Coronary Atherosclerosis in Women

1. Introduction

Despite numerous studies focused on women’s cardiac health, deaths from cardiovascular disease continue to rise in women. Cardiovascular disease (CVD) continues to be the leading cause of death even in women in many areas of the world. It has been note that despite higher frequency of chest pain/angina in women compared to men, the incidence of obstructive coronary artery disease (CAD) remains lower in the female population compared with men presenting with similar symptoms [1]. It is critical to have a deep understanding of these topics to ensure a meaningful communication between public, patients, and healthcare professionals.

It is important to note that despite all the literature diagnoses, cardiovascular illness in women remains underdeveloped. One of the reasons which it has been attributed to is that chest pain in women is less likely to be secondary to obstructive or flow-limiting coronary stenosis in comparison to men presenting with similar symptoms [1]. The other issue is that the gold standard for coronary atherosclerosis continues to coronary angiography [1]. This is a key limitation in cardiovascular atherosclerosis management since endothelial dysfunction, in addition to a higher risk of atherosclerosis is prevalent in women with hypertension, diabetes, and dyslipidemia [2].

Gianturco et al. [3] have also explained the role of systemic inflammation as a potential under-recognized player in endothelial dysfunction. Both inflammation and immunity seem to be the critical players [3]. The authors have emphasized on the need for preventive strategies after detailed understanding of the possible underlying pathogenesis [3].

In this chapter, we will focus on the aspects of coronary atherosclerosis that deserve attention with respect to gender specific considerations, particularly with respect to clinical practice.

2. Pathogenesis

Endothelial dysfunction, inflammation, and atheromatous plaque in women, as well as men, is primarily caused as a result of aging, dyslipidemia, hypertension, cigarette smoking, and diabetes. These five risk factors mentioned are all well-known traditional risk factors with well-documented correlation to pathophysiology of CAD [4].

3. Management strategies of atherosclerosis in women

It has been shown in studies that in female patients with coronary artery disease, persistent impairment of endothelial vasomotor function despite optimized therapy to reduce risk factors can adversely affect clinical outcomes [11].

The following, however, should be aggressively managed to combat atherosclerotic disease in female patients:

1. 1. Life style modifications (diet, exercise, smoking, weight reduction)

Adherence with healthy eating habits, regular exercising and weight reduction are all important determinants of atherosclerosis and should be recommended in both genders [12]. Smoking cessation is critical and dedicated time should be spent with patients to generate that awareness [12].

1. 2. Receptor and enzyme pathways (beta-blockers, ET, ACE-I, ARB)

Just as the traditional risk factors play a critical role in the pathogenesis of atherosclerotic CAD in females, the routine therapies should be considered in this patient population [13].

Most studies have found the benefit of statins in ameliorating and even eliminating endothelial dysfunction [13]. These medications are well known mainstay in decreasing CVD risk in most patients secondary to their lipid-lowering and anti-inflammatory mechanism [13]. Addition of ACE-inhibition to statin therapy has been shown to improve endothelial-dependent relaxation in the coronary vasculature through NO-dependent mechanism [14, 15].

1. 3. NO pathway (L-arginine, PDE-I)

Both intravenous and intracoronary administration of L-arginine, the physiologic precursor for NO, has been shown to acutely improve endothelium-dependent, but not endothelium-independent, vasodilation in participants with hypercholesterolemia or CAD [16]. The longer-term effects of oral L-arginine have additionally been evaluated. Among patients who have underlying heart failure, oral L-arginine improved endothelial function, arterial compliance, and functional status [17].

The other agent is Nicorandil, which is a potent antianginal, however, unavailable in the US. It has dual nitrate and potassium-ATP channel agonist properties and increases the formation of cyclic GMP. This agent has been shown to improve endothelial function in patients without prior CAD at 1 year follow up with concomitant documented reductions in inflammatory markers [18].

1. 4. Channel pathways (Ca, K)

Nifedipine has been shown to have antioxidant effects with additional effect on endothelial nitric oxide synthase expression. In a study including 454 patients undergoing percutaneous coronary intervention, endothelium dependent vasodilatation was evaluated with intracoronary acetylcholine following 6 months of therapy with nifedipine. There was well documented improvement in endothelial function, however, no plaque regression [19].

Ranolazine is a sodium channel inhibitor used in patients who have refractory angina. It has been shown to improve symptoms of microvascular angina, however there was no clear change seen in microvascular function with the use of ranolazine [20].

4. Conclusion

In summary, atherosclerosis in females is a complex process. There is an integral role of endothelial dysfunction. In order to close the gaps in care of cardiac disease in women, the steps must include timely recognition of the symptoms of cardiac disease with the effective management. Treatment strategies are diverse with decent evidence base. Larger studies dedicated to address atherosclerosis in women are urgently required.