• Impaired Volume Regulation in Cardiovascular Disease in Two Distinct Populations

      Beavers, Melinda L. C.; Georgia Prevention Institute (2012-05)
      Volume dysregulation leads to congestive heart failure and death. The condition has been well-documented in both obesity-related cardiovascular disease and congenital heart disease. Our hypotheses are as follows: 1) Volume dysregulation, in the form of elevated systolic blood pressure and left ventricular mass index, is related to adiposity and aldosterone in adolescent boys but not girls. 2) Volume dysregulation, in the form of decreased nocturnal decline in blood pressure (non-dipping) is present in patients with tetralogy of Fallot, and is related to decreased left and right ventricular function. To test our first hypothesis, 100 healthy adolescents, recruited from area schools, were studied. Subjects were placed on a sodium-controlled diet for 4 days. Blood and urine samples were collected after one hour of rest. The protocol was repeated twice for each individual. Data were averaged between visits for greater statistical power. Adiposity and echocardiography measures were collected within 1 month of testing. Stepwise regression indicated that race and adiposity both contributed to the effects of aldosterone. For example, body mass index and race contributed to the model for aldosterone (Adjusted R2=0.303, p=0.002). In the aldosterone-hypertension risk relationship, stepwise regression indicated that only aldosterone contributed to the model for systolic blood pressure (Adjusted R2=0.098, p=0.023). To test our second hypothesis, 20 patients with repaired tetralogy of Fallot were recruited from clinic. Subjects completed a submaximal exercise test (modified Bruce) with echocardiography, and then wore an ambulatory blood pressure monitor for 24 hours. Of the 20 subjects with tetralogy of Fallot, 60% were 'non-dippers'. Race was significantly different between the dippers and non-dippers, with 1 of 8 African Americans being a dipper, and the remaining 7 African Americans being non-dippers (t=2.188, p=0.042). Right ventricular stroke volume (t=2.392, p=0.028) and ejection fraction (t=3.484, p=0.003) were significantly different between dippers and non-dippers. In a population of healthy adolescents with a well-distributed range of adiposity, increasing adiposity is associated with increasing aldosterone levels in boys but not girls. This is related to increasing systolic blood pressure and left ventricular mass in boys, but not in girls. These results may indicate an underlying volume dysregulation that contributes to hypertension and cardiovascular disease as a result of prolonged exposure to increased adiposity. In a population of 20 adolescents and young adults with repaired tetralogy of Fallot, nondipping is associated with decreased right ventricular stroke volume and ejection fraction, but is not associated with decreased left ventricular function. Patients with repaired tetralogy of Fallot and non-dipping may be at greater risk for failure due to the combination of pulmonary regurgitation with increased nocturnal pressures.