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Physician Resources Home arrow Physician Practice arrow General Medical Practice arrow Coronary Artery Disease in Women—the Venusian Difference
Coronary Artery Disease in Women—the Venusian Difference
Written by Jeffrey R. Waggoner, MD   

Coronary artery disease in women

Doctor John Gray made a rather large splash by suggesting that Men are from Mars. Women are from Venus. His book concerned relationships, but its theme—that there are profound differences between men and women—appears to hold true for other biologic arenas. There is increasing evidence that atherosclerosis (ASCVD) and coronary artery disease (CAD) in women is a much different phenomena than it is in men.

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As one might predict—it is more complicated. It is so complicated that even as masses of data are being accumulated, no single theory has yet been proposed akin to the “response to vascular injury” theory that explains CAD in most males.

In the mid-1990s, such masses of data did not exist. Most of the large angiographic studies had been done in males. As it became obvious that CAD in females was equally important, this discrepancy engendered pointed observations about medical chauvinism. Female—and male—cardiologists responded with a far more aggressive approach to symptomatic women.  
The result was an uncomfortable reality: in matched populations of patients complaining of chest pain, normal coronary arteries were found in five times as many females as males (when studied angiographically.) Some members of the medical community rolled their eyes. Fortunately, others scratched their heads, smoothed their hair, and put on their thinking caps.

For a time, it seemed as though more studies simply equaled more confusion. Perhaps the height of this confusion was reached when it was announced that the Women’s Health Initiative was being halted because a disturbing number of women being treated with estrogen were dying of cardiovascular complications. It had been anticipated that the study would validate earlier studies suggesting that estrogen was cardioprotective.

The announcement was like someone crying “Fire!” in a crowded theater and then adding, “And I’ll bet all the doors are locked.” There was a tremendous amount of pushing and shoving. The manufacturer of the estrogen replacement used in the study was trampled, most women were summarily taken off estrogen, but fortunately, once again, a few in the medical community scratched their heads, smoothed their hair, and crammed their thinking caps on even tighter.

There is still no simple explanation for the cardiovascular Mars versus Venus quandary. But new findings and rational thought have burned away some of its fog. Women appear to respond to the inflammatory injuries associated with ASCVD by remodeling arteries in a different fashion than do men. Rather than forming individual plaques, this response is spread out through the entire length of arteries—essentially amortizing damage rather than “lump summing” it. This is revealed by a new technique, intravascular ultrasound (IVUS). IVUS shows flattened plaques present throughout the “narrower’ but apparently “normal” coronary arteries that have undergone this female form arterial remodeling. Even though these plaques are flat, they may rupture and cause an acute coronary syndrome (ACS) [ref. 1].

Further, women with coronary artery dysfunction may have either endothelial-dependent or non-endothelial dependent dysfunction. The former group suffers more adverse episodes but the latter group experiences more hospitalizations for angina.

What this means is that there is a population of women with angina who when perfused with adenosine get chest pain—the non-endothelial dependent group. The endothelial-dependent group doesn’t. The non-endothelial group appears to be reacting with vascular smooth muscle, i.e. experiencing coronary artery spasm. The endothelial-dependent group is subject to the complications of ACS [ref. 2].

There also appears to be a complicated interaction between the factors of inflammatory mediators (such as C reactive protein), estrogen, metabolic syndrome, and even red blood cell counts that influences a woman’s propensity to develop coronary dysfunction. That this interaction is not yet understood is demonstrated by a recent study suggesting that small doses of estrogen decreased symptoms in women who had myocardial ischemia but did not have obstructive CAD. However, those who called out “Fire!” have not yet called out “Never mind.”  [ref. 3]

One other study is remindful of an enduring truth. The title of the study is “Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease.” Even in this confusing arena, it appears that doctors who listen to their patients have access to medicine’s most accurate data base—what their patients tell them [ref. 4].

Cardiovascular centers of excellence will probably continue their technological arms race by investing in IVUS units. But if one looks at all the studies and puts on that thinking cap, it would appear that aggressively treating risk factors, using coronary dilators for persistent angina, and judging a patient’s clinical progress by listening to their complaints provides the best evidence based approach to Venusian CAD.

Hardly surprising. It might well be said that listening to patients and keeping one’s thinking cap in place are the heart and soul of approaching all clinical problems.

References

1. R.N. Fogoros "Female-pattern" Coronary Artery Disease, May 9, 2005. About.com

2. S. Midwall et al. "In Women without Obstructive Coronary Artery Disease, Endothelial-Dependent and Non-Endothelial Dependent Coronary Reactivity Dysfunction are Associated with Different Types of Adverse Outcomes. The NHLBI Women's Ischemia Syndrome Evaluation (WISE)." The American Heart Association Scientific Sessions 2007, Abstract 2870.

3. C. Bairey Merz et al. "A Randomized Controlled Trial of Low Dose Hormone Therapy on Myocardial Ischemia in Postmenopausal Women with No Obstructive Coronary Artery Disease:Results from the NHLBI-sponsored WISE" The American Heart Association Scientific Sessions 2007, Abstract 2450. 

4. B.D. Johnson et al. "Persistent chest pain predicts cardiovascular events in women without obstructive coronary artery disease: results from the NIH-NHLBI-sponsored Women's Ischaemia Syndrome Evaluation (WISE) study." Eur Heart J. 2006 27:1408-1415.

About the Author

Dr. Jeff Wagonner

J.R. Waggoner, M.D. practiced family medicine for thirty years in Aurora, Colorado. He also worked as a consultant and herded cats as the managing general partner of a general partnership of physicians. Three years ago, he left his practice to study health care policy and write. During his time away from clinical work, he has written two books and worked as a Senior Clinical Content Specialist and freelance writer.

His current book Medical Metamorphosis: The three step cure for America's health care crisis is available at Lulu.com. 

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