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Factors Affecting the Association of Coffee Consumption With All-Cause and Cardiovascular Disease Mortality

      To the Editor:
      We read with great interest the recent article by Liu et al
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      concerning the association of coffee consumption with all-cause and cardiovascular disease mortality. We particularly applaud the thoroughness of their data collection, including 43,727 participants over a median follow-up of 17 years. Considering the pervasive nature of global coffee consumption, studies of this scale are both valuable and ubiquitously relevant. However, we have some concerns regarding the conclusions drawn from the data and would be interested if the authors could clarify some of these points.
      One apparent trend was that participants with the highest coffee consumption were less healthy than participants with lower coffee consumption. The authors confirm this by reporting, “Men and women who consumed higher amounts of coffee were more likely to smoke and had lower levels of [cardiorespiratory fitness].”
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      These participants managed the least time on a treadmill and had the highest level of inactivity, and the men in this category had the highest rate of parental cardiovascular disease. Although it appears that any individual confounding effect from cardiorespiratory fitness was statistically addressed, it is not clear that the cumulative effects of multiple risk factors were accounted for in the statistical analysis.
      Most concerning was that the confounding effect from smoking was not adequately addressed. The authors concede this point in their discussion, stating that “smoking is likely to be one of the most important factors to cause residual confounding in this investigation.”
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      It is well known that smoking can induce changes in hepatic enzymes and increase the clearance of caffeine, in turn leading to a higher rate of coffee consumption in smokers.
      • Plowchalk D.R.
      • Rowland Yeo K.
      Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2.
      • Parsons W.D.
      • Neims A.H.
      Effect of smoking on caffeine clearance.
      It is also widely established that smoking is a strong independent predictor of mortality.
      • Kenfield S.A.
      • Wei E.K.
      • Rosner B.A.
      • Glynn R.J.
      • Stampfer M.J.
      • Colditz G.A.
      Burden of smoking on cause-specific mortality: application to the Nurses' Health Study.
      Further, a recent study that evaluated the association of coffee drinking with all-cause mortality confirmed that coffee drinkers were more likely to smoke, and after adjusting for the confounding variable of smoking, coffee consumption was actually associated with decreased mortality.
      • Freedman N.D.
      • Park Y.
      • Abnet C.C.
      • Hollenbeck A.R.
      • Sinha R.
      Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
      We question whether the conclusions of the study by Liu et al can be supported without accounting for this “residual confounding” of smoking.
      The authors also comment on the homogeneity of the cohort, stating that the uniformity of the participants increases the internal validity of the study.
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      Although this may lend credence to the data, we suggest that external validity may be more critical, because the widespread use of coffee begs the immediate question of how applicable these results are beyond the confines of this study.
      The pervasive use of coffee worldwide behooves us as research scientists to report conclusions about its use with utmost accuracy. This is particularly important in light of the multiple studies that have touted the health benefits of coffee consumption. Although we applaud Liu et al for their important study, we are cautious about a potential disconnect between the data and their conclusions. Ultimately, it is evident that future investigations are merited to elucidate the relationship between coffee consumption and mortality.

      References

        • Liu J.
        • Sui X.
        • Lavie C.J.
        • et al.
        Association of coffee consumption with all-cause and cardiovascular disease mortality.
        Mayo Clin Proc. 2013; 88: 1066-1074
        • Plowchalk D.R.
        • Rowland Yeo K.
        Prediction of drug clearance in a smoking population: modeling the impact of variable cigarette consumption on the induction of CYP1A2.
        Eur J Clin Pharmacol. 2012; 68: 951-960
        • Parsons W.D.
        • Neims A.H.
        Effect of smoking on caffeine clearance.
        Clin Pharmacol Ther. 1978; 24: 40-45
        • Kenfield S.A.
        • Wei E.K.
        • Rosner B.A.
        • Glynn R.J.
        • Stampfer M.J.
        • Colditz G.A.
        Burden of smoking on cause-specific mortality: application to the Nurses' Health Study.
        Tob Control. 2010; 19: 248-254
        • Freedman N.D.
        • Park Y.
        • Abnet C.C.
        • Hollenbeck A.R.
        • Sinha R.
        Association of coffee drinking with total and cause-specific mortality [published correction appears in N Engl J Med. 2012;367(3):285].
        N Engl J Med. 2012; 366: 1891-1904

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