HTN: Caffeine (2007)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To compare blood pressure and hemodynamic responses to caffeine between men and women.
Inclusion Criteria:
  • Women were pre-menopausal and men were age-matched
  • All participants (men and women) were not obese, were in good health (by physical exam), were normotensive (BPs <135/85mmHG), regularly consumed caffeine (50mg to 700mg per day), smoked fewer than six cigarettes per day, used no medications with cardiovascular or metabolic effects
  • Women were not taking oral contraceptives and were not pregnant (according to pregnancy test).
Exclusion Criteria:
None specified.
Description of Study Protocol:
  • Recruitment: Not specified
  • Design: Randomized, placebo-controlled trial 
  • Blinding used: Double-blind.

Intervention

3.3mg per kg caffeine (equivalent to two or three cups of coffee) or placebo

Protocol timeline:

  • Overnight abstinence from caffeine
  • Consume light breakfast
  • Instrumentation (20 minutes)
  • Adaptation (30 minutes)
  • Baseline (10 minutes)
  • Caffeine given with grapefruit juice or grapefruit juice alone (placebo; five minutes)
  • Drug absorption (45 minutes)
  • Task I (reading or public speaking*; six minutes)
  • recovery (30 minutes)
  • Task II (alternate task; six minutes)
  • Recovery (30 minutes).

*The subject was given a topic and spent three minutes preparing and three minutes delivering a speech to a video camera in front of two experimenters wearing white coats. This is expected to cause anxiety and increased blood pressure, heart rate and stress hormones. Control task was three minutes of studying and three minutes of reading aloud a neutral passage while alone.

Statistical Analysis

  • ANOVA for baseline activity
  • Multivariate ANOVA for gender differences in caffeine response
  • Univariate ANOVA for interactions.
Data Collection Summary:

Timing of Measurements

  • Blood pressure: Every two minutes throughout the study
  • Impedence cardiography (stroke volume and systolic time intervals): Recorded continuously and then averaged for 12 time periods (baseline (10 minutes), caffeine or placebo response (15, 30 and 45 minutes after taking the drug), task I and recovery periods 1 and 2 (15 minutes each) and task II and recovery periods 1 and 2 (15 minutes each).

Dependent Variables

  • Blood pressure (systolic and diastolic), measured with a Dinamap monitor
  • Mean arterial pressure
  • Pulse pressure (systolic, diastolic)
  • Heart rate
  • Stroke volume, measured with model 304B impedence cardiograph by Minnesota Impedance cardiograph, Minneapolis, MN)
  • Cardiac output (stroke volume x heart rate)
  • Total peripheral resistance (mean arterial pressure x 80, cardiac output)
  • Vascular compliance index (stroke volume, pulse pressure).

Independent Variables

3.3mg per kg caffeine or placebo.
Description of Actual Data Sample:
  • Initial N: 42 women, 35 men
  • Attrition (final N): Not specified
  • Age: Average age (SEM) of women, 29 (0.98); average age (SEM) of men, 27 (0.79)
  • Ethnicity: Not specified
  • Other relevant demographics: None
  • Anthropometrics: Height and weight significantly different between groups, as expected with comparison of women to men
  • Location: Oklahoma City, OK. 
Summary of Results:

Other Findings

  • Caffeine caused nearly identical systolic and diastolic blood pressure elevations in women and men
  • Men given caffeine vs. placebo showed elevated vascular resistance throughout the remainder of the protocol (P<0.001), with no difference in cardiac output
  • Women given caffeine vs. placebo showed increased stroke volume (P<0.001) and cardiac output (P<0.001), but no difference in vascular resistance. 

 

 

 

Author Conclusion:
  • Male and female regular consumers of caffeine had comparable increases in blood pressure after modest doses of caffeine, but women sustained their blood pressure response by greater cardiac output, whereas men showed an increase in vascular resistance
  • The gender difference in cardiovascular effects of caffeine may have implications for the long-term effects of caffeine on blood pressure regulation in men vs. women, in relation to their level of hypertension risk.
Funding Source:
Government: Dept. of Veterans Affairs, NHLBI
Reviewer Comments:
  • Recruitment methods were not specified
  • At baseline, men had statistically significant higher systolic blood pressure than women
  • Question the choice to administer caffeine with grapefruit juice. The authors state that grapefruit juice does not interfere with caffeine metabolism, but cite their own small (N=10) study as the evidence. A larger (N=30) study by a different group did find 25% inhibition of caffeine metabolism, due to grapefruit juice, which implies potentiation of caffeine effects with grapefruit juice. Furthermore, in vitro studies show bioactive compounds found in grapefruit juice are potent CYP1A2 inhibitors, the enzyme primarily responsible for caffeine metabolism.
  • Also question the choice to not design the study as a crossover study in order to compare individuals to themselves regarding effects with placebo vs. caffeine
  • It also unclear whether their statistical analyses were appropriate for the use of repeated-measures data.
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? 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? No
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) No
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? No
  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? 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%.) N/A
  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? 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? 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? 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? 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? ???
  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? ???
  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? No
  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