12.2: Gender Differences in the Pathophysiology of Atherosclerosis
- Page ID
- 42797
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\(\newcommand{\avec}{\mathbf a}\) \(\newcommand{\bvec}{\mathbf b}\) \(\newcommand{\cvec}{\mathbf c}\) \(\newcommand{\dvec}{\mathbf d}\) \(\newcommand{\dtil}{\widetilde{\mathbf d}}\) \(\newcommand{\evec}{\mathbf e}\) \(\newcommand{\fvec}{\mathbf f}\) \(\newcommand{\nvec}{\mathbf n}\) \(\newcommand{\pvec}{\mathbf p}\) \(\newcommand{\qvec}{\mathbf q}\) \(\newcommand{\svec}{\mathbf s}\) \(\newcommand{\tvec}{\mathbf t}\) \(\newcommand{\uvec}{\mathbf u}\) \(\newcommand{\vvec}{\mathbf v}\) \(\newcommand{\wvec}{\mathbf w}\) \(\newcommand{\xvec}{\mathbf x}\) \(\newcommand{\yvec}{\mathbf y}\) \(\newcommand{\zvec}{\mathbf z}\) \(\newcommand{\rvec}{\mathbf r}\) \(\newcommand{\mvec}{\mathbf m}\) \(\newcommand{\zerovec}{\mathbf 0}\) \(\newcommand{\onevec}{\mathbf 1}\) \(\newcommand{\real}{\mathbb R}\) \(\newcommand{\twovec}[2]{\left[\begin{array}{r}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\ctwovec}[2]{\left[\begin{array}{c}#1 \\ #2 \end{array}\right]}\) \(\newcommand{\threevec}[3]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\cthreevec}[3]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \end{array}\right]}\) \(\newcommand{\fourvec}[4]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\cfourvec}[4]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \end{array}\right]}\) \(\newcommand{\fivevec}[5]{\left[\begin{array}{r}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\cfivevec}[5]{\left[\begin{array}{c}#1 \\ #2 \\ #3 \\ #4 \\ #5 \\ \end{array}\right]}\) \(\newcommand{\mattwo}[4]{\left[\begin{array}{rr}#1 \amp #2 \\ #3 \amp #4 \\ \end{array}\right]}\) \(\newcommand{\laspan}[1]{\text{Span}\{#1\}}\) \(\newcommand{\bcal}{\cal B}\) \(\newcommand{\ccal}{\cal C}\) \(\newcommand{\scal}{\cal S}\) \(\newcommand{\wcal}{\cal W}\) \(\newcommand{\ecal}{\cal E}\) \(\newcommand{\coords}[2]{\left\{#1\right\}_{#2}}\) \(\newcommand{\gray}[1]{\color{gray}{#1}}\) \(\newcommand{\lgray}[1]{\color{lightgray}{#1}}\) \(\newcommand{\rank}{\operatorname{rank}}\) \(\newcommand{\row}{\text{Row}}\) \(\newcommand{\col}{\text{Col}}\) \(\renewcommand{\row}{\text{Row}}\) \(\newcommand{\nul}{\text{Nul}}\) \(\newcommand{\var}{\text{Var}}\) \(\newcommand{\corr}{\text{corr}}\) \(\newcommand{\len}[1]{\left|#1\right|}\) \(\newcommand{\bbar}{\overline{\bvec}}\) \(\newcommand{\bhat}{\widehat{\bvec}}\) \(\newcommand{\bperp}{\bvec^\perp}\) \(\newcommand{\xhat}{\widehat{\xvec}}\) \(\newcommand{\vhat}{\widehat{\vvec}}\) \(\newcommand{\uhat}{\widehat{\uvec}}\) \(\newcommand{\what}{\widehat{\wvec}}\) \(\newcommand{\Sighat}{\widehat{\Sigma}}\) \(\newcommand{\lt}{<}\) \(\newcommand{\gt}{>}\) \(\newcommand{\amp}{&}\) \(\definecolor{fillinmathshade}{gray}{0.9}\)Atheroma burden and vascular function
There is emerging evidence that there are gender- differences in the atherosclerotic process and the mechanisms underlying ischemic heart disease. Recent data support a sex-specific role for microvascular dysfunction in ischemic heart diseases. Most important findings are listed below:
- Women have more symptoms and physical limitations but less obstructive coronary artery disease then men along the entire spectrum of acute coronary syndromes.
- The syndrome of chest pain without obstructive coronary artery disease is distinctly more common in women than in men.
- In women chest pain symptoms and disability do not correlate with severity of coronary stenoses.
- Young and middle-aged females show higher rates of adverse outcomes after acute MI than men of similar age, despite less severe coronary narrowing, smaller infarcts, and more preserved systolic function.
Given the lower burden of obstructive coronary artery disease (CAD) and preserved systolic function in women, which contrasts with greater rates of myocardial ischemia and near-term mortality compared with men, we propose the term “ischemic heart disease” as more appropriate specific to women rather than CAD or coronary heart disease (CHD).
Microvascular angina pectoris
This paradoxical difference, where women have lower rates of anatomical CAD but more symptoms, ischemia, and adverse outcomes, appears linked to abnormal coronary reactivity that includes microvascular dysfunction. Symptoms as the result of microvascular dysfunction should be called microvascular angina. Abnormal coronary reactivity is often the result of diffuse (microvascular) atherosclerosis which is often seen in women, in contrast to the obstructive atherosclerosis which is more common in men (Figure 12.2.1).
Studies have shown that the plaque morphology changes after menopause. At younger age (<65 yrs) women with an acute myocardial infarction have more often plaques erosions then the classical pattern of plaque rupture and thrombus formation as seen in men. These erosive plaques can cause distal embolization with micro-emboli, leading to endothelial dysfunction of the microvascular beds with angina-like chest pain. This diffuse pattern of atherosclerosis often translates in atypical chest pain.
When obstructive coronary artery is absent these women do not receive the proper preventive medication as the atherosclerosis in the microvasculature progresses, leading to ischemia an possibly fatal arrhythmia’s. After menopause it is known that the microvascular atherosclerosis can progress towards more pronounced atherosclerosis with eventually obstructive plaque formation.
It is this combination of non-obstructive cardiovascular disease with loss of endothelial function in the epicardial and microvascular beds which can lead to chest pain which is not well understood.
For women with evidence of ischemia but no obstructive CAD, anti-anginal and anti-ischemic therapies can improve symptoms, endothelial function, and quality of life; however, trials evaluating impact on adverse outcomes are needed. Women experience more adverse outcomes compared with men because obstructive CAD remains the current focus of therapeutic strategies. Continued research is indicated to devise therapeutic regimens to improve symptom burden and reduce risk in women with ischemic heart disease.
Syndrome X
Cardiac syndrome X (CSX; differentiated from the metabolic syndrome X) is currently defined by typical, angina like chest pain without flow-limiting stenoses on coronary angiography and exclusion of non-cardiac chest pain. Microvascular angina is more prevalent in women then in men. There is a whole range of factors that contribute to the dysfunction of the microvascular beds:
- Distal embolization of erosive plaques
- Chronic inflammation
- Spasm which is often a result of disfunctional smooth muscle cells
- Smoking, hypertension and dyslipidemia can result in endothelial dysfunction