EAL

HTN: Caffeine (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine caffeine's ability to increase blood pressure (BP) and cortisol during periods of low vs. high occupational demand (hypothesis: Caffeine would increase ambulatory BP and cortisol on both low- and high-stress days and the combined effects would result in the highest BP and cortisol levels in those at risk for hypertension).

Inclusion Criteria:

First- and second-year medical students
Healthy
Regular consumer of caffeine
No major illness
No current or prior treatment for hypertension
Not taking prescription medication
Weighed within 20% of Metropolitan Life Insurance Company norms
Smoked fewer than 10 cigarettes per day
Consumed fewer than 15 drinks of alcohol per week
Had normal night-time sleep schedule
Passed a symptom-limited exercise treadmill test.

Exclusion Criteria:

None specified.

Description of Study Protocol:

Recruitment: Not described
Design: Randomized crossover trial
Blinding used: Double-blind
Intervention: 3.3mg per kg caffeine
Statistical analysis: Not described.

Data Collection Summary:

Timing of Measurements

Data were collected on two lecture days and two exam days
The ABPM was programmed to take readings every 10 minutes from 6:45 a.m. to 12:30 p.m.
On lecture days, saliva samples were collected at 7:10 a.m., then placebo or 3.3mg per kg of caffeine was administered in grapefruit juice at 7:15 a.m. and additional saliva samples collected at 7:55 a.m., 12:00 p.m. and 12:30 p.m.
Self-reports of mood states were obtained at the time of saliva collections
On exam days, the procedure was modified such that the placebo or caffeine in grapefruit juice was administered at 8:15 a.m. (45 minutes prior to the exam to allow peak blood levels to coincide with the exam)
Saliva samples were collected at 8:55 a.m., after finishing the exam (two to three hours later) and at 12:30 p.m.

Dependent Variables

Systolic blood pressure, measured by an Accutracker 1.02 APBM (Suntech Medical Instruments, Raleigh, NC)
Diastolic blood pressure, measured by an Accutracker 1.02 APBM (Suntech Medical Instruments, Raleigh, NC)
Salivary cortisol, measured by radioimmunoassay kit (Coat-A-Count, Diagnostic Products, Los Angeles, CA)
Mood report, measured by the Multiple Affect Adjective Checklist and Subjective States Questionnaire to assess degree of anxiety, depression, hostility, activation and distress.

Independent Variables

3.3 mg/kg caffeine.

Control Variables

Not specified.

Description of Actual Data Sample:

Initial N

31 males
11 of them were designated high-risk for essential hypertension (between 125mm and 140mm Hg systolic or 78mm to 90mm Hg diastolic in two screenings and a positive parental history of hypertension); 20 were designated as low-risk (all blood pressures less than 125/78mm Hg and a negative history of hypertension in both parents).

Attrition (final N)

Not specified; assume final N=31.

Age

Only mean age reported: 24 years.

Ethnicity

All subjects were white males.

Other Relevant Demographics

None specified.

Anthropometrics

Not applicable; crossover design.

Location

Oklahoma City, OK.

Summary of Results:

Caffeine consumption had no effect on feelings of distress
Greater subjective activation reported on caffeine days than on placebo days
Greater subjective activation reported after caffeine ingestion on the exam day compared to after caffeine ingestion on lecture day
High-risk subjects had higher systolic blood pressure (SBP) and diastolic blood pressure (DBP) across days (P<0.001), compared to low-risk subjects (134/80 and 123-71, respectively)
Stress of exams caused significant increases in SBP/DBP (low-risk, +4/1mm Hg; high-risk, +7/3mm Hg) and in heart rate (P<0.02)
BPs on caffeine days were significantly elevated relative to placebo days (low-risk, +5/4mmHg; high-risk, +3/3mm Hg; P<0.05)
Pressor effect of caffeine was similar on low- and high-stress days (lecture vs. exam days)
Additive BP effects of stress and caffeine resulted in the highest sustained BP occurring in the high-risk men on stress days after caffeine consumption.

Other Findings

No difference in cortisol concentration between high-risk and low-risk individuals
Cortisol levels were elevated by exam stress and presence of caffeine (P<0.05)
Effects of caffeine on cortisol were most pronounced 40 minutes post-consumption
Caffeine and stress combined increased cortisol by 7.4nmol per L.

Author Conclusion:

A dietary dose of caffeine significantly increases blood pressure in men at low and high risk for hypertension on days of low and high work stress
The combination of caffeine and stress in the high-risk men resulted in a significant number having sustained blood pressure in the hypertensive range.

Funding Source:

Government:

Dept. of Veterans Affairs, NHLBI

Reviewer Comments:

There was no explanation of statistical analyses
The number of subjects that smoked up to nine cigarettes per day (the allowable limit in the inclusion criteria) is unknown and whether they were equally distributed between high-risk and low-risk subjects
Cigarette smoking induces the activity of CYP1A2, the primary enzyme involved in caffeine metabolism
Of similar concern, subjects could also drink up to 15 drinks per week and still be included in the study
Alcohol consumption can also induce the activity of many biotransformation enzymes
It is unknown if low-risk and high-risk subjects had the same habitual alcohol consumption. Although subjects were asked to refrain from alcohol and caffeine for 12 hours and smoking for four hours prior to study days, it is quite possible that is not a long enough time period for biotransformation enzymes to return to baseline levels
Hence, there could be some issues with comparisons if alcohol, caffeine and smoking use and habits varied between low-risk and high-risk individuals
Additionally, administration of caffeine via grapefruit juice may enhance or exaggerate the effect of caffeine as some evidence exists that grapefruit juice may inhibit caffeine metabolism.

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)	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?	???
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)	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
	3.4.	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?		???
	4.1.	Were follow-up methods described and the same for all groups?	???
	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%.)	???
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	???
	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?		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
	5.3.	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?	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?	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?		???
	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?	N/A
	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?	???
	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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	No
	8.2.	Were correct statistical tests used and assumptions of test not violated?	???
	8.3.	Were statistics reported with levels of significance and/or confidence intervals?	???
	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)?	???
	8.5.	Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)?	???
	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?		No
	9.1.	Is there a discussion of findings?	No
	9.2.	Are biases and study limitations identified and discussed?	No
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