dissolved with 1–2 years of treatment. Stone formation may recur after cessation of the
therapy. Not surprisingly, surgical therapy is still preferred in the treatment of gallstones,
rather than the slow and somewhat inefficient use of these pharmacological agents.
5.6.2 Cholesterol and Vascular DiseaseMore important than its involvement in gallstone formation, cholesterol’s role as a
central culprit in the dreaded pathological process of atherosclerosis(“hardening of the
arteries”) has attracted extensive attention. Cholesterol metabolism and its involvement
in atherosclerosis play a fundamental role in research efforts directed at decreasing
the incidence of cardiovascular disease, the number-one killer in Western civilization,
and cerebrovascular disease, the number-three killer. There is a statistical correlation
between serum cholesterol levels and the incidence of atherosclerosis. In the latter
condition, damaging lesions (called atheromasoratherosclerotic plaques), which con-
tain cholesterol and other lipids, form in arterial walls. Initial atheroma formation is
followed by fibrosis of these plaques, with narrowing of the arterial diameter, causing
a decrease in blood flow, changes in the blood-clotting mechanism, and eventual total
arterial occlusion. When arteries become blocked and cannot supply blood, the patho-
logical process of ischemiaoccurs (ischemia is death or injury to cells arising from an
interruption of the blood supply to those cells). This, in turn, may lead to myocardial
ischemia(MI, “heart attack”) or cerebral ischemia(“stroke”), arising from reduced
blood supply to the cells of the heart or brain, respectively. (Some people, with exten-
sive atherosclerosis throughout their entire body, are called “vasculopaths” and are sus-
ceptible to heart attacks, strokes, and a variety of other vascular problems throughout
their body.) Regrettably, the effects of cholesterol metabolism, dietary factors (e.g.,
excessive consumption of saturated fatty acids), exercise, and life-style in the etiology
of cardiovascular disease is a highly controversial topic, fraught with half-truths and
misinformation, especially in popular press reports and from the so-called “health
gurus” who promote their products on the world-wide web.
Encouragingly, there is increasing, robust scientific evidence that atherosclerosis
can be arrested and even decreased by pharmacologic approaches. However, the evalu-
ation of drug therapy for this condition is complicated by the fact that the regulation
of cholesterol metabolism alone does not necessarily have a beneficial effect on
atherosclerosis.
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