Comorbidity

Comorbidity is a commonly proposed reason for explaining gender discrepancies in bypass surgery. In other words, women tend to develop heart disease along with other complicating conditions that increase the risk of cardiovascular intervention, especially surgery.

Comorbid conditions include diabetes, dysrhythmia, heart failure, hypertension, and old infarction. Presence of any comorbid condition in a patient greatly reduces the likelihood that he/she will receive bypass surgery.

One of the comorbidity conditions that has been thoroughly investigated is diabetes. It is commonly observed that Coronary heart disease (CHD) is less common among pre-menopausal women than in men; below the age of 55 years, the incidence of CHD in women is one third of that of men. Interestingly, this difference disappears after the onset of menopause, and at age 75 years, women are at an equal risk as men. This is attributed to the reduced levels of female sex hormones in post-menopausal women.

Female sex hormone, especially estrogen, is known to have cardiovascular protective effect due to several mechanisms

Estrogen increases High Density Lipoprotein (HDL). HDL is considered to be “good” lipoproteins since it removes cholesterol from atheroma within arteries, and transport it back to the liver.
Estrogen decreases Low Density Lipoprotein (LDL). LDL is considered to be “bad cholesterol” since it transports cholesterol to the arteries increasing the risk of cardiovascular disease.
Estrogen stimulates the release of vasodilators such as nitric oxide and prostacyclin from the vessel wall, decreasing the blood pressure as a result.
Nitric oxide is also known to diminish platelet aggregation and inhibit vascular growth, minimizing vascular constriction.
Lastly, estrogen attenuates calcium concentration in vascular muscle cells. High calcium concentration is known to stimulate cell proliferation resulting in vascular constriction.

Below is a chart that summarizes the cardiovascular protective effect of estrogen.

Due to mechanisms not yet understood, diabetes is known to interfere with the cardiovascular protective effects of female sex hormone in pre-menopausal women. Clinically, poor glycemic control in the body due to diabetes is manifested in the following ways.

Diabetes patients are known to be more prone to hypertension. Studies indicate that women with diabetes are more likely to have hypertension than are men. In the United Kingdom Prospective Diabetes Study (UKPDS), 35% of 2136 men with diabetes were hypertensive, in contrast to 46% of 1512 women with diabetes who were hypertensive.
Diabetes patients also develop imbalance in HDL and LDL cholesterol levels. People with diabetes usually show decrease in HDL, good lipoproteins, and increase in LDL, bad lipoprotein. The Strong Heart Study showed that this symptom tends to be more exaggerated in women with diabetes.
Since women have less severe coronary atherosclerosis and less collateral vessels than men, they tend to sustain greater myocardial damage with coronary occlusion and thus diabetes may impact women more than men, both for coronary heart disease morbidity and mortality.
Endothelial dysfunction: Endothelial cells line the lumen of the vessel and play an important role in vascular relaxation, and researchers propose that there is a sex difference in endothelial function, which may be a mechanism by which diabetes exerts differential effects in women. One of the factors that determines the vascular smooth muscle tone is nitric oxide. Nondiabetic premenopausal women, compared to men, show enhanced nitric oxide dependent vascular tone and endothelial-dependent vasodilation. However, women with diabetes show impairment in endothelium-dependent vasodilation that is worse than that of men with diabetes.

Results of studies presented above indicate that there is a sex difference in the risk for CHD in individuals with diabetes. Below is a table that quantitatively compares the effect of diabetes and established CHD (previous history of heart disease) on subsequent cardiovascular disease mortality for the two sexes.

Even after adjusting for other risk factors such as age, smoking, hypertension, and etc., diabetic women have a larger increase in risk for CHD than diabetic men. (3.8 vs. 2.1) Since the intensity of management of diabetic patients is based on their risk for cardiovascular disease, and because diabetic women may be at a higher risk than diabetic men, current guidelines for treatment of women with diabetes may need to be more aggressive.