Decreasing cholesterol: drugs and dietThere is a persistent belief that lifestyle can take care of all cholesterol problems. Lifestyle can make things worse, but once things are worse, it cannot make things better.Once you have disease, or cholesterol is higher, you need treatment often beyond lifestyle management.This distresses many people, who wish to have control over their fate.High cholesterol is one of the main causes of heart attacks, strokes, and peripheral vascular disease. You can lower cholesterol through diet and exercise by as much as 15 percent. Lifestyle changes are the first choice to decrease cholesterol. Modern drugs, however, will lower cholesterol levels far more than diet or exercise.The progressive changes of a vesselThe normal artery, as shown below, is a free-flowing blood vessel. When a person is in their late teens, there is already fatty formation on the inside of the vessel wall.As more fat is deposited in the vessel wall, blood flow decreases, leading to ischemia in the end organ.Angina, or heart pain, occurs when there is insufficient blood flow to the heart secondary to an artery narrowed by plaque.Factors contributing to atherosclerotic plaque formationDamage to the blood vessel begins the process ofSmokingHypertensionHigh blood sugarsDiets rich in saturated fats and refined grainsHowever, the lower the level of LDL, the less risk those factors become, as you shall see.Anatomy of the Blood VesselIf you examine the autopsy specimen of the coronary artery above, the blood flows through that lumen. The inner wall, the wall the blood comes into contact with, is called the endothelium. There are three layers to the wall of an artery:Tunica intimaTunica MediaTunica AdventiciaAtherosclerosis begins when the cholesterol transport protein enters the wall of the tunica media, whose first layer is the endothelium.Discovery of LDLIn 1954, Dr. John Gofman reported the discovery of LDL and HDL. These were the particles found when he separated plasma cholesterol-carrying lipoproteins with an ultracentrifuge. Gofman was the first to note that heart attack patients had high LDL levels. The correlation of high LDL and heart attacks has been called “one of the most profound epidemiologic correlations in all of medicine.”High LDL levels have been shown to correlate with atherosclerosis in all species studied.High LDL and AtherosclerosisThe higher the LDL level, the faster atherosclerosis develops. Factors that increase atherosclerosis are those which injure blood vessels: smoking, hypertension, hyperglycemia, and genetic factors that predispose endothelium to early injury.High LDL levels can lead to heart attacks in children as young as 6 years old. This rare form of homozygous familial hypercholesterolemia inspired Brown and Goldstein to elucidate the genetic defect in the receptor for LDL.Discovery of the LDL receptor defect