Reverse epidemiology: paradoxical observations in haemodialysis patients

Traditional risk factors, such as high blood pressure (BP), obesity and hypercholesterolaemia, play an important role in the development of cardiovascular disease (CVD), not only in the general population but also in patients with chronic renal disease. In recent years, it has become less clear whether these conventional risk factors are responsible for the extremely high risk of CVD in chronic haemodialysis (CHD) patients. Recent studies have shown that low BP, body mass index (BMI) and serum cholesterol are often correlated with an unfavourable clinical outcome. Thus, whereas traditional risk factors of CVD are correlated with an unfavourable outcome in the general population and patients with chronic renal failure not yet on dialysis, in CHD patients these factors appear to be protective and associated with an improved survival. Therefore, these phenomena have been referred to as 'paradoxical or reverse epidemiology'. The aetiology of this inverse relationship is not clear. Interestingly, in CHD patients, both C-reactive protein, a marker of inflammation, and (pre)albumin, a marker of nutrition, are important independent predictors of mortality. It has been speculated that what is known as the malnutritioninflammation-atherosclerosis complex underlies, at least partly, the phenomenon of reverse epidemiology, since malnutrition causes a low BMI and hypocholesterolaemia. Hence, besides care for adequate nutrition, attempts should be made to reduce inflammation. In this respect, various haemodialysis-related factors, such as the purity of the dialysate and several characteristics of the dialyser, deserve attention.