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DLM: Hypertension (2010)

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

The effect of an acute, large reduction in salt intake on blood pressure and the renin system was tested in untreated hypertensive and normotensive white adults.  

Inclusion Criteria:
  • Hypertensives, systolic blood pressure (BP) more than 140mm Hg and diastolic BP more than 90mm Hg
  • Normotensives, systolic BP less than 140mm Hg and diastolic BP less than 90mm Hg.
Exclusion Criteria:

Hypertensive patients who received treatment for their hypertension in the three previous months.

Description of Study Protocol:

Recruitment

No information was given about recruitment.

Design

The two groups each consumed high sodium intake for five days followed by a low sodium intake for five days. Blood pressure, urinary sodium excretion and renin activity were measured at the start of the study and at the end of each five-day period.

Intervention

  • High sodium intake of approximately 350mm per day for five days was followed by a low sodium intake of 10mm to 20mm per day for five days
  • High sodium intake, normal diet plus sodium supplement tablets (200mmol per day)
  • Low sodium intake, diet provided by metabolic kitchen.

Statistical Analysis

  • Data were expressed as mean±SD
  • Changes in continuous variables within each group were analyzed by paired T-tests
  • Comparisons between groups at baseline (normal diet) were made with unpaired T-tests for continuous variables and Chi-square test for categorical data
  • A multiple linear regression was used to compare between the two groups for changes in continuous variables such as blood pressure while controlling for age.

 

Data Collection Summary:

Timing of Measurements

  • BP was measured and blood samples were collected at baseline and after five days on the high sodium intake and five days on the low sodium intake
  • 24-hour urinary samples were collected before the interventions and during the last two days on each dietary regimen. 

Dependent Variables

  • Blood pressure: The same arm was always used. Participants were in the supine position. Five measurements were taken at one- to two-minute intervals using semiautomatic ultrasound sphygmomanometers. The readings were averaged.
  • Urinary sodium, potassium and creatinine: Determined from analysis of two 24-hour urine samples
  • Plasma sodium, potassium, creatinine, renin activity and aldosterone.

Independent Variables

Dietary sodium intake: High and low. 

Control Variables

Age: Controlled for by multiple linear regression.

 

Description of Actual Data Sample:

 Initial N

  • 93 hypertensives: 46 male and 47 female
  • 39 normotensives: 25 male and 14 female.

Attrition (final N):

There was no report of any attrition, which is conceivable given the short duration of the intervention.

Age

The hypertensives were significantly older than the normotensives.

  • Hypertensives: Mean age of 50 (19 to 70)
  • Normotensives: Mean age of 28 (19 to 62).

Ethnicity

All participants were white.

Anthropometrics

The hypertensives tended to weigh more (72.4±1.4) than the normotensives (69.4±1.5) but the difference was not significant.

Location

London, United Kingdom.

 

Summary of Results:
Variables

 

 Normotensives Hypertensives Statistical Significance of Group Difference

 

Measures and confidence intervals
Mean, CI

Measures and confidence intervals
Mean, CI

Baseline

 

  

Statistically Significant Difference Between Groups
Supine blood pressure, mm Hg Systolic 116±2.2
170±2.4
P=0.000

Diastolic
74±1.2
106±1.2
 P=0.000

Mean arterial pressure
88±1.3
127±1.4
 P=0.000

Pulse, BPM
75±1.9
77±1.0
 P=0.342
Urinary, mmol per 24 hours

Sodium
149.9±9.7
139.9±14.8
 P=0.308

Potassium
65.5±3.5
63.1±2.1
 P=0.545

Creatinine
10.8±1.5
10.3±0.5
 P=0.673

Volume, L per 24 hours
1.67±0.13
1.67±0.06
 P=0.999
Plasma Renin Activity, ng .mL-1.h-1
2.26±0.20
1.27±0.11
 P=0.000

Aldosterone, pmol per L
540.4±48.1
458.2±30.5
 P=0.136

Sodium
140.2±0.4
140.0±0.2
 P=0.653

Potassium
3.98±0.06
3.99±0.04
 P=0.888

Creatinine
81.8±0.23
83.3±1.8
 P=0.669
After High Sodium Intake, After Low Sodium Intake, Difference    
Adjusted Differences1,
Hypertensives vs. Normotensives,
Adjusted P
Supine blood pressure, mm Hg

Systolic

116±2.2, 115±2.0, -1.6

168±2.3, 152±2.1, -16.8*
 
-7, P=0.041

Diastolic

73±1.5, 76±1.8 , +2.9

105±2.2, 115±2.0, -5.7*

 -7, P=0.004

Mean arterial pressure

88±1.6, 89±1.7, +1.4

126±1.4, 117±1.4, -9.4*

 -7, P=0.004

Pulse, BPM

74± + 2.1, 75± + 2.2, +0.4

79±1.3, 80±1.2, ±+0.9

 -1.8, P=0.601
Urinary, mmol per 24 hours

Sodium

313.3± + 14.3, 20.2± 2.2, -293.1*

287.5±10.9, 21.9±1.6, -265.6*

-9.38, P=0.736

Potassium

69.5±4.1, 64.9±3.7, -4.6

61.5±2.1, 52.7±1.9, -8.8*

-5.66, P=0.295

Creatinine

11.5±0.9, 11.3±0.8, -0.1

11.2±1.2, 10.3±0.4, -0.9

0.49, P=0.867
Plasma
Renin activity, ng .mL-1.h-1

0.9±0.13, 5.99±0.48, +5.09*

0.73 ±0.07, 3.14±0.25, +2.41*

-1.38, P=0.036

Aldosterone, pmol per L

231.0±20.99, 1627.2±122.4, +1,396*

288.2±18.9, 799.6±59.6, +511*

-331.8, P=0.033

Sodium, mmol per L

141.6±0.6, 138.5±0.5, -3.1*

140.8±0.2, 137.9±0.3, -2.98*

0.45, P=0.596

Potassium, mol per L

 3.9±0.08, 3.97±0.07, 0.06

3.8±0.04, 3.9±0.04, 0.12 ∑

-0.16, P=0.186

Creatinine, micromol per L

 79.4±2, 83.5±2.2, 4.04¥ 82.8±1.9, 90.2±1.7, 7.5*

2.24, P=0.629

1. Differences in response to high and low salt intake were adjusted for age
* P<0.001, High-salt vs. low-salt diet
¥ P<0.05
∑ P<0.01.

Other Findings

  • At baseline, plasma renin activity was significantly lower in the hypertensives than in the normotensives. For a similar reduction in 24-hour urinary sodium excretion, the hypertensives had a greater fall in BP and smaller rise in plasma renin activity and aldosterone compared with normotensives.
  • Taking all patients together, the fall in systolic blood pressure with the low sodium diet was significantly correlated with age (R=0.47, P<0.0001)
  • There was also a significant inverse correlation between the fall in mean arterial pressure with salt restriction and,
    1. Plasma renin activity on the low-salt diet
    2. Rise in plasma renin activity from the high salt to the low-salt diet
    3. Plasma aldosterone on the low-salt diet
    4. Rise in plasma aldosterone
    • These inverse correlations were not significant in normotensives alone.
  • An analysis was done on a sub-group of normotensive and hypertensive subjects, matched for age and sex to exclude bias from the age difference of the two groups in the study as a whole [N=17 in each group, 10 males and seven females; age was 35±3.0 years (normotensive) and 36±3.0 years (hypertensive)]. In this analysis, there was a significant inverse correlation between the fall in mean arterial pressure, with salt restriction and the rise in plasma renin activity from the high-salt to the low-salt diet. There was no association between the change in blood pressure and plasma renin activity on the low-salt diet, plasma aldosterone on the low-salt diet and rise in plasma aldosterone with salt restriction.
Author Conclusion:

This study simultaneously investigated the response of hypertensive and normotensive persons to an acute reduction in dietary salt intake. It found that hypertensive persons respond with a greater fall in BP and with smaller rises in plasma renin activity and aldosterone. These results suggest that the greater fall in BP in response to salt restriction in hypertensives is due, at least in part, to a decreased responsiveness of the renin-angiotensin-aldosterone system in hypertensives. However, many other mechanisms, which merit further study, must explain the variability of blood pressure responses to acute salt restriction.

Funding Source:
University/Hospital: St. George's Hospital Medical School, London, UK
Reviewer Comments:
  • There is no information on how these participants were recruited, nor is there an explanation of how the study was funded. This is of particular interest because the hypertensives had received no treatment for at least three months. All the participants were white. The issue of whether the socioeconomic circumstances of the two groups was comparable was not addressed.
  • Age had a confounding effect on the results of this study because the normotensives were, on average, significantly younger than the hypertensives
  • The sodium content of the normal diet consumed by the participants was not investigated; of particular interest is the issue of how the sodium content compared between the normotensive and hypertensive group
  • This study involved a rather small number of participants (N=132) over a short time-period (five days on each diet)
  • This study does not provide information as to whether this effect would be maintained over time.
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? ???
  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? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  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")? Yes
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? Yes
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  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.) No
  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? Yes
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? ???
  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)? N/A
  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? N/A
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? No
  10.2. Was the study free from apparent conflict of interest? Yes