Caffeine: A Not So Stiff Drink

There is also evidence that the tonic level of vascular stiffness is linked to increased sympathetic activity.³ In this context, caffeine can raise sympathetic activity, and its effect on both all-cause and cardiovascular mortality has been of interest for many years.⁴ So the question is, what does caffeine consumption do to vascular stiffness?

In the article by Ponte et al⁵ in this issue of Mayo Clinic Proceedings, a large family-based sample of generally healthy “free-living” Swiss adults was studied to address the relationship between caffeine consumption and vascular stiffness. More than 1100 individuals were recruited and subjected to detailed cardiovascular and renal physiologic phenotyping. Key measurements included blood pressure, pulse pressure (a surrogate marker for vascular stiffness), and pulse wave velocity, a more direct measurement of vascular stiffness. Urinary caffeine and related metabolites were measured, which eliminated the uncertainty associated with survey research techniques that are frequently used to estimate dietary intake.

After exclusion of individuals for missing data and technical issues, a total of 863 participants were included in the final analysis and divided into quartiles of caffeine excretion. The main findings were that mean brachial pulse pressure decreased with increasing caffeine excretion and that mean pulse wave velocity was lower in participants with the highest quartile of caffeine consumption compared with the lowest quartile. The potential explanations for these inverse relationships include mechanisms such as a direct vasodilator action of caffeine and/or perhaps the antioxidants contained in coffee that may, among other things, have an inhibitory effect on vascular smooth muscle proliferation.⁶

This study is important because it is another piece of evidence that caffeine and coffee consumption have, if anything, positive health effects as opposed to the widespread and unsubstantiated concerns about negative health effects from these products. It is also important for two larger reasons. First, the data were collected as a part of a bigger effort to gain insight into “genes and hypertension.” In this context, the cohort studied was “medium-sized” and permitted the sort of detailed phenotyping reported in the article. What the cohort lacks in size compared with very large genetic association studies it perhaps makes up for by its detailed and high-resolution phenotyping performed in the participants. Along these lines, a key question going forward in the era of big data will be how to handle poorly controlled and curated phenotypic data from sources like electronic health records.⁷ In the enthusiasm for paradigms like “big data,” it is perhaps easy to get caught up in the breathless enthusiasm and forget that no matter the amount of data, the old adage “garbage in, garbage out” likely holds.⁷

Second, the use of urinary metabolites as opposed to questionnaires was impressive. In more and more areas of clinical research on free-living humans, these sorts of measurements are providing invaluable insights into long-term environmental and behavioral exposures. This is especially true for topics like prescription drug adherence in the real world.⁸

In summary, Ponte et al have provided us with key insights about caffeine consumption and vascular stiffness in humans. Their results generally confirm the safety of caffeine in specific dietary products like coffee. Additionally, their study is an outstanding example of why there is no substitute for high-resolution phenotyping in clinical investigation.