Reverse epidemiology of cardiovascular risk factors in maintenance dialysis patients

Abstract

Conventional risk factors of cardiovascular disease and mortality in the general population such as body mass, serum cholesterol, and blood pressure are also found to relate to outcome in maintenance dialysis patients, but often in an opposite direction. Obesity, hypercholesterolemia, and hypertension appear to be protective features that are associated with a greater survival among dialysis patients. A similar protective role has been described for high serum creatinine and possibly homocysteine levels in end-stage renal disease (ESRD) patients. These findings are in contrast to the well-known association between over-nutrition and poor outcome in the general population. The association between under-nutrition and adverse cardiovascular outcome in dialysis patients, which stands in contrast to that seen in non-ESRD individuals, has been referred to as "reverse epidemiology." Publication bias may have handicapped or delayed additional reports with such paradoxical findings in ESRD patients. The etiology of this inverse association between conventional risk factors and clinical outcome in dialysis patients is not clear. Several possible causes are hypothesized. First, survival bias may play a role since only a small number of patients with chronic kidney disease (CKD) survive long enough to reach ESRD. Hence, the dialysis patients are probably a distinctively selected population out of CKD patients and may not represent the risk factor constellations of their CKD predecessors. Second, the time discrepancy between competitive risk factors may play a role. For example, the survival disadvantages of under-nutrition, which is frequently present in dialysis patients, may have a major impact on mortality in a shorter period of time, and this overwhelms the long-term negative effects of over-nutrition on survival. Third, the presence of the "malnutrition-inflammation complex syndrome" (MICS) in dialysis patients may also explain the existence of reverse epidemiology in dialysis patients. Both protein-energy malnutrition and inflammation or the combination of the two are much more common in dialysis patients than in the general population and many elements of MICS, such as low weight-for-height, hypocholesterolemia, or hypocreatininemia, are known risk factors of poor outcome in dialysis patients. The existence of reverse epidemiology may have a bearing on the management of dialysis patients. It is possible that new standards or goals for such traditional risk factors as body mass, serum cholesterol, and blood pressure should be considered for these individuals.

The Relationship Between Nontraditional Risk Factors and Outcomes in Individuals With Stage 3 to 4 CKD

“…This phenomenon, sometimes dubbed "reverse epidemiology", remains poorly understood and the time of onset unknown. 26 In the current study, general population risk factors including higher BMI and elevated diastolic blood pressure did not independently predict adverse outcomes in individuals with CKD. 27,28 Rather than reflecting different pathophysiology, it may be that these altered relationships are due to confounding from malnutrition and cardiomyopathy, respectively, such that BMI and blood pressure decrease as patients become progressively more infirm.…”

Associations of Glycemic Control With Cardiovascular Outcomes Among US Hemodialysis Patients With Diabetes Mellitus

“…In this study we observed only moderate associations between higher HbA 1c and increased rates of cardiovascular mortality and MI. Because ESRD patients constitute fewer than 5% of the chronic kidney disease patients in the United States, a majority of chronic kidney disease patients do not live long enough to develop ESRD or to start dialysis due to high rates of morbidity and mortality in these patients 35. Advanced kidney disease is also an independent risk factor for increased morbidity and mortality associated with atherosclerotic heart and cerebrovascular diseases 36.…”

Potential impact of renin–angiotensin system inhibitors and calcium channel blockers on plasma high-molecular-weight adiponectin levels in hemodialysis patients

“…[18][19][20] However, there is the possibility that the protective link observed between obesity and mortality may not actually exist. Most studies have not completely accounted for known mortality risk factors such as smoking, BP and medication.…”