Branched-chain amino acid levels are associated with improvement in insulin resistance with weight loss.

AIMS/HYPOTHESIS: Insulin resistance (IR) improves with weight loss, but this response is heterogeneous. We hypothesised that metabolomic profiling would identify biomarkers predicting changes in IR with weight loss. METHODS: Targeted mass spectrometry-based profiling of 60 metabolites, plus biochemical assays of NEFA, ß-hydroxybutyrate, ketones, insulin and glucose were performed in baseline and 6 month plasma samples from 500 participants who had lost ≥4 kg during Phase I of the Weight Loss Maintenance (WLM) trial. Homeostatic model assessment of insulin resistance (HOMA-IR) and change in HOMA-IR with weight loss (∆HOMA-IR) were calculated. Principal components analysis (PCA) and mixed models adjusted for race, sex, baseline weight, and amount of weight loss were used; findings were validated in an independent cohort of patients (n = 22). RESULTS: Mean weight loss was 8.67 ± 4.28 kg; mean ∆HOMA-IR was -0.80 ± 1.73, range -28.9 to 4.82). Baseline PCA-derived factor 3 (branched chain amino acids [BCAAs] and associated catabolites) correlated with baseline HOMA-IR (r = 0.50, p < 0.0001) and independently associated with ∆HOMA-IR (p < 0.0001). ∆HOMA-IR increased in a linear fashion with increasing baseline factor 3 quartiles. Amount of weight loss was only modestly correlated with ∆HOMA-IR (r = 0.24). These findings were validated in the independent cohort, with a factor composed of BCAAs and related metabolites predicting ∆HOMA-IR (p = 0.007). CONCLUSIONS/INTERPRETATION: A cluster of metabolites comprising BCAAs and related analytes predicts improvement in HOMA-IR independent of the amount of weight lost. These results may help identify individuals most likely to benefit from moderate weight loss and elucidate novel mechanisms of IR in obesity.

Microalbuminuria predicts overt proteinuria among patients with HIV infection.

BACKGROUND: This study examines the association between microalbuminuria and the development of proteinuria among HIV-infected persons. METHODS: A total of 948 subjects provided urine samples for albumin, protein and creatinine measurements semiannually. Microalbuminuria was defined as an albumin-to-creatinine ratio of >30 mg/g. Proteinuria was defined as a protein-to-creatinine ratio of > or =0.350 mg/mg. The progression from microalbuminuria to proteinuria was described. RESULTS: At baseline, 69.4% of the subjects had no detectable proteinuria, 20.2% had microalbuminuria, and 10.4% had proteinuria. Subjects with microalbuminuria and proteinuria were more likely to be black (P=0.02), have lower CD4 cell counts (P=0.02 comparing subjects without abnormal urine protein excretion to subjects with microalbuminuria; P=0.0001 comparing subjects with microalbuminuria to subjects with proteinuria), and have a higher HIV RNA level (P=0.08 and 0.04, respectively). Among 658 subjects with normal urine protein, 82.7% continued to have no abnormality, 14.3% developed microalbuminuria, and 3.0% developed proteinuria. Subjects without baseline proteinuria (i.e. either normal protein excretion or microalbuminuria) who developed proteinuria were more likely to have microalbuminuria (P=0.001), a lower CD4 cell count (P=0.06), and a higher plasma HIV RNA (P=0.03) than those who did not progress to proteinuria. In multivariate analysis, only microalbuminuria remained associated with the development of proteinuria (odds ratio 2.9; 95% confidence interval 1.5, 5.5; P=0.001). CONCLUSION: Microalbuminuria predicts the development of proteinuria among HIV-infected persons. Because proteinuria has been linked to poorer outcomes, strategies to affect microalbuminuria should be tested.

Comparing office-based and ambulatory blood pressure monitoring in clinical trials.

Ambulatory blood pressure monitoring (ABPM) is commonly used in clinical trials. Yet, its ability to detect blood pressure (BP) change in comparison to multiple office-based measurements has received limited attention. We recorded ambulatory and five daily pairs of random zero (RZ) BPs pre- and post-intervention on 321 adult participants in the multicentre Dietary Approaches to Stop Hypertension trial. Treatment effect estimates measured by ambulatory monitoring were similar to those measured by RZ and did not differ significantly for waking vs 24-h ambulatory measurements. For systolic BP, the standard deviations of change in mean 24-h ambulatory BP (8.0 mmHg among hypertensives and 6.0 mmHg among nonhypertensives) were comparable to or lower than the corresponding standard deviations of change in RZ-BP based on five daily readings (8.9 and 5.9 mmHg). The standard deviations of change for mean waking ambulatory BP (8.7 and 6.7 mmHg) were comparable to those obtained using three to four daily RZ readings. Results for diastolic BP were qualitatively similar. Ambulatory monitoring was more efficient (ie, a smaller sample size could detect a given BP change) than three to four sets of daily RZ readings and required fewer clinic visits. The average of 33 ambulatory BP readings during the waking hours had an efficiency comparable to that from the mean of four daily pairs of RZ-BPs. Participants readily accepted the ABPM devices, and their use requires less staff training. ABPM provides a useful alternative to RZ-BP measurements in clinical trials.

Effect of lifestyle modifications on blood pressure by race, sex, hypertension status, and age.

Recommendations for control of high blood pressure (BP) emphasize lifestyle modification, including weight loss, reduced sodium intake, increased physical activity, and limited alcohol consumption. The Dietary Approaches to Stop Hypertension (DASH) dietary pattern also lowers BP. The PREMIER randomized trial tested multicomponent lifestyle interventions on BP in demographic and clinical subgroups. Participants with above-optimal BP through stage 1 hypertension were randomized to an Advice Only group or one of two behavioural interventions that implement established recommendations (Est) or established recommendations plus DASH diet (Est plus DASH). The primary outcome was change in systolic BP at 6 months. The study population was 810 individuals with an average age of 50 years, 62% women, 34% African American (AA), 95% overweight/obese, and 38% hypertensive. Participants in all the three groups made lifestyle changes. Mean net reductions in systolic (S) BP in the Est intervention were 1.2 mmHg in AA women, 6.0 in AA men, 4.5 in non-AA women, and 4.2 in non-AA men. The mean effects of the Est Plus DASH intervention were 2.1, 4.6, 4.2, and 5.7 mmHg in the four race-sex subgroups, respectively. BP changes were consistently greater in hypertensives than in nonhypertensives, although interaction tests were nonsignificant. The Est intervention caused statistically significant BP reductions in individuals over and under age 50. The Est Plus DASH intervention lowered BP in both age groups, and significantly more so in older individuals. In conclusion, diverse groups of people can adopt multiple lifestyle changes that can lead to improved BP control and reduced CVD risk.

Effects of dietary patterns on blood pressure: subgroup analysis of the Dietary Approaches to Stop Hypertension (DASH) randomized clinical trial.

OBJECTIVE: To determine the effects of dietary patterns on blood pressure in subgroups. METHODS: Dietary Approaches to Stop Hypertension (DASH) was a randomized controlled feeding study conducted at 4 academic medical centers. Participants were 459 adults with untreated systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. For 3 weeks, participants were fed a "control" diet. They were then randomized to 8 weeks of (1) control diet; (2) a diet rich in fruits and vegetables; or (3) a combination diet rich in fruits, vegetables, and low-fat dairy foods, and reduced in saturated fat, total fat, and cholesterol (the DASH combination diet). Weight and salt intake were held constant. Change in diastolic blood pressure was the primary outcome variable, and systolic blood pressure a secondary outcome. Subgroups analyzed included race, sex, age, body mass index, years of education, income, physical activity, alcohol intake, and hypertension status. RESULTS: The combination diet significantly lowered systolic blood pressure in all subgroups (P<.008), and significantly lowered diastolic blood pressure (P<.01) in all but 2 subgroups. The fruits-and-vegetables diet also reduced blood pressure in the same subgroups, but to a lesser extent. The combination diet lowered systolic blood pressure significantly more in African Americans (6.8 mm Hg) than in whites (3.0 mm Hg), and in hypertensive subjects (11.4 mm Hg) than in nonhypertensive subjects (3.4 mm Hg) (P<.05 for both interactions). CONCLUSIONS: The DASH combination diet, without sodium reduction or weight loss, significantly lowered blood pressure in virtually all subgroups examined, and was particularly effective in African Americans and those with hypertension. The DASH combination diet may be an effective strategy for preventing and treating hypertension in a broad cross section of the population, including segments of the population at highest risk for blood pressure-related cardiovascular disease.

Heritability of salt sensitivity in black Americans.

Salt sensitivity is defined as a change in blood pressure in response to changes in salt and water homeostasis. Found in 73% of hypertensive and 36% of normotensive blacks, it is generally considered a hallmark of hypertension in blacks. The higher prevalence of salt sensitivity in blacks compared with whites suggests a genetic influence on this trait, but there is little direct evidence of heritability. We determined the extent to which salt sensitivity is correlated in black families and estimated the heritability of this phenotype. Black families were recruited through a hypertensive proband. Both hypertensive and normotensive adults were phenotyped with respect to salt sensitivity with an intravenous sodium-loading, furosemide volume-depletion protocol. Salt sensitivity was defined as the difference between sodium-loaded and volume-depleted blood pressure. We enrolled 20 families, comprising 30 parent-offspring pairs and 115 adult sibling pairs. Age-adjusted familial correlations ranged from .33 to .44, .19 to .37, and .12 to .21 for mean arterial and systolic and diastolic pressure responses to the salt sensitivity maneuver, respectively. Corresponding heritability estimates were 0.26 to 0.84, 0.26 to 0.74, and 0.004 to 0.24, respectively. These data strongly suggest a heritable component of salt sensitivity.

Double-blind, placebo-controlled trial of potassium chloride in the treatment of mild hypertension.

Epidemiological and experimental data suggest blood pressure-lowering effects of dietary potassium. A randomized, double-blind clinical trial was used to assess blood pressure response to orally administered potassium, 120 mEq/day, and to placebo in 101 adults with mild hypertension. Blood pressure was measured with a random-zero sphygmomanometer every 2 weeks of this 8-week trial. Systolic blood pressure in the potassium-treated group decreased by 6.4 +/- 13.7 (SD) mm Hg (p less than or equal to 0.025) compared with 0.11 +/- 13.0 mm Hg in the placebo-treated group (p = 0.96). Diastolic blood pressure in the potassium-treated group decreased by 4.1 +/- 8.3 mm Hg (p less than or equal to 0.05) compared with a 1.6 +/- 6.5 mm Hg decrease in placebo-treated subjects (p = 0.09). Baseline blood pressure of potassium-treated subjects was unexpectedly higher than that of controls. After correcting for baseline variation, blood pressure still decreased 3.4/1.8 mm Hg more in potassium recipients than in placebo recipients (p = 0.14 and 0.24, respectively). Blood pressure decreased by 19/13 mm Hg in five blacks taking potassium versus a 1/0 mm Hg increase in seven blacks taking placebo. Compliance with the potassium regimen was 91.5% by pill count; only one subject discontinued treatment because of side effects. In conclusion, 120 mEq/day of microencapsulated potassium chloride was well tolerated in adults with mild hypertension. An antihypertensive effect of potassium cannot be ruled out despite the fact that there was no statistically significant difference between potassium-treated and placebo-treated subjects after adjustment for differences in baseline blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Association of hypertension with beta2- and alpha2c10-adrenergic receptor genotype.

The adrenergic receptors have been implicated in the pathogenesis of essential hypertension. We hypothesized that hypertension is associated with variants at the beta2-adrenergic receptor locus and at one of the alpha2-adrenergic receptor loci. In unrelated individuals, we measured untreated blood pressure and characterized each subject as hypertensive or normotensive. We then used genomic DNA to identify beta2- and alpha2c10-adrenergic receptor restriction fragment length polymorphisms. In 175 subjects (49 percent with hypertension, 55 percent black), both hypertension and race were associated with genotype at the beta2 locus (chi2 for hypertension = 11, P = .004, chi2 for race = 8.8, P = .012). The association with hypertension persisted in each race group separately (blacks only: chi2 = 9.6, P = .008; whites only; chi2 = 14.2, P = .001). This association persisted in a logistic model that controlled for race (P = .01). Genotype was also significantly associated with baseline systolic, diastolic, and mean arterial blood pressures (P = .05, .01, and .02, respectively). These data suggest that the beta2-adrenergic receptor gene is a candidate gene for hypertension in blacks and whites. We also genotyped subjects at the alpha2-adrenergic receptor coded on chromosome 10. There was no association between hypertension and genotype at the alpah2c10 locus in the total group or in blacks, but there was significant association in whites (chi2 = 6.7, P = .03). These data suggest that the beta2- and alph2c10-adrenergic receptor genes may contribute, in a race-specific manner, to the inheritance of essential hypertension. Linkage studies in related individuals are needed to confirm these findings.

Preliminary evidence of linkage of salt sensitivity in black Americans at the beta 2-adrenergic receptor locus.

Salt sensitivity is a heritable trait that is a hallmark of hypertension in black Americans. Genes encoding adrenergic receptors are candidate loci for the inheritance of this hypertension-related trait because of the role of these receptors in the regulation of renal sodium excretion and vascular tone. We performed this study to determine whether these loci are responsible for some of the phenotypic variation in salt sensitivity. Hypertensive black American probands were ascertained, followed by sequential ascertainment of adult sib pairs among the first-, second- and third-degree relatives of the proband. Both hypertensive and normotensive siblings were tested for salt sensitivity by an intravenous sodium-loading, lasix volume-depletion protocol. Genotyping was performed with restriction fragment length polymorphisms in genomic DNA probed with clones containing the beta 2- and alpha 2c10-adrenergic receptor genes. A total of 109 sib pairs was evaluated. Salt sensitivity was defined as the change in blood pressure in each individual, comparing the sodium-loaded with the volume-depleted state. Systolic pressure decreased by an average of 9.0 +/- 9%, diastolic pressure by 1.5 +/- 11%, and mean arterial pressure by 5.0 +/- 9%. Neither blood pressure nor salt sensitivity was linked at the alpha 2c10-adrenergic receptor locus. No evidence suggested that systolic salt sensitivity and baseline blood pressure were linked at the beta 2-adrenergic receptor locus. Model-independent sib pair linkage analysis suggested that diastolic blood pressure response to sodium loading/volume depletion is linked at the beta 2-adrenergic receptor locus (P < .006). Evidence for linkage was significant at the .05 level after adjustment for the number of phenotypic traits examined.

Similar prevalence of renovascular hypertension in selected blacks and whites.

Renovascular hypertension is a potentially curable form of high blood pressure that is thought to be extremely rare among blacks. We demonstrate, however, that in a clinically selected population, the prevalence of renovascular hypertension is similar in blacks and whites. We prospectively evaluated 167 hypertensive subjects who had one or more clinical features known to be associated with renovascular hypertension. All subjects had captopril-stimulated peripheral renin measurements and conventional renal arteriography. All significant renal artery stenoses (greater than 50% luminal narrowing) were treated with percutaneous transluminal angioplasty or surgery. Renovascular hypertension was diagnosed if there was a blood pressure response to interventional therapy, according to the criteria established by the Cooperative Study of Renovascular Hypertension. Of the total group evaluated, 24% (39 of 167) had renal artery stenosis and 14% (23 of 167) had renovascular hypertension. Renal artery stenosis or occlusion was found in 27% (26 of 97) of whites and 19% (13 of 67) of blacks (p = 0.27). Renovascular hypertension was diagnosed in 18% (17 of 97) of whites and 9% (6 of 67) of blacks evaluated (p = 0.25). Renovascular hypertension was associated with severe or refractory hypertension and with smoking, but there were no racial differences in these associations. Blacks with renovascular hypertension tended to have low captopril-stimulated peripheral renin activity. We conclude that blacks with clinical features suggestive of renovascular hypertension should be evaluated with angiography. Captopril-stimulated plasma renin may not be useful in detecting blacks with renovascular hypertension, but this and other potential screening tests require further evaluation.

Prospective analysis of strategies for diagnosing renovascular hypertension.

Renovascular hypertension is a potentially curable form of high blood pressure. However, it is unclear how best to select patients who are likely to have renovascular hypertension, what diagnostic strategy to use in these selected patients, and how to predict the hemodynamic significance of a renal artery stenosis. We determined the prevalence of renovascular hypertension in adults who exhibited suggestive clinical features. In these clinically selected patients, we then determined the test characteristics of various diagnostic and potential screening tests. Renovascular hypertension was diagnosed if correction of renal artery stenosis resulted in decreased blood pressure. Of the 66 hypertensive adults evaluated, 11 (16.7%) had renovascular hypertension. Captopril-stimulated peripheral renin activity detected renovascular hypertension with 73% sensitivity, 72% specificity, 38% positive predictive value, and 92% negative predictive value. Less optimal combinations of sensitivity and specificity were found for differential glomerular filtration rate renography, differential effective renal plasma flow renography, and selective renal vein renin ratios, each performed after a single dose of captopril. Intravenous digital subtraction renal angiography detected all patients with renovascular hypertension and was normal in 71% of patients with essential hypertension. To evaluate potential screening tests for renovascular hypertension, we calculated predictive values applied to a low prevalence population. If the observed sensitivities and specificities apply to a population with 5% prevalence of renovascular hypertension, captopril-stimulated peripheral renin would have a positive predictive value of 12% and a negative predictive value of 98%. In 16 patients with known renal artery stenosis, neither the captopril-stimulated renal vein renin ratio nor captopril-stimulated differential renography accurately predicted blood pressure response to correction of the stenosis. We conclude that clinical criteria can identify a subgroup with 16.7% prevalence of renovascular hypertension. In this high prevalence group, intravenous digital subtraction renal angiography will identify virtually all patients with renovascular hypertension, and a normal study will be sufficient to exclude renovascular hypertension. In unselected hypertensive patients, screening with captopril-stimulated peripheral renin activity may be the most useful and efficient procedure for identification of patients with renovascular hypertension. Functional tests do not accurately predict the hemodynamic significance of a renal artery stenosis.

Effect of dietary patterns on ambulatory blood pressure : results from the Dietary Approaches to Stop Hypertension (DASH) Trial. DASH Collaborative Research Group.

We measured ambulatory blood pressure (ABP) in 354 participants in the Dietary Approaches to Stop Hypertension (DASH) Trial to determine the effect of dietary treatment on ABP (24-hour, day and night) and to assess participants' acceptance of and compliance with the ABP monitoring (ABPM) technique. After a 3-week run-in period on a control "typical" American diet, subjects (diastolic blood pressure [BP], 80 to 95 mm Hg; systolic BP, <160 mm Hg; mean age, 45 years) were randomly assigned to 1 of 3 diets for an 8-week intervention period: a continuation of the control diet; a diet rich in fruits and vegetables; and a "combination" diet that emphasized fruits, vegetables, and low-fat dairy products. We measured ABP at the end of the run-in and intervention periods. Both the fruit/vegetable and combination diets lowered 24-hour ABP significantly compared with the control diet (P<0. 0001 for systolic and diastolic pressures on both diets: control diet, -0.2/+0.1 mm Hg; fruit/vegetable diet, -3.2/-1.9 mm Hg; combination diet, -4.6/-2. 6 mm Hg). The combination diet lowered pressure during both day and night. Hypertensive subjects had a significantly greater response than normotensives to the combination diet (24-hour ABP, -10.1/-5.5 versus -2.3/-1.6 mm Hg, respectively). After correction for the control diet responses, the magnitude of BP lowering was not significantly different whether measured by ABPM or random-zero sphygmomanometry. Participant acceptance of ABPM was excellent: only 1 participant refused to wear the ABP monitor, and 7 subjects (2%) provided incomplete recordings. These results demonstrate that the DASH combination diet provides significant round-the-clock reduction in BP, especially in hypertensive participants.

Angiotensinogen genotype and blood pressure response in the Dietary Approaches to Stop Hypertension (DASH) study.

OBJECTIVE: To determine the relationship between angiotensinogen (ANG) genotype and blood pressure response to the dietary patterns of the Dietary Approaches to Stop Hypertension (DASH) trial. The angiotensin converting enzyme (ACE) gene was also tested. DESIGN: The DASH trial was a randomized outpatient feeding study comparing the effects on blood pressure (BP) of three dietary patterns: a control diet, similar to typical American intake; a 'fruits and vegetables' diet (F/V) that is rich in fruits and vegetables but otherwise resembles the control diet; and the DASH diet that is reduced in fats and that emphasizes fruits, vegetables and low-fat dairy products. Participants' genotype was also determined. SETTING: Four clinical sites. PARTICIPANTS: Adults with above-optimal BP or stage 1 hypertension. INTERVENTION: Participants ate one of the three dietary patterns for 8 weeks. Sodium intake and weight were held constant. In 355 of 459 DASH participants, DNA was extracted from leukocytes and genotyped for the G-6A ANG polymorphism and the D/I ACE polymorphism, by the polymerase chain reaction. MAIN OUTCOMES: Genotype at ANG and ACE loci; BP after 8 weeks of intervention diet. RESULTS: There was no association between ACE genotype and BP response. Associations with ANG polymorphism were significant: net systolic and diastolic BP response to the DASH diet was greatest in individuals with the AA genotype (-6.93/-3.68 mmHg) and least in those with the GG genotype (-2.80/0.20 mmHg). A similar relationship existed for the F/V diet. CONCLUSIONS: ANG genotype is associated with BP response to the DASH diet. The AA genotype confers excess risk of hypertension and is associated with increased responsiveness to diet.

Comparison of intravenous digital subtraction angiography and conventional arteriography in defining renal anatomy.

Intravenous digital subtraction renal angiography (IV-DSRA) is frequently used in the preoperative evaluation of living-related (LR) kidney donors. However, the true accuracy of IV-DSRA in the donor population is difficult to assess since abnormalities of the kidney and its circulation are uncommon in this group. Therefore, we evaluated IV-DSRA in a group of patients more likely to have anomalies and abnormalities that would affect LR donor selection, donor nephrectomy, and subsequent transplantation. Hypertensive adults being evaluated for renovascular hypertension had IV-DSRA and conventional renal arteriograms, which were interpreted independently. We determined the accuracy of IV-DSRA, compared with conventional arteriography, in detecting multiple renal arteries, renal artery stenosis, fibromuscular dysplasia, and abnormal renal parenchyma. Technically unsatisfactory studies were excluded from analysis. Of 59 patients evaluated, 37 had abnormalities or anomalies. IV-DSRA failed to detect 28 of 50 findings in these 37 patients. In 21 patients with multiple renal arteries, IV-DSRA underestimated the number of main renal arteries in 8. Significant renal artery stenosis, present in 16 patients, was undetected by IV-DSRA in 3 of these patients. Mild fibromuscular dysplasia was not detected by IV-DSRA in any of the 5 patients with this condition, and abnormalities of renal parenchyma were not detected in 6 of the 8 patients with scarred or cystic kidneys. When compared with conventional renal arteriography in a hypertensive population, the IV-DSRA does not accurately detect abnormalities of the kidney and its circulation. If these data are confirmed in nonhypertensive subjects, preoperative evaluation of LR kidney donors using IV-DSRA alone may fail to detect potentially important anatomic abnormalities.

Rationale and design of the Dietary Approaches to Stop Hypertension trial (DASH). A multicenter controlled-feeding study of dietary patterns to lower blood pressure.

Epidemiologic studies have found that dietary patterns characterized by high intakes of certain minerals and fiber are associated with low blood pressure. Dietary Approaches to Stop Hypertension (DASH) is a multicenter, randomized, controlled-feeding trial designed to test the effects on blood pressure of two such dietary patterns consumed for 8 weeks. The two experimental diets will be compared with each other and with a control dietary pattern that is relatively low in potassium, magnesium, calcium, and fiber, and has a fat and protein profile mirroring current consumption. The first experimental diet, arguably termed "ideal," is high in fruits, vegetables, whole cereal products, low-fat dairy products, fish, chicken, and lean meats designed to be low in saturated fat and cholesterol; moderately high in protein; and high in minerals and fiber. The second experimental diet tests the effect of fruits and vegetables alone. Its potassium, magnesium, and dietary fiber content will be at the same high levels as the ideal dietary pattern, while its fat, protein, and calcium content will resemble that of the control dietary pattern. The study population will consist of 456 healthy men and women, aged 22 years or older, with systolic blood pressure less than 160 mm Hg and diastolic blood pressure 80 to 95 mm Hg. African-American and other minority groups will comprise 67% of the population. Participants will eat one of the three dietary patterns. The DASH trial has unique features. First, dietary patterns rather than single nutrients are being tested. Second, all food for the experimental diets is provided to the participants using a standardized multicenter protocol. Because the dietary patterns are constructed with commonly consumed food items, the results, if positive, may be conveniently implemented in dietary recommendations to the general public.

Renovascular hypertension in blacks.

To define the clinical characteristics of renovascular hypertension (RVH) and determine the clinical usefulness of captopril stimulated peripheral renin and postcaptopril renography in blacks at risk for RVH, 79 clinically selected hypertensive blacks were evaluated. Unstimulated (U-PRA), captopril stimulated (S-PRA) peripheral renin, and postcaptopril renography (PC-RENO) were obtained. All subjects underwent conventional renal arteriography. Renal artery stenosis (RAS) was present in 14 of 79 (18%) patients. Renovascular hypertension (RVH) was found in 7 of 79 (9%) patients. S-PRA had a sensitivity and specificity of 38% and 86% respectively to detect RAS; and a sensitivity and a specificity of 17% and 85% respectively to detect RVH. PC-RENO had a sensitivity and a specificity of 64% and 58% respectively to detect RAS; and a sensitivity and a specificity of 67% and 58% respectively to detect RVH. This study suggests that RAS occurs in 18% of clinically selected hypertensive blacks. RVH was present in 9% of this population. Captopril stimulated peripheral renin and postcaptopril renography are not useful as screening tools for the diagnosis of renovascular disease in blacks. Blacks at high risk should be evaluated with angiography.

Captopril renography in the diagnosis of renovascular disease.

Several investigators have reported methods for the use of renal scintigraphy in the diagnosis of renal artery stenosis. We report the experience of Duke University Medical Center, and offer some suggestions for standardizing and optimizing the use of this potential screening tool. We evaluated 140 clinically selected hypertensive adults with postcaptopril renal scintigraphy (renography), pre- and postcaptopril peripheral renin activity, and conventional renal arteriography. Postcaptopril renography (using 99mTc-diethylenetriaminepentaacetic acid (DTPA) to measure glomerular filtration and [131I]iodohippurate to measure renal plasma flow) was considered abnormal if one kidney contributed 47% or less of total activity. Postcaptopril renin was considered elevated if it was at least 4 ng/mL/h. Renovascular disease was defined as 50% or greater main renal artery stenosis. Of 140 subjects, 31 (22%) had significant renovascular disease. Captopril-stimulated DTPA renography suggested asymmetric function in 24 (74%) of these, but was also abnormal in 61 of 109 (56%) with normal renal arteries. Captopril-stimulated hippuran renography performed in a similar manner. Captopril-stimulated renin activity was elevated in only 58% of subjects with renal artery stenosis, and had a false positive rate of 24%. These data differ from reports from other centers, perhaps due to differences in renography methods, criteria for interpretation of renography, and/or patient selection criteria.

Effects of gender and ethnic group on blood pressure control in the elderly.

In order to determine the adequacy of blood pressure treatment in black and white elderly men and women, the authors performed a cross-sectional population survey in Central North Carolina in 1986-1987. Participants included a random sample of noninstitutionalized individuals age 65 years or older. Blacks were oversampled. A health questionnaire was administered, and blood pressure was measured. Of 5,223 eligible persons, 4,162 (80%) participated. Fifty-four percent of subjects were black and 65% were women. Sixteen percent of the study subjects were white men, 30% white women, 19% black men, and 35% black women. The mean age was 73 years. Fifty-three percent had hypertension. Among hypertensives, 80.8% were taking blood pressure medication. Among treated hypertensives, blood pressure was adequately controlled, (measured diastolic blood pressure of 90 mm Hg or lower) in 85.6%. Women were 52% more likely than men and blacks were 40% less likely than whites to exhibit adequate blood pressure control. Older age and smoking were also associated with better blood pressure control. The authors conclude that hypertension is more likely to be controlled in elderly women than men and less likely to be well-controlled in elderly blacks than whites. The choice of antihypertensive agent may also be important. Further investigation is needed into the mechanisms accounting for the observed sex and race differences.

The effect of dietary patterns on blood pressure control in hypertensive patients: results from the Dietary Approaches to Stop Hypertension (DASH) trial.

To determine the impact of dietary patterns on the control of hypertension we studied the subgroup of 133 participants with systolic blood pressure (BP) of 140 to 159 mm Hg and/or diastolic BP of 90 to 95 mm Hg enrolled in the Dietary Approaches to Stop Hypertension (DASH) study. Participants were fed a control diet for a 3-week period and were then randomized to receive for 8 weeks either the control diet; a diet rich in fruits and vegetables, but otherwise similar to control; or a combination diet rich in fruits, vegetables, and low-fat dairy products, including whole grains, fish, poultry, and nuts, and reduced in fats, red meats, sweets, and sugar-containing beverages. Sodium intake and body weight were held constant throughout the study. The combination diet significantly reduced systolic BP (-11.4 mm Hg, P < .001) and diastolic BP (-5.5 mm Hg, P < .001). The fruits-and-vegetables diet also significantly reduced systolic BP (-7.2 mm Hg, P < .001) and diastolic BP (-2.8 mm Hg, P = .013). The combination diet produced significantly greater BP effects (P < .05) than the fruits-and-vegetables diet. Blood pressure changes were evident within 2 weeks of starting the intervention feeding. After the 8-week intervention period, 70% of participants eating the combination diet had a normal BP (systolic BP < 140 and diastolic BP < 90 mm Hg) compared with 45% on the fruits-and-vegetables diet and 23% on the control diet. In patients with hypertension, the DASH combination diet effectively lowers BP and may be useful in achieving control of Stage 1 hypertension.

Evaluation of the clinical pharmacology of nilvadipine in patients with mild to moderate essential hypertension.

Eighty-four patients with diastolic blood pressure ranging from 100-115 mm Hg were randomized into a multicenter, parallel, double-blind, placebo-controlled, dose response study with nilvadipine (6 mg, 8 mg, 10 mg tid for 28 days). The hypotensive response pattern to nilvadipine was similar with all three doses although duration of response was dose dependent. Maximal decreases in diastolic blood pressure occurred at 1 hour when assessed on days 1 and 15 (16.0, 17.4, and 15.8 mm Hg, vs 17.2, 18.7, and 17.5 mm Hg, respectively). The hypotensive effect remained significant compared to placebo for at least 4 hours after dosing. The increase in heart rate associated with the maximal hypotensive response was minimal and not clinically significant (day 1: 7.6, 5.2, and 4.0 beats/min with 6, 8, and 10 mg; day 15: 4.0, 5.1, 2.6 beats/min with 6, 8, 9, and 10 mg, respectively). Finally, a correlation between plasma drug concentrations and nilvadipine-induced hypotensive response was observed (r = 0.48). Black and white hypertensive patients had similar hypotensive responses. Plasma nilvadipine concentrations on day 15 were similar to those on day 1 suggesting no accumulation of drug with a tid regimen. The most common drug related side effect was headache; less frequently seen were dizziness, edema, palpitations, and abdominal pain. Nilvadipine was well tolerated (only three patients were discontinued due to side effects). The efficacy, lack of tachycardia, and side effect profile observed in this study suggest that nilvadipine may be an important addition to the treatment of hypertension.