Cardiovascular Morbidity in Hemodialysis: The Reverse Epidemiology Phenomenon

The Framingham study that begun more than 60 years ago (1948) has shaped the way Western societies face cardiovascular disease (CVD). The relative impact of this study (now on its 3rd generation of participants) [1] has been so impressive that both public health authorities and the medical community have fully endorsed its results: since then, hypertension, dyslipidemia, tobacco smoking, diabetes mellitus and more recently obesity and hypertriglyceridemia are considered as the major risk factors for new cardiovascular morbidity and overall mortality. Major advances aiming both at prevention and management have had a significant impact on survival of patients with CVD. These advances, together with the extinction of undernutrition after the 2nd World War, have led to an increase in survival and thus in the number of patients with chronic disease states (congestive heart failure, chronic kidney disease, dialysis patients, cancer etc) that survive over prolonged time periods. Numerous epidemiological studies over the last decade, have observed that in these subgroups of patients, the well established-for the general populationsurrogates of cardiovascular risk and metabolic syndrome as obesity, hypercholesterolemia and hypertension are paradoxically associated with greater survival. Hence the term “reverse epidemiology paradox” was coined in medical literature. Approximately 9% of the US adult population (about 20 million people) has chronic kidney d stage 1 (CKD-1) and 2% are receiving maintenance dialysis. It has been projected that dialysis patients will exceed 1 million by 2018. It should be emphasized that although dialysis for CKD-5 is expected to be life-prolonging, 5-year survival in the US is only about 35% for patients on dialysis [2,3]. Robust observational studies have repeatedly shown that even after adjustments for comorbidities, moderately higher levels of blood pressure, higher body mass index (BMI) and higher cholesterol levels are associated with improved survival. This chapter will review data concerning the role of arterial hypertension, obesity, and cholesterol levels on cardiovascular morbidity and mortality in hemodialysis (HD) patients and discuss potential pathogenetic mechanisms that could possibly explain the so called “reverse epidemiology paradox”.