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

In the paper

“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.”

In the paper

“Thirty-six studies remained in the meta-analysis (Figure 1).”

In the paper

“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.”

In the paper

“Our results remained largely unchanged and non-linear curves were found with including either CHD or stroke as the outcome”

In the paper

“Since the vast majority of our participants were Caucasians, the allele frequency was expected to be consistent across various cohorts.”

In the paper

“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.”

In the paper

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

In the paper

“We assessed the potential for publication bias using Egger's regression symmetry test.25”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“The Newcastle-Ottawa quality assessment scale (NOS) 22was used to evaluate the quality of the included studies.”

What the sources say

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

In the paper

“one recent meta-analysis paper showed that heavy coffee consumption was not associated with risk of CVD mortality.20”

What the sources say

• Not checked yetcites [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

In the paper

“We followed the Meta-Analysis of Observational Studies in Epidemiology21 protocol throughout the design, implementation, analysis, and reporting of our meta-analysis.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“The scores of the NOS quality assessment ranged from 3 to 8, and 31 studies had scores of 5 or higher.”

In the paper

“Possible reasons for this discrepancy include a relatively small size, lack of updated dietary assessment, and subgroup analysis.”

What the sources say

• Not checked yetcites [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

In the paper

“Recently, a genome-wide association study (GWAS) found a highly significant association between a variant on CYP1A2 and coffee intake48.”

What the sources say

• Not checked yetcites [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

In the paper

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

In the paper

“It has been shown that drinking boiled coffee increases serum cholesterol, an important risk factor for CVD5.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“a previous meta-analysis summarizing 21 prospective cohort studies31 found no association between moderate coffee consumption and CHD risk in the overall population.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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 yetcites [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 yetcites [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 yetcites [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

In the paper

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

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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.”

In the paper

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

In the paper

“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”

What the sources say

• Not checked yetcites [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 yetcites [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

In the paper

“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.”

What the sources say

• Not checked yetcites [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

In the paper

“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”

What the sources say

• Not checked yetcites [10] Greenland S A meta-analysis of coffee, myocardial infarction, and coronary death Epidemiology 1993 4 366 374 8347748 source

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

“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.”

In the paper

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

In the paper

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

In the paper

“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.”

In the paper

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

In the paper

“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.”