The role of adiponectin in metabolic and vascular disease: a review.

Adiponectin is a protein secreted by adipose tissue. Unlike other adipocytokines produced by adipose tissue, adiponectin appears to have anti-inflammatory, anti-diabetic, and anti-atherogenic properties. Although secreted solely by adipose tissue, plasma levels of adiponectin are generally negatively related to total adipose mass; with higher plasma adiponectin levels in lean individuals and lower adiponectin levels in obese individuals. Plasma concentrations of adiponectin are lower in patients with insulin resistance compared to insulin sensitive patients; and lower in patients with diabetes compared to non-diabetics. A similar inverse relationship of plasma adiponectin level has been reported with hypertension (HTN), blood pressure level, and albuminuria. However, in chronic kidney disease (CKD) marked elevations in plasma adiponectin concentrations have been described. Plasma adiponectin levels are markedly elevated among patients with end-stage renal disease and are lower following kidney transplantation. Considering the inverse relationship of plasma adiponectin with renal function, the cardiovascular protective role of adiponectin in patients with CKD remains controversial. Further research on the distribution and function of different circulating fractions of adiponectin in patients with CKD will be needed in order to determine if adiponectin is a useful biomarker in patients with CKD.

Determination of blood pressure percentiles in normal-weight children: some methodological issues.

Blood pressure in children has consistently been related to adult blood pressure, with implications for long-term prevention of cardiovascular disease. The epidemic of obesity in children has resulted in corresponding increases in childhood blood pressure. In this paper, the authors develop norms for childhood blood pressure among normal-weight children (body mass index <85th percentile based on Centers for Disease Control and Prevention guidelines) as a function of age, sex, and height, using data from 49,967 children included in the database of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents (the Pediatric Task Force). The authors considered three types of models for pediatric blood pressure data, including polynomial regression, restricted cubic splines, and quantile regression, with the latter providing the best fit. The sex-specific norms presented here are a nonlinear function of both age and height and are generally slightly lower than previously developed norms based on Pediatric Task Force data including both normal-weight and overweight children.

Subpopulations of peripheral lymphocytes in juvenile diabetes.

Subpopulations of peripheral lymphocytes were studied in 26 children with insulin-treated juvenile diabetes and in 27 control children of comparable age. T-lymphocytes were quantitated by spontaneous rosette-formation with sheep erythrocytes and B-lymphocytes by indirect immunofluorescence with the use of monovalent, fluorescein-labeled rabbit antiserum specific to the heavy chains of human IgG IgM, or IgA. No significant quantitative difference in subpopulations of the peripheral lymphocytes, T-cells, and B-cells with IgG, IgA, or IgM markers found between children with juvenile diabetes and the control group, although the B-lymphocytes with IgG or IgA markers tended to be higher and those with IgM markers lower in the diabetic than in the control group.

Sex differences in African-Americans regarding sensitivity to insulin's glucoregulatory and antilipolytic actions.

OBJECTIVE: The purpose of this study was to determine if there are sex differences in African-Americans regarding the effect of obesity on sensitivity to insulin as a glucoregulatory and antilipolytic hormone. RESEARCH DESIGN AND METHODS: Data from study participants, 127 nondiabetic African-Americans (mean age 32 +/- 4 years), included anthropometric measurements, an oral glucose tolerance test (OGTT), a 2-h euglycemic-hyperinsulinemic clamp, and a fasting triglyceride level. Sensitivity to insulin as a glucoregulatory hormone was determined by M/FFM, where M is the mean glucose infusion rate during the second hour of the clamp and FFM is fat-free mass. Sensitivity to insulin's antilipolytic action was assessed during the OGTT by the percent suppression of free fatty acid (FFA) concentrations between 0 and 120 min. The higher the suppression of FFAs, the greater the sensitivity to insulin's antilipolytic action. RESULTS: The participants were classified by BMI into three groups: nonobese (31 men, 24 women), obese (17 men, 14 women), and severely obese (12 men, 29 women). The women had higher percentages of body fat (P < 0.001), and the men had greater FFM (P < 0.001). The M/FFM values for men versus women in each BMI group were nonobese, 8.8 +/- 2.8 vs. 10.8 +/- 4.4; obese, 7.2 +/- 3.4 vs. 8.5 +/- 3.4; and severely obese, 4.7 +/- 2.1 vs. 6.1 +/- 2.2. The difference between the BMI groups was significant (P < 0.001), as was the difference between men and women (P < 0.01). In addition, there was a significant sex difference in percent suppression of FFAS (P < 0.001). The men and women had similar fasting insulin and FFA concentrations; however, in the men only, the percent suppression of FFA declined with increasing obesity (nonobese, 83 +/- 15%; obese, 73 +/- 18%; and severely obese, 69 +/- 19%; P = 0.02). The women in all three BMI groups had lower FFA levels of 86-88%. CONCLUSIONS: Obese African-American men and women are resistant to insulin as a glucoregulatory hormone, but only obese men are resistant to insulin's antilipolytic action; obese African-American women are sensitive to insulin's antilipolytic action. The combined presence of sensitivity to insulin's antilipolytic action with resistance to insulin's glucoregulatory action in obese African-American women may contribute to their high prevalence of obesity and type 2 diabetes.

The effects of celecoxib or naproxen on blood pressure in pediatric patients with juvenile idiopathic arthritis.

BACKGROUND: Selective and nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) are indicated for the treatment of juvenile idiopathic arthritis (JIA). However, the effect of NSAIDs on blood pressure (BP) in children has not been rigorously examined. METHODS: In this randomized, double-blind, multicenter, active-controlled, 6-week trial, the safety and efficacy of celecoxib (50 mg twice daily [bid] or 100 mg bid) or naproxen (7.5 mg/kg bid) was evaluated in patients aged 2-17 years with JIA. RESULTS: The least squares (LS) mean difference (celecoxib - naproxen) in change from baseline to week 6/final visit in systolic BP was 1.10 (90% confidence interval, -0.56, 2.76). No significant LS mean differences in diastolic BP relative to baseline were reported. Treatment-emergent adverse events occurred in 48% of patients in each treatment group. CONCLUSION: Both celecoxib and naproxen had no impact on BP, and both treatments had comparable safety profiles. Celecoxib, or naproxen, could be seen as suitable treatment options for pediatric patients with JIA.

Differences in blacks and whites with essential hypertension: biochemistry and endocrine. State of the art lecture.

Overall, there is agreement that the origins of hypertension have a genetic basis. The genetic factors interact with environmental factors that influence expression and intensity of the disorder. As summarized in Table 1, there is evidence from the literature to identify pathways for the development of hypertension in blacks. Organ pathology, characteristic of the clinical phenotypic hypertension, consists of increased peripheral vascular resistance and left ventricular hypertrophy, and, particularly in blacks, nephrosclerosis. In this scheme, an intermediate phenotype is a biochemical or endocrine marker of gene expression that participates in the regulation of blood pressure. Intermediate phenotypic characteristics of essential hypertension include sodium sensitivity, adrenergic activity, cation transport, and endocrine function including renin-angiotensin-aldosterone, kallikrein-kinin, and prostaglandin. Another intermediate phenotype to be included in this discussion is insulin resistance. These intermediate phenotypes of cell and subcellular function are regulated by candidate genes. Alternatively, an intermediate phenotype can be expressed in response to another intermediate phenotype. For example, sodium sensitivity could be mediated by the cation transport mechanism of Na,K-ATPase, or insulin resistance could be induced by an elevated level of adrenergic activity. Gene expression of the intermediate phenotype is also modulated by environmental factors such as dietary sodium, potassium, or calcium, and social stresses or patterns of physical activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of sodium sensitivity and stress in young adults.

The interaction of sodium sensitivity and stress-induced cardiovascular reactivity was studied in white and black young adults aged 18-23 years. The cardiovascular response to difficult mental arithmetic was measured before and after 14 days of oral sodium loading (10 g NaCl/day added to the usual diet). A sodium-sensitive blood pressure response occurred in 18.4% of whites and 37.3% of blacks. A significant correlation between blood pressure change and sodium excretion occurred in the sodium-sensitive group (r = - 0.28, p less than 0.01). High sodium intake did not augment blood pressure or heart rate response to the beta-adrenergic-mediated stimulus of mental arithmetic in the population, which was grouped by blood pressure, race, or sodium sensitivity.

Effect of chronic sodium loading on cardiovascular response in young blacks and whites.

The effect of long-term oral sodium loading on blood pressure and on stress-induced cardiovascular response was studied in normotensive and marginally hypertensive young adults. The 121 subjects, 18-23 years old, included 38 whites and 83 blacks. Blood pressure and heart rate response to the stress of mental arithmetic was measured before and after 14 days of sodium load, which consisted of 10 g NaCl/day added to the usual diet. A sodium-sensitive response to sodium load occurred in 18.4% of whites and 37.3% of blacks. Sodium-insensitive subjects had a higher rate of sodium excretion (p less than 0.001). Sodium-sensitive hypertensive subjects had a significantly greater weight gain (p less than 0.001). A significant correlation between blood pressure change and sodium excretion (r = -0.28, p less than 0.01) occurred in the sodium-sensitive group. The high sodium intake did not augment the blood pressure or heart rate response to the beta-adrenergic-mediated stimulus of mental arithmetic in the population when grouped by blood pressure, race, or sodium sensitivity. These results suggest that blood pressure increase in response to sodium load, particularly in blacks, is related to functional changes in peripheral vascular resistance.

Birth weight versus childhood growth as determinants of adult blood pressure.

In older white American adults, recent retrospective studies have demonstrated a relationship between lower birth weight and hypertension. Black Americans have a higher occurrence of both lower birth weight and hypertension than do white Americans. To test the low birth weight-high blood pressure hypothesis, data from a prospective study (Perinatal Collaborative Project) were examined. The study followed a sample of 137 black Americans, with nine examinations. Data on birth weight, growth, and blood pressure from birth through 28.0+/-2.7 years were obtained longitudinally. Bivariate correlations among parameters were computed with the Pearson r. Birth weight and blood pressure at age 28 years are not correlated (Pearson r=.06). However, systolic blood pressures measured at 0.3 years and thereafter are correlated with adult systolic blood pressure. Also, weight at 0.3 years and body mass index at 7 years and thereafter are correlated with adult weight. Our data did not confirm the birth weight-blood pressure hypothesis. Rather, we detected significant correlations between preadult measurements of blood pressure and weight with adult measurements. These results indicate that in black Americans, childhood growth is a stronger determinant than intrauterine growth of adult blood pressure.

Red blood cell Na+ transport as a predictor of blood pressure response to Na+ load in young blacks and whites.

The present study was designed to investigate the role of abnormalities in red blood cell sodium-potassium-chloride (Na-K-Cl) cotransport and Na+ pump as predictors of the pressor response to chronic oral Na+ loading in young whites and blacks. Subjects were healthy adults from 18 to 23 years of age and included normotensive whites (n = 24) and normotensive blacks (n = 35). Red blood cell transport studies were performed before Na+ loading. The Na+ load consisted of 10 g NaCl daily added to the usual diet. A sodium-sensitive response was defined as an increase of 5 mm Hg or more in mean arterial pressure after the Na+ load; a sodium-insensitive response was a less than 5 mm Hg increase in mean arterial pressure. A sodium-sensitive response occurred in 16% of whites and 57% of blacks. Black subjects have a significantly lower (p less than 0.005) maximal rate of furosemide-sensitive Na+ efflux and a higher Km for cellular Na+ (p less than 0.05) to activate Na-K-Cl cotransport than white subjects. Normotensive blacks with sodium-sensitive blood pressure response had a higher Km (14.4 +/- 6 mmol/l cell, n = 17, mean +/- SD) to activate the cotransport than sodium-insensitive blacks (9.9 +/- 3.7 mmol/l cell, n = 13, p less than 0.001). Normotensive whites had a significantly lower red blood cell Na+ content (p less than 0.05) and a higher maximal rate of cotransport (p less than 0.005) than young normotensive blacks.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin-stimulated glucose utilization and borderline hypertension in young adult blacks.

The purpose of this investigation was to determine whether there is a relation between impaired insulin-stimulated glucose utilization, or insulin resistance, and blood pressure (BP) in a young adult black population. Clinically well, young black men and women, including normotensive (BP < 135/85 mm Hg, n = 23) and borderline hypertensive (BP > or = 135/85 mm Hg, n = 27) individuals, were studied. Each subject had an oral glucose tolerance test (OGTT) and underwent a euglycemic hyperinsulinemic clamp procedure. A two-way analysis of variance demonstrated a significantly greater fasting insulin plasma concentration (P < .02) and sum of insulin levels during the OGTT (P = .04) in the borderline hypertensive compared with normotensive subjects. In both BP groups, women had significantly higher fasting plasma insulin levels than men (P < .02 and P = .009). Body mass index was a significantly covariate of the plasma insulin concentration. Data obtained from the clamp demonstrated significant insulin resistance in borderline hypertensive compared with normotensive subjects (4.69 +/- 0.50 versus 6.57 +/- 0.63 mg/kg per minute, P = .002). A stepwise multiple linear regression analysis demonstrated that there are significant multiple correlations of insulin resistance with body mass index, clamped insulin level, BP group, and systolic BP (multiple R = .7862, P < .001). Application of this analysis to the nonobese sample (n = 33) found significant correlations of insulin resistance with sex, BP group, and systolic BP (multiple R = .6817, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Red blood cell sodium-proton exchange in hypertensive blacks with insulin-resistant glucose disposal.

To define the potential pathogenic role of hyperinsulinemia as a mediator of alterations in sodium transport, we have examined red blood cell Na(+)-H+ and Na(+)-Li+ exchanges in a young adult black population characterized for blood pressure and insulin-mediated glucose disposal. Normotensive and mildly hypertensive blacks (blood pressure, 120 +/- 2/76 +/- 2 and 139 +/- 3/94 +/- 2 mm Hg, respectively) with a mean age of 26.1 years were studied for insulin sensitivity with the euglycemic hyperinsulinemic clamp (molar index of insulin sensitivity, M/I = moles glucose metabolized/insulin in milliliters of plasma). Na(+)-H+ exchange (U = mmol/L cell.h) was measured before and after the insulin clamp as a function of cell pH to determine the maximum transport rate. In the normotensive subjects, 18 were insulin sensitive (M/I = 9.37 +/- 0.6 x 10(4)) and 4 were insulin resistant (M/I = 3.64 +/- 0.6 x 10(4)). In the hypertensive subjects, 4 were insulin sensitive (M/I = 9.15 +/- 1.1 x 10(4)) and 16 were insulin resistant (M/I = 3.02 +/- 0.3 x 10(4)). The maximum rate of Na(+)-H+ exchange was significantly higher in all hypertensive vs normotensive individuals (35 +/- 3 vs 23 +/- 3 U, P < .005). Na(+)-H+ exchange activity was higher in insulin-resistant vs insulin-sensitive hypertensive subjects (40 +/- 3 vs 20 +/- 2 U, P < .001) but not in insulin-resistant normotensive subjects. Na(+)-Li+ exchange was not different in hypertensive and normotensive individuals but was higher in all insulin-resistant compared with all insulin-sensitive subjects (0.26 +/- 0.03 vs 0.16 +/- 0.02 U, P < .01). Na(+)-Li+ exchange also was higher in insulin-resistant vs insulin-sensitive normotensive subjects (0.35 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001) and in insulin-resistant hypertensive subjects vs insulin-sensitive normotensive subjects (0.24 +/- 0.03 vs 0.15 +/- 0.02 U, P < .001). A stepwise multiple regression analysis for all variables revealed that with Na(+)-H+ exchange as a dependent variable the main determinant was blood pressure, which in turn had insulin sensitivity as the main determinant. In conclusion, these results indicate that in hypertensive blacks, insulin-resistant glucose disposal is strongly associated with elevated red blood cell Na(+)-H+ exchange activity. Thus, despite impaired insulin-mediated glucose disposal, cellular Na+ gain via enhanced activity of Na(+)-H+ exchange is not blunted in hypertensive blacks.

Effect of salt loading on the cardiovascular response to stress in adolescents.

This study investigated, in normotensive adolescents, three accepted risk factors for essential hypertension (EH): stress, dietary salt, and parental history (genetic risk). The cardiovascular response to mental stress was evaluated before and after salt loading in eight subjects without, and in seven with, a family history (FH) of EH. The effect of salt loading on the FH positive group was to increase significantly the stress-induced systolic and diastolic pressure while the heart rate response decreased. Salt loading resulted in no change in cardiovascular response to stress in the FH negative group.

Red cell sodium countertransport and cotransport in normotensive and hypertensive blacks.

We have previously described elevated Lii -Nao countertransport (CT) and Na-K cotransport (CO) in red cells of Caucasian patients from Boston. In this study, we report both transport systems in black patients from Philadelphia. The maximal rate (Vmax) of CT was assayed by measuring the Nao-stimulated Li efflux from cells containing +/- 6 mmol Li/liter. The Vmax of outward cotransport was assayed by measuring the furosemide-sensitive component of Na and K efflux into Mg medium from cells containing 50 mmol/liter of both ions. The mean value of CT for 18 normotensive (NT) subjects with no family history of hypertension, (-) FHH , was 0.18 +/- 0.05 (mmol/liter cells X hour); and in 14 hypertensive (HT) patients, 0.18 +/- 0.07. The mean values of Na and K cotransport were, respectively (mmol/liter cells X hour), in 18 NT subjects with (-) FHH , 0.38 +/- 0.24 and 0.50 +/- 0.28 in 18 HT subjects, 0.25 +/- 0.17 and 0.24 +/- 0.14. We conclude that there is no difference in the Vmax for CT between the two groups of black subjects, but that the Vmax for Na-K CO was significantly reduced in the HT group. Notably, the offspring of HT patients (age 14 years, n = 17) also had a marked reduction in the Vmax of Na (0.15 +/- 0.17) K cotransport (0.19 +/- 14) in comparison with the mean value of Na (0.40 +/- 0.2) and K (0.60 +/- 0.3) cotransport measured in offspring (n = 10) of NT subjects (age 14 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance and blood pressure in young black men.

Insulin resistance, independent of obesity or non-insulin-dependent diabetes mellitus, has been demonstrated to be associated with high blood pressure. To determine if insulin resistance could be an antecedent to hypertension in a high-risk population, we studied normotensive (112 +/- 12/70 +/- 10 mm Hg) and borderline hypertensive (135 +/- 8/85 +/- 5 mm Hg) lean young black men (22-26 years old) with the euglycemic hyperinsulinemic clamp technique. All subjects had clinically normal oral glucose tolerance. Body mass index and percent adipose mass were the same in both groups. Fasting plasma insulin concentration was significantly higher in the borderline hypertensive group (p less than 0.01). Insulin-directed exogenous glucose metabolism at the same degree of steady-state hyperinsulinemia was significantly lower in the borderline hypertensive group (5.98 +/- 2.22 versus 8.22 +/- 1.96 mg/kg/min; p less than 0.01). For the total population, a significant inverse correlation existed between the glucose infusion rate and systolic blood pressure (p less than 0.01). These data indicate that there is a relation between insulin-mediated glucose uptake and blood pressure. Furthermore, in this high-risk population insulin resistance may precede the onset of established essential hypertension.

Albuminuria in association with insulin and sodium-lithium countertransport in young African Americans with borderline hypertension.

The purpose of this study was to determine whether early nephropathy, evidenced by urinary albumin excretion, can be detected in young African American subjects with only borderline hypertension, and whether there is a relationship of albuminuria with insulin resistance and with sodium-lithium countertransport activity. Clinically well young African American men and women including normotensive (blood pressure < 135/85 mm Hg, n = 41) and borderline hypertensive (blood pressure > or = 135/85 mm Hg, n = 26) individuals were studied. Each subject underwent an oral glucose tolerance test and euglycemic hyperinsulinemic clamp study. Albuminuria was measured on timed urine collections. Sodium-lithium countertransport activity was assayed in fresh red blood cells at 280 mmol/L Na+ for full saturation of external Na+ sites. The sum of insulin levels during glucose tolerance was significantly greater in the borderline hypertensive compared with the normotensive subjects (P = .014), and insulin-stimulated glucose utilization during the clamp was significantly lower in borderline hypertensive compared with normotensive subjects (P = .016). Albuminuria was greater in borderline hypertensive compared with normotensive subjects (P = .002). Albuminuria was significantly correlated with fasting plasma insulin concentration (r = .44, P < .002) and the sum of insulins during the glucose tolerance test (r = .45, P < .002). Sodium-lithium countertransport correlated with albuminuria (r = .31, P < .05) as well as significantly with insulin-stimulated glucose utilization during the clamp (r = .44, P < .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiovascular characteristics in adolescents who develop essential hypertension.

The risk parameters for the development of essential hypertension (EH) were evaluated in a group of adolescents with borderline hypertension. A population comprised of 50 adolescents with systolic or diastolic blood pressure between the 90th and 95th percentile was compared to a normotensive (less than 90%) family history-negative control population. Evaluative parameters included genetic risk, resting blood pressure, resting heart rate, and cardiovascular response to mental stress. In a follow-up period of up to 41 months, 28 borderline hypertensive adolescents (56%) developed fixed EH. At the time of initial evaluation, these 28 hypertensive adolescents had a strong family history of EH, higher resting heart rate (p less than 0.01) and blood pressure (p less than 0.01), and a greater cardiovascular response to mental stress (p less than 0.001) compared to the normotensive family history-negative control population. Time series analysis of the stress phase also demonstrated a rhythmic cardiovascular response in the normotensive group (p less than 0.05) that was not present in the hypertensive group. These results indicate that adolescents with borderline hypertension displaying these characteristics have a greater risk for EH than previously reported.

Cardiovascular response to mental stress in normal adolescents with hypertensive parents. Hemodynamics and mental stress in adolescents.

The hemodynamic response to mental stress (mental arithmetic) was studied in adolscents with varying risk factors for essential hypertension (EH), One group (genetic) consisted of normotensive well adolescents who had at least one parentnt with EH. Another group (labile) consisted of adolescents with labile hypertension each of whom also had at least one pare with EH. The control population consisted of normotensive adolescents with a negative family history of EH. Subjects with labile hypertension demonstrated a sustained increase in systolic and diastolic pressure and heart rate during stress. This response was significantly different than the control population (P less than THE CONTROL POPULATION (P LESS THAN 0.001). The stress response of the normotensive genetic population was qualitatively similar to the group with labile hypertension and significantly different than the controls in diastolic pressure and heart rate (p less than 0.001, less than 0.02). Post-stress plasma catecholamines were higher in the labile hypertensive and genetic groups than in the control group. These findings demonstrate increased central nervous system mediated adrenergic activity and cardiovascular response in labile hypertension and also in some normotensive subjects with a genetic risk for hypertension.

Lisinopril versus hydrochlorothiazide in obese hypertensive patients: a multicenter placebo-controlled trial. Treatment in Obese Patients With Hypertension (TROPHY) Study Group.

Because obesity-associated hypertension has unique hemodynamic and hormonal profiles, certain classes of antihypertensive agents may be more effective than others as monotherapy. Thus, we compared the efficacy and safety of the angiotensin-converting enzyme inhibitor lisinopril and the diuretic hydrochlorothiazide in a 12-week, multicenter, double-blind trial in 232 obese patients with hypertension. Patients with an office diastolic pressure between 90 and 109 mm Hg were randomized to treatment with daily doses of lisinopril (10, 20, or 40 mg), hydrochlorothiazide (12.5, 25, or 50 mg), or placebo. Mean body mass indexes were similar for all patients. At week 12, lisinopril and hydrochlorothiazide effectively lowered office diastolic (-8.3 and -7.7 versus -3.3 mm Hg, respectively; P<.005) and systolic (-9.2 and -10.0 versus -4.6 mm Hg, respectively; P<.05) pressures compared with placebo. Ambulatory blood pressure monitoring confirmed that lisinopril and hydrochlorothiazide effectively lowered 24-hour blood pressure compared with placebo (P<.001). Significant dose-response differences were observed between treatments. Sixty percent of patients treated with lisinopril had an office diastolic pressure <90 mm Hg compared with 43% of patients treated with hydrochlorothiazide (P<.05). Responses to therapies differed with both race and age. Neither treatment significantly affected insulin or lipid profiles; however, plasma glucose increased significantly after 12 weeks of hydrochlorothiazide therapy compared with lisinopril (+0.31 versus -0.21 mmol/L; P<.001). Hydrochlorothiazide also decreased serum potassium levels by 0.4 mmol/L from baseline. In conclusion, lisinopril was as effective as hydrochlorothiazide in treating obese patients with hypertension. Treatment with angiotensin-converting enzyme inhibitors may show greater efficacy as monotherapy at lower doses compared with thiazide diuretics, may have a more rapid rate of response, and may offer advantages in patients at high risk of metabolic disorders.

Effectiveness of centrally acting drugs and diuretics in adolescent hypertension.

The effectiveness and tolerance of a centrally acting antihypertensive agent (clonidine) was compared to that of a diuretic (hydrochlorothiazide) in treatment of adolescents with essential hypertension. After a phase on placebo 29 adolescents with fixed primary hypertension were randomly assigned, double blind, to one of two treatment groups. Active therapy was initiated at a low dose (0.1 mg clonidine b.i.d. or 24 mg hydrochlorothiazide b.i.d.) for 12 wk. In those in whom treatment goals for blood pressure control had not been reached, the dose was increased (clonidine to 0.2 mg and hydrochlorothiazide to 50 mg) for 12 wk. In the clonidine-treated group there was a reduction during low-dose therapy in systolic (P less than 0.05) and diastolic pressure (P less than 0.01) and heart rate (P less than 0.01). With low-dose diuretic therapy there was a reduction in systolic pressure only (P less than 0.05). Linear growth patterns were normal for both groups, but there was a reduction in serum potassium in the diuretic group (P less than 0.001). Of the two drugs investigated the centrally acting clonidine was more effective in blood pressure control (85%) than the diuretic (40%).