Cardiac Syndrome X

Working in cardiology for many years I have seen and
heard of the difficult female patient with angina
symptoms that appear to be ‘in their head’ because they
have normal coronary arteries on angiography, and no or
questionable ECG changes, yet presenting with angina
like chest pain.  Have you seen or heard of these
patients?  Many of these women are well educated and
they know that their chest pain is real, yet the
cardiologist and emergency physician do not believe
them.  Some are admitted, others are instructed to
return to their family doctor for follow-up.  Do we just
believe what we are told that women have different signs
and symptoms of angina and that unless the coronary
artery arteriogram reveals occlusion these women are
crazy?  When faced with yourself, your mother or a
female or male patient and asked “am I really crazy?”
how do you respond, as a nurse and soon to become Nurse
Practitioner?

I have been interested in this phenomenon for many
years.  There is a dearth of literature on the subject
but can be found if you dig deeply enough.  In 1973,
Kemp introduced the term cardiac syndrome X to describe
patients (both genders) with chest pain and a normal
coronary angiography.  The phenomenon is found in the
literature by using microvascular dysfunction as a
search term.  Interestingly, syndrome X has also been
called metabolic syndrome but the metabolic syndrome or
term cardiometabolic syndrome used within the literature
in the past decade and a half, is different than cardiac
syndrome X or microvascular dysfunction.   

Currently, cardiac syndrome X is described by numerous
authors as angina with normal (<40% stenotic) coronary
angiogram with or without electrocardiographic (ECG)
changes or atypical angina with normal or near normal
coronary angiogram plus a positive non-invasive test
(exercise tolerance test or myocardial perfusion scan)
with or without ECG changes (Cavusoglu, Entok, Timuralp,
Vardareli, Kudaiberdieva, Birdane, et al., 2005; Crea &
Lanza, 2004; Asbury & Collins, 2005; Kaski, 2002; Kaski,
Aldama, & Cosín-Sales, 2004; Reis, Holubkov, Smith,
Kelsey, Scharaf, Reichek, et al., 2001; Lanza, 2007;
Arroyo-Espliguero & Kaski, 2006; Rosen 2001).  Some have
alluded to the presence of ischemia related to
microvascular dysfunction (Hurst, Olson, Olson &
Appleton, 2006; Reis, Holubkov, Smith, Kelsey, Scharaf,
Reichek, et al., 2001; Lanza, 2007; Arroyo-Espliguero &
Kaski, 2006; Rosen 2001) and others have indicated that
the pathophysiology of syndrome X has not been clearly
established (Kaski, 2002; Crea & Lanza, 2004). In a
small study, Demir and colleagues (2008) found abnormal
myocardial perfusion, wall motion abnormalities and poor
left ventricular ejection fraction responses in their
cohort of cardiac syndrome X patients.  They concluded
“post-stress prolonged stunning” is attributable in some
cardiac syndrome X patients similar to true ischemic
patients but, further studies with larger number and
long-term follow-up are needed to support their findings
(p.212). 

Arroyo-Espliguero and Kaski, (2006) looked at the role
of inflammation and nitric oxide in microvascular
dysfunction of syndrome X.  They believe C-reactive
protein is not only an inflammatory marker but a marker
in those with syndrome X who have impaired microvascular
endothelium.  C-reactive protein has been associated
with inflammation and thrombosis (Brasher, 2006)
enhanced levels of cell adhesion molecules, endothelin 1
and reduced nitric oxide (NO) (Arroyo-Espliguero,
Mollichelli & Avanzas, 2006).  The decreased NO,
enhanced endothelin 1 and cell adhesion molecules are
similar to those expressed in coronary artery risk
factors (Arroyo-Espliguero & Kaski, 2006).  I query if
cardiacmetabolic syndrome is a part of syndrome X
because of the relationship of smoking, obesity, insulin
resistance, abnormal lipid profile and estrogen
deficiency in post menopausal females implicated in both
syndromes? Lerman and Sopko (2006) believe the metabolic
syndrome is a major risk factor for women with syndrome
X.

Back to what we do or say to the patient that is told
the angina that they are experiencing is ‘in their
heads’.  Hurst and colleagues (2006) report that the
prognosis of these patients is good yet there is a lot
of animosity among health care providers because of the
diversity of the mechanisms within the syndrome,
frustrations with the patient and no clear treatment
management plan.  I propose that we listen to these
patients and provide them with information that not all
angina is typically from occlusive larger coronary
arteries, and many pharmacological agents are available
and those may also include estrogen and L-arginine that
may not be typically prescribed to other cardiac
patients.  Risk factor reduction information should be
provided and followed.  Discussions around pain
modulation with imipramine have been proposed when there
is poor response to risk reduction strategies and
pharmacologic agents (Kaski, Aldama, & Cosín-Sales,
2004; Gibbons, Abrams Chatterjee et al, 2003).  Maybe as
the NP following this challenging population we need to
engage in the Mediterranean diet, enjoy the occasional
dark chocolate and perhaps a glass of red wine every now
and then (Helmut, Tankred & Christian, 2005; Price,
Estabrooks, & Tapp, 1999) to decrease our own
frustration and improve formation of our endogenous NO!
:)Lorna

References

Arroyo-Espliguero, R., & Kaski, J.  (2006). 
Microvascular dysfunction in cardiac syndrome X: the
role of inflammation.  Canadian Medical Association
Journal, 174, 1833-1834.

Arroyo-Espliguero, R., Mollichelli, N., & Avanzas, P. 
(2003).  Chronic inflammation and increased arterial
stiffness in patients with cardiac syndrome X.  European
Heart Journal, 24, 2006-2011.

Asbury, E., & Collins, P. (2005).  Cardiac syndrome X.
International Journal of Clinical Practice, 59,
1063–1069.

Brasher, V.  (2006).  Alterations of cardiovascular
function.  In K.L. McCance, & S.E. Huether, (Eds.), 
Pathophysiology: The biologic basis for disease in
adults and children (5th ed., pp. 333-374). St. Louis,
MO: Elsevier Mosby.

Cavusoglu, Y., Entok, E., Timuralp, B., Vardareli, E.,
Kudaiberdieva, G., Birdane, A., et al. (2004).  Regional
distribution and extent of perfusion abnormalities, and
the lung to heart uptake ratios during exercise
thallium-201 SPECT imaging in patients with cardiac
syndrome X. Canadian Journal of Cardiology, 21, 57–62.

Crea, F., &  Lanza, G.  (2004).  Angina pectoris and
normal coronary arteries: cardiac syndrome X. Heart, 90,
457–463.

Demir, H.,  Kahraman, G.,  Isgoren, S., Tan, Y.,  Kilic,
T., &  Berk, F. (2008).  Evaluation of post-stress left
ventricular dysfunction and its relationship with
perfusion abnormalities using gated SPECT in patients
with cardiac syndrome X.  Nuclear medicine
communications, 29(3), 208-214.  

Gibbons, R., Abrams, J., Chatterjee, K., et al.  (2003)>
 ACC/ACA 2002 guideline update for the management of
patients with chronic stable angina – summary article. 
Journal of the American College of Cardiology, 41,
159-168.

Helmut, S., Tankred, S., & Christian, H.  (2005).  Cocoa
polyphenols and inflammatory mediators.  American
Journal of Clinical Nutrition, 81,  304S-312S.

Hurst, T., Olson, T., Olson, L., & Appleton, C.  (2006).
 Cardiac syndrome X and endothelial dysfunction: New
concepts in prognosis and treatment.  The American
Journal of Medicine, 119, 560-566.

Kaski, J., Aldama, G. & Cosín-Sales, J.  (2004). 
Cardiac syndrome X. Diagnosis, pathogenesis and
management. American Journal of Cardiovascular Drugs, 4
(3), 179-194.

Kaski, J.  (2002).  Overview of gender aspects of
cardiac syndrome X.  Cardiovascular Research, 53 (30),
620-626.  

Kemp, H. (1973).  Left ventricular function in patients
with the anginal syndrome and normal coronary arteries.
American Journal of Cardiology, 32, 375–376.

Lanza, G.  (2007). Cardiac syndrome X: a critical
overview and future perspectives. Heart, 93, 159-166.  

Lerman, A., & Sopko, G.  (2006).  Woman and
cardiovascular heart disease: clinical implications from
the woman’s ischemia syndrome evaluation (WISE) study. 
Are we smarter?  Journal of American College of
Cardiology 43(3), S59-S62.  

Price, P., Estabrooks, L., & Tapp, D.  (1999,
September).  The French Paradox: Wine and Heart. 
Canadian Association of Cardiac Rehabilitation
Newsletter.

Reis, S., Holubkov, R., Smith, C., Kelsey, S., Scharaf,
B., Reichek, N., et al., (2001).  Coronary microvascular
dysfunction is highly prevalent in woman with chest pain
in the absence of coronary artery disease: results from
the NHLBI WISE study.  American Heart Journal, 141(5),
735-741.