EAL

Disorders of Lipid Metabolism and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

Ambulatory blood pressure monitoring (ABPM) was used to assess salt sensitivity and salt resistance and to determine the effects of a high-salt diet on the blood pressure circadian rhythm.

Inclusion Criteria:

Patients with essential hypertension based on having no known cause for high blood pressure after a thorough examination
Diastolic blood pressure above 90mm Hg at least three times, measured in the office.

Exclusion Criteria:

Patients with essential hypertension who also had renal impairment (serum creatinine over 1.5mg per dL), papilloedema, cardiac failure or evidence of coronary heart disease.

Description of Study Protocol:

Recruitment: From the Hypertension Unit of the Department of Internal Medicine, Hospital Clinic, Barcelona, Spain.

Design: Diagnostic study.

Blinding Used: Single-blind to the subjects.

Intervention

All subjects were admitted to the hospital for 14 days. The diet was 20mmol of sodium chloride per day. Potassium was 60mmol, calcium was 20mmol and calories were adjusted to maintain weight.
Placebo tablets were given during the first week (low-salt diet)
A tablet of 240mmol was given during the last seven days (high-salt diet)
24-hour urinary excretion was measured daily to assess scheduled salt intake.

Statistical Analysis

Values are expressed as mean +SD
The nondipper profile was arbitrarily defined by a reduction in blood pressure readings of
less than 10% from awake to asleep. Otherwise, the profile was dipper.
Records from ABPM that were taken during either diet period were individually analyzed using BMDP Statistical Software
The Shapiro-Wilk test was used to test the normal distribution of 24-hour blood pressure values for individuals. The subject had normal distribution in both records, the Student's T-test was used for comparison. The nonparametric Mann-Whitney test was used if there was not normal distribution.
Salt sensitivity was defined as a significant rise in a 24-hour mean blood pressure from low-salt to high-salt
Analysis of variance with repeated measures design was used to compare blood pressure measurements at the end of the low-salt and high-salt periods
Analysis of variance with repeated measures design was also used to compare blood pressure values between salt-sensitve and salt-resistant hypertensive subjects.

Data Collection Summary:

Timing of Measurements

Subjects consumed six weeks of a baseline unrestricted salt diet
Subjects were admitted to the hospital for 14 days and fed a diet of 20mmol sodium chloride per day for the study
Placebo tablets were administered in a single-blind way during the first seven days (low-salt)
Sodium chloride tablets were added during the last seven days (high-salt)
24-hour urine specimens were obtained from each subject daily
Blood pressure was measured manually on the last day of each period after a 10-minute seated rest period, with a total of three measurements taken at three-minute intervals
Also on the last day of each diet period, automated blood pressure measurements were obtained on each subject every 15 minutes for 24 hours.

Dependent Variables

Ambulatory blood pressure
Systolic blood pressure
Diastolic blood pressure
Mean blood pressure.

Independent Variables

20mmol low-salt diet (~0.46 grams)
240mmol high-salt diet (~5.5 grams).

Description of Actual Data Sample:

Initial N: 53

Attrition (final N): 40 (20 males, 20 females)

Salt-sensitive subjects: N=18 (10 males, eight females)
Salt-resistant subjects: N=22 (10 males, 12 females).

Age: 25 to 72 years (mean ±SD 52.1±12.2 years)

Salt-sensitive subjects: 54.2±10.1 years
Salt-resistant subjects: 50.3±13.7 years.

Ethnicity: White.

Anthropometrics

Mean 24-hour diastolic blood pressure over 90mm Hg
24-hour systolic blood pressure 151.4±16.1mm Hg
24-hour diastolic blood pressure 92.6±12.0mm Hg
24-hour mean blood pressure 111.6±12.6mm Hg
Weight 76.6±14.4kg
Body mass index 29.3±4.9kg per m².

Salt-sensitive subjects

24-hour systolic blood pressure 150.4±16.7mm Hg
24-hour diastolic blood pressure 93.0±12.3mm Hg
24-hour mean blood pressure 111.6±12.9mm Hg
Weight 80.3±10.7kg
Body mass index 30.9±4.6kg per m².

Salt-resistant subjects

24-hour systolic blood pressure 152.2±16.0mm Hg
24-hour diastolic blood pressure 92.3±12.0mm Hg
24-hour mean blood pressure 111.7±12.5mm Hg
Weight 73.7±16.5kg
Body mass index 27.9±4.9kg per m².

Location: Hypertension Unit of the Department of Internal Medicine, Hospital Clinic, Barcelona, Spain.

Summary of Results:

Mean Values of 24-hour Systolic, Mean and Diastolic Blood Pressure Measurements

	Salt-sensitive (N=18)		Salt-resistant (N=22)		Total (N=40)
	Low-salt	High-salt	Low-salt	High-salt	Low-salt	High-salt
24-hour systolic BP (mm Hg)	145.1±15.7	154.2±16.1^*	148.1±17.1	147.9±20.2	146.8+16.4	150.8+18.5
24-hour mean BP (mm Hg)	110.0±11.9	116.6±12.6^*	110.9±13.0	110.1±14.6	110.5±12.4	113.0±13.9
24-hour diastolic BP (mm Hg)	91.2±11.0	95.8±12.2^*	90.4±11.9	88.6±12.8	90.8±11.4	91.9±12.9

^*P<0.0001, comparing low-salt and high-salt periods.

Mean Values of Systolic and Diastolic Blood Pressure Load (Percent of Readings above
140/90 during the Day and 120/80 at Night) and Area under the Curves at the End of
Each Diet Period

	Salt-sensitive (N=18)		Salt-resistant (N=22)		Total (N=40)
	Low-salt	High-salt	Low-salt	High-salt	Low-salt	High-salt
Systolic BP load (%)	66.9±25.2	81.0±20.2^*	74.0±23.5	67.6±27.1	70.8+24.2	73.6+24.9
Diastolic BP load (%)	58.7±25.9	72.1±23.5^*	58.4±28.7	49.2±30.4	58.5±27.2	59.5±29.6
Area under SBP curve (mm HG • 24 hours)	3,398±375	3,562±482⁺	3,472±403	3,470±478	3,439±388	3,511±476
Area under DBP curve (mm HG • 24 hours)	2,128±243	2,273±370⁺	2,113±269	2,075±301	2,120±254	2,119±333

^*P<0.001, comparing low-salt and high-salt diets.
⁺P<0.05, comparing the low-salt and high-salt diets.

Mean Values of Awake and Asleep Systolic, Mean and Diastolic Blood Pressures
Nocturnal fall in salt-sensitive and salt-resistant subjects at the end of each diet period (absolute difference between mean day and night blood pressure values). Values are expressed in mm Hg.

	Salt-sensitive (N=18)		Salt-resistant (N=22)		Total (N=40)
	Low-salt	High-salt	Low-salt	High-salt	Low-salt	High-salt
Awake systolic BP	146.9±16.4	156.5±16.7^*	150.7±18.4	149.5±21.2	148.9+17.0	52.7+19.3
Awake mean BP	112.8±12.8	119.7±12.7^*	112.6±14.7	110.4±15.6⁺	112.7±13.8	114.7±14.4
Awake diastolic BP	94.7±12.6	99.6±12.7^*	92.0±13.6	89.5±14.4⁺	93.0±12.7	94.2±13.3
Asleep systolic BP	140.9±16.7	150.1±18.7^*	140.9±17.8	144.1±20.4⁺	140.9±17.4	146.4±19.5
Asleep mean BP	107.1±13.3	113.4±16.0^*	103.2±13.5	105.3±15.1⁺	105.0±12.5	108.5±14.1
Asleep diastolic BP	88.9±12.7	93.5±15.4*	82.5±11.6	83.7±13.7	85.5±11.5	88.7±15.4
SBP nocturnal fall	2.9±7.8	2.5±12.1	10.3±7.7	4.2±7.5^*	7.0±8.5	3.4±9.7
DBP nocturnal fall	4.0±7.1	3.6±9.0	10.7±6.5	6.8±7.4^*	7.7±7.5	5.4±8.3

* P<0.001, comparing low-salt and high-salt diets.
⁺ P<0.05, comparing low-salt and high-salt diets.

Author Conclusion:

The low-salt diet decreased blood pressure during the night in salt-sensitive and salt-resistant subjects. However, decreased blood pressure during the day was noted only in salt-sensitive subjects. Ambulatory blood pressure monitoring (ABPM) is useful for the assessment of salt-sensitivity.

Funding Source:

University/Hospital:

Hypertension Unit of the Department of Internal Medicine, Hospital Clinic, Barcelona, Spain, Fondo de Investigacion Sanitaria

Reviewer Comments:

ABPM can be used a clinical setting and is noninvasive. This method may provide a better overall picture of true blood pressure readings than what may be obtained in an office setting. This study supports this measurement as a reliable tool to detect salt sensitivity.

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")?	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%.)	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?	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?	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	No
	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)?	No
	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)?	No
	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