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Ten years follow up of the precursors of early atherosclerosis in children
238A
POSTERS: Pediatric Hypertension
AJH–May 2003–VOL. 16, NO. 5, PART 2
Supported by Heart and Stroke Foundation of Ontario grants NA3478 and T4136. Key Words: New Pressor Protein, coagulation FXIIa, hemodialysis
P-553 TEN YEARS FOLLOW UP OF THE PRECURSORS OF EARLY ATHEROSCLEROSIS IN CHILDREN Veronika S. Petrova, Rumiana D. Rachneva. University Children Hospital, Sofia, Bulgaria.
P-552 ELEVATED PLASMA COAGULATION FXIIA LEVELS AND HIGH ‘NEW PRESSOR PROTEIN’ (NPP) ACTIVITY IN PEDIATRIC HEMODIALYSIS PATIENTS WITH UNEXPLAINED RENOPRIVAL HYPERTENSION Peter C Papageorgiou, Rachel J Pearl, Michael Goldman, Akis A Amfilochiadis, Rasmus Rojkjaer, Denis F Geary, Daniel H Osmond. Physiology & Medicine & Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada; Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Hemostasis Biology, Novo Nordisk, Maaloev, Denmark. Unexplained hypertension was observed in three anephric children on hemodialysis. We therefore investigated possible involvement by the novel extra-renal enzyme ‘New Pressor Protein’ (NPP) which is structurally related to coagulation -FXIIa (J Hypertens 16:311-320, 1998; Can J Cardiol 18(10):1077-1086; 1093-1103, 2002) and produces potent hypertensive cardiovascular and sympatho-adrenal effects. NPP activity (⌬SBP mmHg) from normal human plasma (NHP, 250L i.v.) and from our patients’ plasmas (250L i.v.) were measured in male Wistar bioassay rats (⬃300g), anesthetized with Inactin (100 mg/kg i.p.) and given Pentolinium (19.2 mg/kg s.c.) and Captopril (2.5 mg/kg i.v.). The SBP increments (⌬ mmHg) were recorded using a MacLab/8 PowerMac 7200 computerized system. Plasma FXIIa levels in NHP and patients’ plasmas were determined by immunoassay (Axis-Shield Diagnostics Ltd., Dundee, UK).
Pre-Dialysis NPP Activity† Normal Human Plasma Patient AS Plasma Patient HI Plasma Patient JS Plasma
0.8 ⫾ 1 45 35 9
Post-Dialysis FXIIa (ng/mL) 1.00 ⫾ 0.06 7.70 ⫾ 0.16* 8.18 ⫾ 0.45* 1.74 ⫾ 0.14*
NPP Activity† 0.6 ⫾ 1 22 14 9
FXIIa (ng/mL) 1.00 ⫾ 0.06 5.09 ⫾ 0.35* 6.40 ⫾ 0.48* 2.03 ⫾ 0.20*
† NPP activity (⌬SBP, mmHg). Means ⫾ SEM. * p ⬍ 0.01 vs. NHP.
Pre-dialysis, patients AS and HI were hypertensive and their plasmas exhibited abnormally high NPP activity and plasma FXIIa levels. Postdialysis, patients AS and HI reached their estimated dry body weight and their systemic pressures dropped in parallel with both NPP activity and plasma FXIIa levels. Patient JS remained hypertensive and hypervolemic, both pre- and post-dialysis, and NPP activity and plasma FXIIa levels dropped but still remained abnormally high. Our data suggest that high endogenous plasma NPP activity and FXIIa levels exist in these hemodialysis patients and change in relation to systemic BP and fluid volume status enough to suggest involvement in their hypertension.
The frequency of the arterial hypertension and the lipid disturbances have been studied in 29 healthy children with family history of early coronary disease in a 10 year period. The evaluation in arterial hypertension (AH) has been carried out by a WHO methodology. In boys the frequency of AH is 56% and remains in the 10 years follow-up at 80%, while in girls it is 70% and falls to 30% in the follow-up. The hypercholesterolemia established in childhood continues into young age – 100% in cases of men and 80% in female. Increased levels of triglycerides in childhood are normalized later. The apoproteins and lipoprotein “a” levels are within the normal limits. Both genders have lower HDL-cholesterol (x⫽4,51 mmol/l) in the standard risk limits. The obtained results confirm the data of persistence of precursors of early atherosclerosis development from childhood to later age and the necessity of early prophylaxis. Key Words: early atherosclerosis, juvenile hypertension, dislipidemias
P-554 ALTERED ASSESSMENT OF ANTIHYPERTENSIVE EFFECTIVENESS IN HYPERTENSIVE (HTN) CHILDREN USING AMBULATORY BLOOD PRESSURE (ABP) COMPARED TO CASUAL BLOOD PRESSURE (CBP) MEASUREMENTS Ronald J Portman, Howard Trachtman, John Mahan, Timothy Poffenbarger, Michael Klibaner. Pediatric Nephrology and Hypertension, University of Texas-Houston, Medical School, Houston, TX; Pediatric Nephrology, Schneider Children’s Hospital, New Hyde Park, NY; Pediatric Nephrology, Children’s Hospital and Pediatric Clinical Trials International, Columbus, OH; AstraZeneca, Wayne, PA. Background: ABP monitoring (ABPM) is an effective tool for the diagnosis of HTN and predicts end organ damage in HTN children. In adults ABPM is also valuable in assessing antihypertensive efficacy. Objective: To determine if variations exist in the assessment of response to a antihypertensive drug (felodipine ER) in HTN children by ABP compared to CBP. Design/Methods: A diagnosis of HTN was made if CBP exceeded the 95th%ile for age, gender and height based on Task Force data. Patients were eligible for this study if ABPM was performed before receiving study drug. Following completion of the felodipine ER double-blind phase (Peds Nephrol, under review), pts entered an open-label phase and were given an investigator-determined dose to achieve CBP control. ABPM was performed after 2 and 4 months of treatment; these results were not used for dose adjustment. 24-hr ABPM was performed with SpaceLabs 90217 oscillometric monitor with readings q20 min with appropriately-sized cuffs. Pts were classified as responder (R) if the BP fell by ⱖ5 mmHg for SBP; ⱖ3 mmHg for DBP for either CBP or 24 hr mean ABP readings. Non-responders (NR) did not achieve this level of BP reduction. CBP measurements were trough values. Results: Of 17 children treated with felodipine ER, 11 pts (12yo,10 males, 5 white, 3AA, 3 Hispanic) were enrolled in this study. The mean Felodipine ER dose was 0.1 mg/kg at both 2 and 4 mos. At 2 mos, the two techniques were congruent in the identification of R pts for SBP in 55% and DBP in 45% of subjects. Among R, the mean decline in BP determined by CBP was 12.6/12.5 mm Hg. In contrast, the
POSTERS: Pediatric Hypertension
AJH–May 2003–VOL. 16, NO. 5, PART 2
Supported by Heart and Stroke Foundation of Ontario grants NA3478 and T4136. Key Words: New Pressor Protein, coagulation FXIIa, hemodialysis
P-553 TEN YEARS FOLLOW UP OF THE PRECURSORS OF EARLY ATHEROSCLEROSIS IN CHILDREN Veronika S. Petrova, Rumiana D. Rachneva. University Children Hospital, Sofia, Bulgaria.
P-552 ELEVATED PLASMA COAGULATION FXIIA LEVELS AND HIGH ‘NEW PRESSOR PROTEIN’ (NPP) ACTIVITY IN PEDIATRIC HEMODIALYSIS PATIENTS WITH UNEXPLAINED RENOPRIVAL HYPERTENSION Peter C Papageorgiou, Rachel J Pearl, Michael Goldman, Akis A Amfilochiadis, Rasmus Rojkjaer, Denis F Geary, Daniel H Osmond. Physiology & Medicine & Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Ontario, Canada; Nephrology, The Hospital for Sick Children, Toronto, Ontario, Canada; Hemostasis Biology, Novo Nordisk, Maaloev, Denmark. Unexplained hypertension was observed in three anephric children on hemodialysis. We therefore investigated possible involvement by the novel extra-renal enzyme ‘New Pressor Protein’ (NPP) which is structurally related to coagulation -FXIIa (J Hypertens 16:311-320, 1998; Can J Cardiol 18(10):1077-1086; 1093-1103, 2002) and produces potent hypertensive cardiovascular and sympatho-adrenal effects. NPP activity (⌬SBP mmHg) from normal human plasma (NHP, 250L i.v.) and from our patients’ plasmas (250L i.v.) were measured in male Wistar bioassay rats (⬃300g), anesthetized with Inactin (100 mg/kg i.p.) and given Pentolinium (19.2 mg/kg s.c.) and Captopril (2.5 mg/kg i.v.). The SBP increments (⌬ mmHg) were recorded using a MacLab/8 PowerMac 7200 computerized system. Plasma FXIIa levels in NHP and patients’ plasmas were determined by immunoassay (Axis-Shield Diagnostics Ltd., Dundee, UK).
Pre-Dialysis NPP Activity† Normal Human Plasma Patient AS Plasma Patient HI Plasma Patient JS Plasma
0.8 ⫾ 1 45 35 9
Post-Dialysis FXIIa (ng/mL) 1.00 ⫾ 0.06 7.70 ⫾ 0.16* 8.18 ⫾ 0.45* 1.74 ⫾ 0.14*
NPP Activity† 0.6 ⫾ 1 22 14 9
FXIIa (ng/mL) 1.00 ⫾ 0.06 5.09 ⫾ 0.35* 6.40 ⫾ 0.48* 2.03 ⫾ 0.20*
† NPP activity (⌬SBP, mmHg). Means ⫾ SEM. * p ⬍ 0.01 vs. NHP.
Pre-dialysis, patients AS and HI were hypertensive and their plasmas exhibited abnormally high NPP activity and plasma FXIIa levels. Postdialysis, patients AS and HI reached their estimated dry body weight and their systemic pressures dropped in parallel with both NPP activity and plasma FXIIa levels. Patient JS remained hypertensive and hypervolemic, both pre- and post-dialysis, and NPP activity and plasma FXIIa levels dropped but still remained abnormally high. Our data suggest that high endogenous plasma NPP activity and FXIIa levels exist in these hemodialysis patients and change in relation to systemic BP and fluid volume status enough to suggest involvement in their hypertension.
The frequency of the arterial hypertension and the lipid disturbances have been studied in 29 healthy children with family history of early coronary disease in a 10 year period. The evaluation in arterial hypertension (AH) has been carried out by a WHO methodology. In boys the frequency of AH is 56% and remains in the 10 years follow-up at 80%, while in girls it is 70% and falls to 30% in the follow-up. The hypercholesterolemia established in childhood continues into young age – 100% in cases of men and 80% in female. Increased levels of triglycerides in childhood are normalized later. The apoproteins and lipoprotein “a” levels are within the normal limits. Both genders have lower HDL-cholesterol (x⫽4,51 mmol/l) in the standard risk limits. The obtained results confirm the data of persistence of precursors of early atherosclerosis development from childhood to later age and the necessity of early prophylaxis. Key Words: early atherosclerosis, juvenile hypertension, dislipidemias
P-554 ALTERED ASSESSMENT OF ANTIHYPERTENSIVE EFFECTIVENESS IN HYPERTENSIVE (HTN) CHILDREN USING AMBULATORY BLOOD PRESSURE (ABP) COMPARED TO CASUAL BLOOD PRESSURE (CBP) MEASUREMENTS Ronald J Portman, Howard Trachtman, John Mahan, Timothy Poffenbarger, Michael Klibaner. Pediatric Nephrology and Hypertension, University of Texas-Houston, Medical School, Houston, TX; Pediatric Nephrology, Schneider Children’s Hospital, New Hyde Park, NY; Pediatric Nephrology, Children’s Hospital and Pediatric Clinical Trials International, Columbus, OH; AstraZeneca, Wayne, PA. Background: ABP monitoring (ABPM) is an effective tool for the diagnosis of HTN and predicts end organ damage in HTN children. In adults ABPM is also valuable in assessing antihypertensive efficacy. Objective: To determine if variations exist in the assessment of response to a antihypertensive drug (felodipine ER) in HTN children by ABP compared to CBP. Design/Methods: A diagnosis of HTN was made if CBP exceeded the 95th%ile for age, gender and height based on Task Force data. Patients were eligible for this study if ABPM was performed before receiving study drug. Following completion of the felodipine ER double-blind phase (Peds Nephrol, under review), pts entered an open-label phase and were given an investigator-determined dose to achieve CBP control. ABPM was performed after 2 and 4 months of treatment; these results were not used for dose adjustment. 24-hr ABPM was performed with SpaceLabs 90217 oscillometric monitor with readings q20 min with appropriately-sized cuffs. Pts were classified as responder (R) if the BP fell by ⱖ5 mmHg for SBP; ⱖ3 mmHg for DBP for either CBP or 24 hr mean ABP readings. Non-responders (NR) did not achieve this level of BP reduction. CBP measurements were trough values. Results: Of 17 children treated with felodipine ER, 11 pts (12yo,10 males, 5 white, 3AA, 3 Hispanic) were enrolled in this study. The mean Felodipine ER dose was 0.1 mg/kg at both 2 and 4 mos. At 2 mos, the two techniques were congruent in the identification of R pts for SBP in 55% and DBP in 45% of subjects. Among R, the mean decline in BP determined by CBP was 12.6/12.5 mm Hg. In contrast, the