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Cited by 565Coffee research and impactsNutritional Studies and DietAlcohol Consumption and Health Effects

Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies

Open access
Ding, Ming, Bhupathiraju, Shilpa N., Satija, Ambika, van Dam, Rob M., Hu, Frank B.·2014·Circulation
DOI 10.1161/circulationaha.113.005925PMC PMC3945962
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Abstract

Background—: Considerable controversy exists on the association between coffee consumption and cardiovascular disease (CVD) risk. A meta-analysis was performed to assess the dose–response relationship of long-term coffee consumption with CVD risk. Methods and Results—: PubMed and EMBASE were searched for prospective cohort studies of the relationship between coffee consumption and CVD risk, which included coronary heart disease, stroke, heart failure, and CVD mortality. Thirty-six studies were included with 1 279 804 participants and 36 352 CVD cases. A nonlinear relationship of coffee consumption with CVD risk was identified ( P for heterogeneity=0.09, P for trend <0.001, P for nonlinearity <0.001). Compared with the lowest category of coffee consumption (median, 0 cups per day), the relative risk of CVD was 0.95 (95% confidence interval, 0.87–1.03) for the highest category (median, 5 cups per day) category, 0.85 (95% confidence interval, 0.80–0.90) for the second highest category (median, 3.5 cups per day), and 0.89 (95% confidence interval, 0.84–0.94) for the third highest category (median, 1.5 cups per day). Looking at separate outcomes, coffee consumption was nonlinearly associated with both coronary heart disease ( P for heterogeneity=0.001, P for trend <0.001, P for nonlinearity <0.001) and stroke ( P for heterogeneity=0.07, P for trend <0.001, P for nonlinearity <0.001; P for trend differences >0.05) risks. Conclusions—: A nonlinear association between coffee consumption and CVD risk was observed in this meta-analysis. Moderate coffee consumption was inversely significantly associated with CVD risk, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with elevated CVD risk.

AI snapshot

Written from the paper’s full text.

TL;DR

This systematic review and dose–response meta-analysis found a non-linear, U-shaped association between long-term coffee consumption and cardiovascular disease risk, with the lowest risk at 3 to 5 cups/day. Moderate coffee consumption was inversely associated with CVD, CHD, and stroke, while heavy consumption was not associated with elevated CVD risk.

Key findings

  • Compared with the lowest coffee consumption category (median 0 cups/day), pooled relative risks for CVD were 0.89 (95% CI, 0.84–0.94) for the third highest category (median 1.5 cups/day), 0.85 (95% CI, 0.80–0.90) for the second highest category (median 3.5 cups/day), and 0.95 (95% CI, 0.87–1.03) for the highest category (median 5 cups/day).
  • In the dose–response spline model, RRs versus no coffee consumption were 0.95 (0.93–0.97) at 1 cup/day, 0.92 (0.88–0.95) at 2 cups/day, 0.89 (0.85–0.93) at 3 cups/day, 0.88 (0.83–0.93) at 4 cups/day, 0.89 (0.83–0.95) at 5 cups/day, 0.91 (0.84–0.99) at 6 cups/day, and 0.93 (0.85–1.03) at 7 cups/day.
  • Non-linear associations with significant trends were found for both CHD and stroke; heterogeneity was stronger for CHD (P for heterogeneity = 0.001) than for stroke (P for heterogeneity = 0.07).
  • Stratified analyses found no significant interactions between categorized coffee consumption and baseline hypertension/MI, smoking status, publication year, NOS quality score, dietary assessment method, outcome, country, sex, or coffee type (all P for interactions > 0.05). Egger tests did not suggest publication bias.

Methods

  • Systematic review and dose–response meta-analysis of prospective cohort studies, following the MOOSE protocol; PubMed and EMBASE were searched from January 1966 to March 2013.
  • The abstract reports 36 included studies with 1,279,804 participants and 36,352 CVD cases; the Results and Discussion report approximately 1,283,685 participants and 47,779 CVD cases, including 28,347 CHD, 12,030 stroke, and 7,402 other CVD cases. The main analysis included 35 studies, and 29 studies were included in the dose–response analysis.
  • Analyses used semi-parametric and parametric methods, random- or fixed-effects models, generalized least squares, and restricted cubic splines with 3 knots; stratified analyses and Egger’s regression symmetry test were also performed.

Limitations

  • The paper states that, given the observational nature of included studies, residual confounding cannot be excluded and a causal relationship cannot be established; residual confounding by smoking may have biased heavy coffee consumption upward.
  • The paper states that coffee brewing methods were not assessed, so results may not apply to unfiltered coffee (e.g., French press, Scandinavian boiled, or Turkish/Greek coffee).
  • The paper states that none of the included cohorts assessed CYP1A2 genotype, so genotype-stratified analysis was not possible. Evident from the text: participant and CVD case counts differ between the abstract and the Results/Discussion sections.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1161/circulationaha.113.005925

Cites

74 of 74 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 41 cited sources checked · 0 supported · 0 flagged

  • Findingnone given

    The imputed correlation coefficient between risks of stroke and CHD within the same cohort (0 < ρ ≤ 1) did not affect the relative risk of CVD for each category of coffee consumption.

    “the imputed correlation coefficient between the risks of stroke and CHD within the same cohort (0 < ρ ≤ 1) did not have an effect on the relative risk of CVD for each category of coffee consumption.”
    Quote in the paperNot a substantial claim
  • Findingown data

    Compared with the lowest category of coffee consumption, the RR of CHD was 0.90 (95% CI 0.84 to 0.97; P for heterogeneity = 0.02; I2 = 40.3%) for the second highest category.

    “0.90 (95% CI, 0.84 to 0.97; P for heterogeneity = 0.02; I2 = 40.3%) for the second highest category”
    Quote in the paperSubstantial claim
  • Findingown data

    Compared with the lowest category of coffee consumption (median and mean 0 cups/d), the pooled relative risk of incident CVD was 0.85 (95% CI 0.80 to 0.90) for the second highest category (median 3.5 cups/d; mean 3 cups/d).

    “0.85 (95% CI, 0.80 to 0.90) for the second highest (median: 3.5 cups/d; mean: 3 cups/d)”
    • Also stated in: § Methods and Results · plain
      “0.85 (0.80 to 0.90) for the second highest (median: 3.5 cups/d)”
    Quote in the paperSubstantial claim
  • Findingown data

    Among four studies providing age-stratified results, comparing highest with lowest coffee intake, the RR of CVD was 0.96 (95% CI 0.65 to 1.42) for age < 65 years.

    “the RR of CVD was 0.96 (95% CI, 0.65 to 1.42) for age < 65 years”
    Quote in the paperNot a substantial claim0 of 4 sources checked
    • cites [27] Klatsky AL Friedman GD Armstrong MA Coffee use prior to myocardial infarction restudied: Heavier intake may increase the risk Am J Epidemiol 1990 132 479 488 2389752 source

      Not checked in the free run.

    • cites [28] Lindsted KD Kuzma JW Anderson JL Coffee consumption and cause-specific mortality. Association with age at death and compression of mortality J Clin Epidemiol 1992 45 733 742 1619453 source

      Not checked in the free run.

    • cites [29] Bidel S Hu G Qiao Q Jousilahti P Antikainen R Tuomilehto J Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes Diabetologia 2006 49 2618 2626 17019600 source

      Not checked in the free run.

    • cites [30] Greenberg JA Dunbar CC Schnoll R Kokolis R Kokolis S Kassotis J Caffeinated beverage intake and the risk of heart disease mortality in the elderly: A prospective analysis AmJ Clin Nutr 2007 85 392 398 17284734 source

      Not checked in the free run.

  • Findingown data

    No interactions between categorized coffee consumption and stratification variables in relation to CVD risk were observed (all P for interactions > 0.05).

    “No interactions between categorized coffee consumption and stratification variables in relation to CVD risk were observed (all P for interactions >0.05)”
    Quote in the paperNot a substantial claim
  • May combine two claims. 32
  • Classified as probably not a substantial claim. 20

  • May combine two claims.

    Findingown data

    A non-linear association between coffee consumption and risk of CVD was observed (P for non-linearity < 0.001), with a significant trend (P for trend < 0.001) and limited heterogeneity (P for heterogeneity = 0.09).

    “we observed a non-linear association between coffee consumption and risk of CVD (P for non-linearity < 0.001) with a significant trend (P for trend <0.001) and limited heterogeneity in study results (P for heterogeneity = 0.09)”
    • Also stated in: § Methods and Results · plain
      “A non-linear relationship of coffee consumption with CVD risk was identified (P for heterogeneity = 0.09, P for trend < 0.001, P for non-linearity < 0.001).”
    • Also stated in: § Conclusions · plain
      “A non-linear association between coffee consumption with CVD risk was observed in this meta-analysis.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingreasoning

    Thirty-six prospective cohort studies remained in the meta-analysis after screening and exclusions.

    “Thirty-six studies remained in the meta-analysis (Figure 1).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The included studies comprised approximately 1,283,685 participants and 47,779 CVD cases, including 28,347 CHD cases, 12,030 stroke cases and 7,402 other CVD cases.

    “The included studies comprised approximately 1,283,685 study participants and 47,779 CVD cases, including 28,347 CHD cases, 12,030 stroke cases and 7,402 other CVD cases.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Sensitivity analysis including only one of CHD or stroke as the outcome left results largely unchanged and non-linear curves were found.

    “Our results remained largely unchanged and non-linear curves were found with including either CHD or stroke as the outcome”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Findingreasoning

    The vast majority of participants in this meta-analysis were Caucasians, so the allele frequency was expected to be consistent across various cohorts.

    “Since the vast majority of our participants were Caucasians, the allele frequency was expected to be consistent across various cohorts.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingreasoning

    After adjustment for smoking and other covariates, heavy coffee consumption was not significantly associated with CVD, and the inverse association between moderate coffee consumption and CVD became stronger.

    “After adjustment for smoking and other covariates, heavy coffee was consumption was not significantly associated with CVD and the inverse association between moderate consumption and CVD became stronger.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Study eligibility assessment and data extraction were performed by one author and independently double-checked by another author.

    “One author (M. D.) assessed study eligibility and extracted the data, the other author (A. S.) independently double-checked the available data.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Potential for publication bias was assessed using Egger's regression symmetry test.

    “We assessed the potential for publication bias using Egger's regression symmetry test.25”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Egger M Davey Smith G Schneider M Minder C Bias in meta-analysis detected by a simple, graphical test BMJ 1997 315 629 634 9310563 PMC2127453 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Sensitivity analysis was conducted by imputing different correlation coefficients (0 < ρ ≤ 1) between CHD and stroke outcomes to evaluate robustness of effect estimates.

    “Sensitivity analysis was conducted by imputing different ρ (0 < ρ ≤ 1) to evaluate the robustness of the effect estimates.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The Newcastle-Ottawa quality assessment scale was used to evaluate the quality of included studies.

    “The Newcastle-Ottawa quality assessment scale (NOS) 22was used to evaluate the quality of the included studies.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Wells GA SB O'Connell D Peterson J Welch V Losos M Tugwell P The newcastle-ottawa scale (nos) for assessing the quality of nonrandomized studies in meta-analysis 2011 www.ohri.ca/programs/clinical_epidemiology/oxford.asp

      Couldn’t be matched to a paper in Crossref, so it can’t be checked.

  • Classified as probably not a substantial claim.

    Premisecitation

    A recent meta-analysis showed that heavy coffee consumption was not associated with risk of cardiovascular disease mortality.

    “one recent meta-analysis paper showed that heavy coffee consumption was not associated with risk of CVD mortality.20”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Malerba S Turati F Galeone C Pelucchi C Verga F La Vecchia C Tavani A A meta-analysis of prospective studies of coffee consumption and mortality for all causes, cancers and cardiovascular diseases Eur J Epidemiol 2013 28 527 39 doi: 10.1007/s10654-013-9834-7. Epub 2013 Aug 11 23934579 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    The meta-analysis was designed, implemented, analysed and reported following the Meta-Analysis of Observational Studies in Epidemiology (MOOSE) protocol.

    “We followed the Meta-Analysis of Observational Studies in Epidemiology21 protocol throughout the design, implementation, analysis, and reporting of our meta-analysis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [21] Stroup DF Berlin JA Morton SC Olkin I Williamson GD Rennie D Moher D Becker BJ Sipe TA Thacker SB Meta-analysis of observational studies in epidemiology: A proposal for reporting. Meta-analysis of observational studies in epidemiology (moose) group JAMA 2000 283 2008 2012 10789670 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductown data

    PubMed and EMBASE were searched for prospective studies evaluating the association between coffee consumption and cardiovascular disease risk from January 1966 to March 2013.

    “We searched the PubMed and EMBASE databases for prospective studies that had evaluated the association between coffee consumption and risk of CVD between January 1966 and March 2013.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    The Newcastle-Ottawa quality assessment scores of included studies ranged from 3 to 8, and 31 studies had scores of 5 or higher.

    “The scores of the NOS quality assessment ranged from 3 to 8, and 31 studies had scores of 5 or higher.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    Possible reasons for the discrepancy between the Liu et al study and this meta-analysis include a relatively small sample size, lack of updated dietary assessment, and subgroup analysis.

    “Possible reasons for this discrepancy include a relatively small size, lack of updated dietary assessment, and subgroup analysis.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Liu J Sui X Lavie CJ Hebert JR Earnest CP Zhang J Blair SN Association of coffee consumption with all-cause and cardiovascular disease mortality Mayo Clin Proc 2013 88 1066 74 doi: 10.1016/j.mayocp.2013.06.020. Epub 2013 Aug 15 23953850 PMC3835155 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A genome-wide association study found a highly significant association between a variant on CYP1A2 and coffee intake.

    “Recently, a genome-wide association study (GWAS) found a highly significant association between a variant on CYP1A2 and coffee intake48.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [48] Cornelis MC Monda KL Yu K Paynter N Azzato EM Bennett SN Berndt SI Boerwinkle E Chanock S Chatterjee N Couper D Curhan G Heiss G Hu FB Hunter DJ Jacobs K Jensen MK Kraft P Landi MT Nettleton JA Purdue MP Rajaraman P Rimm EB Rose LM Rothman N Silverman D Stolzenberg-Solomon R Subar A Yeager M Chasman DI van Dam RM Caporaso NE Genome-wide meta-analysis identifies regions on 7p21 (ahr) and 15q24 (cyp1a2) as determinants of habitual caffeine consumption PLoS Genet 2011 7 e1002033 21490707 PMC3071630 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationnone given

    The consumption of decaffeinated coffee was much lower than caffeinated coffee, diminishing the power to detect any association.

    “First, the consumption of decaffeinated coffee was much lower than caffeinated coffee, diminishing the power to detect any association.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Drinking boiled coffee increases serum cholesterol, an important risk factor for CVD.

    “It has been shown that drinking boiled coffee increases serum cholesterol, an important risk factor for CVD5.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [5] Bak AA Grobbee DE The effect on serum cholesterol levels of coffee brewed by filtering or boiling N Engl J Med 1989 321 1432 1437 2811958 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    The Cornelis et al. analysis was based on a case-control study conducted in Costa Rica, and the results have not been replicated in prospective cohort studies.

    “However, this analysis was based on a case-control study conducted in Costa Rico and the results have not been replicated in prospective cohort studies yet.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Cornelis MC El-Sohemy A Kabagambe EK Campos H Coffee, cyp1a2 genotype, and risk of myocardial infarction JAMA 2006 295 1135 1141 16522833 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A study by Cornelis et al. showed that CYP1A2 genotype was an effect modifier between coffee consumption and risk of myocardial infarction: coffee consumption was related to higher risk of myocardial infarction for slow caffeine metabolizers and was not related for fast caffeine metabolizers.

    “A study by Cornelis MC et al.47 showed that CYP1A2 genotype was an effect modifier between coffee consumption and risk of myocardial infarction: coffee consumption was related to higher risk of myocardial infarction for the slow caffeine metabolizer, and was not related to myocardial infarction for the fast caffeine metabolizer.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Cornelis MC El-Sohemy A Kabagambe EK Campos H Coffee, cyp1a2 genotype, and risk of myocardial infarction JAMA 2006 295 1135 1141 16522833 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Results from case-crossover studies suggest that coffee consumption transiently increases the risk of nonfatal myocardial infarction, ischemic stroke onset, and sudden cardiac death.

    “Results from case crossover studies suggest that coffee consumption transiently increases risk of nonfatal myocardial infarction, ischemic stroke onset, and sudden cardiac death.44–46”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [44] Baylin A Hernandez-Diaz S Kabagambe EK Siles X Campos H Transient exposure to coffee as a trigger of a first nonfatal myocardial infarction Epidemiology 2006 17 506 511 16837823 source

      Not checked in the free run.

    • cites [45] Selb Semerl J Selb K Coffee and alcohol consumption as triggering factors for sudden cardiac death: Case-crossover study Croat Med J 2004 45 775 780 15578815

      Not checked in the free run.

    • cites [46] Mostofsky E Schlaug G Mukamal KJ Rosamond WD Mittleman MA Coffee and acute ischemic stroke onset: The stroke onset study Neurology 2010 75 1583 1588 20881275 PMC3120108 source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    A previous meta-analysis of 21 prospective cohort studies found no association between moderate coffee consumption and CHD risk in the overall population.

    “a previous meta-analysis summarizing 21 prospective cohort studies31 found no association between moderate coffee consumption and CHD risk in the overall population.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [31] Wu JN Ho SC Zhou C Ling WH Chen WQ Wang CL Chen YM Coffee consumption and risk of coronary heart diseases: A meta-analysis of 21 prospective cohort studies Int JCardiol 2009 137 216 225 18707777 source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Smoking is likely an important confounder for the association between coffee consumption and CVD risk and could bias the relative risks upwards.

    “Second, smoking is likely to be an important confounder for the association between coffee consumption and CVD risk, and could bias the relative risks upwards.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Premisecitation

    Long-term heavy coffee consumption has been associated with a slightly elevated risk of hypertension and a higher level of plasma homocysteine.

    “Long-term heavy coffee consumption has been associated with a slightly elevated risk of hypertension,40 and a higher level of plasma homocysteine.41, 42”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [40] Zhang Z Hu G Caballero B Appel L Chen L Habitual coffee consumption and risk of hypertension: A systematic review and meta-analysis of prospective observational studies Am JClin Nutr 2011 93 1212 1219 21450934 source

      Not checked in the free run.

    • cites [41] Verhoef P Pasman WJ Van Vliet T Urgert R Katan MB Contribution of caffeine to the homocysteine-raising effect of coffee: A randomized controlled trial in humans Am J Clin Nutr 2002 76 1244 1248 12450889 source

      Not checked in the free run.

    • cites [42] Olthof MR Hollman PC Zock PL Katan MB Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans Am J Clin Nutr 2001 73 532 538 11237928 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Short-term metabolic studies have shown that caffeine can acutely increase blood pressure and could also acutely adversely affect arterial stiffness and endothelium-dependent vasodilation.

    “However, short-term metabolic studies have shown that caffeine can acutely increase blood pressure by antagonizing the adenosine A1 and A2A receptor,35–37 and could also acutely adversely affect arterial stiffness and endothelium dependent vasodilation.38, 39”
    Quote in the paperNot a substantial claim0 of 5 sources checked
    • cites [35] Nurminen ML Niittynen L Korpela R Vapaatalo H Coffee, caffeine and blood pressure: A critical review Eur J Clin Nutr 1999 53 831 839 10556993 source

      Not checked in the free run.

    • cites [36] Mesas AE Leon-Munoz LM Rodriguez-Artalejo F Lopez-Garcia E The effect of coffee on blood pressure and cardiovascular disease in hypertensive individuals: A systematic review and meta-analysis Am J Clin Nutr 2011 94 1113 1126 21880846 source

      Not checked in the free run.

    • cites [37] Fredholm BB Battig K Holmen J Nehlig A Zvartau EE Actions of caffeine in the brain with special reference to factors that contribute to its widespread use Pharmacol Rev 1999 51 83 133 10049999 source

      Not checked in the free run.

    • cites [38] Karatzis E Papaioannou TG Aznaouridis K Karatzi K Stamatelopoulos K Zampelas A Papamichael C Lekakis J Mavrikakis M. Acute effects of caffeine on blood pressure and wave reflections in healthy subjects: Should we consider monitoring central blood pressure? Int JCardiol 2005 98 425 430 15708175 source

      Not checked in the free run.

    • cites [39] Papamichael CM Aznaouridis KA Karatzis EN Karatzi KN Stamatelopoulos KS Vamvakou G Lekakis JP Mavrikakis ME Effect of coffee on endothelial function in healthy subjects: The role of caffeine Clin Sci (Lond) 2005 109 55 60 15799717 source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    None of the included cohorts assessed CYP1A2 genotypes, so this meta-analysis was unable to conduct a stratified analysis by genotype.

    “However, none of the included cohorts assessed the genotypes and thus we were unable to conduct such a stratified analysis.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    Coffee brewing methods have changed over time, with filter method becoming more popular and replacing unfiltered forms such as boiled coffee that were more widely consumed in earlier studies.

    “First, coffee brewing methods have changed over time and nowadays the filter method has become more popular, effectively replacing unfiltered forms of coffee such as boiled coffee that was more widely consumed by participants in earlier studies.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because the true association between coffee consumption and CVD risk is likely modest and nonlinear, differences in coffee assessments and covariate adjustments may change the magnitude and even the direction of the associations and thus lead to different conclusions.

    “Since the true association between coffee consumption and CVD risk is likely to be modest and nonlinear, the differences in coffee assessments and covariate adjustments may result in changes the magnitude and even the direction of the associations and thus lead to different conclusions.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    A possible reason the previous meta-analysis found no association is that it included 7 studies without adjustment for confounders, which might have biased the relative risks upwards because of confounding by factors such as smoking.

    “One possible reason is that the previous meta-analysis included 7 studies without adjustment for confounders, which might have biased the relative risks upwards because of confounding by factors such as smoking.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [31] Wu JN Ho SC Zhou C Ling WH Chen WQ Wang CL Chen YM Coffee consumption and risk of coronary heart diseases: A meta-analysis of 21 prospective cohort studies Int JCardiol 2009 137 216 225 18707777 source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Interpretationnone given

    Individuals with hypertension or other conditions related to CVD risk might have changed their coffee consumption before baseline, so baseline disease, especially hypertension, as a confounder could result in reverse causation.

    “First, individuals with hypertension or other conditions related to CVD risk might have changed their coffee consumption before baseline. Thus, baseline disease, especially hypertension, as a confounder could result in reverse causation.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    The non-linear U-shaped association between coffee consumption and CVD risk might also be true based on plausible biological mechanisms.

    “The non-linear U-shaped between coffee consumption and CVD risk might also be true based on plausible biological mechanisms.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Coffee consumption has been associated with higher insulin sensitivity, a lower risk of type 2 diabetes, and lower concentrations of inflammatory markers such as C-reactive protein and E-selectin.

    “Coffee consumption has been associated with higher insulin sensitivity, a lower risk of type 2 diabetes, and lower concentrations of inflammatory markers such as C-reactive protein and E-selectin.33, 34”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [33] van Dam RM Hu FB Coffee consumption and risk of type 2 diabetes: A systematic review JAMA 2005 294 97 104 15998896 source

      Not checked in the free run.

    • cites [34] Williams CJ Fargnoli JL Hwang JJ van Dam RM Blackburn GL Hu FB Mantzoros CS Coffee consumption is associated with higher plasma adiponectin concentrations in women with or without type 2 diabetes: A prospective cohort study Diabetes Care 2008 31 504 507 18070989 PMC2737446 source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A recent cohort study found that 4 cups/day of coffee consumption was associated with increased mortality, but the association was significant only for participants under 55 years old.

    “A recent cohort study by Liu et al32 found that 4 cups per day of coffee consumption was associated with increased mortality, but the association was only significant for participants under 55 years old.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [32] Liu J Sui X Lavie CJ Hebert JR Earnest CP Zhang J Blair SN Association of coffee consumption with all-cause and cardiovascular disease mortality Mayo Clin Proc 2013 88 1066 74 doi: 10.1016/j.mayocp.2013.06.020. Epub 2013 Aug 15 23953850 PMC3835155 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Case-control studies, which are prone to recall bias and selection bias, tended to show a positive association between coffee consumption and CVD risk, whereas cohort studies generally showed a null association.

    “Case-control studies, which are prone to recall bias and selection bias, tended to show a positive association, whereas cohort studies generally showed a null association.10”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Greenland S A meta-analysis of coffee, myocardial infarction, and coronary death Epidemiology 1993 4 366 374 8347748 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    In earlier studies, the sample size was typically small, measurement of baseline characteristics was typically crude, statistical control of confounders such as diet was inadequate, and the average NOS study quality score was lower.

    “Second, in earlier studies, the sample size was typically small; the measurement of baseline characteristics was typically crude; statistical control of confounders such as diet was inadequate; and the average NOS study quality score was lower.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    The non-linear U-shaped association between coffee consumption and CVD risk might be due to a combination of beneficial and detrimental effects: for moderate coffee consumption, beneficial effects may be greater than adverse effects, whereas for heavy consumption, detrimental effects may counterbalance beneficial effects.

    “The non-linear U-shaped between coffee consumption and risk of CVD might be due to a combination of beneficial and detrimental effects: for moderate coffee consumption, beneficial effects may be greater than adverse effects; whereas for heavy consumption, detrimental effect may counterbalance beneficial effects.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Because higher coffee consumption was generally associated with a less healthy lifestyle such as higher prevalence of cigarette smoking, less physical activity, and a less healthy diet, the observed association between moderate coffee consumption and lower CVD risk is unlikely to be explained by these confounders.

    “However, since higher coffee consumption was generally associated with a less healthy lifestyle such as a higher prevalence of cigarette smoking, less physical activity, and a less healthy diet, the observed association between moderate coffee consumption and a lower CVD risk is unlikely to be explained by these confounders.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationreasoning

    Residual confounding by smoking may have biased the association for heavy coffee consumption upward, which may explain the finding that adjustment for smoking and other covariates strengthened the inverse association.

    “In addition, residual confounding by smoking may have biased the association for heavy coffee consumption upward, which may explain our finding that adjustment for smoking and other covariates actually strengthened the inverse association.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Both semi-parametric and parametric methods indicated a U-shaped relationship between coffee consumption and CVD risk.

    “Third, we used both semi-parametric and parametric methods, and both analyses indicated a U-shaped relationship between coffee consumption and CVD risk.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S4 (based).

    Interpretationnone given

    Given coffee consumption habits in the studied populations, most consumed coffee is likely to have been filtered coffee.

    “However, given coffee consumption habits in the studied populations most consumed coffee is likely to have been filtered coffee.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Study design and conductown data

    Stratified analyses according to disease endpoints, geographic locations, type of coffee, and baseline characteristics of study populations were conducted, and the subgroup results are highly consistent and robust.

    “Finally, we conducted stratified analyses according to disease endpoints, geographic locations of the studies, type of coffee, and baseline characteristics of the study populations. The subgroup results are highly consistent and robust.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductown data

    This meta-analysis included 35 cohort studies and 1,283,685 participants, which provided sufficient power to detect modest associations.

    “First, our meta-analysis included 35 cohort studies and 1,283,685 participants, which provided sufficient power to detect modest associations.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Study design and conductreasoning

    Because all included studies had a prospective design, differential misclassification of coffee consumption due to recall bias was minimized and the likelihood of selection bias was reduced.

    “Second, because of the prospective design of all included studies, differential misclassification of coffee consumption due to recall bias was minimized and the likelihood of selection bias is reduced.”
    Quote in the paperSubstantial claim
43 of 43

  • The paper relies on this without support.

    Coffee is one of the most widely consumed beverages around the world.

    “Coffee is one of the most widely consumed beverages around the world; thus, investigating whether or not coffee consumption is associated with chronic disease risk has important public health implications.”

  • The paper relies on this without support.

    The shape of the association between coffee consumption and cardiovascular disease risk remains uncertain.

    “These meta-analyses did not support an association between coffee consumption and a higher CVD risk, but the shape of the association remains uncertain.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • In Ding et al. (2014), compared with the lowest coffee consumption, RRs of CHD were 0.89 (95% CI 0.85-0.94) for the first category (median 1.5 cups/day), 0.90 (0.84-0.97) for the second (3.5 cups/day), and 0.93 (0.84-1.02) for the third (5 cups/day).

    “Compared with the lowest category of coffee consumption (median zero cups per day), the RRs of CHD were 0.89 (95 % CI = 0.85-0.94)for the first category (median 1.5 cups per day), 0.90 (95 % CI = 0.84-0.97)for the second category (median 3.5 cups per day) and 0.93 (95 % CI = 0.84-1.02)for the third category of coffee consumption (median five cups per day).”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Ding et al., 2014

  • In Ding et al. (2014), coffee consumption was inversely associated with risk of CVD up to eight cups/day; no association was observed between coffee consumption and CHD risk at higher intake.

    “Coffee consumption was inversely associated with the risk of CVD up to eight cups per day.No association was observed between coffee consumption and CHD risk at higher intake.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Ding et al., 2014

  • In the dose-response meta-analysis by Ding et al. (2014), coffee consumption was inversely associated with the risk of CVD up to six cups per day.

    “In the dose-response analysis, coffee consumption was inversely associated with the risk of CVD up to six cups per day.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Ding et al. (2014)

  • In the dose-response meta-analysis by Ding et al. (2014), no association was observed between coffee consumption of higher intakes and the risk of stroke.

    “No association was observed between coffee consumption of higher intakes and the risk of stroke.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Ding et al. (2014)

  • In the dose-response meta-analysis by Ding et al. (2014), coffee consumption up to about four cups per day was inversely associated with the risk of stroke.

    “Coffee consumption up to about four cups per day was inversely associated with the risk of stroke.”

    From Scientific Opinion on the safety of caffeine (2015) · cites this paper as Ding et al. (2014)

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Participant totals differ between abstract and results

    Major

    The abstract reports 1,279,804 participants in 36 studies, whereas the Results reports approximately 1,283,685 participants in the same number of studies.

1 of 1

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Authors
Ding, M., Bhupathiraju, S. N., Satija, A., van Dam, R. M., & Hu, F. B.
Affiliations
  • Brigham and Women's Hospital (US)
  • From the Departments of Nutrition (M.D., S.N.B., A.S., R.M.v.D., F.B.H.) and Epidemiology (F.B.H.), Harvard School of Public Health, Boston, MA; Saw Swee Hock School of Public Health and Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore (R.M.v.D.); and Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA (F.B.H.).
ORCID
Venue
Circulation
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2014-02-11
Volume
129
Issue
6
Pages
643-659
ISSN
  • 0009-7322 (ISSN-L)
  • 1524-4539
DOI
10.1161/circulationaha.113.005925
PMC
PMC3945962
OpenAlex
W2137201442
Cited by
565
References
74
Citations by year
2026: 29 · 2025: 49 · 2024: 64 · 2023: 45 · 2022: 56 · 2021: 43 · 2020: 54 · 2019: 34 · 2018: 51 · 2017: 51 · 2016: 41 · 2015: 30 · 2014: 17 · 2013: 1
FWCI
21.82
Type
journal article
Language
en
Open access
Locations
  • Circulation (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • National University of Singapore (submittedVersion)
Funders
National Heart, Lung, and Blood Institute (HL60712, R01HL060712)
Topics
  • Health Sciences › Medicine › Pharmacology › Coffee research and impacts
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Nutritional Studies and Diet
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Alcohol Consumption and Health Effects
Keywords
coffee consumption, cardiovascular risk, coronary artery disease, stroke, heart failure, cardiovascular mortality, dose-response relationship, nonlinear relationship
MeSH terms
Cardiovascular Diseases, Coffee, Coronary Disease, Heart Failure, Humans, Prospective Studies, Risk Factors, Nonlinear Dynamics, Stroke

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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