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In Reply—Association of Coffee Consumption With All-Cause and Cardiovascular Disease Mortality

      We thank Drs Katz, Wagner, Card, and Greitzer et al for their interest in our article on coffee consumption and mortality.
      • Liu J.
      • Sui X.
      • Lavie C.J.
      • et al.
      Association of coffee consumption with all-cause and cardiovascular disease mortality.
      Due to the observational nature of our study design, the association of coffee consumption with all-cause mortality or disease-specific mortality could not be verified as representing causality because of unmeasured or unknown potential confounding factors or alternative explanations. We agree with Wagner et al that the confounding effect from smoking could potentially play an important role in this association. Hence, we controlled for smoking status in the multivariate modeling. However, simply controlling for smoking status as a dichotomous variable does not eliminate the possibility of residual confounding from smoking because simplified binary smoking status could not provide the precise information to reflect the true influence of smoking. Therefore, we further stratified the analysis by smoking status, and the results were shown in supplemental online material. We did not observe any significant association between coffee consumption and all-cause motality either in current smokers or in non–current smokers. In males, the magnitude and pattern of the association between coffee consumption and all-cause mortality were similiar across smoking status. In females, however, the point estimate among nonsmokers tended to be lower than among smokers; nevertheless, no statistical significance was observed. Regarding the cumulative effects of multiple risk factors such as parental history of cardiovascular disease and other cardiovascular disease risk factors, they were accounted for in the multivariate statistical analyses, which were presented in Table 3.
      Another important point from Wagner et al concerns internal and external validity. The homogeneity of our cohort highly enhanced the internal validity of our findings because of the minimized likelihood of confounding by ethnicity, education, and socioeconomic status. Regarding external validity, previous studies also documented that our study participants were similar on key clinical variables such as lipids, glucose, and blood pressure to participants in other large epidemiological studies in the United States.
      • Blair S.N.
      • Kohl III, H.W.
      • Paffenbarger Jr., R.S.
      • Clark D.G.
      • Cooper K.H.
      • Gibbons L.W.
      Physical fitness and all-cause mortality: a prospective study of healthy men and women.
      • Huang Z.
      • Willett W.C.
      • Manson J.E.
      • et al.
      Body weight, weight change, and risk for hypertension in women.
      However, our study patients may have differed from the general population in other important ways. Although we urge caution against overgeneralizing the results we reported, it is unlikely that the observed association between coffee consumption and mortality would be any less important among other populations. Unlike other studies in the literature, we also accounted for the important variable of cardiorespiratory fitness, which was precisely measured by exercise treadmill testing. We do believe that more research is needed in other diverse populations to elucidate not only the relationship between coffee consumption and mortality but also the mechinism behind any observed relationships.
      In addition to chance and confounding, we agree with Card that sleep disorders might act as an important mediator or an effect modifier on the causal pathway between coffee consumption and mortality. As he suggested, future research with multiple time measures of coffee consumption and sleep status data is warranted to clarify the temporal sequence and determine how changes in these variables over time affect the association between coffee consumption and mortality.
      Finally, in comparison with previous studies, one of our important findings was the positive association of heavy coffee consumption with all-cause mortality among both men and women who were younger than 55 years. The underlying potential mechanism could be the hypothesis proposed by Greitzer that the levels of reactive oxygen species are modified by heavy coffee consumption and that this modification varies by age. Further research is also needed to test this hypothesis.
      Regarding the comments by Katz, we agree that our data are not strong enough to be used to “scare” young people from drinking 4 or more cups of coffee per day. However, our data suggest that the association between high coffee consumption and higher mortality in younger people seems to be mostly independent of smoking. Nevertheless, we cannot say that the coffee per se caused the higher mortality because other factors involved in this association, including sleep disorders as discussed by Card, or other confounders, such as a stress-prone personality or high-stress lifestyle, as well as other factors may also be involved. As Katz suggested, there is some sense in moderation, and as we stated in the video that accompanied the online publication of our article (http://youtu.be/Y0wwDSBwVqU), we agree with Mark Twain's comments, “All things in moderation, including moderation.” And as Hippocrates said centuries ago, “If we could give every individual the right amount of nourishment and exercise, not too little and not too much, we would have found the safest way to health.” Considering this, we believe that it is quite reasonable for most young individuals to consider keeping their coffee intake at less than 4 cups per day (eg, 2-3 cups), at least on most days, which is keeping with the theme of moderation and has been suggested elsewhere.
      • O'Keefe J.H.
      • Bhatti S.K.
      • Patil H.R.
      • Dinicolantonio J.J.
      • Lucan S.C.
      • Lavie C.J.
      Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause 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
        • Blair S.N.
        • Kohl III, H.W.
        • Paffenbarger Jr., R.S.
        • Clark D.G.
        • Cooper K.H.
        • Gibbons L.W.
        Physical fitness and all-cause mortality: a prospective study of healthy men and women.
        JAMA. 1989; 262: 2395-2401
        • Huang Z.
        • Willett W.C.
        • Manson J.E.
        • et al.
        Body weight, weight change, and risk for hypertension in women.
        Ann Intern Med. 1998; 128: 81-88
        • O'Keefe J.H.
        • Bhatti S.K.
        • Patil H.R.
        • Dinicolantonio J.J.
        • Lucan S.C.
        • Lavie C.J.
        Effects of habitual coffee consumption on cardiometabolic disease, cardiovascular health, and all-cause mortality.
        J Am Coll Cardiol. 2013; 62: 1043-1051

      Linked Article

      • Factors Affecting the Association of Coffee Consumption With All-Cause and Cardiovascular Disease Mortality
        Mayo Clinic ProceedingsVol. 88Issue 12
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          We read with great interest the recent article by Liu et al1 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.
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      • Importance of Sleep Disorders in Assessing the Association Between Coffee Consumption and All-Cause Mortality
        Mayo Clinic ProceedingsVol. 88Issue 12
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          Liu et al1 have reported an interesting observational study in which they found a positive relationship between very high coffee consumption and all-cause mortality among men and among both men and women aged less than 55 years.1 Because the general finding for men appears to be attributable to the increased risk among those younger than 55 years, the authors concluded that “on the basis of these findings, it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day).” However, while this study's findings are suggestive, it may be premature to make any clinical recommendations based on these results.
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      • Coffee Consumption and All-Cause Mortality: It May Be Premature to Advise Limiting Coffee Consumption in Younger Nonsmokers
        Mayo Clinic ProceedingsVol. 88Issue 12
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          I read with great interest the recent article by Liu et al1 on the health consequences of coffee consumption. Their methodological approach was strong, and their findings were reported clearly. However, I disagree with their conclusion that on the basis of the study's findings, “it seems appropriate to suggest that younger people avoid heavy coffee consumption (ie, averaging >4 cups per day).”
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      • Heavy Coffee Drinking and Age-Dependent All-Cause Mortality
        Mayo Clinic ProceedingsVol. 88Issue 12
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          The study by Liu et al1 reported in the October 2013 issue of Mayo Clinic Proceedings associated heavy coffee drinking with increased all-cause mortality in people younger than 55 years. A previous study,2 however, associated heavy coffee drinking with a decrease in all-cause mortality. Both studies included large populations with long follow-up and made adjustments for smoking, alcohol consumption, and other potential health effectors. In both studies, a similar effect was attributed to either caffeine or caffeine-free drinks.
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