EAL

Disorders of Lipid Metabolism and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Assessment of salt sensitivity usually includes recording blood pressure changes when going from a low-salt to a high-salt diet. This study assessed salt sensitivity by using 24-hour urine samples and 24-hour ambulatory blood pressure measurements during salt repletion and depletion.

Inclusion Criteria:

Not described.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

Obtained from referrals to the Outpatient Hypertension Clinic at Haukeland Hospital in Bergen, Norway.

Design

Diagnostic study.

Intervention

Salt restricted diet after baseline for six days. Salt depletion was achieved by giving a single dose of 80mg furosemide on the first salt-restricted day
After salt restriction, the subjects resumed their usual diets for six days
Salt repletion was then performed for six days, during which subjects were given salt tablets containing nine grams of sodium chloride.

Statistical Analysis

SPSS for Windows was used for analyses
Values are given as mean ± standard error for the effects of salt restriction and repletion on blood pressure
All other values were mean ± standard deviation
Salt-sensitive and salt-resistant groups were compared using the Mann-Whitney U test
Wilcoxon test for paired samples was performed for within group analyses
Statistical significance was noted at P<0.05.

Data Collection Summary:

Timing of Measurements

Casual and 24-hour ambulatory blood pressures were recorded at baseline and on the sixth day of salt depletion and repletion
24-hour urine samples were collected
Some lab measurements were obtained between 8:00 A.M. and 10:00 A.M. on the day after the 24-hour blood pressure monitoring. The 24-hour ambulatory blood pressure monitoring was started during the same hours and ended 24 hours later.
Three casual blood pressure measurements were obtained after 10 minutes of rest in the sitting position with about one-minute intervals.

Dependent Variables

Ambulatory blood pressure (measured with an Accutracker I)
Casual blood pressure (measured with a regularly calibrated Tyco aneroid manometer)
Hemoglobin, hematocrit, electrolytes, creatinine, blood and plasma volume, atrial natriuretic peptide, aldosterone and renin were measured in venous blood that was drawn from an intravenous cannula.

Independent Variables

Salt restriction
Salt repletion.

Description of Actual Data Sample:

Initial N: 30 males
Attrition (final N): 30
Age: 23 to 61 (mean age 43)
Ethnicity: White males
Location: Department of Heart Disease, Haukeland Hospital, Bergen, Norway.

Summary of Results:

Casual and 24-hour blood pressure measurements defined different subjects as salt sensitive. No difference was found in plasma norepinephrine, renin, aldosterone, plasma volume, blood volume or 24-hour sodium excretion between salt-sensitive and salt-resistant subjects.

**Casual and 24-hour Blood Pressure (24hBP) in Salt-Sensitive and Salt-Resistant Subjects**
	Salt Sensitive			Salt Resistant
	Baseline	Low Salt	High Salt	Baseline	Low Salt	High Salt
Casual BP mm Hg
Mean	120±8	108±6^#	115±10^¤	120±11	113±8^#	116±7
Systolic	160±10	144±11^#	155±11^¤	155±18	147±14^#	150±13
Diastolic	101±8	90±6^#	95±11	102±10	96±9^#	100±9
24hBP mm Hg
Mean	109±10	99±9^#	115±10^¤	106±10	105±11	106±11
Systolic	151±14	137±11^#	163±13^¤	148±15	145±16	149±17
Diastolic	88±8	80±8^#	91±9^¤	86±8	85±10	84±9

# P< 0.01 versus baseline within group.
¤ P< 0.01 versus low salt within group.

Weight, Diuresis, Urinary Sodium Concentration (Na-conc), Excretion of Sodium (U-Na) and Potassium (U-K), Creatinine Clearance (clear), Plasma Atrial Natriuretic Peptide (P-ANP), Epinephrine (E), Norepinephrine (NE), Aldosterone (Aldo) and Plasma Volume in Salt Sensitive (SS) and Salt Resistant (SR) Subjects
	Salt Sensitive			Salt Resistant
	Baseline	Low Salt	High Salt	Baseline	Low Salt	High Salt
Weight kg	88.0±10.0	86.8±10.6^#	89.2±9.7^¤	88.4±10.5	87.2±10.5^#	88.4±10.5^¤
Diuresis	1,450±580	1,964±448*	1,980±490	1,390±487	1,223±414*	2,077±503^¤
Na-conc mmol per L	112±38	18±13*^#	152±51^¤	100±25	44±34*^#	138±35^¤
U-Na mmol per 24 hours	144±41	34±21^#	296±114^¤	132±40	54±42^#	281±78^¤
U-K mmol per 24 hours	90±27	101±28	99±22	102±28	91±33	96±24
Clear ml per s	2.03±0.31	1.82±0.38	2.19±0.29	2.21±0.54	1.93±0.34	2.08±0.45
P-ANP pM	10.4±2.5	7.7±1.5^#	13.1±3.9^¤	11.9±4.5	10.6±4.8	13.7±5.5^¤
P-renin mcg per L per hour	1.1±0.6	2.3±1.9^#	1.3±1.0^¤	1.7±1.2	2.1±1.3	1.0±0.7^¤
P-aldo pM	535±227	770±401	338±178	431±230	754±430^#	396±284^¤
P-E nM	0.13±0.11	0.20±0.11	0.14±0.07	0.13±0.09	0.17±0.16	0.13±0.09
P-NE nM	1.76±0.74	1.76±0.62	1.21±0.35	1.73±0.78	1.82±0.90	1.94±1.35
Plasma volume ml	3,684±382	3,751±383	4,620±1,570	3,681±652	3,666±496	3,967±808

* P<0.01 between groups.
^# P<0.01 versus baseline within group.
^¤ P<0.01 versus low-salt within the same group.

Other Findings

Salt depletion:
- Overall daily sodium excretion fell from 135mmol to 144mmol (34mmol and 54 mmol) in the salt-sensitive and salt-resistant group, respectively
- 24-hour ambulatory blood pressure was significantly reduced, from an average of 151/88 to 137/80mm Hg (P<0.001). Mean 24-hour ambulatory blood pressure decreased from 109 to 99mm Hg (P<0.001)
- Diuresis increased by 35%, which was significantly higher diuresis and lower urinary sodium than in the salt-resistant group (P<0.01)
Salt repletion:
- Overall daily sodium excretion increased from 44mmol to 290mmol (296mmol and 281mmol) in the salt sensitive and salt resistant group, respectively
- 24-hour ambulatory blood pressure increased from 137/80 to 163/91mm Hg in the salt-sensitive group. The mean ambulatory blood pressure increased from 99 to 115mm Hg (P<0.001).
- Mean daytime blood pressure increased by an average of 16%, and mean nocturnal blood pressure by 18% (both P<0.01)
- Casual blood pressure increased significantly in the salt-sensitive subjects. The blood pressure measurements in the salt-resistant group remained virtually unchanged.
- Five salt-resistant subjects increased their mean casual blood pressure more than 10% during this phase
- Plasma atrial natriuretic peptide increased by 74% in salt-sensitive subjects and by 35% in salt-resistant subjects (both P<0.01). Multiple regression analysis found a possible correlation between the 24-hour ambulatory blood pressure and the increase in plasma atrial natriuretic peptide (R=0.64, P<0.01), with inverse correlation to plasma concentration of atrial natriuretic peptide after salt depletion (R=0.26, P<0.01).
Casual blood pressure:
- A separate analysis was performed for casual blood pressure measurements due to individual discrepancy in casual blood pressure during salt repletion
- Nine subjects had an increase in mean casual blood pressure of 10% or more during salt repletion. Four of these also had increased 24-hour ambulatory blood pressure by 10% or more during salt repletion.
- Salt-sensitive subjects could not be differentiated from salt-resistant subjects based on hormone or urinary electrolyte profiles.

Author Conclusion:

Salt sensitivity may be associated with lower levels of atrial natriuretic peptide and a different response to salt depletion. The optimal method for assessing salt sensitivity is unclear.

Funding Source:

University/Hospital:

Department of Heart Disease, Haukeland Hospital, Bergen, Norway

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
	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?	Yes
	1.3.	Were the target population and setting specified?	Yes
	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?	No
	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?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
	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.)	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
	3.4.	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")?	Yes
	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?	N/A
4.	Was method of handling withdrawals described?		N/A
	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.)	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.)	N/A
	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?	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
	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.	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?	N/A
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	N/A
	6.6.	Were extra or unplanned treatments described?	N/A
	6.6.	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)?	Yes
	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
	8.6.	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
	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.	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?	Yes
10.	Is bias due to study's funding or sponsorship unlikely?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes