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Biomedical subjects

Laura P Svetkey

Publications and source records attributed to Laura P Svetkey.

At least 19 recordsLinked to original sources

The Take Control of Your Blood pressure (TCYB) study: study design and methodology.

BACKGROUND: Among the 65 million Americans with hypertension, only approximately 31% have their blood pressure under control (<140/90 mm/Hg). Despite the damaging impact of hypertension and the availability of evidence-based target values for blood pressure, interventions to improve blood pressure control have had limited success. OBJECTIVES: A randomized controlled health services intervention trial with a two by two design is being conducted to improve blood pressure control. This five-year trial evaluates two patient-directed interventions designed to improve blood pressure control among patients diagnosed with hypertension in a community-based primary care setting. METHODS: Patients are randomized to one of four groups: usual care, home blood pressure monitoring, tailored behavioral self-management intervention that is administered via telephone by a nurse, or a combination of the home blood pressure monitoring and tailored behavioral intervention. Patients receiving the home blood pressure monitoring are trained in the use of an electronic blood pressure measurement device, are asked to measure their blood pressure 3 times/week, and send in two-month blood pressure recordings throughout the 24-month study duration. The behavioral intervention incorporates patients' need assessments and involves tailored behavioral and education modules to promote medication adherence and improve specific health behaviors. A nurse delivers all behavioral self-management modules over the telephone bi-monthly for 24 months. The primary outcome is the proportion of patients who achieve control of their blood pressure based on evidence-based guidelines (for patients without diabetes <140/90 mm/Hg, for patients with diabetes <130/80 mm/Hg) evaluated at six-month intervals over 24 months (five measurements) using a random-zero sphygmomanometer. CONCLUSION: Despite the known risk of poor blood pressure control, and the wide availability of effective treatment strategies, a majority of adults still do not have their blood pressure controlled. This study will be an important step in defining two explicit interventions to improve blood pressure control. To our knowledge, this study is the first to combine both a tailored behavioral self-management intervention and self-monitoring home blood pressure intervention to improve blood pressure control among patients in a primary care setting.

Antihypertensive Agents↗

Effects of comprehensive lifestyle modification on diet, weight, physical fitness, and blood pressure control: 18-month results of a randomized trial.

BACKGROUND: The main 6-month results from the PREMIER trial showed that comprehensive behavioral intervention programs improve lifestyle behaviors and lower blood pressure. OBJECTIVE: To compare the 18-month effects of 2 multicomponent behavioral interventions versus advice only on hypertension status, lifestyle changes, and blood pressure. DESIGN: Multicenter, 3-arm, randomized trial conducted from January 2000 through November 2002. SETTING: 4 clinical centers and a coordinating center. PATIENTS: 810 adult volunteers with prehypertension or stage 1 hypertension (systolic blood pressure, 120 to 159 mm Hg; diastolic blood pressure, 80 to 95 mm Hg). INTERVENTIONS: A multicomponent behavioral intervention that implemented long-established recommendations ("established"); a multicomponent behavioral intervention that implemented the established recommendations plus the Dietary Approaches to Stop Hypertension (DASH) diet ("established plus DASH"); and advice only. MEASUREMENTS: Lifestyle variables and blood pressure status. Follow-up for blood pressure measurement at 18 months was 94%. RESULTS: Compared with advice only, both behavioral interventions statistically significantly reduced weight, fat intake, and sodium intake. The established plus DASH intervention also statistically significantly increased fruit, vegetable, dairy, fiber, and mineral intakes. Relative to the advice only group, the odds ratios for hypertension at 18 months were 0.83 (95% CI, 0.67 to 1.04) for the established group and 0.77 (CI, 0.62 to 0.97) for the established plus DASH group. Although reductions in absolute blood pressure at 18 months were greater for participants in the established and the established plus DASH groups than for the advice only group, the differences were not statistically significant. LIMITATIONS: The exclusion criteria and the volunteer nature of this cohort may limit generalizability. Although blood pressure is a well-accepted risk factor for cardiovascular disease, the authors were not able to assess intervention effects on clinical cardiovascular events in this limited time and with this sample size. CONCLUSIONS: Over 18 months, persons with prehypertension and stage 1 hypertension can sustain multiple lifestyle modifications that improve control of blood pressure and could reduce the risk for chronic disease.

Adult↗

The Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project: Rationale and design.

This paper outlines the rationale and design of the Study of the Effects of Diet on Metabolism and Nutrition (STEDMAN) weight loss project, in which detailed biologic profiling of three hundred and fifty obese individuals (body mass index (BMI): 30-50 kg/m(2)) will be conducted as they lose weight via seven distinct interventions. These profiles will be compared to those of fifty normal, healthy, control participants (BMI: 18.5-24.9 kg/m(2)). The interventions include the following: Roux-en-Y gastric bypass surgery, dietary interventions of differing macronutrient composition and diverse pharmacologic interventions. Outcome variables include eight conventional metabolites and CRP measured by standard clinical chemistry techniques, twenty hormones of energy balance and fuel homeostasis measured by radioimmunoassay (RIA) or by enzyme-linked Immunosorbent assay (ELISA), ten pro- and anti-inflammatory cytokines measured using Luminex xMAP technology, one hundred and one intermediary metabolites measured by targeted mass-spectrometry-based methods, and physiologic variables such as body composition measured by dual energy X-ray absorptiometry (DEXA), air displacement plethysmography, and abdominal computerized tomography (CT), insulin sensitivity measured by intravenous glucose tolerance test (IV-GTT) and metabolic rate measured by indirect calorimetry. Results from this study will expand our knowledge of the biology of obesity and weight regulation and may lead to targeted strategies for its treatment and control.

Adolescent↗

A dietary pattern that lowers oxidative stress increases antibodies to oxidized LDL: results from a randomized controlled feeding study.

BACKGROUND: Oxidation of LDL (oxLDL) is thought to have an important role in early stages of atherogenesis. Antibody to oxLDL (Ab-oxLDL) has been proposed as a biomarker which might be directly associated with oxidative stress. Yet studies designed to test this hypothesis are lacking. We tested the hypothesis that consumption of a healthy diet rich in fruits and vegetables and reduced in saturated fat, total fat, and cholesterol will concomitantly reduce oxidative stress and Ab-oxLDL. METHODS: One hundred and three healthy individuals were randomly assigned to consume a typical American (control) diet or the DASH diet rich in fruits, vegetables and low-fat dairy products and reduced in fat (27%), saturated fat (7%), and cholesterol (150 mg/day) for 3 months. Outcomes were urinary isoprostanes (in vivo marker of oxidative stress), oxygen radical absorbing capacity (ORAC, an in vitro assay measuring antioxidant activity in serum), and Ab-oxLDL measured at baseline, 1-3 months of feeding. RESULTS: Compared to the control diet, consumption of the DASH diet significantly lowered urinary isoprostane (-226 pg/ml, 95% CI: -420 to -32, P=0.023). Compared with the control group, change in ORAC was higher in the DASH group, 143 trolox units/ml (95% CI: -23 to 308, P=0.091). In comparison with the control diet, increased titers of Ab-oxLDL (37 mU/ml [95% CI: 16-57, P=0.006]) were seen after consumption of the DASH diet. Higher titers of Ab-oxLDL occurred at month 2 (56 mU/ml, 95% CI: 20-90, P=0.004) and month 3 (41 mU/ml, 95% CI: -6 to 88, P=0.082), after initially small increases at month 1 (20 mU/ml, 95% CI: -10 to 51, P=0.176). End-of-study increases in AB-oxLDL were highly correlated with increased ORAC (Spearman's rho=0.46, P<0.0001), but not with changes in specific carotenoids, tocopherols or with change in LDL cholesterol (each: P>0.10). CONCLUSION: Consumption of a healthy diet replete in antioxidants reduced oxidative stress (urinary isoprostanes) yet increased Ab-oxLDL. This indirect association of Ab-oxLDL with urinary isoprostanes hinders use of Ab-oxLDL as a marker of oxidative damage.

Adult↗

Novel human alpha1a-adrenoceptor single nucleotide polymorphisms alter receptor pharmacology and biological function.

We identified nine naturally-occurring human single nucleotide polymorphisms (SNPs) in the alpha(1a)-adrenoceptor (alpha(1a)AR) coding region, seven of which result in amino acid change. Utilizing rat-1 fibroblasts stably expressing wild type alpha(1a)AR or each SNP at both high and low levels, we investigated the effect of these SNPs on receptor function. Compared with wild type, two SNPs (R166K, V311I) cause a decrease in binding affinity for agonists norepinephrine, epinephrine, and phenylephrine, and also shift the dose-response curve for norepinephrine stimulation of inositol phosphate (IP) production to the right (reduced potency) without altering maximal IP activity. In addition, SNP V311I and I200S display altered antagonist binding. Interestingly, a receptor with SNP G247R (located in the third intracellular loop) displays increased maximal receptor IP activity and stimulates cell growth. The increased receptor signaling for alpha(1a)AR G247R is not mediated by altered ligand binding or a deficiency in agonist-mediated desensitization, but appears to be related to enhanced receptor-G protein coupling. In conclusion, four naturally-occurring human alpha(1a)AR SNPs induce altered receptor pharmacology and/or biological activity. This finding has potentially important implications in many areas of medicine and can be used to guide alpha(1a)AR SNP choice for future clinical studies.

Adrenergic alpha-Agonists↗

Informing cancer prevention strategies for African Americans: the relationship of African American acculturation to fruit, vegetable, and fat intake.

Acculturation has been associated with health-related behaviors in African Americans. We sought to determine if there is a relationship between acculturation and dietary intake in African Americans. African Americans in the PREMIER trial completed the African American Acculturation Scale (AAAS) and 2 nonconsecutive 24-h dietary recalls (n = 238). Analysis of variance (ANOVA) and canonical correlation were used to assess relationships between acculturation and dietary intakes. Canonical correlation (p = 0.05) showed that traditional African Americans had lower intakes of fruits/vegetables and milk/dairy with higher intakes of fats, meat, and nuts. This pattern was supported by differences in the ANOVA. African American acculturation is related to dietary intake. These findings have implications for the design of cancer-related public health messages targeted to African Americans.

Acculturation↗

Perceptions of African-American culture and implications for clinical trial design.

OBJECTIVE: To identify unique cultural variables for African Americans that might limit the effectiveness of behavioral interventions in clinical trials. DESIGN: Focus group discussions lasting 90 minutes. SETTING: Outpatient, clinical research center. PATIENTS: Twenty-six African-American men and women, who completed the screening process but were ineligible for the PREMIER study, participated in six focus group sessions. PREMIER is a multicenter, randomized clinical trial that studies the effects of three different lifestyle interventions designed to reduce blood pressure without medication. MEASUREMENTS AND MAIN RESULTS: Participants used a value sort of cultural characteristics to select items that make them unique as African Americans. The following seven themes were consistently identified: 1) extensive use of nontraditional support systems; 2) general mistrust of European Americans; 3) African Americans' being undervalued as human beings and members of American society; 4) effective use of improvisation; 5) uneven playing field as a result of persistent discrimination; 6) preservation of a unique ethnic identity; 7) socioeconomic status as a major influence and predictor of behaviors. CONCLUSIONS: Cultural variables can affect African-American perceptions of the feasibility of certain behavior modifications as health interventions and their perceptions of clinical research. Using these themes, investigators can design trials and interventions that capitalize on certain cultural variables and avoid strategies that conflict with others. The identification of such cultural characteristics unique to African Americans may help to enhance the outcomes achieved by African Americans in clinical trials, improving the generalizability of results from behavior modification research.

Adult↗

A further subgroup analysis of the effects of the DASH diet and three dietary sodium levels on blood pressure: results of the DASH-Sodium Trial.

This study presents an extensive analysis of the effects on blood pressure (BP) of changes in sodium intake over a wide array of subgroups, including joint subgroups defined by age and hypertension status, race or ethnicity and hypertension status, and gender and race or ethnicity. Participants were given 3 levels of sodium (50, 100, and 150 mmol/2,100 kcal) for 30 days while consuming the Dietary Approaches to Stop Hypertension (DASH) diet (rich in fruits, vegetables, and low-fat dairy) or a more typical American diet. Within each diet and subgroup, there was a general pattern such that the lower the sodium level, the greater the mean reduction in BP. Sodium reduction from 100 to 50 mmol/2,100 kcal generally had twice the effect on BP as reduction from 150 to 100 mmol/2,100 kcal. Age had a strong and graded influence on the effect of sodium within the typical and DASH diets, respectively: -4.8 and -1.0 mm Hg systolic for 23 to 41 years, -5.9 and -1.8 mm Hg for 42 to 47 years, -7.5 and -4.3 mm Hg for 48 to 54 years, and -8.1 and -6.0 mm Hg for 55 to 76 years. The influence of age on the effect of sodium reduction was particularly strong in nonhypertensive patients: -3.7 mm Hg systolic for <45 years and -7.0 mm Hg for >45 years with the typical diet and -0.7 and -2.8 mm Hg with the DASH diet. Reduced sodium intake and the DASH diet should be advocated for the prevention and treatment of high BP, particularly because the benefits to BP strengthen as subjects enter middle age, when the rate of cardiovascular disease increases sharply.

Adult↗

Effect of dietary sodium intake on blood lipids: results from the DASH-sodium trial.

We evaluated the effect on serum lipids of sodium intake in 2 diets. Participants were randomly assigned to a typical American control diet or the Dietary Approaches to Stop Hypertension (DASH) diet, each prepared with 3 levels of sodium (targeted at 50, 100, and 150 mmol/d per 2100 kcal). The DASH diet is increased in fruits, vegetables, and low-fat dairy products and is reduced in saturated and total fat. Within assigned diet, participants ate each sodium level for 30 days. The order of sodium intake was random. Participants were 390 adults, age 22 years or older, with blood pressure of 120 to 159 mm Hg systolic and 80 to 95 mm Hg diastolic. Serum lipids were measured at baseline and at the end of each sodium period. Within each diet, sodium intake did not significantly affect serum total cholesterol, LDL cholesterol, HDL cholesterol, or triglycerides. On the control diet, the ratio of total cholesterol-to-HDL cholesterol increased by 2% from 4.53 on higher sodium to 4.63 on lower sodium intake (P=0.04). On the DASH diet, sodium intake did not affect this ratio. There was no dose-response of sodium intake on serum lipids or the cholesterol ratio in either diet. At each sodium level, total cholesterol, LDL cholesterol, and HDL cholesterol were lower on the DASH diet versus the typical American diet. There were no significant interactions between the effects of sodium and the DASH diet on serum lipids. In conclusion, changes in dietary sodium intake over the range of 50 to 150 mmol/d did not affect blood lipid concentrations.

Adult↗

One-year follow-up study of blood pressure and dietary patterns in dietary approaches to stop hypertension (DASH)-sodium participants.

BACKGROUND: We conducted a 12-month follow-up study on participants in the Dietary Approaches to Stop Hypertension (DASH)-Sodium trial to determine the impact of the DASH diet and 150, 100, or 50 mmol/day of sodium after discontinuation of the feeding intervention. METHODS: Upon completion of the trial, 56 of the 113 participants at the clinical center at Duke University entered a longitudinal observational study. Measurements including 24-h ambulatory systolic and diastolic blood pressure (BP), weight, and 24-h urinary electrolytes were obtained at 1, 6, and 12 months after completion of the DASH-Sodium trial. Block food frequency questionnaires were completed at the 12-month visit. Linear mixed-effects regression models were used to analyze the effect of the diet and sodium intake on longitudinal changes in BP during the final feeding period. RESULTS: The DASH participants significantly increased their intakes of fruits or juices and vegetables at 12 months. Control participants had no change in DASH food group intake. Both groups increased sodium intake. Among control participants, systolic and diastolic BP increased 5.33 (95% confidence interval [CI] 0.28, 10.37) and 3.20 mm Hg (95% CI 0.25, 6.16), respectively. Among DASH participants, systolic and diastolic BP increased 3.12 (95% CI -0.44, 6.68) and 0.79 mm Hg (95% CI -1.15, 2.72), respectively. There was a significant effect of the final sodium level by diet on the change in SBP over time (P = .04 for three-way interaction among diet, time of visit, and sodium). CONCLUSIONS: After the feeding intervention, DASH diet participants ate more fruits/vegetables and had sustained reductions in BP despite increased sodium intake.

Adult↗

The clinical epidemiology and course of the spectrum of renal diseases associated with HIV infection.

BACKGROUND: While an understanding of the epidemiology and clinical course of HIV-associated nephropathy (HIVAN) is growing, little is known about the risk factors and clinical course of the other renal diseases that may also occur as a complication of HIV infection. This study was undertaken to compare HIVAN to the spectrum of other kidney diseases seen among HIV-infected patients. METHODS: This retrospective cohort study included all HIV-infected patients who underwent renal biopsy during the course of their clinical care at six major medical centers. Demographic and clinical information were abstracted from each patient's clinical record. Time to initiation of renal replacement therapy was compared for patients with lesions other than HIVAN to patients with HIVAN using Cox proportional hazards regression. RESULTS: Eighty-nine patients (47 with lesions other than HIVAN and 42 with HIVAN) were available for inclusion. Patients with lesions other than HIVAN were less likely to be black (37/47 vs. 42/42, P= 0.02), more likely to have a positive hepatitis B surface antigen (10/37 vs. 4/42, P= 0.04), less likely to have the diagnosis of hypertension (24/46 vs. 31/42, P= 0.03), more likely to have a greater creatinine clearance at time of biopsy (60.6 vs. 39.0 cc/min, P= 0.008), and have a greater CD4 lymphocyte count at time of biopsy (287 vs. 187 cells/mL, P= 0.04) compared to patients with HIVAN. Lesions other than HIVAN were associated with a longer time to initiation of renal replacement therapy compared with HIVAN (HR 0.33, 95% CI 0.15-0.71, P= 0.005). Other factors associated with a longer time to renal replacement therapy included higher creatinine clearance at time of biopsy, greater CD4(+) lymphocyte count, the absence of hepatitis C antibody, and the use of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. The type of renal disease (HIVAN vs. other) interacted significantly with HIV-1 RNA level and the use of antiretroviral therapy (P= 0.0001 and 0.006, respectively). Among patients with lesions other than HIVAN, the presence of nondetectable HIV-1 RNA was not associated with a greater risk of progression of renal disease (HR 0.27, P= 0.24). Among patients with HIVAN, because all patients had detectable virus at the time of institution of renal replacement therapy, this highly significant association could not be quantified. Among patients with lesions other than HIVAN, the use of antiretroviral therapy was not associated with the progression to renal replacement therapy (HR 3.29, P= 0.06). Among patients with HIVAN, the use of antiretroviral therapy was associated with a slower progression to renal replacement therapy (HR 0.24, P= 0.03). CONCLUSION: Among HIV-infected patients with renal disease other than HIVAN, viral suppression and the use of antiretroviral therapy are not associated with a beneficial effect on renal function; thus, additional therapeutic strategies may need to be utilized. Because renal histology is associated with prognostic differences, these data provide outcomes information that will improve the clinical utility of renal biopsy among HIV-infected patients with renal disease.

AIDS-Associated Nephropathy↗

Comprehensive lifestyle modification and blood pressure control: a review of the PREMIER trial.

The PREMIER trial assessed the aggregate effect on blood pressure (BP) of nationally recommended lifestyle modifications in free-living adults with high-normal (stage 1) hypertension. Participants (N=810) were randomized to the advice-only group; the established group (consisting of weight loss, increased physical activity, and reduced sodium and alcohol intake); or the established plus Dietary Approaches to Stop Hypertension (DASH) diet group (consisting of the established interventions in addition to the DASH dietary pattern). The primary outcome was change in systolic BP at 6 months. Net of advice only, mean systolic BP declined by 3.7 mm Hg for members of the established group (p<0.001) and 4.3 mm Hg for the established plus DASH group (p<0.001). The prevalence of hypertension decreased from a baseline of 38% to 17% in the established group (p=0.01) and to 12% in the established plus DASH group (p<0.001) compared with a decrease to 26% in the advice-only group. The PREMIER trial demonstrated that persons with above-optimal BP and stage 1 hypertension can make multiple lifestyle changes leading to better control of BP.

Behavior↗

Effect of the dietary approaches to stop hypertension diet and reduced sodium intake on blood pressure control.

The authors hypothesized that the Dietary Approaches to Stop Hypertension (DASH) diet and reduced sodium intake would control stage 1 hypertension and reduce high-normal blood pressure (BP) to optimal levels. Adults with systolic BP 120-159 mm Hg and diastolic BP 80-95 mm Hg were randomly assigned to receive the DASH diet or a typical American (control) diet, consuming three different sodium intakes (higher=142 mmol/d, intermediate=107 mmol/d, and lower=65 mmol/d) for 30 days each. BP control was defined as systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Among subjects with hypertension at baseline, at higher sodium intake the DASH diet increased BP control two-fold over control (63% vs. 32%; 95% confidence interval, 1.4-2.9). Reducing sodium intake in the control diet group increased BP control 2.3-fold (74% vs. 32%; 95% confidence interval, 1.7-3.2). The maximum BP control rate (84%) was achieved with the DASH/lower sodium diet. BP became normal or optimal in 71% of persons consuming the control/lower sodium diet and 77% of persons consuming the DASH/lower sodium diet. Both the DASH diet and reduced sodium intake improved BP control.

Adult↗

The effect of the PREMIER interventions on insulin sensitivity.

OBJECTIVE: This ancillary study of PREMIER sought to determine the effects on insulin sensitivity of a comprehensive behavioral intervention for hypertension with and without the Dietary Approaches to Stop Hypertension (DASH) dietary pattern. RESEARCH DESIGN AND METHODS: Participants were assigned to one of three nonpharmacologic interventions for blood pressure (group A, advice only; group B, established; and group C, established plus DASH). The established intervention included weight loss, reduced sodium intake, increased physical activity, and moderate alcohol intake; the DASH dietary pattern was added to the established intervention for those in group C. The DASH dietary pattern is high in fruits, vegetables, and low-fat dairy products while being lower in total fat, saturated fat, and cholesterol. It is abundant in nutrients such as magnesium, calcium, and protein, which have been associated with improved insulin sensitivity. Insulin sensitivity was measured at baseline and at 6 months using the frequently sampled intravenous glucose tolerance test with minimal model analysis. RESULTS: Both intervention groups decreased total calories, percentage of calories from fat, and sodium intake to similar levels, with similar amounts of energy expenditure and weight loss. Covariate differences seen only in group C included increased intake of protein, potassium, calcium, and magnesium. Compared with control subjects, insulin sensitivity improved significantly only in group C, from 1.96 to 2.95 (P = 0.047). Group B did have a significant decrease in fasting insulin and glucose, but the changes in insulin sensitivity did not reach statistical significance when compared with control subjects. CONCLUSIONS: These results suggest that including the DASH dietary pattern as part of a comprehensive intervention for blood pressure control enhances insulin action beyond the effects of a comprehensive intervention that does not include DASH.

Adult↗

Individual blood pressure responses to changes in salt intake: results from the DASH-Sodium trial.

Although group characteristics are known to influence average blood pressure response to changes in salt intake, predictability of individual responses is less clear. We examined variability and consistency of individual systolic blood pressure responses to changes in salt intake in 188 participants who ate the same diet at higher, medium, and lower (140, 104, 62 mmol/d) sodium levels for 30 days each, in random order, after 2 weeks of run-in at the higher sodium level. Regarding variability in systolic blood pressure changes over time, changes from run-in to higher sodium (no sodium level change) ranged from -24 to +25 mm Hg; 8.0% of participants decreased > or =10 mm Hg. Regarding variability in systolic blood pressure response to change in sodium intake, with higher versus lower sodium levels (78-mmol sodium difference), the range of systolic blood pressure change was -32 to +17 mm Hg; 33.5% decreased > or =10 mm Hg. Regarding consistency of response, systolic blood pressure change with run-in versus lower sodium was modestly correlated with systolic blood pressure change with higher versus medium sodium; systolic blood pressure change with higher versus lower sodium was similarly correlated with run-in versus medium sodium (combined Spearman r=0.27, P=0.002). These results show low-order consistency of response and confirm that identifying individuals as sodium responders is difficult. They support current recommendations for lower salt intake directed at the general public rather than "susceptible" individuals as one of several strategies to prevent and control adverse blood pressures widely prevalent in the adult population.

Adult↗