 99%

Treatment of Angina: Where Are We?

Balla

Pavasini

Ferrari³

2018

Cardiology

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Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the “classical” obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.

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Sex differences in nonobstructive coronary artery disease: Recent insights and substantial knowledge gaps

Cited by 27 publications

References 39 publications

A 'diamond' approach to personalized treatment of angina

A 'diamond' approach to personalized treatment of angina

Sex Differences in the Coronary System

Treatment of Angina: Where Are We?

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