EAL

DLM: Hypertension (2010)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate water immersion (WI) to the neck-induced changes in blood pressure, sodium potassium and calcium urinary excretion and plasma levels of vasoactive hormones during normal or low potassium intake in hypertensive subjects evaluated for salt sensitivity.

Inclusion Criteria:

Hypertensive: Outpatient diastolic blood pressure in excess of 95mm Hg (seated posture) with the arm in the horizontal position after five minutes of sitting, on at least three occasions documented for at least three months before study, using conventional sphygmomanometry
Otherwise healthy.

Exclusion Criteria:

Hypertension treatment
Major signs or symptoms of target organ damage
Major diseases besides hypertension
Renal disease (by documenting normal urinalysis and creatinine clearance)
Cardiac hypertrophy (by complete M-mode echocardiogram monitored by two-dimensional echocardiography)
Those receiving estrogens, nonsteroidal anti-inflamatory agents, or drugs known to influence salt, potassium, calcium, water or hemodynamic function.

Description of Study Protocol:

Recruitment

Details were not explained on how subjects came to know about the study.

Design

Experimental protocol:
- This was an outpatient study
- Each potential subject was instructed by an institution dietitian to follow a diet of approximately:
  - 75g protein
  - 200mmol sodium
  - 60mmol potassium daily
  - After complying with diet for three days, the subjects were allowed to enter the study
- Each subject was studied on two separate occasions while receiving either a high (80mmol per day) or low (18mmol per day) potassium diet
- Each study period lasted for 10 days
- Body weight, blood pressure, potassium, calcium and creatinine excretion were monitored for the last three days of each 10-day study period
- Diets contained low-protein bread, cream cheese, skimmed milk, oil, rice, margarine, pasta and tomato, ship-biscuit and tea and provided 25cal to 40cal per kg, BW energy 0.8g to 1.0g per kg BW protein, 900mg calcium per day and 30mmol sodium per day. Caloric content was adjusted for individual requirements to keep weight constant.
- Except for potassium, the diets were the same during both study periods. Appropriate amounts of sodium chloride were added to the diets to maintain daily sodium intake of 220mmol.
WI studies:
- On day 11 (after 10-day diet period) of either high- or low-potassium intake, each participant was subjected to acute extracellular volume expansion by water immersion (WI):
  - At 8:00 A.M., after overnight fast and fluid deprivation (10 hours), an antecubital vein was catheterized for blood sampling
  - Subjects voided
  - Subjects received 200ml water to drink
  - They then sat quietly outside the immersion tank for two hours at room temperature between 26+0.4C and 27+0.4C
- The water load was repeated hourly throughout the study
- Subject then stepped into the immersion tank and sat on adjustable chair with water to the neck at constant temp (34+0.5C) with arms outside the tank in the horizontal position
- Subjects remained in the tank for 2 hours (immersion study) and stepped out at hourly intervals to void urine
- At the end of each hour of the test, before the subjects stood to void, blood was drawn for serum sodium, potassium, hematocrit, creatinine, PRA and plasma aldosterone (PA) measurements
- The hourly urine volumes were measured and concentrations of creatinine, sodium, potassium and calcium were determined
- Both resting and WI arterial BP were measured in the seated posture with a noninvasive fully automatic monitor with the arm in the same position before and during WI, using model 90207, Spacelabs, Redmond, WA
- Blood for PRA and PA measurements was drawn with plastic syringes and then placed immediately into chilled plastic tubes containing ethylenediamine tetra-acetate (potassium salt)
- Plasma was separated in refrigerated centrifuge at 4.0C
- Samples were frozen and stores at -20C until assayed
Assessment of salt sensitivity (salt-sensitive response and salt-resistant response): Salt-sensitivity index was used to determine classification. This is calculated as the change in mean arterial pressure divided by the change in urinary sodium excretion rate, which shows the effect that changes in sodium intake have on blood pressure.

Blinding Used

WI and salt-sensitivity tests were randomly assigned (details not explained).

Statistical Analysis

Student's T-test for paired and unpaired values
ANOVA
Regression analysis by Pearson's correlation coefficient test
Significance set at P<0.05.

Data Collection Summary:

Timing of Measurements

Experimental protocol: Monitored for the last three days of each 10-day study period
- Body weight
- Blood pressure
- 24-hour urinary sodium
- Potassium
- Calcium
- Creatinine excretion.
WI Studies
- On day 11 (after 10-day diet period) of either high- or low-potassium intake, each participant was subjected to acute extracellular volume expansion by water immersion (WI), acting as his or her own control
- At the end of each hour of the test, before the subjects stood to void, blood was drawn for serum sodium, potassium, hematocrit, creatinine, PRA and plasma aldosterone (PA) measurements. The hourly urine volumes were measured and concentrations of creatinine, sodium, potassium and calcium were determined.
- Both resting and WI arterial BP were measured in the seated posture with a noninvasive fully automatic monitor with the arm in the same position before and during WI, using model 90207, Spacelabs, Redmond, WA
- Blood for PRA and PA measurements was drawn with plastic syringes and then placed immediately into chilled plastic tubes containing ethylenediamine tetraacetate (potassium salt).

Dependent Variables

Blood pressure
Sodium
Potassium
Calcium urinary excretion
Plasma levels of vasoactive hormones.

Independent Variables

Normal potassium intake
Low potassium intake.

Description of Actual Data Sample:

Initial N: 11 (eight males, three females)
Attrition (final N): 11 (eight males, three females)
Age: 23 to 46 years old
Location: Parma, Italy.

Summary of Results:

After 10-day period of low K+ intake, systolic BP increased (P<0.02) by 5.0mm Hg, whereas serum K+ decreased (P<0.001) by 0.9mmol per L
PRA (P<0.02) and plasma aldosterone (P<0.04) concentrations also decreased during low K+ intake in hypertensive patients.

**Clinical and Biochemical Data in 11 Hypertensive Subjects after Ingesting 80mmol and 18mmol Potassium Daily for 10 Days**
Variable	After 80mmol/d K+ intake	After 18mmol/d K+ intake
Serum Sodium (mmol per L)	143±1	142±1
Serum Potassium (mmol per L)	4.1±0.05	3.2±0.1 (a)
BW (kg)	73.5±3	72.4±3 (b)
Systolic pressure (mm Hg)	141±2	146±2 (c)
Diastolic pressure (mm Hg)	95±1	95±1
PRA (ng per L*s)	0.47±0.08	0.25±0.05 (c)
Plasma aldosterone (pmol per L)	1,082±161	710±101 (d)

Values are the mean±SE. Significant differences compared with values noted on day 10 with 80 mmol K+ diet shown.

(a) P<0.001.

(b) P<0.005.

(d) P<0.04.

Changes in K+ did not significantly modify urinary sodium excretion
There was a marked decrease in urinary K+ excretion (P<0.0001) in addition to an increase in urinary calcium excretion (P<0.001) during the 10-day low potassium intake
Strong correlation between urinary sodium and calcium excretion in the WI control period during low K+ intake (P<0.001)
Calcium depletion is the most important consequence of K+ depletion in those exhibiting a higher salt-sensitivity index.

Author Conclusion:

This study confirms that potassium depletion may exacerbate essential hypertension by modifying natriuretic ability and calcium excretion in hypertensive subjects evaluated for degree of salt sensitivity; it also suggests that not only sodium restriction, but also potassium and calcium supplementation could be particularly advisable in salt-sensitive hypertensive patients.

Funding Source:

University/Hospital:

University of Parma, Italy

Reviewer Comments:

Very small sample size (11)
Finances not explained. There are a number of Italian institutions listed at the top of the article, but their involvement is not described.

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
	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
	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
	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
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	Yes

Validity Questions
	1.	Was the research question clearly stated?	Yes
1.	Was the research question clearly stated?		Yes
	1.1.	Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified?	Yes
	1.1.	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
	1.2.	Was (were) the outcome(s) [dependent variable(s)] clearly indicated?	Yes
	1.3.	Were the target population and setting specified?	No
	1.3.	Were the target population and setting specified?	No
	2.	Was the selection of study subjects/patients free from bias?	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
	2.1.	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
	2.2.	Were criteria applied equally to all study groups?	Yes
	2.3.	Were health, demographics, and other characteristics of subjects described?	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?	???
	2.4.	Were the subjects/patients a representative sample of the relevant population?	???
	3.	Were study groups comparable?	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)	N/A
	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?	Yes
	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.)	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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
	3.4.	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
	3.5.	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")?	No
	3.6.	If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")?	No
	4.	Was method of handling withdrawals described?	Yes
4.	Was method of handling withdrawals described?		Yes
	4.1.	Were follow-up methods described and the same for all groups?	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%.)	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	N/A
	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?	N/A
5.	Was blinding used to prevent introduction of bias?		N/A
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	N/A
	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
	5.2.	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
	5.3.	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?	Yes
	5.4.	In case control study, was case definition explicit and case ascertainment not influenced by exposure status?	Yes
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	???
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	???
	6.	Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described?	Yes
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?	N/A
	6.1.	In RCT or other intervention trial, were protocols described for all regimens studied?	N/A
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.2.	In observational study, were interventions, study settings, and clinicians/provider described?	Yes
	6.3.	Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect?	Yes
	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
	6.4.	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?	Yes
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	6.6.	Were extra or unplanned treatments 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
	6.7.	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
	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.	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
	7.1.	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
	7.2.	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
	7.3.	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
	7.4.	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
	7.5.	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	Yes
	7.7.	Were the measurements conducted consistently across groups?	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.	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
	8.1.	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
	8.2.	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
	8.3.	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
	8.4.	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)?	No
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	No
	8.6.	Was clinical significance as well as statistical significance reported?	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
	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.	Are conclusions supported by results with biases and limitations taken into consideration?		Yes
	9.1.	Is there a discussion of findings?	Yes
	9.1.	Is there a discussion of findings?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	9.2.	Are biases and study limitations identified and discussed?	Yes
	10.	Is bias due to study's funding or sponsorship unlikely?	???
10.	Is bias due to study's funding or sponsorship unlikely?		???
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.1.	Were sources of funding and investigators' affiliations described?	No
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes