The Concept of Risk

In the old days, doctors treated patients who sought medical care because they had symptoms they wanted to get rid of. Then came medical treatment of easily measured physical parameters, like high blood pressure, even when not associated with splitting headaches and red cheeks. A normal blood pressure is essentially the same number for everyone. Recently, we have spent a lot of time and energy treating risk factors, like elevated cholesterol.

I find a lot of my patients have trouble thinking about risk; many still think of what we do as treating disease. For example, the National Cholesterol Education Program has set target values for the bad LDL-cholesterol. According to NCEP, a low risk person, for example a twenty-five year old non-smoking woman with ideal weight and blood pressure, has little reason to worry about a mildly “elevated” LDL, whereas a sixty-five year old diabetic chain-smoking man with a history of poor circulation in his legs with the same LDL number would be an obvious candidate for aggressive lipid lowering efforts.

As I counsel patients about cardiovascular risk, I usually first calculate their risk according to the Framingham Heart Study data, then I show how the presence or absence of inflammation, as measured by Highly Sensitive C-Reactive Protein (CRP), can tip the scales. My last step has been to look at the NCEP guidelines with the patient. I have found that not all my colleagues do the same – some seem to look at elevated cholesterol with less attention to individual risk.

Today the author of the original CRP study has published a study showing upwards of 50% reduction in heart attacks and strokes among people with normal cholesterol but with elevated CRP levels, when taking the cholesterol-lowering drug rosuvastatin (Crestor).

This is essentially the same risk reduction we have seen in traditional high risk (high LDL-cholesterol) patients. But bear with me here: Half of all heart attacks occur among a “relatively small” number of people with high cholesterol, and the remainder of all heart attacks occur among the much larger group of people with fairly normal cholesterol. Reducing heart attack risk by half does mean more for someone with a 25% risk of heart disease than for someone with a 5% risk.

My first read of the JUPITER study is that you have to provide as many as 300 patient-years of medication to high-CRP patients with normal LDL-cholesterol to prevent one heart attack. The JUPITER study saw 142 heart “events” (including not only heart attacks, but also strokes, hospital admissions for angina and elective coronary stenting) among 8,000 Crestor-treated patients and 251 heart events among 8,000 placebo treated individuals. That means the untreated group had a 3% risk of having an “event” during the study period of two years.

Any time you prescribe medication to someone who isn’t terribly ill, you have to stop and consider whether you might be trading one problem for another. A person with pneumonia or cancer will clearly tolerate all kinds of medication risks and even side effects in order to save their life, but a person who is more likely to live out their life free from heart disease should be more concerned about the long term safety of medications prescribed to lower their already low risk of having a heart attack.

One of my professors in medical school once gave a talk about blood pressure medications I still refer to today when talking to patients. He said that a good blood pressure medication should be effective, inexpensive, and side effect free, because high blood pressure is dangerous, common, and generally asymptomatic. Said differently, the treatment must really work, it must be easily available to all who need it, and you cannot ask people who feel well to take a medication that makes them feel bad.

The statin drugs were first developed in the 1970’s and it took many years before they became widely used. There are still enough unanswered questions about their very-long-term safety to make us think hard about when they are worth using and when they are not.

The night I suffered my vitreous detachment during my visit to Sweden a couple of months ago, I noticed the spider web visual distortions as I looked out my aunt’s living room window and saw he Astra-Zeneca pharmaceutical plant in the distance. It had come up in our conversation as they had laid off many workers shortly before my visit.

Maybe Astra-Zeneca will do better now – Comments I read suggest that it may cost up to half a million dollars worth of Crestor at $3.50 per pill to save one life in the lower risk group in the JUPITER study. Yes, we’re talking health care in a way. Health care is really big business these days, but still delivered one patient at a time.

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Osler said “Listen to your patient, he is telling you the diagnosis”. Duvefelt says “Listen to your patient, he is telling you what kind of doctor he needs you to be”.


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