EAL

Disorders of Lipid Metabolism and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the effectiveness and reliability of a rapid, easy-to-standardize protocol for the assessment of salt sensitivity against blood pressure response to dietary salt restriction.

Inclusion Criteria:

Mild or moderate essential hypertension patients consecutively referred to the outpatient clinic
DBP over 95mm Hg on three consecutive visits
Age between 20-65 years
BMI below 30kg/m².

Exclusion Criteria:

Patients with diabetes mellitus, CHF, ischemic cardiac or cerebrovascular disease.
Patients with plasma creatinine greater than 140umol per L
Premenopausal status.

Description of Study Protocol:

Recruitment: Mild or moderate essential hypertensive patients consecutively referred to the outpatient clinic.

Design: Cohort.

Intervention: None.

Rapid Protocol

No treatment for at least two weeks prior to entering study
Day 1 to Day 3: A standard 200mmol per day sodium diet and then hospitalized for four days to be screened for sodium chloride sensitivity
Day 4: Kept on 200 mmol per day sodium diet
Day 5: Sodium chloride load given between 8 a.m. and 12 noon as IV infusion of two liters of normal saline at constant rate of 500ml per hour. At end of infusion BP measured every three minutes for 30 minutes.
Day 6: Acute sodium chloride depletion induced by switching to 10mmol per day sodium diet and administering three oral doses of 37.5mg frusemide at 8 a.m., 2 p.m. and 8 p.m. Patients also drank 25ml per kg body weight of water.
Day 7: BP measured at 8 a.m. every three minutes for 30 minutes and patient discharged.

Dietary Study

18 patients found as salt sensitive or salt resistant from above were placed on two consecutive diets of one week with either normal (200mmol per day) or low (50mmol per day) dietary sodium chloride and constant potassium intake of 50mmol to 70mmol per day.

Statistical Analysis

Statistical Package for the Social Sciences
Kolmogorow-Smirnov test
One-way ANOVA
Paired, two-tailed Student's T-test

Data Collection Summary:

Timing of Measurements

Rapid Protocol: BP measured on Day 5 and Day 7 every three minutes for 30 minutes. Body weight every morning from Day 4 to Day 7.
Dietary Study: BP and body weight measured on last day of each dietary period
24-hour urine volume and sodium excretion at baseline, on days of sodium chloride load and depletion procedure and during two dietary periods
Plasma renin activity (PRA) measured in a subgroup of patients (N=53) during rapid protocol at end of sodium chloride load and contraction maneuver. Measured in all patients in dietary study at end of low and high sodium diets.

Dependent Variables

BP measured in supine position using automated sphygmomanometer (Sentron Bard Biomedical, Lombard, IL) and mean of last five measurements used for analysis
Urinary sodium assayed by ion selective electrode using a Beckman EA-2 Electrolyte Analyzer
PRA measured by radioimmunoassay using the Renin Kit (Technogenetics, Milan, Italy)
Rapid Protocol: Sodium chloride sensitivity was mean of BP at end of sodium chloride load minus mean BP after sodium chloride depletion
Dietary Study: Sodium chloride sensitivity was mean BP at end of high sodium chloride diet minus mean BP after sodium chloride restriction.

Independent Variables: Sodium chloride content of diet.

Control Variables: Timing of measurements.

Description of Actual Data Sample:

Initial Number

Rapid Protocol: 108
Dietary Study: 18.

Attrition (final N): Same as initial.

Age

20 years to 65 years
Rapid Protocol: Patients with high sodium chloride sensitivity were older (50±1 year) than those in low sodium chloride sensitivity (45±1 year, P<0.01)
Dietary Study: Patients with high sodium chloride sensitivity were older (53±2 years) than those in low sodium chloride sensitivity (46±2 years, P<0.01).

Ethnicity: Assume Italian as study was in Italy.

Other relevant demographics

Anthropometrics (e.g., were groups same or different on important measures)
- Rapid Protocol: At baseline, BMIs were 27.9±0.4 kg/m²for low sodium chloride sensitivity, 27.4±0.3 kg/m²for moderate sodium chloride sensitivity and 27.5±0.2 kg/m²for high sodium chloride sensitivity
- Dietary Study: At baseline, weight was 79.0±3kg for low sodium chloride sensitivity and 75.0±3kg for high sodium chloride sensitivity and BMI was 28.3+0.5 kg/m²for low sodium chloride sensitivity and 27.7±0.7 kg/m²for high sodium chloride sensitivity.
Location
- Naples, Italy.

Summary of Results:

Rapid Protocol

Patients with high sodium chloride sensitivity had higher SBP (165±2mm Hg) than those in low sodium chloride sensitivity (153±2mm Hg, P<0.01)
During salt-sensitivity test, low, moderate and high sodium chloride sensitivity groups had similar 24-hour sodium excretion
Inverse relationship between salt sensitivity and PRA at all times
- After IV sodium chloride load
  - LS group (N=23): PRA 0.82±0.16ng per mL per hour
  - MS group (N= 13): 0.66±0.09ng per mL per hour
  - HS group (N=16): 0.43±0.07ng per mL per hour
- After sodium chloride depletion
  - LS group: 2.32±0.38ng per mL per hour
  - MS group: 1.54±0.39ng per mL per hour
  - HS group: 0.86±0.20ng per mL per hour (P<0.02 LS vs. HS).

Dietary Study

Patients with high sodium chloride sensitivity had higher SBP (168±4mm Hg) than those in low sodium chloride sensitivity (145±3mm Hg, P<0.01)
PRA was higher in LS compared with HS group on both high-sodium diet (1.92±0.24 vs. 1.11±0.34ng per mL per hour) and low-sodium diet (2.42±0.20 vs. 1.50±0.46ng per mL per hour, P<0.05 between diets and LS vs. HS)
No differences in basal 24-hour urinary sodium excretion between the two groups
- LS: 238±22
- HS: 221±23
HS patients had drop in BP after low-sodium diet (absolute value=-9±3mm Hg, percentage fall of BP=-7±2 percent, P<0.05 to high-sodium diet)
HS patients had drop during low-sodium diet for SBP (172±5 vs. 160±6mm Hg, P<0.01) and DBP (108±3 vs. 98±3mm Hg)
LS patients had no drop in BP after low-sodium diet
Direct correlation between individual changes in 24-hour sodium excretion, upon shifting from high- to low-sodium diet, and corresponding changes in mean BP for the HS subgroup (r=0.69, P<0.01); but no correlation in LS group (r=-0.06).

Author Conclusion:

In conclusion, the modified Grim protocol tested in this study was able to correctly predict a significant blood pressure response to dietary salt restriction in the majority of cases.

Funding Source:

University/Hospital:

University of Naples Medical School, Naples, Italy

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?	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?	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?	Yes
	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?	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%.)	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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	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?	???
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	???
	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.)	???
	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.)	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	???
	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?	???
	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?	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?	N/A
	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.	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?	Yes
	8.7.	If negative findings, was a power calculation reported to address type 2 error?	Yes
	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?	???
	9.2.	Are biases and study limitations identified and discussed?	???
	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