Recently, I read in a national newspaper that arterial disease, including ischemic heart disease, was described as a “man’s disease that kills women.” The headline’s sensationalism was somewhat tempered by the article’s clarification, which acknowledged that atherosclerotic arterial disease affects both genders equally and is the leading cause of morbidity and mortality in both sexes.
However, the unique physiological and hormonal differences between men and women cause the disease to manifest differently, which may result in a clinical recognition and therapeutic algorithms that are skewed towards the male profile due to its higher prevalence. Just as “a child is not a small adult,” perhaps we should not equate arterial disease in women to that in men.
The protective vascular effect during a woman’s fertile years results in a lower overall incidence and prevalence compared to men. Nevertheless, when coronary artery disease occurs in women, it presents more aggressively and poses a greater therapeutic challenge. These factors impact various arterial disease presentations, including ischemic heart disease, with distinct sex-based outcome variations:
Current diagnostic and therapeutic algorithms have been developed based on the male population. They are predicated on the male pathology profile, whereas women more frequently present with a broader spectrum of symptoms, such as atypical chest pain, dyspnea as an angina equivalent, or silent angina without chest pain. At times, this symptomatology can be mistaken for anxiety or respiratory or rheumatological conditions, leading to delays in diagnosis and appropriate therapeutic intervention.
Additionally, diagnostic and therapeutic delays are inherent to a woman’s life course, with post-menopausal disease acceleration causing the condition to manifest up to 10 years later than in men. This delay means that women present for revascularization with higher morbidity due to age and an accumulation of cardiovascular risk factors, such as hypertension, diabetes, and dyslipidemia. This scenario leads to an increased likelihood of requiring revascularization under higher-risk conditions, such as heart failure or in emergency/urgent settings, including cardiogenic shock or acute myocardial infarction. These circumstances often compromise revascularization quality (fewer arterial grafts), increase early complication risks, and adversely affect long-term outcomes.
Physiologically, women’s vessels are narrower, including both coronary arteries and arterial grafts, which adds technical difficulty to revascularization, increasing the risk of technical errors that may impair graft patency. Moreover, whereas ischemia in men mainly results from epicardial disease, in women, endothelial dysfunction, microvascular dysfunction, hyperreactivity, vasospasm, and microembolization are more prevalent, which are not entirely addressed by revascularization surgery.
Finally, after revascularization, women tend to report lower quality of life, which may reflect the differences in disease presentation, symptomatology, and pathophysiology.
In summary, coronary artery bypass surgery in women is characterized by a compromised quality if we define quality as maximum revascularization coverage with the highest number of arterial grafts and minimal complication rates. For various reasons, including older age, higher diabetes mellitus rates, and increased risk of mediastinitis with bilateral internal mammary artery grafts (particularly in diabetic and obese women), arterial graft utilization is lower. Radial artery use is also limited in women due to underdevelopment or contraindications, such as carpal tunnel syndrome, graft underdevelopment, or vasospastic disorders. Regarding coronary vessels, certain territories are deemed non-amenable for grafting due to their naturally smaller caliber, which is characteristic of the female population in regions like Spain.
Following this review, the authors offer various data on the evidence available regarding revascularization outcomes in women, which we will discuss below.
COMMENTARY:
The existing evidence on revascularization, both surgical and percutaneous, has consistently shown poorer outcomes in women compared to men. These findings parallel a limited data pool based on recruitment that reflects disease incidence and procedural frequency. Indeed, the EuroSCORE II penalizes female sex due to the poorer outcomes observed in women undergoing revascularization surgery.
The physiopathology differences in ischemic heart disease among women, coupled with the smaller luminal areas following stent implantation (often oversized for smaller vessels), may influence these outcomes. Additionally, women might experience a distinct inflammatory and intimal hyperplasia response compared to men. Thus, despite poorer outcomes observed in men, certain patient profiles may benefit more from surgery based on sex, alongside established coronary anatomy and diabetes mellitus indications.
In the United States, coronary bypass procedures involve women in only 20% of cases, although this percentage might be higher in Europe. However, this low representation still results in limited female inclusion in clinical trials, reducing their representativeness. Trials investigating the benefits of multiple arterial revascularization have shown minimal female enrollment. For example, the ART trial included only 14% women, while RAPCO included 19%. However, studies such as RADIAL and RAPCO demonstrated greater benefits of multiple arterial grafts, specifically radial artery usage, in women relative to men. Women may benefit more from using arterial grafts due to their vasodilatory agent release, which mitigates endothelial dysfunction and vasospasm, as well as better rheology due to proportionate calibers in native vessels.
Finally, the ROMA:woman study recruitment is now underway. This extension of the ROMA (Randomized Comparison of the Outcome of Single Versus Multiple Arterial Grafts trial) has already enrolled 690 women, with plans to include 1310 more. With the same design and inclusion criteria, it aims to provide definitive evidence on the benefits of multiple arterial grafting in women. Similar initiatives in percutaneous interventions would be desirable, although until then, we rely on meta-evidence from existing cohort studies. Beyond racial considerations that likely impact outcomes in an Anglo-Saxon evidence base, we must continue providing optimal care across both sexes. Indeed, revascularization outcomes might be a gender issue that remains overlooked.
REFERENCE:
Gaudino M, Bairey Merz CN, Sandner S, Creber RM, Ballman KV, O’Brien SM, Harik L, Perezgrovas-Olaria R, Mehran R, Safford MM, Fremes SE. Randomized Comparison of the Outcome of Single Versus Multiple Arterial Grafts trial (ROMA):Women-a trial dedicated to women to improve coronary bypass outcomes. J Thorac Cardiovasc Surg. 2024 Apr;167(4):1316-1321. doi: 10.1016/j.jtcvs.2023.06.006.
