EAL

HTN: Alcohol (2015)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effects of repeated intake of alcohol and its withdrawal on blood pressure and sodium and water metabolism in Japanese males with essential hypertension.

Inclusion Criteria:

Japanese
Male
Mild to moderate essential hypertension
Drinking habits
Informed consent.

Exclusion Criteria:

No serious cardiovascular, hepatic or renal disorders
No drinking habit
No mild or moderate hypertension diagnosis.

Description of Study Protocol:

Design

Time series.

Intervention

Hospitalized in the ward of National Cardiovascular Center, where they consumed a regular hospital diet (120mmol sodium, 1,600kcal per day)
Subjects hospitalized for several days prior to start of protocol to minimize effect of hospitalization on blood pressure
Study divided into three consecutive phases:
- Control phase: Three-day period during which non-alcoholic drinks having the same number of calories as the alcoholic drinks were added to the dinners
- Alcohol phase: Seven-day period during which one ml per kg of ethanol was administered with dinner in the form of vodka, lime juice and water
- Recovery phase: Three-day period during which the non-alcoholic drinks were added to dinner as were in the control phase.

Statistical Analysis

Values expressed as the mean SEM
Comparisons made by repeated measures analysis of variance followed by the contrast method.

Data Collection Summary:

Timing of Measurements

Heart rate and supine blood pressure was measured five times daily at 6:00 a.m., 10:00 a.m., 2:00 p.m., 6:00 p.m. and 9 p.m. each day throughout the study
A 24-hour urine collection and measurement of fasting body weight were completed daily
Venous blood samples were performed before dinner, 60 minutes to 90 minutes after dinner and before breakfast on the morning following the last day of the control period, as well as on Day One and Day Seven of the alcohol period.

Dependent Variables

Supine blood pressure measured by trained nurses using mercury sphygmomanometers
Heart rate measured manually immediately before blood pressure measurements
Urine sodium excretion
Urine volume
Serum concentrations of sodium and potassium.

Independent Variables

Alcohol intake.

Control Variables

Body weight.

Description of Actual Data Sample:

Initial N: N=14 males
Attrition (final N): N=14 males
Age: Aged 37 years to 68 years (54±2 years, mean SEM)
Ethnicity: Japanese
Other relevant demographics: Conducted in a ward of the National Cardiovascular Center
Anthropometrics: Usual alcohol intake ranged from 30ml to 105ml per day (67±5ml per day)
Location: Japan.

Summary of Results:

Key Findings

Daily average systolic BP decreased significantly (P<0.05) during the early phase of the alcohol period compared with the control period with reduction blunted during the late phase of alcohol period
Daily average diastolic BP showed a similar tendency although its change was not significant
Changes in blood pressure returned to control level during the recovery period
Evening blood pressure during the alcohol period (systolic BP 145.4±4.9mm Hg) was consistently lower than that during the control period (systolic BP 130.7±3.2mm Hg), P<0.05
Morning and afternoon blood pressure did not change during the alcohol period, although they tended to increase during the late phase (systolic BP at 2:00 p.m. was 146.1+6.2mm Hg on last day of control period and 151.8+4.9mm Hg on Day Seven of alcohol period)
Average heart rate increased during the alcohol period and returned to baseline during the recovery period (P<0.05)
Heart rate increased significantly both in the morning and evening during the alcohol period
Changes in heart rate returned to baseline in recovery phase
Biphasic changes in urinary sodium excretion observed during the alcohol period as compared to the control (P<0.05)
No significant changes in serum sodium concentrations
Serum potassium decreased after meals both during the control and alcohol periods, with the level of serum potassium after ingestion of alcohol significantly lower than that during the control period (P<0.05)
Urine volume did not change during the early phase of the alcohol period but increased significantly on days four through six (P<0.05)
No significant changes in urinary excretion of creatinine or potassium.

	Control Phase	Alcohol Phase	Statistical Significance of Group Difference
Systolic daily average blood pressure (mm Hg)	Day One: 147.2±4.7mm Hg	Day One: 140.2±3.2mm Hg Day Seven: 144.7±3.6mm Hg	P<0.05
Average heart rate (beats per minute)	64.0±1.0	Day One: 68.7±1.4 Day Seven: 66.5±1.1	P<0.05
Urine sodium excretion (mmol per day)	112±8	Day Two: 97±6 Day Four: 130±8	P<0.05

Other Findings

Body weight decreased slightly but significantly during the late phase of the alcohol period and the recovery period (P<0.05).

Author Conclusion:

In the study, repeated intake of alcohol for seven days caused significant changes in blood pressure and sodium balance in Japanese males with hypertension. The findings show that average blood pressure decreases during the early phase but returns to baseline during the late phase during repeated alcohol intake. The changes in blood pressure were associated with early sodium retention followed by natriuresis during the alcohol period. The findings demonstrate that repeated alcohol intake causes biphasic changes in blood pressure and sodium metabolism and suggests these changes may interact with each other.

Funding Source:

Government:

Ministry of Health and Welfare of Japan

Industry:

Takeda Medical Research Foundation

Pharmaceutical/Dietary Supplement Company:

Reviewer Comments:

Standard 1,600kcal diet used for all subjects, which may have led to significant weight loss that occurred over the study period
Water intake was not restricted or measured.

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
	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)	Yes

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?		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
	2.3.	Were health, demographics, and other characteristics of subjects described?	Yes
	2.4.	Were the subjects/patients a representative sample of the relevant population?	Yes
3.	Were study groups comparable?		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?	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?	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")?	N/A
4.	Was method of handling withdrawals described?		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
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	Yes
	4.4.	Were reasons for withdrawals similar across groups?	N/A
	4.5.	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?		No
	5.1.	In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate?	No
	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.)	No
	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
	5.5.	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
	6.1.	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
	6.3.	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
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?		No
	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?	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
	7.6.	Were other factors accounted for (measured) that could affect outcomes?	No
	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)?	No
	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
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