Coronary Artery Disease (CAD) has afflicted man throughout history.

Diet and hereditary

factors obviously are the key components in developing this condition. Foods high in cholesterol and
saturated fats are often implicated in hastening or aggravating heart disease. Many disease states such
as diabetes mellitus and hypertension have also been shown to increase a persons chances for CAD.
Heart disease usually affects persons over age 60, but can be seen in people who are much younger
for various reasons. This disease remains the number one cause of hospitalization and death in the
adult population in western society (McCance and Huether, 1994).

The purpose of this literature review is to investigate research dealing with the subject of increased
serum iron levels and the prevalence of CAD. Medical journals were primarily used for research data
due to the nature of the subject and the need for in-depth analysis.

While it has the highest prevalence of any disease, women experience only 30-50% of the coronary
artery disease incidence and mortality of age-matched men (Meyers, 1996). Many feel that this may
be due to the protective effect that estrogen has on the blood vessels of females. There may actually
be a direct correlation to reduced serum iron levels due to menses. Whereas men " build-up" iron in
the blood, women cleanse themselves of iron buildup on the monthly basis. Meyers (1996) also states
that oxidation, the process in which an atom increases its positive charges (Miller and Keane, 1992),
of low density lipoprotein cholesterol is important in atherosclerosis, and since oxidation is catalyzed
by iron, it has been hypothesized that the lower iron stores of women reduce their risk of CAD through
lessened lipid peroxide, a by-product of oxidation.

Numerous studies have been conducted to actually see if a relationship between serum iron or serum
transferrin, (serum iron concentration divided by total iron-binding capacity), and heart disease or
myocardial infarction, (heart attacks) exists. Sempos and Looker, (1994) used a total of 4518 men and
women to conduct the first study of its kind on the subject of iron and CAD. Frequent serum iron levels,
collected from 1971-74, and followed up through 1987, showed the risk of CAD was not related to
serum transferrin levels in white men or women. Indeed, an inverse association of total body iron stores
and overall mortality was shown, that is moderate to high serum transferrin associated with lower
mortality.

In a similar study, 6086 men and 6102 women, who were randomly chosen, were followed for 14 years
having frequent serum iron and total iron binding capacity (TIBC) levels drawn. Total Iron Binding
Capacity refers to the amount of red bloods cells that are actively bound with iron at any given time. At
the end of the study, 739 men and 245 women died from coronary artery disease. It was concluded
that there was no relationship between TIBC and coronary mortality observed in men. In women, an
inverse although not statistically significant association was found (Reunanen et al, 1995).

Sullivan (1996) states that the iron hypothesis, which hypothesizes increased serum iron causes CAD,
provides a conceptual tool for study of the mechanisms by which age and gender influence the
development of ischemic heart disease. The assumption that age and gender exert unalterable effects
has diverted attention from these strong risk factors, and has led to intense preoccupation with weaker
risk factors such as cholesterol. Which as he states, "has become a rigid and institutional point of view
to determine CAD risk".

High iron may indirectly cause damage to coronary arteries due to increased oxidation. Hauenschild et
al, (1997) report that the association between nutrition and coronary heart disease is mainly due to the
effect of nutrients on serum lipoproteins, the form in which fats are transported in the blood (Miller and
Keane, 1992). Cholesterol intake does not play a very important role for plasma cholesterol although
there is a strong interindividual difference in response. Low iron intake leads to an accelerated uptake
of low-density lipoprotein into the macrophage. In another interesting study, Fields and Lewis, (1997),
investigated low iron levels in rats and the incidence of CAD. They found that reduction of iron intake
reduced blood levels of both triglycerides and cholesterol in rats fed a copper deficient diet containing
fructose. They hypothesized that the combination of high iron, low copper, and fructose may be
responsible for increased levels of risk-factor metabolites associated with heart disease.

In regard to the above information, the research concludes that it is unlikely that high serum iron or
transferrin is the direct cause of CAD. It may be likely though that having a high iron intake may
indirectly effect the progression of heart disease by influencing oxidation of cholesterol and lipoproteins.
No research concluded that the lower incidence of heart disease in women is based in-part by lower
serum iron levels due to menses.