EAL

Disorders of Lipid Metabolism and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To quantify the validity of rapid sodium load and depletion test in the diagnosis of salt-sensitive hypertension and compared to a dietary approach in which sodium intake is set at varying levels and blood pressure changes are monitored.

Inclusion Criteria:

Subjects with essential hypertension who had at least three office visits with a blood pressure above 140/90mm Hg while on no antihypertensive medications and consuming an unrestricted salt diet.

Exclusion Criteria:

Not described.

Description of Study Protocol:

Recruitment

Patients from the Hypertension Unit in the Department of Internal Medicine at the Hospital Clinic in Barcelona, Spain.

Design

Diagnostic study.

Blinding Used

Single blind.

Intervention

Low-salt diet with added placebo and sodium chloride tablets.

Statistical Analysis

Values are expressed as mean±SD and absolute frequencies
Pearson's correlation coefficient was used to assess the relationship between 24-hour mean BP changes induced by DP (dietary protocol) or IP (intravenous protocol)
Cut points were established at 3.0, 4.0 and 5.0mm Hg for absolute change in 24-hour mean BP induced by dietary protocol
Cut points were also set at 5.0 and 10mm Hg of absolute change in 24-hour mean BP induced by intravenous protocol.

Data Collection Summary:

Timing of Measurements

Dietary protocol:
- Subjects were in a metabolic ward for the length of the study
- A low-sodium diet was given to all subjects for 14 days
- This was the baseline diet was and was supplemented with random, single-blind dose of placebo tablets for seven days (low-salt period) and sodium chloride tablets for the other seven days (the high-salt period)
- 24-hour urinary excretion measured dietary compliance
- Blood pressure was measured once on the last day of both the low-salt and high-salt periods, with automatic measurements every 15 minutes for 24 hours
Intravenous protocol:
- The blood pressure response to a saline infusion and furosemide was measured at least one month after the dietary protocol
- Subjects were kept in the metabolic ward and on a normal sodium diet for the first day
- The second day included volume expansion via intravenous administration of two liters of 0.9% saline in four hours, between 8:00 A.M. and 12:00 noon. A 24-hour blood pressure was done on this day at 8:00 A.M. and for every 15 minutes thereafter.
- The third day consisted of volume depletion via a low-sodium diet and 120mg of furosemide in three separate doses. A new 24-hour blood pressure was obtained at 8:00 A.M.

Dependent Variables

Variable one: Systolic blood pressure
Variable two: Diastolic blood pressure.

Independent Variables

Salt intake
Sodium administration (sodium load)
Furosemide administration (volume depletion).

Description of Actual Data Sample:

Initial N: 29 (12 males, 17 females)
Attrition (final N): 29 (12 males, 17 females). The results indicate that all participants were compliant with the protocol, so there was no attrition.
Age: 54.8±9.3.

Anthropometrics

Weight (kg): 75.2±13.6
BMI: 27.9±4.5.

Location

Barecelona, Spain.

Summary of Results:

Mean values (SD) of 24-hour systolic, mean, and diastolic blood pressures (BP) obtained at the end of low- and high-salt intakes, and during saline and furosemide administration in all subjects.

Variables	High-salt Intake	Low-salt Intake	Statistical Significance	Saline	Furosemide	Statistical Significance
24-hour systolic BP(mm Hg)	145.2±15.0	141.8±13.6	P=0.007	152.2±13.3	141.0±11.7	P=0.001
24-hour mean BP (mm Hg)	110.2±10.6	107.5±9.2	P=0.007	113.1±7.7	107.2±7.4	P=0.001
24-hour diastolic BP (mm Hg)	90.6±9.3	88.9±8.2	P=0.041	90.6±7.7	87.2±7.7	P=0.003

Pearson’s correlation coefficients between changes in 24-hour systolic, mean and diastolic blood pressures (BP) obtained by either changes in dietary salt and saline-furosemide administration. Correlation coefficients were calculated non-adjusted, and also after adjustment for the corresponding BP obtained in all four steps of the study.

Non-adjusted

Adjusted for BP Value Obtained at Low-salt Intake

Adjusted for BP Value Obtained at High-salt Intake

Adjusted for BP Value Obtained During Furosemide

Adjusted for BP Value Obtained During Saline Infusion

24-hour systolic BP changes

R=0.337
P=0.074

R=0.338
P=0.078

R=0.257
P=0.187

R=0.411
P=0.03

R=0.118
P=0.549

24-hour mean BP changes

R=0.383
P=0.041

R=0.386
P=0.042

R=0.375
P=0.049

R=0.453
P=0.015

R=0.262
P=0.178

24-hour diastolic BP changes

R=0.374
P=0.046

R=0.374
P=0.05

R=0.327
P=0.089

R=0.384
P=0.044

R=0.321
P=0.096

Coefficients of agreement (K), sensitivity, specificity, and positive and negative predictive values of the diagnosis of salt-sensitive hypertension by different cut-off values of 24-hour mean blood pressure (BP) change during sodium load and depletion compared with 24-hour mean BP changes during low- and high-salt diets.

	K	Sens (%)	Spec (%)	PPV (%)	NPP (%)
For 3.0mm decrease in 24-hour mean blood pressure (MBP) induced by low salt intake and 5.0mm Hg decrease in 24-hour MBP with furosemide 10mm Hg decrease in 24-hour MBP with furosemide	0.386** 0.26	77 31	63 94	63 80	77 63
For 4.0mm decrease in 24-hour MBP induced by low salt intake and 5.0mm Hg decrease in 24-hour MBP with furosemide 10mm Hg decrease in 24-hour MBP with furosemide	0.403** 0.449*	89 44	60 95	50 80	92 79
For 5.0mm decrease in 24-hour MBP induced by low salt intake and 5.0mm Hg decrease in 24-hour MBP with furosemide 10mm Hg decrease in 24-hour MBP with furosemide	0.341** 0.512*	88 50	57 95	44 80	92 83
Statistical significance of the variation in 24-hour MBP induced by low salt intake 5.0mm Hg decrease in 24-hour MBP with furosemide 10mm Hg decrease in 24-hour MBP with furosemide	0.187 0.300**	67 33	53 94	50 80	69 67
P<0.01; *P<0.05.

Mean BP Characteristics

Office systolic BP (mm Hg): 160.7±15.4
Office diastolic BP (mm Hg): 96.6±8.0
Left ventricular mass index (g per m²): 145±24.3.

Author Conclusion:

The method of using rapid salt load and then depletion is not useful in measuring salt sensitivity in essential hypertension, as it may result in misclassification. The diagnosis of salt-sensitive hypertension should be based on blood pressure response to dietary salt changes.

Funding Source:

University/Hospital:

Department of Internal Medicine, Hospital Clinic, Barcelona, Spain

Reviewer Comments:

Dietary intake of sodium provides a better picture of usual habits and is easier to assess in a clinical setting. Salt-sensitive hypertension is best diagnosed based on blood pressure response to salt intake.

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?	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
	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?	N/A
	4.1.	Were follow-up methods described and the same for all groups?	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
	4.2.	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?	Yes
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
	5.1.	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
	5.2.	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
	5.3.	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?	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
	6.2.	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
	6.3.	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)?	N/A
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	N/A
	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