EAL

Disorders of Lipid Metabolism and Micronutrients

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the heterogeneity of blood pressure (BP) responses to changes in NaCl intake in a large number of non-obese normotensive subjects with regard to age, sex, body weight, family history of hypertension and hormonal changes.

Inclusion Criteria:

White non-obese adults with a body mass index (BMI) less than 28kg/m²
No medications
Did not exhibit a current or previous history of hypertension, cardiac or renal diseases, diabetes or hyperlipidemia
Ambulatory sitting BP less than 140/90mm Hg.

Exclusion Criteria:

White adults with a BMI greater than 28kg/m²
Taking medications
Exhibiting a current or previous history of hypertension, cardiac or renal diseases, diabetes or hyperlipidemia
Ambulatory sitting BP greater than 140/90mm Hg
Women taking oral contraceptives or oral or transdermal estrogen.

Description of Study Protocol:

Recruitment

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Design

Diagnostic study, randomized crossover design.

Blinding Used

Yes.

Intervention

Isocaloric low-salt diet (20mmol per day Na) given to all subjects for two weeks according to a seven-day rotating meal plan. During this period, low and high salt diets were given for one week each. During low-salt diet (20mmol per day Na), subjects received 32 placebo capsules per day. During high-salt diet (300mmol per day Na), subjects received 32 capsules per day, each containing 0.5g NaCl.

Statistical Analysis

Analysis of variance
Mann-Whitney U (Wilcoxon) test
Wilcoxon's matched pairs signed rank test
Pearson's correlation coefficients
Multiple regression analysis.

Data Collection Summary:

Timing of Measurements

24-hour urinary electrolyte excretion was measured on days five, six and seven of each dietary period and on the day before the diets were started
On day before diets started, as well as last day of dietary period, subjects were studied at 7:30 A.M. after an overnight fast for BP and heart rate
Blood drawn after last BP reading.

Dependent Variables

BP and heart rate measured with subjects in sitting position for one hour at five-minute intervals using automated BP monitors with integrated printers (Boso Oscillomat, Bosch & Sohn GmbH, Jungingen, Germany)
Mean arterial pressure (MAP) calculated by adding one-third of the pulse pressure to DBP
Serum concentrations of Na, K, creatinine and uric acid measured by standard laboratory methods
Plasma renin activity (PRA) and plasma concentrations of aldosterone and atrial norepinephrine (ANP) were determined by radioimmunoassay
Plasma concentrations of norepinephrine were determined by radioenzymatic method.

Independent Variables

Dietary Na intake measured by 24-hour urinary electrolyte excretion.

Description of Actual Data Sample:

Final N

163 subjects (98 males, 65 females).

30 (14 males, 16 females) classified as salt sensitive (SS) defined as MAP rose by at least 5.0mm Hg during high-salt intake compared to low-salt intake
108 (65 males, 43 females) classified as salt resistant (SR) defined as MAP changed by less than 5.0mm Hg during high-salt intake compared to low-salt intake
25 (19 males, six females) classified as counterregulators (CR) defined as MAP falling by at least 5.0mm Hg during high-salt intake.

Age

38±1.2 years of age.

Ethnicity

Assume German as study took place in Germany.

Anthropometrics

At baseline, SS older (46.4±3.2 years) than SR (36.3±1.4, P<0.05) and CR (35.4±2.9, P<0.05)
At baseline, SS had lower Na excretion (154.5±6.7mmol per 24 hours) than CR (182.7±11.1, P<0.05)
At baseline, SS had lower body weight (67.1±2.0kg) than SR (71.7±1.1, P<0.05)
At baseline, no differences in MAP, heart rate, urinary K and urinary Na over K ratio among three groups.

Location

Bonn, Germany.

Summary of Results:

All Groups

MAP for all groups did not change between low-salt (85.4±0.5mm Hg) and high-salt diet (85.5±0.6mm Hg)
During low-salt intake, heart rate rose compared with high-salt diet in SR (67.25±1.0bpm vs. 63.5±0.9bpm, P<0.001) and CR groups (65.0±2.2bpm vs. 60.6±2.2bpm, P<0.01)
During high-salt intake, body weight increased compared with low-salt diet in SS (67.0±2.0kg vs. 65.9±2.09kg, P<0.001), SR (71.5±1.0kg vs. 70.4±0.9kg, P<0.001) and CR groups (71.8±2.4kg vs. 70.4±2.4kg, P<0.001)
During high-salt intake, serum Na increased compared with low-salt diet in SS (138.8±0.3mmol vs. 137.5±2.09mmol per L, P<0.001), SR (139.2±0.2mmol vs. 137.6±0.2mmol per L, P<0.001) and CR groups (138.6±0.2mmol vs. 137.6±0.3mmol per L, P<0.001)
During high-salt intake, urinary volume increased compared with low-salt diet in SS (1,989±123ml vs. 1,692±110ml per 24 hours, P<0.001), SR (2,006±55ml vs. 1,618±51ml per 24 hours, P<0.001) and CR groups (1,806±126ml vs. 1,426±72ml per 24 hours, P<0.001)
During high-salt intake, Na excretion increased compared with low-salt diet in SS (285.6±4.4mmol vs. 15.9±1.3mmol per 24 hours, P<0.001), SR (291.6±3.2mmol vs. 17.1±0.9mmol per 24 hours, P<0.001) and CR groups (294.6±5.2mmol vs. 15.4±1.6mmol per 24 hours, P<0.001)
During high-salt intake,creatinine clearance increased compared with low-salt diet in SS (104.6±4.2ml vs. 95.2±3.7ml per minutes, P<0.001), SR (110.7±2.4ml vs. 100.4±2.3ml per minute, P<0.001) and CR groups (111.7±4.6ml vs. 100.4±3.8ml per minute, P<0.001).

Family History of Hypertension

Individuals with a family history of hypertension (N=54) were younger than those with a negative history (N=97) (33.0±1.6 vs. 40.7±1.7 years, P<0.050)
MAP at baseline higher in those with a positive history vs. a negative history (89.1±1.1 vs. 85.9±0.8mm Hg, P<0.01).

Age

Baseline MAP was 85.8±0.8mm Hg in subjects older than 30 years (N=78), 87.0±1.1mm Hg in subjects between 30 to 50 years (N=42), and 89.6±1.3mm Hg in subjects younger than 50 years (N=43) (for younger than 30 vs. older than 50 years, P<0.01)
In subjects younger 50 years, MAP rose during high-salt compared with low-salt diet (89.6±1.2 vs. 87.2±1.1mm Hg, P<0.01)
Baseline MAP and change in MAP between low- and high-salt diets were correlated to age (R=0.225, P<0.01 and R=0.236, P<0.01, respectively)
At baseline, body weight and BMI were positively related to age (R=0.372, P<0.001 and R=0.375, P<0.001, respectively)
Change in MAP between low- and high-salt diets was inversely related to baseline body weight (R=-0.202, P<0.01)
At baseline and during high-salt intake, PRA in those younger than 50 years was lower (1.7±0.2ng and 0.9±0.2ng per ml per three hours) than in subjects older than 30 years (2.3±0.2ng vs. 1.4±0.1ng per ml per three hours, P<0.05)
Plasma concentrations of norepinephrine at baseline and during low- and high-salt intake were higher in those older than 50 years (437±39pg, 602±57pg and 436±36pg per ml) than younger than 30 and older than 50 years (253±29pg, 375±38pg and 253±23pg per ml) and in those subjects older than 30 years (253±16pg, 346±31pg and 253±19pg per ml, P<0.001)
Plasma concentrations of ANP at baseline and during low- and high-salt intake were higher in those younger than 50 years (64.9±6.5pg, 48.1±5.8pg and 81.8±7.1pg per ml) than in those between 30 and 50 years (43.1±3.3pg, 28.9±2.8pg and 49.3±3.4pg per ml) and in those subjects more than 30 years (36.3±2.0pg, 21.3±1.3pg and 37.1±2.2pg per ml, P<0.001).

Author Conclusion:

In conclusion, in the present study of nonobese normotensive subjects, salt sensitivity was found in 18.4% and an increase in BP during Na restriction compared with salt loading in 15.3%. Age, body weight and family history of hypertension contributed significantly to the change in BP after different salt intakes. Salt sensitivity was more likely to occur in older subjects and in individuals with a lower body weight and a positive family history of hypertension. In contrast, an increase in BP with salt restriction could be observed more often in younger subjects and in those with a higher body weight and a negative family history of hypertension. Women tended to be salt sensitive more often than men. At least on the short-term basis of our study, an increase in BP after salt restriction in normotensive subjects was almost as likely as a decrease. This increase in BP in counterregulating subjects may be partially due to an overstimulation of the renin-angiotensin-aldosterone system during salt restriction. The exaggerated response of ANP to a high-salt intake in salt-sensitive subjects may point to an impaired ability of the kidney to excrete a salt load in these subjects.

Funding Source:

University/Hospital:

Medizinische Universitats Poliklinik, Bonn, Germany

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.)	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.)	Yes
	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?	Yes
	4.5.	If diagnostic test, was decision to perform reference test not dependent on results of test under study?	Yes
	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?	Yes
	5.3.	In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded?	Yes
	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?	Yes
	5.5.	In diagnostic study, were test results blinded to patient history and other test results?	Yes
	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)?	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?	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