Thiazide diuretics enhance nocturnal blood pressure fall and reduce proteinuria in immunoglobulin A nephropathy treated with angiotensin II modulators.

Uzu T, Harada T, Namba T, Yamamoto R, Takahara K, Yamauchi A, Kimura G.

aDivision of Nephrology, Osaka Rosai Hospital, Sakai, Osaka bDepartment of Internal Medicine and Pathophysiology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi, Japan.

OBJECTIVE: We examined whether thiazide diuretics could restore nocturnal blood pressure (BP) decline and reduce urinary protein excretion in patients with glomerulopathy treated with angiotensin II modulators (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers). METHODS: Twenty-five Japanese outpatients (11 men, 14 women; mean age 43 +/- 12 years) with biopsy-proven immunoglobulin (Ig)A nephropathy, preserved renal function (serum creatinine concentration </=1.2 mg/dl), stable non-nephrotic proteinuria (0.5-3 g daily), and treatment with angiotensin II modulators were studied. The patients received a diuretic, trichlormethiazide (2 mg daily) for 4 weeks after a baseline period lasting for 4 weeks. RESULTS: Diuretic therapy significantly reduced conventional, 24-h, daytime and night-time blood pressures. Nocturnal blood pressure fall was significantly enhanced by diuretic therapy and a significant interaction existed between diuretic therapy and nocturnal fall in mean arterial pressure, which indicated that the degree of nocturnal blood pressure fall was affected by diuretic therapy. The urinary protein excretion rate was significantly reduced from 1.10 +/- 0.62 to 0.63 +/- 0.39 g/day by diuretic therapy. Diuretic/baseline ratio of urinary protein excretion rate was not correlated with diuretic/baseline ratio of conventional, 24-h and daytime mean arterial pressures, but with diuretic/baseline ratio of night-time mean arterial pressure (r = 0.54, P = 0.006). CONCLUSIONS: Diuretics enhanced nocturnal BP decline and reduced urinary protein excretion in patients with IgA nephropathy treated with angiotensin II modulators. The combination of angiotensin II modulators and diuretics may have additional therapeutic advantages in relieving the renal and cardiovascular risks by reducing nocturnal high blood pressure.

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Validation of a noninvasive blood pressure monitoring device in normotensive and hypertensive pediatric intensive care patients.

Wankum PC, Thurman TL, Holt SJ, Hall RA, Simpson PM, Heulitt MJ.

Arkansas Children's Hospital, Little Rock, AR, USA. wankump health.missouri.edu

OBJECTIVE: To evaluate the performance and to define limitations of a noninvasive blood pressure monitoring device in the critically ill pediatric population. METHOD: Patients were included in the study if they were admitted to the Pediatric Intensive Care Unit, were between the ages of 1 month and 18 years with wrist circumferences of > or =10 cm, and had an indwelling arterial line. Patients were excluded if their systolic blood pressure differed by > or =7.5% between their upper extremities. The measurements were collected simultaneously with those from an arterial line by a computer interfaced with the noninvasive blood pressure monitoring system and the patient's monitor. Heart rates were calculated from the recorded pulse waveforms of the arterial lines. Comparison analyses were performed via bias and precision plots of the blood pressure and heart rate data in addition to calculation of Pearson's correlation coefficients and concordance correlation coefficients. As a nonparametric method of comparison, the proportion of measurements that differed by greater than 10% was calculated. Results. Blood pressures and heart rates of 20 patients between the ages of 12 months and 17 years were monitored by a noninvasive blood pressure monitor for 30 min per patient. This data collection resulted in 2015 data points for each blood pressure and heart rate for comparison of methods. Concordance correlation coefficients were the following: systolic blood pressure, 0.93; diastolic blood pressure, 0.93; mean blood pressure, 0.94; and heart rate, 0.85. CONCLUSIONS: The noninvasive blood pressure monitor is capable of producing an accurate blood pressure measurement every 12-15 heartbeats in addition to providing a pulse waveform and digital display of the heart rate. Our study showed good agreement between the methods in the normotensive and hypertensive critically ill pediatric population with a wrist circumference limitation defined at > or =11 cm.

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Development of Cardiovascular Function in the Horse Fetus.

Giussani DA, Forhead AJ, Fowden AL.

University of Cambridge.

In mammals, the mechanisms regulating an increase in fetal arterial blood pressure with advancing gestational age remain unidentified. In all species studied to date, the prepartum increase in fetal plasma cortisol has an important role in the maturation of physiological systems essential for neonatal survival. In the horse, the prepartum elevation in fetal cortisol and arterial blood pressure are delayed relative to other species. Hence, the mechanisms governing the ontogenic increase in arterial blood pressure in the horse fetus may mature much closer to term than in other fetal animals. In the chronically-instrumented pony mare and fetus, this study investigated how changes in fetal peripheral vascular resistance, in plasma concentrations of noradrenaline, adrenaline and vasopressin, and in the maternal-to-fetal plasma concentration gradient of oxygen and glucose relate to the ontogenic changes in fetal arterial blood pressure and fetal plasma cortisol concentration as term approaches. The data show that, towards term in the horse fetus, the increase in arterial blood pressure occurs together with reductions in metatarsal vascular resistance, elevations in plasma concentrations of cortisol, vasopressin, adrenaline and noradrenaline, and falls in the fetal: maternal ratio of blood PaO2 and glucose concentration. Correlation analysis revealed that arterial blood pressure was positively related with plasma concentrations of vasopressin and noradrenaline, but not adrenaline in the fetus, and inversely related to the fetal: maternal ratio of blood PaO2, but not glucose, concentration. This suggests that increasing vasopressinergic and noradrenergic influences as well as changes in oxygen availability to the fetus and uteroplacental tissues may contribute to the ontogenic increase in fetal arterial blood pressure towards term in the horse.

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Evolution of Blood Pressure in Patients with Alzheimer's Disease: A One Year Survey of a French Cohort (REAL.FR).

Hanon O, Latour F, Seux ML, Lenoir H, Forette F, Rigaud AS.

O. Hanon, Hopital Broca, CHU Cochin Port-Royal, Universite Rene Descartes, Paris V, 54/56 Rue Pascal, 75013 Paris, France. Tel : 00 33 1 44 08 35 03, Fax : 00 33 1 44 08 35 10. Email: olivier.hanon brc.ap-hop-paris.fr.

Objectives : To determine the evolution of blood pressure in patients with moderate Alzheimer's disease among a one year longitudinal survey and to evaluate the relationship between blood pressure and cognitive functions. Methods : In 327 subjects selected from the French research program on Alzheimer's disease (REAL.FR), systolic and diastolic blood pressure (SBP, DBP) were measured at the time of inclusion (M0), after 6 months (M6) and after 12 months (M12). All subjects were assessed to determine both cognitive functions and capabilities in the activities of daily living using validated cognitive scales [Mini Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale - Cognitive part (ADAS-Cog), Instrumental Activities of Daily Living (IADL), Activities of Daily Living (ADL), Clinical Dementia Rating (CDR)], at M0, M6, M12. Results: In this population of patients with moderate Alzheimer's disease, mean age was 78 +/- 7 years and 242 subjects were females (74%). After adjustment for age, gender, body mass index (BMI) and antihypertensive therapy, a significant decrease of blood pressure was observed between M0 and M12, for SBP (139.1 +/- 18 to 136.5 +/- 17 mmHg, p < 0.05) and DBP, (77.6 +/- 12 to 75.8 +/- 10 mmHg , p < 0.05). Demented subjects with the worst cognitive impairment at baseline (tertile1 MMSE, tertile 3 ADAS-Cog, ADL scores between 0 and 4, CDR scores between 10 to 18) showed a larger decrease in SBP and DBP after 12 months. The worst impairment in dementia at baseline was associated with the highest SBP decrease between M0 and M12 (deltaSBP tertile 1 MMSE vs tertile 3 MMSE = -5.9 vs + 1.0 mmHg , p < 0.05; delta SBP tertile 3 ADAS-Cog vs tertile 1 ADAS-Cog = - 5.98 vs + 2.98 mmHg, p < 0.05, delta SBP ADL 0 - 4 vs ADL 5 - 6 = - 8.7 vs - 1.5 mmHg, p < 0.05, delta SBP CDR 10 - 18 vs CDR 0.5 - 9.5 = - 6.9 vs - 1.7 mmHg, p < 0.05). All these results persisted after adjustment for age, gender and the antihypertensive therapy. Baseline SBP [OR 95% CI = 1.05 (1.02 - 1.08), BMI [OR 95% CI = 0.88 (0.81 - 0.95)], ADL score [OR 95% CI = 0.42 (0.22 - 0.81)] and ADAS-Cog score [OR 95% CI = 1.07 (1.01 -1.14)] were significantly associated with the decrease of blood pressure after one year of follow up, independently of age, gender and antihypertensive therapy. In contrast, patients with larger blood pressure decrease (over 10 mmHg reduction of SBP and/or 5 mmHg of DBP) did not demonstrate a more significant worsening of dementia at 12 months in the different scales used. Conclusions : This study indicates a significant decrease in blood pressure in patients with Alzheimer's disease after one year of follow up, independently of age, gender, BMI and antihypertensive therapy. The largest decrease in blood pressure was observed in patients with the most severe impairment in dementia at baseline, suggesting that blood pressure decrease seems to be mainly a secondary phenomenon in Alzheimer's disorders.

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Hypertension management: the care gap between clinical guidelines and clinical practice.

Andrade SE, Gurwitz JH, Field TS, Kelleher M, Majumdar SR, Reed G, Black R.

Meyers Primary Care Institute, Fallon Foundation, and University of Massachusetts Medical School, Worcester, Mass 01605, USA.

OBJECTIVE: To evaluate how well hypertension is managed in HMO patients and to assess opportunities for improvement. STUDY DESIGN: Retrospective cohort study. PATIENTS AND METHODS: The study population included HMO members (age 45-84 years) who had at least 1 ambulatory encounter with an ICD-9-CM diagnosis code of essential hypertension during the first 6 months of 1999. Medical records were reviewed to obtain information on blood pressure measurements, sex, age, coexisting medical conditions, smoking status, and changes made to the antihypertensive drug regimen. RESULTS: We identified 681 members with 3347 encounters related to hypertension management during 1999. Overall, 74 (11%) patients were at target blood pressure for all visits and 260 (38%) were at target blood pressure for at least 50% of the visits; 222 (33%) patients were not at target blood pressure for any visit. A history of coronary artery disease or cerebrovascular disease was associated with better blood pressure control (defined as being at goal levels during at least 50% of visits), while being older (age > or = 75) or having diabetes mellitus was associated with poorer control. Medication regimen intensifications occurred in 10% of visits with systolic blood pressure levels of 140-149 mm Hg, compared with 45% of visits with levels of > or = 180 mm Hg. Medication regimen intensifications occurred in 21% of visits with diastolic blood pressure levels of 90-99 mm Hg and 43% of visits with levels of > or = 100 mm Hg. CONCLUSION: Efforts are required to reduce "therapeutic inertia," particularly in patients with modestly elevated systolic blood pressure levels.

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Comparison of the effect of venovenous versus venoarterial extracorporeal membrane oxygenation on renal blood flow in newborn lambs.

Ingyinn M, Rais-Bahrami K, Evangelista R, Hogan I, Rivera O, Mikesell GT, Short BL.

Department of Neonatology, Children's National Medical Center and The George Washington University School of Medicine, Washington, DC, USA. Ingyinn aol.com

Venovenous extracorporeal membrane oxygenation (VV ECMO) using double lumen catheters is an alternative to venoarterial (VA) ECMO and allows for total blood flow using the patient's cardiac output in comparison to partial blood flow provided during VA ECMO. OBJECTIVE: To compare the effects of VV versus VA ECMO on renal blood flow. DESIGN: Prospective study. SETTING: Research laboratory in a hospital. SUBJECT: Newborn lambs 1-7 days of age (n = 15). Interventions: In anesthetized, ventilated lambs, femoral artery and vein were cannulated for monitoring and renal venous blood sampling. An ultrasonic flow probe was placed on the left renal artery for continuous renal blood flow measurements. Animals were randomly assigned to control (non-ECMO), VV ECMO and VA ECMO groups. After systemic heparinization, the animals were cannulated and studied at bypass flows of 120 mL/kg/min (partial bypass) for two hours in both ECMO groups and 200 mL/kg/min (full bypass) for an additional 30 min in the VA group. Changes in blood pressure and renal flow on ECMO and during ECMO bridge unclamping were recorded continuously. Plasma renin activity (PRA) levels were sequentially sampled. RESULTS: Systemic blood pressure was not different in VV or VA ECMO at partial bypass flow. However, systemic blood pressure increased significantly at maximal bypass flow in the VA ECMO group. There was no change in renal flow in either VV or VA ECMO groups. PRA levels did not correlate with bypass flow change. During unclamping of the ECMO bridge, blood pressure and renal flow drop significantly in the VA group, but not in the VV group. CONCLUSION: VV and VA ECMO at partial bypass flows had comparable effect on blood pressure, renal blood flow and PRA level in this short-term study. However, unclamping of the ECMO bridges did differentially affect blood pressure and renal blood flow between VV and VA groups. We speculate that this repeated acute change in long-run VA ECMO support may play a role in the persistent hypertension seen in some patients.

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Cadmium-induced nephropathy in the development of high blood pressure.

Satarug S, Nishijo M, Ujjin P, Vanavanitkun Y, Moore MR.

National Research Centre for Environmental Toxicology, The University of Queensland, 39 Kessels Road, Coopers Plains, Brisbane, Qld. 4108, Australia.

In recognition of a central role of the kidney in long-term blood pressure control, we undertook an in-depth analysis of the relationship between blood pressure and kidney damage caused by environmental exposure to the common pollutants cadmium and lead. The subjects were 200 healthy Thais, 16 and 60 years of age (100 female non-smokers, 53 male non-smokers, and 47 male smokers). None of these subjects had been exposed to Cd or Pb in the workplace and their urinary Cd concentrations ranged from 0.4 to 37nM, whereas their urinary Pb concentrations ranged from 0.1 to 30nM. The prevalence of high blood pressure was 2%, 8% and 19%, respectively in subjects with low, average and high Cd-burden (linear trend chi(2)=6.4, P=0.01). Multiple regression analysis revealed a significant positive association between Cd-burden and blood pressure in male non-smokers (adjusted beta=0.31, P=0.02) and an inverse association between blood pressure and urinary Pb excretion rate in male smokers (adjusted beta=-0.38, P=0.005). Associations between Cd-burden and nephropathies were evidenced by increases in urinary excretion of beta2-microglobulin (P=0.02) and N-acetyl-beta-d-glucosaminidase (P=0.005) in subjects with high Cd-burden, compared with the subjects with average Cd-burden. In addition, an association between Cd-related nephropathy and high blood pressure was evidenced by a 20% increase in the prevalence of high blood pressure in people with NAG-uria (linear trend chi(2)=4.3, P=0.04). Our present study provides first evidence for a possible link between renal tubular damage and dysfunction caused by environmental Cd exposure and increased risk of high blood pressure.

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Chronotherapy of hypertension.

Hermida RC, Smolensky MH.

Bioengineering & Chronobiology Laboratories, University of Vigo, Campus Universitario, Vigo, 36200, Spain. rhermida tsc.uvigo.es

PURPOSE OF REVIEW: Blood pressure displays appreciable predictable-in-time circadian variation. The chronotherapy of hypertension takes into account the clinically relevant features of the 24-h pattern of blood pressure, e.g. the accelerated morning rise and nighttime decline during sleep, plus potential administration circadian time determinants of the pharmacokinetics and dynamics of antihypertensive medications. RECENT FINDINGS: Significant administration-time differences in the kinetics (i.e. chronokinetics) plus the beneficial and adverse effects (termed chronodynamics) of antihypertensive drugs are well known. Thus, bedtime, but not morning, dosing with cilnidipine significantly reduces nocturnal blood pressure. In addition, the dose-response curve, therapeutic coverage, and efficacy of the doxazosin gastrointestinal therapeutic system are all markedly dependent on the circadian time of drug administration. Moreover, valsartan administration at bedtime as opposed to upon awakening results in improved diurnal/nocturnal blood pressure ratio, such that the dosing time of valsartan can be chosen in relation to the dipper status of any given patient to improve therapeutic benefit and reduce cardiovascular risk. SUMMARY: Nocturnal hypertension, which is characterized by the loss or even reversal of the expected 10-20% sleep-time blood-pressure decline, increases the risk of cardiac and cerebrovascular events. Chronotherapy provides a means of individualizing treatment of hypertension according to the circadian profile of blood pressure of each patient. The chronotherapeutic strategy constitutes a new option to optimize blood-pressure control and to reduce risk.

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