HTN: Protein (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
  • The purpose of the research was to examine the association between BP and animal protein intake [assessed by measuring urinary excretion of 3-methylhistidine (3MH)] in 1,991 individuals from 11 Chinese co-operative study centers
  • The data were collected from 1985 to 1999 with a standard study design and the same research methods. 

 

 

Inclusion Criteria:
  • Age between 48 and 56 years
  • Proximity to one of 11 centers in China that were part of the WHO-CARDIAC study.
Exclusion Criteria:
None noted.
Description of Study Protocol:

Recruitment

Methods were published elsewhere, but men and women were selected randomly from the general population and invited to attend a free physical examination.

Design

  • Multi-center, cross-sectional study with 100 men and 100 women between the ages of 48 and 56 selected at each of 11 centers throughout China
  • Each participant received a physical examination, was trained on 24-hour urine collection methods and returned the urine collection to the center
  • A 15ml blood sample was obtained and BP was taken in sitting position, according to standard criteria
  • All laboratory specimens were analyzed in a single lab
  • Hypertension was defined as SBP≥140mm Hg or DBP≥90mm Hg or those on anti-hypertensive medications.

Statistical Analysis

  • Pearson correlation analysis for estimate of BP in relation to 3MH, 3MH:cre and other factors with adjustments for age and sex
  • Participants who failed to complete the 24-hour urine collection and who were on anti-hypertensive medications were excluded from this part of the analysis
  • Further analysis included division of participants into normotensive and hypertensive groups
  • Multiple linear regression analysis (with adjustement for age and sex) was used for within center analysis of individuals BP, 3MH and 3MH:cre 
  • Pooled regression coefficients were weighted according to the variance at each center and relative risks of less protein intake associated with hypertension were estimated with logistic regression.
Data Collection Summary:

Timing of Measurements

  • Measures were made once
  • There is no mention of whether or not participants were fasting when blood was drawn or of the time of day.

Dependent Variables

Hypertension (yes, no according to criteria above).

Independent Variables

Urinary 3MH, 3MH:cre ratio, Sodium, Potassium, Calcium, Magnesium and BMI. 

Control Variables

Anti-hypertensive medications.
Description of Actual Data Sample:
  • Initial N: 2,200
  • Attrition (final N): 1,991 (996 men and 1,025 women)
  • Age: 51.8 (±SD of 1.7) for men and 51.7 (±SD of 1.5) for women
  • Ethnicity: Chinese from centers widely dispersed across the country
  • Other relevant demographics: None noted
  • Location: 11 different centers across China.
Summary of Results:
  • Men and women were similar in age (51.8±1.7 years for men and 51.7±1.5 years for women), systolic blood pressure (123.1±20.3 for men and 122.1±22.3 for women) diastolic blood pressure (74.4±13.4 for men and 72.4±13.9 for women), body mass index (22.7±4.1 for men and 22.8±4.0 for women), anti-hypertensive therapy (8.1% of men and 10.5% of women) and percentage of completion of 24-hour urine collection (64.9% for men and 62.1% for women)
  • Results from men and women were combined after adjustment for age, sex and other factors.  

Relative Risk of Subjects with Less 3-Methylhistidine (3MH) Excretion Associated with Hypertensiona,b

  Model One Model Two Model Three
3MH (umol/day) OR (95%CI) P OR (95%CI) P OR (95%CI) P
≥253 1 1 1 1 1 1 1 1 1
<253 1.33 (0.91-1.95) 0.14  1.35 (0.93-2.04) 0.11 1.68 (1.11-2.53) 0.01
3MH:cre ratioc                    
224  1 1 1 1 1 1 1 1 1
<224   2.72 (1.78-4.12) ≤0.01  2.81 (1.84-4.30) <0.01  2.63 (1.69-4.09) <0.01 

a Relative risks were estimated by odds ratios (OR) using logistic regression analysis. In the analysis, hypertension (0 and 1 for none and yes) was the dependent variable, and 3MH and 3MH:cre were independent variables.
b Model One: Adjusted for age (years), sex (0 and 1 for men and women). Model Two: Adjusted for age (years), sex (0 and 1 for men and women) and ratio of sodium to potassium (Na/K). Model Three: Adjusted for age (years), sex (0 and 1 for men and women), Na/K, body mass index (kg/m2), calcium (mg/day) and magnesium (mg/day).
c Ratio of 3MH to creatinine (mg/day).

Other Findings

Descriptive statistics for the sub-sample who completed the 24-hour urine collection in the 11 study centers:

  Men; Mean (SD) Women; Mean (SD)

Total sample (N)

572 563

Age (years)

51.7 (1.6) 51.6 (1.6)
SBP (mm Hg) 121.9 (17.9) 121.7 (21.2)
DBP (mm Hg) 73.1 (12.4) 71.6 (13.3)
BMI (kg/m2)      22.3 (3.6) 22.3 (3.6)
Creatinine (mg/day)      1.3 (0.3) 0.8 (0.2)
3MH (umol/day)      222.5 (95.8) 171.8 (79.4)
3MH:creg 177.2 (64.3) 204.0 (84.5)
Na (mmoL/day) 205.1 (84.8) 175.4 (83.9)
K (mmol/day)   38.0 (21.8) 32.0 (19.8)

Ca (mg/day)

194.0 (123.5) 151.1 (92.5)
Mg (mg/day) 121.8 (72.0) 90.8 (49.4)

Sub-sample included those with complete 24-hour urine collections and without anti-hypertensive drug therapy.

Author Conclusion:
The study provides strong confirmatory evidence that dietary animal protein intake is associated inversely with BP in the Chinese population. 
Funding Source:
Government: World Health Organization
Reviewer Comments:
  • This study shows an inverse relationship between animal protein intake and blood pressure levels. However, the study is weakened by the lack of defined inclusion and exclusion criteria and failure to measure or estimate protein intake of participants
  • In addition, fewer than 65% of the study participants completed the urine collection portion of the protocol.  
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) N/A
  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
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) N/A
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  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? No
  2.2. Were criteria applied equally to all study groups? ???
  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? ???
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
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) 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? 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")? 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
  4.2. 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? 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? ???
5. Was blinding used to prevent introduction of bias? ???
  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
  5.3. 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
  5.5. 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? ???
  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
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? No
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? 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
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
  7.2. 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? N/A
  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
  7.6. Were other factors accounted for (measured) that could affect outcomes? 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
  8.1. 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
  8.3. 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
  8.5. 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? ???
  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
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes