A 46 year old male sees you for a first visit with symptoms of atypical chest pain. The pain is occasionally exertional, lasts less than a minute, is sharp in nature and the patient felt that he wanted it checked out. After undergoing a negative stress test, you and he discuss risk factors for the development of coronary artery disease in detail.
"You know, Doc," he states, "one of the reasons I thought it would be important to see you is because my dad died of a heart attack at age 52." His physical exam is unremarkable other than an early arcus, body weight 15% over ideal, and a social history consistent with "a cigarette now and then". Because of his risk factors, a total cholesterol was drawn which was 286. As recommended by the National Cholesterol Education Program, a non-fasting total cholesterol and HDL value were initially drawn. Unfortunately, in this patient, only the total cholesterol was reported. Since the NCEP recommends that when a non-fasting total cholesterol is found to be greater than 240 mgs/dl, one should move on and perform a full lipoprotein analysis, a subsequent full fasting profile revealed a total cholesterol of 266, triglycerides 100, HDL 30, LDL 204. A TSH was slightly elevated at 7.8 and a fasting blood sugar was 89.
The patient and his wife met with you to discuss the results of the blood tests and the next steps in the evaluation and treatment of his problem.
See questions 1 & 2
The patient and his wife are instructed by the dietician in the Step II AHA diet. He continues on the diet for six months when repeat exam shows his body weight to be only 5% above ideal, fasting blood sugar normal, and normal TSH on low dose thyroid replacement. The patient states that he has been able to quit smoking successfully and states that "I feel better, Doc. But frankly, I'm a bit sick of the rabbit food." Repeat lipid profile shows a total cholesterol of 254, triglycerides 96, HDL 33, LDL 188. The wife and
patient ask, "What now?"
See questions 3 & 4
As a practicing General Internist, you are aware of the recent data evaluating antilipemic medicines in the primary prevention of coronary artery disease.
There are seven large-scale primary prevention trials of cholesterol-lowering alone. The most recent include the:
West of Scotland Coronary Prevention Study
New England Journal of Medicine 333:1301-1307, 1995
Showed that when randomly assigning 6595 men aged 45 to 64 with a mean plasma cholesterol level of 272 + 23, to either Pravastatin 40 mgs. each evening or placebo, that in the treated group there was a 31% relative reduction in risk for non-fatal myocardial infarction or death from coronary artery disease. Also observed was a 22% reduction in the risk of death from any cause in the Pravastatin group (95% confidence interval, 0 - 40%; p=0.051).
Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS)
JAMA 279:1615-1622, 1998
Showed that in 6605 patients with only a modest elevation in LDL cholesterol ( LDL 130-190), low HDL (HDL <45 for men, <47 for women), and Triglycerides <400, Lovastatin reduced LDL by 25%. This gave clear reduction in risk of MI, unstable angina, coronary revascularization procedures, total coronary events and total cardiovascular events.
You feel that this risk reduction in subsequent coronary death is clinically significant and therefore you recommend starting the patient on Pravastatin 10mg. a day to lower his LDL cholesterol to less than 130. A prescription is provided and the patient and wife are sent on their way. A few days later, the patient calls you in your office and says "This medicine costs a lot of money Doc, and my insurance won't pay for it!"
See question 5
Unfortunately, the patient is lost to follow up, but six years later you are informed he has been admitted with unstable angina. Coronary arteriography performed shows two vessel disease, normal LV function and medical therapy is recommended. "I should have listened to you years ago, Doc. Maybe those cholesterol medicines could have helped prevent some of this." Lipid profile drawn at the office visit now reveals a total cholesterol of 320, triglycerides 120, HDL 30, LDL 266, TSH normal (the patient continued with his Synthroid) and the patient is proud to announce that he has maintained his smoking cessation. Re-instruction and diet is provided since body weight has returned to his baseline 15% above ideal. In addition to his anti-anginals and aspirin, you prescribed Simvastatin 20 mg every night based on the results of the Scandinavian Simvastatin Survival Study. You recall that the 4-S Study was a trial designed to evaluate the effect of cholesterol lowering with Simvastatin on mortality and morbidity in patients with known coronary artery disease. 4,444 patients with angina pectoris or previous myocardial infarction and elevated serum cholesterol levels on a lipid-lowering diet were randomized to double-blind treatment with either Simvastatin or placebo. The study showed numerous benefits; in particular, a decrease in the risk of undergoing myocardial revascularization procedures, and decreased coronary deaths, but most importantly, the relative risk of death of any kind in the Simvastatin group was 0.70 (95% confidence interval .58 -.85, p=0.0003). This was the first major study to show a mortality benefit in patients with known coronary artery disease when aggressive lipid-lowering therapy was provided.
See question 6