EAL

HTN: Caffeine (2007)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To examine the effects of acute caffeine intake on central blood pressure (BP) and large artery stiffness using pulse wave analysis (PWA) and sympathetic cardiac influence using power spectral analysis of pulse interval during rest and sustained isometric hand-grip exercise.

Inclusion Criteria:

Men and women, aged 18-45 years, regularly consuming 350ml to 700ml of coffee per day.

Exclusion Criteria:

Elevated BP (above 160/100mm Hg)
Clinical history of diabetes or cardiovascular disease
Regular use of any prescribed medication or use of any over-the-counter medication in the week before examination.

Description of Study Protocol:

Recruitment: Subjects identified from a community database
Design: Randomized, placebo-controlled, crossover trial
Blinding used: Double-blind.

Intervention

On the morning of each examination, subjects arrived having fasted and refrained from caffeine since 10:00 p.m. the night before
After application of chest electrodes and insertion of venous cannula, subjects rested supine for 20 minutes and were then given 300mg of caffeine or a placebo.

Statistical Analysis

Two-way ANOVA for BP and augmentation index (AIx); Student T-tests for baseline, post-treatment and handgrip measures of low-frequency to high-frequency (LF:HF) ratio
Subject numbers were determined from previous experiments to give at least 80% power to detect a 10% difference in primary outcome variables.

Data Collection Summary:

Timing of Measurements

At baseline and one hour after administration, five ml of blood were drawn for caffeine concentration
Hemodynamic measurements were recorded at baseline and at 15-minute intervals for one hour
At one hour, subjects performed sustained isometric handgrip exercise at 30% of maximal voluntary contraction for five minutes using the dominant hand as a sympathetic cardiac stimulus
Electrocardiographic signals recorded at baseline, at one hour and during the handgrip exercise were used for heart rate variability (HRV) analysis.

Dependent Variables

BP, using brachial artery of dominant arm and Omron HEM-705CP oscillometric device
Cardiac index (CI), using the non-invasive NCCOM3-R7 transthoracic bioimpedance technique
Mean arterial pressure (MAP), calculated by integration of arterial pressure waveform using SphygomoCor PWA software
Systemic vascular resistance index, calculated as MAP divided by CI
Peripheral pressure waveforms, using radial artery at the wrist of dominant hand and an applanation tonometer (SPC-301 micromanometer), linked to SphygomoCor PWA apparatus
Augmentation Index (AIx), SphygmoCor PWA software generates averaged peripheral and centrail aortic pressure waveforms and calculates AIx as the difference between the first and second central systolic BP peaks expressed as a percentage of pulse pressure
Pressure amplification, calculated as the ratio of peripheral to central pulse pressure
Heart rate variability, expressed as very low-frequency (under 0.04Hz), low-frequency (LF; 0.04 to 0.149Hz), and high-frequency (HF; 0.15 to 0.4Hz) domains; LF:HF ratio was used to represent relative sympatho-vagal cardiac influence.

Independent Variables

300mg caffeine or placebo.

Control Variables

None specified.

Description of Actual Data Sample:

Initial N: 20 adults, 12 women, eight men
Attrition (final N): 20 assumed; not specified
Age: Mean, 23±years
Ethnicity: Not specified
Other relevant demographics: None.
Anthropometrics: Not applicable; crossover design.
Location: University of Edinburgh, Scotland.

Summary of Results:

Variable (at Significant Time Points Only)

Caffeine

Measures ± SEM

Placebo

Measures ± SEM

Statistical Significance

Heart rate (beats per minute)

45 minute

64±2

71±2

P<0.05

Aortic SBP

(mm Hg)

30 minute

45 minute

60 minute

97±2

100±2

98±2

93±3

P<0.05

P<0.01

P<0.05

Aortic DBP (mm Hg)

45 minute

60 minute

82±2

83±2

80±2

P<0.05

Brachial SBP (mm Hg)

No significant differences at any time point

Brachial DBP(mm Hg)

No significant differences at any time point

MAP (mm Hg)

60 minute

87±2

82±1

P<0.05

AIx (%)

45 minute

60 minute

-6±4

-8±3

-11±3

-10±3

P<0.01

P<0.05

Pressure amplification

15 minute

30 minute

45 minute

60 minute

1.3±0.2

1.2±0.2

1.0±0.1

1.2±0.1

1.9±0.2

1.8±0.2

P<0.01

P<0.001

Cardiac index

No significant differences at any time point

Systemic vascular resistance index
30 min

11.2±0.7

9.6±0.6

P<0.05

Other Findings

Sustained isometric handgrip exercise caused a significant rise in LF:HF ration of power spectral HRV domains in the placebo are of the study (P<0.05)
Caffeine tended to lower the LF:HF ratio under resting conditions and attenuated the rise in LF:HF ratio during isometric handgrip exercise.

Author Conclusion:

Acute administration of 300mg caffeine had a significant impact on cardiovascular function in healthy adults accustomed to regular caffeine consumption, with maximal hemodynamic responses 45 minutes after caffeine administration, which coincides with expected peak plasma concentrations
Brachial BP measurement significantly underestimates effects of caffeine on central BP
Changes in LF:HF ratio suggest that caffeine exerts a predominant parasympathetic, rather than sympathetic cardiac influence.

Funding Source:

Industry:

Bristol-Myers Squibb

Pharmaceutical/Dietary Supplement Company:

University/Hospital:

Universtiy of Edinburgh (Scotland UK)

Reviewer Comments:

There is a question whether repeated-measures presents an issue with their data analyses
Authors note that the potential limitation is that the study population was young and healthy.

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?	No
	2.4.	Were the subjects/patients a representative sample of the relevant population?	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)	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?	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?	???
	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?	???
	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)?	???
	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