Long-Term Coffee Consumption and Risk ofCardiovascular DiseaseA Systematic Review and a DoseResponse Meta-Analysis of Prospective Cohort StudiesMing Ding, MS; Shilpa N. Bhupathiraju, PhD; Ambika Satija, BA; Rob M. van Dam, PhD; Frank B. Hu, MD, PhD

Introduction

Coffee is one of the most widely consumed beverages around the world.coffee consumption VS chronic disease = important public health implications.1960s, 1980s, 2000sTo examine the doseresponse association of coffee consumption with CVD risk, we conducted a systematic review and metaanalysis of coffee consumption and incidence of total CVD outcomes.

Methods & Results

Characteristics of Studies2587 potentially relevant citations36 studiesRemainedIn meta-analysis1,283,685 participantsand 47,779 CVD cases,Including28,347 CHD cases12,030 stroke cases7402 other CVD casesfollow-up:6-44 yrs (median 10 yrs)21:Europe, 12:US, 3:Japan

PubMed and EMBASE were searched for prospective cohort studies (coffee consumption and CVD risk) btw JAN 1966 and MAR 2013 coffee, CVD, coronary heart disease, stroke, mortality, heart failure, MI, IHD, sudden cardiac arrest, and ACSIncluding criteria: Prospective exposure: coffee, includes decaffeinated outcomes: CVD including CHD, stroke, heart failure, mortalityExcluding criteria: Retrospective No standard errors outcomes: Af, H/T, venous thrombus no confounders was adjusted for

Risk of CVD for median consumption 1.5 cups/day VS 0 cup/day0.89

Risk of CVD for median consumption 3.5 cups/day VS 0 cup/day0.85

Risk of CVD for median consumption 5.5 cups/day VS 0 cup/day0.95

Discussion

Key Point 1nonlinear association between coffee consumption and risk of CVDModerate coffee consumption (35 cups per day) was associated with lower CVD riskHeavy coffee consumption (6 cups per day) was neither associated with a higher nor a lower risk of CVD

Key Point 2Previous meta-analysis found no association between moderate coffee consumption and CHD risk in the overall populationwithout adjustment for confounders, which might have biased the RRs upward because of confounding by factors such as smoking.

Key Point 3Liu et al found that 4 cups per day of coffee consumption was associated with increased mortality for participants

Key Point 4U-shaped association between coffee consumption and CVD risk observedA) individuals with hypertension or other conditions related to CVD risk might have changed their coffee consumption.However, we observed no significant difference.B) Heavy coffee consumption was associated with higher risk of CVD, but this is likely due to confounding by smoking.After adjustment, heavy coffee consumption was not significantly associated with CVD.

Coffee is a complex chemical mixture the phenolic compound chlorogenic acid, caffeine, minerals such as potassium and magnesium, niacin and its precursor trigonelline, and lignans.associated with higher insulin sensitivity, lower risk of DM, and lower concentrations of inflammatory markers such as CRP and E-selectin.Short-term: caffeine can acutely increase BP and could acutely affect arterial stiffness and endothelium-dependent vasodilation adversely.Long-term: elevated risk of hypertension and a higher level of plasma homocysteine.cafestol in unfiltered coffee increases serum total cholesterol

C) The nonlinear U-shaped relationship 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 effects may counterbalance beneficial effects.

Key Point 5No significant association between decaffeinated coffee consumption with CVD riskconsumption of decaffeinated coffee was much lower than caffeinated coffee, diminishing the power to detectreverse causation problem in that individuals with hypertension or other CVD-related conditions might switch from regular coffee to decaffeinated coffee

Key Point 6Cornelis et al showed that the CYP1A2 genotype was an effect modifier between coffee consumption and risk of myocardial infarctionCoffee consumption = higher risk of MI for the slow metabolizer not related to MI risk for fast metabolizerOnly a case-control study that have not yet been replicated in prospective cohort studies

Key Point 7Our metaanalysis included 35 cohort studies and 1,283,685 participants.Prospective + differential misclassification of coffee consumption = minimized recall bias + selection biasboth semiparametric and parametric methods, and both analyses indicated a U-shaped relationship between coffee consumption and CVD risk.

Key Point 8Given the observational nature of the studies, the possibility of residual confounding cannot be excluded.However, because higher consumption associated with a less healthy lifestyle (cigarette smoking, less physical activity, less healthy diet), the observed association between moderate coffee consumption and a lower CVD risk is unlikely to be explainedResults may not apply to unfiltered coffee (eg, French press, Scandinavian boiled, or Turkish/Greek coffee).

ConclusionOur meta-analysis suggests a nonlinear relationship between coffee consumption and CVD risk.Moderate coffee consumption was associated with lower CVD risk, with the lowest CVD risk at 3 to 5 cups per day of coffee consumption.heavy coffee consumption was not associated with CVD risk.This nonlinear association with coffee consumption was for both CHD and stroke.

Clinical PerspectiveCoffee is one of the most widely consumed beverages around the world, and its association with cardiovascular disease has been investigated in numerous epidemiological studies.A key issue that remains to be resolved is the doseresponse relationship of long-term coffee consumption with cardiovascular disease (CVD) risk.

In the current meta-analysis, we found a nonlinear relationship of coffee consumption with CVD risk: Moderate coffee consumption was associated with lower risk of CVD, with the lowest CVD risk at 3 to 5 cups per day, and heavy coffee consumption was not associated with risk of CVD.

The present study provides strong evidence thatlong-term heavy consumption of coffee is not associated with CVD riskprovides insight into the potential mechanism of the nonlinear relationship between coffee consumption and CVD risk

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