Introduction – Cardiovascular Pharmacology

00:07 The most important thing to remember in Cardiovascular Pharmacology is what disease are we dealing with or rather what diseases are we dealing with.

00:17 Well, there’s one disease that’s exceedingly common in the world. It’s relatively rare in countries without very much economic power, but in countries with considerable economic growth and development, this disease becomes increasingly common.

00:36 So, what is the leading cause of death in the world? Is it Alzheimer’s disease? Is it accidents? Is it cancer? Well, let’s think about that for a moment. In fact, it’s none of the above. Many millions of people are affected by this disease. This disease is atherosclerosis - hardening of the arteries in the layman’s term in English and it causes more deaths than all of the previously mentioned diseases. Alzheimer’s, accidents and cancer put together actually do not equal the number of people who die from the complications of atherosclerotic disease. In fact, in the United States, one in three deaths is the result of atherosclerotic disease and there’s one death every 30 seconds in the US from this disease. Now, it affects different organs, it affects most commonly the heart causing heart attacks or myocardial infarctions. It can cause sudden death and frighteningly, the first manifestation of atherosclerosis of the coronary disease is often sudden death. In cardiology, we refer to it as coronary artery disease because those are the arteries affected that lead to myocardial infarction or heart attack and the abbreviation CAD for “Coronary Artery Disease” is frequently used. It is the number one killer in the United States and it is now the number one killer in the world as many countries have moved from lower economic development phases into more western and highly technical developments. The disease comes along with the western lifestyle.

02:29 And of course, here, again, the point is made that it is the commonest cause for death in the United States, in Western Europe and now, in many parts of Asia, it has also become the commonest cause of death. So, what is the cause of atherosclerosis? Well, there are multiple factors. I think most people have heard from the media that it’s a variety of things. Cigarette smoking, high blood pressure, a whole variety of factors play a role in the development of hardening of the arteries, but the most important element is elevated blood cholesterol. When we examine blood cholesterol in natives, for example, in the highlands of New Guinea, who are healthy and eating well, it is one third the value that you see in Western Europe and the United States.

03:26 In fact, in the United States, we estimate that approximately 50% of the population has a cholesterol value that is too high. And, it is this high level of cholesterol often combined with other factors such as smoking or high blood pressure or diabetes that leads to atherosclerosis. The disease unfortunately starts in childhood and then can rapidly progress depending upon the presence of other risk factors and usually, affects people in the middle of their life at ta time when they are most productive. And as I have said before, the most frightening and disconcerting symptom is sudden death, which in 50% of people, is the first manifestation of coronary disease. We are going to have a whole lecture on coronary disease later in this series, but it’s important, in terms of understanding what drugs we have and what drugs have been developed, to understand what disease we are frequently dealing with.

04:26 Well, let’s talk a little bit about elevated lipids or elevated fats in the blood. The medical term is hyperlipidemia. “Hyper” in Greek means “large” or “increased” and “lipidemia” means “lipid” or “fats in the blood stream”. This is high levels of variety of fats in the blood stream. When we talk about lipids on a clinical basis, we usually refer to four commonly measured lipids. Now, there are a number of others that are particularly useful in various research projects. But at the moment, the ones we concentrate on are total blood cholesterol, LDL cholesterol - so called low density lipoprotein cholesterol, HDL cholesterol - also called high density lipoprotein cholesterol, and triglycerides.

05:21 Let’s talk just a little bit about them for a moment because then you can see, we are going to be talking about drugs for controlling hyperlipidemia to prevent… or heart disease in the first place, in people who are at high risk or in fact, to treat them once they have developed heart disease in an attempt to prevent the disease from progressing.

05:44 So, the point about high fats that’s important to remember is that there are other components in the blood stream beside those, but in the daily clinical activities, we measure the four that were just mentioned. Again, these are the lipids that lead to atherosclerosis and atherosclerosis can lead to myocardial infarction or heart attack or stroke or kidney failure or even heart failure. So, you see the… all of these processes start with levels of cholesterol and triglycerides, but mostly, cholesterol in the blood that are too high. In fact, the higher your blood cholesterol, the greater your risk of having a myocardial infarction or even dying of a… a heart attack or the complications of a heart attack. You will notice from this curve, as we look on the bottom - as total blood cholesterol rises, moving from left to right, you will see that there is an increase in the manifestations of coronary disease including heart attacks, strokes and death.

07:04 So, let’s about each of these individual forms of cholesterol and then we are going to talk about the therapy which is now available for them.