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DLM: Hypertension (2001)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To provide more detailed analysis of weight loss and blood pressure in the Trials of Hypertension Prevention (TOHP) Phase II. The TOHP was designed to examine the effects of weight loss and dietary sodium reduction, alone and in combination, in reducing blood pressure in overweight adults with high normal diastolic blood pressure. Specific interests included:

  • Long term effects of weight loss on blood pressure
  • Magnitude of the dose-response relationship at 36 months
  • Effect of patterns of weight loss on blood pressure
  • Predictors of weight loss and blood pressure response.
Inclusion Criteria:
  • Adults 30 to 54 years of age
  • Nonmedicated diastolic blood pressure (DBP) of 83 to 89mmHg and systolic blood pressure (SBP) less than 140mmHg. 
  • BMI: Men: 26.1 to 37.4kg per m2; women: 24.4 to 37.4kg per m2.
Exclusion Criteria:
  • Current treatment with meds that would alter blood pressure
  • Clinical or laboratory evidence of CVD, diabetes mellitus, renal insufficiency (serum creatinine ≥1.7mg per dL for men and ≥1.5mg per dL for women)
  • Current or planned pregnancy.
Description of Study Protocol:

Multicenter trial (nine clinical centers and coordinating center).

Recruitment

Not described.

Randomization

Subjects were randomly assigned with equal probability to one of four groups:

  • Weight loss only
  • Sodium reduction only
  • Combined weight loss and sodium reduction
  • Usual care (control group).

Blinding

Clinic staff performing measurements were blinded to group assignment.

Intervention

Weight loss intervention: Participants sought to lose at least 4.5kg during the first six months of the intervention and to maintain their weight loss for the remainder of the trial.

  • Timeline 
    • Individual counseling session followed by 14 weekly group meetings led by RDs or health educators
    • 14-week phase was followed by six biweekly group meetings and then monthly group meetings
    • Beginning with the 18th month, participants were offerred a variety of options to keep them involved in the intervention including individual counseling sessions and special group sessions focused on selected weight loss topics
  • Focused on self-directed behavior change, nutrition education, information on physical activity and social suppport for making and maintaining behavior changes
  • Dietary intervention focused on reducing caloric intake by decreasing consumption of excess fat, sugar and alcohol to produce moderate weight loss
    • Not less than 1500kcals per day for men; not less than 1200kcals per day for women
    • Weight loss of more than two pounds per week was discouraged
  • Physical activity: Gradually increase activity to 30 to 45 minutes per day, four to five days per week.

Statistical Analyses

  • Baseline characteristics were compared overall and by sex by using T-tests for means and chi-square tests for proportions
  • Two sample T-tests were used to compare changes in weight and blood pressure from baseline in the weight loss intervention and usual care groups overall, by sex, by ethnicity and by sex and ethnicity
  • Subgoup differences were tested by using terms for the interaction of treatment group with sex and with ethnicity in multiple linear regression models
  • Regression analyses were also used to analyze the dose-response relationship between change in weight and change in blood pressure, overall and within sex and ethnicity subgroups
    • Differences in dose-response were tested by using interaction terms in linear regression models
    • All regressions were adjusted for age and baseline weight and baseline blood pressure in the blood pressure regression models
  • Change in blood pressure was examined in relation to quintile of weight loss which were computed by using the distribution of weight change in the weight loss intervention group
    • Multiple regression analyses were performed in which weight loss participants were categorized according to patterns of weight loss and six and 36 months
  • Cox proportional hazards models were used for survival analyses, with onset of hypertension as the outcome.
Data Collection Summary:

Data Collection

  • Baseline blood pressure measurements taken at three screening visits, each separated by seven to 45 days. Three readings of systolic blood pressure and diastolic blood pressure were averaged.
  • Blood pressure and weight were measured every six months after randomization to the end of follow-up at 36, 42 or 48 months depending on randomization date
  • Dietary intake was assessed by 24-hour recall and physical activity by questionnaire.

Dependent Variables

  • Weight loss
  • Blood pressure.

Independent Variables

  Weight loss intervention.

Control Variables

  • Age
  • Sex
  • Ethnicity
  • Baseline weight
  • Baseline blood pressure.
Description of Actual Data Sample:

Baseline Characteristics (mean±SD)

Characteristic

Weight Loss Group (N=595)

 Usual Care Group (N=596) Overall (N=1,191)
Demographic and Social                                                                                                                                                 

Age, years                                                              

 43.4±6.1 43.2±6.1 43.3±6.1

Men, %

 63.0 68.3 65.7

White, %

 78.0 79.5 78.8

Black, %

 17.8 17.3 17.5

College graduate, %

 50.8 50.8 50.8

Health status

      
Weight, kg      

Men

 98.9±12.3 98.5±11.7 98.7±12.0

Women

 84.1±11.9 82.9±10.9 83.6±11.5
BMI      

Men

 31.0±2.9 31.0±2.9 31.0±2.9

Women

 31.0±3.6 30.8±3.5 30.9±3.6
Systolic blood pressure, mmHg 127.6±6.1 127.3±6.4 127.4±6.2
Diastolic blood pressure, mmHg 86,0±1,9 85.8±1.9 85.9±1.9
Vigorous exercise, times per week 2.0±4.0 1.8±1.9 1.9±3.1
Energy intake, kJ per 24 hours* 9,480±3,605 9,353±3,803 9,416±3,703
Energy from fat, %* 36.0±9.6** 33.9±10.3 34.9±10.0
Energy from saturated fat, % 12.2±3.9§ 11.2±4.1 11.7±4.0

 * Data available for 230 participants in the weight loss group and 234 participants in the usual care group.

**P<0.05       §P<0.01    

Summary of Results:

Weight Loss

  • Mean weight change from baseline in the intervention group was -4.4kg at six months, -2kg at 18 months and -0.2kg at 36 months. Mean weight change in the control group was 0.1, 0.7 and 1.8kg for the same time period. Group differences in mean weight change were stataistically significant at each follow-up point (P<0.001).
  • In the intervention group, men had greater net weight loss than women by 1.6kg at six months (P=0.006), 1.2kg at 18 months (P=0.07), and 1.7kg at 36 months (P=0.02)
  • White persons lost a net 1.8kg more than black persons at both six and 18 months (P=0.01 and 0.03, respectively). At 36 months, weight loss did not differ significantly between white persons and black persons (P>0.2).
  • Age was associated with greater weight loss only at the 36 month assessment
  • Baseline weight correlated with weight change at six months only
  • Weight loss at six months was strongly related to attendance at the intervention sessions, but the relationship between attendance and weight loss diminished later in the trial (P<0.001 at six months, P=0.031 at 18 months).

Blood Pressure

  • At all follow up points, the weight loss and usual care groups differed significantly in diastolic blood pressure (DBP) and systolic blood pressure (SBP)
    • Differences between group means in DBP
      • -2.7mmHg (95% CI: -3.5 to -2.0; P<0.001) at six months
      • -1.3mmHg (95% CI: -2.0 to -0.6; P<0.001) at 18 months
      • -0.9mmHg (95% CI: -1.7 to-0.0; P<0.05) at 36 months
    • Differences between group means in SBP
      • -3.7mmHg (95% CI: -4.7 to -2.8; P<0.001) at six months
      • -1.8mmHg (95% CI: -2.7 to -0.9; P<0.001) at 18 months
      • -1.3mmHg (95% CI: -2.4 to -0.3; P<0.01) at 36 months
  • Participants who lost the most weight had the largest reductions in blood pressure
    • Quintile with the greatest weight loss (mean weight change -8.8kg) had a mean reduction from baseline of 7.0mmHg in DBP and 5.0mmHg in SBP
    • Quintile with the least weight loss (mean weight change 7.3kg) had a mean reduction in DBP of 0.7mmHg and a mean increase in SBP of 2.5mmHg
  • In regression analyses adjusting for age, sex, ethnicity, bseline weight and baseline blood pressure, the overall effect efect on blood pressure at 36 months was a reduction of 0.35mmHg in DBP and 0.45mmHg in SBP per kg of weight lost
    • No differences in response of DBP or SBP to weight loss were observed according to ethnicity.

Relationship Between Patterns of Weight Loss and Blood Pressure

  • Divided into three groups
    • Successful maintenance: Lost ≥4.5kg by six months and maintained at least a 4.5kg weight loss at 36 months (N=73 participants)
      • Mean weight change from baseline at six months: -10.2kg (CI: -11.2 to -9.2kg)
      • 18 months: -9.2kg (CI: -10.7 to -7.6kg)
      • 36 months: -9.1kg (CI: -10.0 to -8.1kg)
    • Relapse: Lost at least 4.5kg at six months, but weight loss at 36 months was less than 2.5kg (N=129 participants).
      • Six months: -8.5kg (CI: -9.3 to -7.8kg)
      • 18 months: -2.9kg (CI: -3.7 to -2.1kg)
      • 36 months: 1.7kg (CI: 1.2 to 2.3kg)
    • No loss: Weight loss at six and 36 months was less than 2.5kg (N=198 participants)
      • Six months: 0.0kg (CI: -0.2 to 0.3kg)
      • 18 months: 1.7kg (CI: 1.2 to 2.3kg)
      • 36 months: 3.6kg (CI: 2.9 to 4.2kg)
    • Remaining participants not classified because their pattern of weight change did not fit one of these categories or because they had missing data at one of the assessments (N=195)
  • Although all subgroups experienced a decrease in blood pressure at six months, the two groups with weight loss at six months had the largest decreases in blood pressure 
  • Relapse group showed a steady increase in blood pressure to near baseline levels at 36 months, whereas those who maintained their weight loss also maintained substantial reductions in blood pressure
  • In repeated measures analysis adjusting for age, sex, ethnicity and baseline weight and blood pressure, the three weight change subgroups differed significantly in blood pressure resonse by time (P=0.04 for SBP; P=0.007 for DBP).

Onset of Hypertension

  • The risk ratio for hypertension in the intervention group was 0.58 (95% CI, 0.36 to 0.94) at six months; 0.78 (CI, 0.62 to 1.00) at 18 months, 0.81 (CI, 0.70 to 0.95) at 36 months and 0.79 (CI: 0.65 to 0.96) at end of study months
  • Relative risk for hypertension (compared with the control gorup) was 0.35 (CI: 0.20 to 0.59; P<0.001) in the successful maintenance subgroup, 0.75 (CI: 0.53 to 1.04) in the relapse subgroup and 1.10 (CI: 0.85 to 1.42) in the no loss subgroup
  • Relative risk for hypertension in the succssful maintenance group compared with the no loss group was 0.31 (CI: 0.18 to 0.55), the RR in the relapse group compared with the no loss group was 0.68 (CI: 0.47 to 1.00) and the RR in the successful maintenance group compared with the relapse group was 0.46 (CI: 0.25 to 0.84).

 Intervention Attendance and Follow-Up

  • 81% of the subjects attended at least half of the sessions they were expected to attend during the first six months
  • 64% attended at least 80% of their assigned sessions
  • Follow-up at the end of the study (36 months) was 92% for the intervention group and 93% for the usual care for weight measurements and 89% and 86% for blood pressure measurements. 

 

Author Conclusion:

Clinically significant long-term reductions in blood pressure and reduced risk for hypertension can be achieved with even modest weight loss.

Funding Source:
Government: National Heart, Lung and Blood Institute (NHLBI)
Reviewer Comments:
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? ???
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? No
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes