What Happens When a Bad CVD Risk Factor Becomes Good? The Phenomenon of "Reverse Epidemiology" in Chronic Disease

George T. Griffing, MD


August 19, 2009

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Your obese hypertensive, hyperlipidemic diabetic patient returns to the office after stopping all of his medications. He was recently diagnosed with heart failure (HF) and chronic kidney disease (CKD). What are you going to do? Recommend weight loss and prescribe medications to normalize his glucose, lipids, and blood pressure?

Wait -- not so fast. Recent data tells us that these traditional cardiovascular disease risk factors may not hold up in patients with certain chronic diseases, such as HF and CKD.[1,2] In fact, these risk factors, which have been established in healthy populations, paradoxically seem to be protective, a reversal of the usual pattern -- hence the term "reverse epidemiology" (RE). In RE, increased body weight, blood pressure (BP), HbA1c, and cholesterol are associated with improved outcomes and mortality.[3,4,5] Furthermore, intervention studies to correct these risk factors have been disappointing in RE populations.[6]

Features of RE have been reported for other chronic diseases, including rheumatoid arthritis, AIDS, post- myocardial infarction, postcoronary revascularization, hypertensives with coronary artery disease, cancer, and the elderly.[7,8,9] It has been estimated that 30 million Americans may be in RE populations.

What accounts for RE? Cachexia is one explanation, but RE findings are still present when these patients are excluded. Other statistical and mechanistic explanations have been posited, but whatever the reason, RE appears to be a real phenomenon.[10,11,12]

The term "RE" has been controversial, and we should not think of the epidemiology as "reversed" but rather counterintuitive.[13,14] It would be a mistake to think of obesity and high cholesterol, glucose, and BP as beneficial. But until we have more data, we cannot blindly correct these abnormalities either. The first goal as a physician is primum non nocere.

That's my opinion.