Case Answers:

Answer 1
Table 242-1, p 1349

The discussion here should revolve around the known risk factor for the development of coronary disease, in particular, diabetes, hypertension, dyslipidemia, family history of premature atherosclerosis, cigarette smoking, etc. There is no need to get into discussions of other topics such as alcohol, estrogen use etc., since some of the questions down the line will focus on these. If the students can walk away with a general understanding about the known risk factors for the development of coronary disease, I think we have met the goal of this question.

Also Appendix A in the Case on Coronary Artery disease gives the risk factors and evidence.

Answer 2
This question is design to alert the students to the fact that all lipids abnormality are not primary in nature. Harrisons delineates the secondary causes of lipoprotein abnormalities well. For example, several entity has been known to increase the LDL cholesterol level such as hypothyroidism, diabetes, nephrotic syndrome, liver disease, progestin and anabolic steroid use. Others have been known to increase triglycerides such as obesity, diabetes, lack of exercise, alcohol intake, renal insufficiency, estrogen use and beta blockers. Those that have been shown to decrease HDL are hypertriglyceridemia, obesity, diabetes, cigarette smoking, lack of exercise, beta blockers, progestin and anabolic steroid. This specific question relates to the fact that this patient has a history of cigarette smoking and hypothyroidism which are common secondary causes for lipoprotein abnormalities.

The physical finding associated with dyslipidemia's can be discussed here. In particular, the students should be aware of xanthoma's, xanthelasma's, and corneal arcus. Specifically, the discussion here should revolve around these particular findings and how to diagnose such things as tendinous xanthoma's (in the fingers and Achilles tendon) etc. A certain amount of time should be spent discussing the corneal arcus, since this is one of the questions that will come up in the exam.

Answer 3
There are several epidemiologic studies relating risk of coronary disease and elevated cholesterol levels. To be specific, I think the students should discuss The Seven Country Study which showed a correlation between elevated cholesterol levels and death from coronary disease in specific populations. It should be emphasized that this is correlation data, it did not demonstrate a causative relationship between cholesterol and coronary disease. The next study of importance is the MRFIT study, which demonstrated in individual patients who had elevated cholesterol levels death from coronary disease was increased.

Diet should be emphasized here as being the first treatment in any lipid abnormality. Diet has been shown to cause between a 5 - 20% reduction in the total cholesterol valves (depending on which study one looks at). However, we emphasize that dietary manipulation is critical to the treatment of lipid abnormalities and is one of the main stays throughout the patients life.

Answer 4
This particular question relates to two recent trials:

The West of Scotland study. In this study patients with elevated cholesterol levels, but without evidence of coronary artery disease, were treated either with pravastatin or placebo. A number of outcomes were measured including mortality rates in the treatment vs. control group. Unfortunately, the study did not show a statistically significant difference in mortality rates (p=0.059) using this cholesterol lowering agent in a primary preventive setting. (The treated group did, incidentally, have a lower death rate than the control group). However, the reduction was considered by many to be clinically significant (since the p value was so close to significant) supporting the value of primary prevention in the treatment of atherosclerosis as it relates to the modification of lipid abnormalities. It should be emphasized that even though this particular study demonstrated there is not a statistically significant change, the clinical impact is such that primary prevention is a very important aspect in the management and prevention of coronary artery disease.

The AFCAPS/TexCAPS study. This study included 6,605 healthy adults ages 45-73 and included a broad spectrum of subjects:

Subjects received either lovastatin or placebo. Target LDL was <100 mg/dl. 50% achieved this on 20 mg/day and the others 50% had the dose increased to 40 mg/day.

LOVASTATIN vs. PLACEBO

Answer 5
At this point, and probably with question #4, the definitions of primary and secondary prevention should be reviewed, since they should have had this at some point in their preventive medicine lectures. This question is more of an ethical question than specifically a medicine question. Given that primary prevention has not shown to be statistically significant, but does have obvious clinical value, should the cost of primary prevention be absorbed by society (or insurance companies) given the high cost of the medicines that are involved? Therefore, the discussion should focus on what primary prevention is, what the results of the West of Scotland and AFCAPS/TexCAPS studies were, and whether or not we should be taking these preventive approaches, since some people may argue there is marginal benefit (including the American College of Physicians).

Answer 6
The discussion here should focus mainly on The 4 S Study (The Scandinavian Simvastatin Survival Study) which showed that in patients with known coronary disease, lowering lipid levels with simvastatin did, in fact, have a statistically significant mortality benefit. Again, this question is design to be epidemiologic in nature. Also, this is probably a good place to expand the discussion from primary prevention to secondary prevention emphasizing the importance of intervening once coronary disease has developed. The discussion could focus on risk factor modification in general as part of secondary prevention (not only with lipid modification but the other risk factors as well). If one wants to jump in full tilt, you could discuss the morality and/or ethics of intervening on patients who have not modified their risk factors (for example, should we spend societal resources to bypass patients who continue to smoke?).

Here again the 27th Bethesda Conference is an excellent resource for only $5.00. See the case discussion of Coronary artery disease for details.