Cardiac disease in chronic uremia: Can it explain the reverse epidemiology of hypertension and survival in dialysis patients?

Definitive randomized trials are rare in the dialysis literature. Treatment decisions are often based on extrapolation from trials in other populations and observational studies in dialysis patients. "Reverse epidemiology" is a term increasingly applied to classic cardiovascular risk factors in studies of dialysis patients. The term is used when outcome associations are the opposite of those seen in general population studies. Hypertension is an archetypal example, with several studies showing inverse associations with mortality. As a term, "reverse epidemiology" is intellectually unsatisfactory because validation of the real direction of an association is only possible with experimental designs. In contrast, blood pressure (BP) is associated with typical association patterns for outcomes other than death, including left ventricular hypertrophy and cardiac failure, which are dominant entities in dialysis populations. There is a strong suspicion that current analytical approaches may partly explain the paradox. For example, it is possible that unmeasured comorbidities are associated with lower BP levels. In addition, few studies use BP as a time-integrated parameter, which is problematic given the variability of this parameter. Several recent studies suggest that using pulse pressure as a BP parameter may normalize associations with mortality. BP, extracellular blood volume, residual renal function, and vasoactive medications are interlinked. Time-integrated analysis that examines all these parameters concurrently makes sense, but has rarely been attempted. A large burden of cardiac disease and insensitive analytical approaches may go a long way toward explaining the reverse epidemiology of hypertension and survival in dialysis patients.