Sex differences in the manifestation and evolution of coronary artery plaques

Abstract

Even though the past decades have brought an increase in the understanding of the pathophysiology of coronary artery disease (CAD), several aspects remain incompletely understood. This is especially true for sex-specific differences in the development, manifestation, and prognosis of coronary artery plaques. While the prevalence of obstructive CAD is higher in men compared to women, non-obstructive CAD and ischemia with no obstructive coronary arteries (INOCA) are relatively more common in women [1][2][3]. Compared to obstructive CAD, fewer established preventive, diagnostic and treatment options are available for INOCA [4], complicating treatment of CAD, especially in younger women at low cardiovascular risk. Atypical symptoms in the clinical setting of suspected CAD are more common in women than in men, which might lead to delayed detection of CAD and acute coronary syndrome [5]. Women present with the disease at higher age [6] and are at higher risk for major adverse cardiovascular events and fatal outcome of myocardial infarction compared to men in the presence of obstructive, and as well in non-obstructive CAD [5,[7][8][9]. Sexdependent disparities seem to diminish when women reach menopause and similar CAD prevalence rates and mortality rates in patients with myocardial infarction are observed in the seventh decade of life for men and women [8,9].Several models were established to explain these findings and encompass sex-specific exposure to cardiovascular risk factors (CVRF), differences in the pathophysiology of plaque formation, and the protective impact of estrogen. Beyond traditional CVRF, several sex-specific riskenhancing conditions may be present in women: the higher prevalence of depression in women, pregnancy-associated