- Email: [email protected]
Coffee and Risk of Cardiovascular Disease
C H A P T E R
41
Coffee and Risk of Cardiovascular Disease: An Overview of Epidemiologic Studies Romina di Giuseppe*, Janine Wirth*, Cornelia Weikert Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
List of Abbreviations AMI Acute myocardial infarction ACS Acute coronary syndrome BP Blood pressure CI Confidence interval CHD Coronary heart disease CVD Cardiovascular disease EPIC European Prospective Investigation into Cancer and Nutrition HF Heart failure HR Hazard ratio MI Myocardial infarction MSA Muscle sympathetic nervous activity OR Odds ratio RR Relative risk
41.1 INTRODUCTION Coffee, one of the most popular (brewed) beverages, is prepared from the roasted coffee beans of the homonymous plant. Its particular and intense taste, flavor and chemical properties make it the most consumed nonalcoholic drink worldwide. Indeed, coffee is particularly appreciated for its stimulatory effects, mainly attributed to the caffeine content, which may help consumers to feel more alert and awake. In fact, coffee helps us to wake up in the morning or to get regenerated during a break from daily work activities. Also, social rituals make coffee particularly pleasant, for instance, by simply sharing a relaxing cup of “espresso” with friends. But, apart from being the main source of caffeine, coffee also contains several other compounds, some with antioxidant properties,1 such as chlorogenic acid, flavonoids, melanoidins, furans, pyrroles, and maltol, to name a few.2 However, some coffee bean compounds, the diterpenoid cafestol and kahweol, have * Both
been accused of raising serum cholesterol levels, thus posing possible cardiovascular health threats.3 In contrast, being a high source of antioxidant, coffee may contribute to a lower risk of coronary heart disease (CHD), at least in moderate drinkers4 who quickly metabolize caffeine.5 Nevertheless, braced by a long history, coffee has generated a plethora of controversial research findings, particularly when they encompass the cardiovascular diseases (CVDs).4 CVDs are the most common cause of morbidity and mortality in developed countries, with CHD, stroke, and heart failure being the familiar contributors.6 Thus, considering the global burden of CVD along with the popularity of coffee, even small health effects of coffee could have substantial public health impact. With the aim to provide the state-of-the-art compilations of current knowledge of the relationship between coffee and risk of major CVD endpoints, this chapter presents an overview of epidemiologic evidence.
41.2 COFFEE AND CHD RISK It was in 1963 that, for the first time, coffee came into the limelight because of its negative effect on human health.7 In particular, in their pioneering study, Paul and colleagues7 observed a positive relationship between coffee consumption and CHD development. However, although some studies found a link between coffee consumption and CHD risk, later epidemiologic studies did not provide any significant evidence.3 Indeed, a major flaw of these early observational studies is the inadequate adjustment for confounding, as already highlighted by others.4
authors contributed equally to this work.
Coffee in Health and Disease Prevention http://dx.doi.org/10.1016/B978-0-12-409517-5.00041-3
377
© 2015 Elsevier Inc. All rights reserved.
378
41. COFFEE AND CARDIOVASCULAR DISEASE
FIGURE 41.1 Confounding diagram of smoking on the relationship between coffee drinking and risk of CHD. The figure shows that the relationship between coffee drinking (exposure) and CHD (outcome) is noncausal but mediated by smoking (confounding factor).
As shown in Figure 41.1, smoking—among others— is a clear confounder in the association between coffee drinking and CHD, as heavy drinkers are also more likely to smoke. And, certainly, this figure may also explain the original finding of Paul et al.7 In fact, in more recent studies taking into account potential confounding risk factors, a moderate coffee consumption did not significantly increase the risk of CHD, especially when only prospective studies were reviewed.8 This concept has been recently supported by the findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study, in which no significant association was observed between caffeinated coffee consumption and risk of myocardial infarction (MI).9 However, large discrepancies exist when results from case–control studies are compared to those from prospective studies (for a summary of these studies and relative references, please refer to Table 41.1), as confirmed by early10–12 and more recent meta-analyses.13,14 At the beginning of the 1990s, three comprehensive meta-analyses investigating coffee consumption in relation to CHD10–12 were published with conflicting results. Myers et al.10 observed a nonsignificant pooled relative risk (RR) of 1.09 (95% confidence interval (CI) 0.97–1.22) for the association between coffee consumption (4–6 and ≥6 cups/day vs ≥1 cup/day) and CHD, when results from 11 cohort studies were considered. One year later, Greenland et al.11 in a meta-analysis of eight case– control and 14 cohort studies, found an increased CHD risk among coffee consumers drinking 5 cups/day versus nonconsumers, but only in case–control studies. These findings were confirmed in a meta-analysis of eight case–control and 15 cohort studies published by Kawachi et al., where an increased CHD risk was observed in case–control data (pooled odds ratio (OR) 1.63, 95% CI 1.50–1.78; pooled cohort study RR 1.05, 95% CI 0.99–1.12).12 Two more recent meta-analyses of, respectively, 1013 and 21 prospective cohort studies14 have indeed confirmed these previous findings. Interestingly, Wu et al.14 instead found a lower CHD risk in both men (RR 0.87, 95% CI 0.80–0.86) and women
(RR 0.82, 95% CI 0.73–0.92) regularly indulging in a moderate coffee consumption (1–3 or 3–4 cups/day).14 As highlighted by Sofi and colleagues,13 the disagreement between case–control and cohort studies could be attributed to systematic errors such as recall bias (i.e., cases are more likely to overreport coffee intake than healthy controls) or to the lack of inclusion of fatal events in case–control studies, which likely contributes to differences among outcome measures.13 However, it cannot be ruled out that coffee may have a transient (acute) effect on CHD, thus making the preservation of the temporal relationship in longitudinal studies particularly weak. Results from a case-crossover study suggested that coffee may act as a trigger of a first MI, with an RR of 1.49 (95% CI 1.17–1.89) in the hour after coffee intake.23 This risk seemed to be particularly strong in occasional coffee drinkers (≤1 cup/day, RR 4.14, 95% CI 2.03–8.42), in sedentary patients (RR 1.72, 95% CI 1.30–2.30), or in patients with three or more risk factors (RR 2.10, 95% CI 1.30–3.39).23 Yet, several other factors should be taken into account when coffee consumption is investigated in relation to CHD, such as the caffeine content of coffee beverages, coffee preparation and metabolism, and the doses of consumption. In a study conducted in six habitual and nine nonhabitual coffee drinkers, the authors observed in the latter group an acute increase in both blood pressure (BP) and muscle sympathetic nervous activity (MSA) after coffee and caffeine intake.24 Because decaffeinated coffee also increased BP and MSA in nonhabitual drinkers, the authors put forward that other compounds present in coffee, other than caffeine, may boost cardiovascular risk.24 Although not confirmed in other studies, Floegel and colleagues found a positive association between decaffeinated coffee consumption and risk of MI.9 However, this association was no longer significant after the authors excluded all MI cases occurred during the first 2 years of follow-up, thus speculating that reverse causation might have been responsible for the observed association. Several lines of evidence suggest that boiled coffee raises cholesterol levels,4 an effect mainly attributed to the diterpene lipids cafestol and kahweol.3 Indeed, the use of a paper filter during coffee preparation seems sufficient to limit the content of these “hypercholesterolemic” compounds,4 thus making a moderate filtered coffee consumption a harmless heart habit.25 Results from the SHEEP and the VHEEP study,19 a population-based case–control study, showed a 1.4 times higher incidence of first nonfatal MI in men drinking boiled coffee versus those drinking filtered coffee, with an even higher risk for women (RR 1.63, 95% CI 1.04–2.56) (Table 41.1). More
II. EFFECTS OF COFFEE CONSUMPTION
379
41.2 Coffee and CHD Risk
TABLE 41.1 Summary of Epidemiologic Studies Relating Coffee Consumption to Coronary Heart Disease (CHD) Risk References
Study
Exposure
Outcome
Summary
Grobbee15
The Health Professional Follow-up Study, longitudinal study
Total coffee consumption ≥4 cups/ day vs none
Nonfatal myocardial infarction (MI) and CHD eath Total CHD
No increase in CHD according to caffeine and caffeinated coffee intake
Caffeinated coffee consumption ≥4 cups/day vs none Decaffeinated coffee consumption ≥4 cups/day vs none
Moderate CHD risk increase for decaffeinated coffee
Myers10
11 prospective studies, meta-analysis
Coffee intake, ≥6 cups/ day vs ≤1 cup/day
Coronary events
No association between coffee consumption and CHD
Greenland11
8 case–control studies + 14 cohort studies, meta-analysis
Coffee intake 5 cups/ day vs none
MI
Weak increase in CHD risk for heavy coffee consumption in cohort studies
Kawachi12
8 case–control and 15 cohort studies, meta-analysis
Coffee drinking, ≥5 cups/ day vs none
CHD
Increased CHD risk in heavy drinkers Weak increased CHD risk in habitual coffee drinkers
Willet16
Prospective cohort study
Coffee intake ≥6 cups/day vs none
CHD
No association between caffeinated and decaffeinated coffee and caffeine consumption and CHD risk
Woodward17
Scottish Heart Health Study, cohort study
Coffee consumption ≥5 vs none
CHD
Moderate benefit from coffee consumption
Kleemola18
Finnish men and women
Coffee consumption >7 cups/ day vs 1–34 cups/day
Non fatal MI
No association between coffee drinking and CHD risk
Hammar19
The SHEEP and the VHEEP study, population-based case–control study
Consumption >9 dl filtered coffee/ day vs ≤3 dl/day
First nonfatal MI
In men drinking boiled coffee incidence of first nonfatal MI 1.4 times higher vs men drinking filtered coffee, with an even higher risk for women
Consumption >9 dl mixed coffee/day vs ≤3 dl/day Consumption >9 dl boiled coffee/day vs ≤3 dl/day Boiled vs filtered coffee
Happonen20
The Kuopio Ischemic Heart Disease Risk Factor Study, prospective study
Boiled coffee increases the occurrence of first nonfatal MI
Moderate drinkers vs heavy drinkers (≥814 ml/day)
Acute coronary events Heavy coffee drinking (MI or coronary raises the risk of acute MI or death) coronary death
Lopez-Garcia21 Prospective cohort study
Coffee intake, ≥6 cups/day vs <1 cup/month
CHD
No indication that coffee (or caffeine) intake increases CHD
Azevedo22
Community-based case–control study
Regular ever coffee drinkers
Acute myocardial infarction (AMI)
Significant decreased MI risk in men with no family history of AMI; nonsignificant increased MI risk in men with family history of AMI
Baylin23
Costa Rica, case-crossover design
Habitual coffee consumption
Nonfatal MI, 1 h after coffee drinking
Coffee intake probably triggers MI risk
≤1 cup/day 2–3 cups/day ≥4 cups/day
Continued
II. EFFECTS OF COFFEE CONSUMPTION
380
41. COFFEE AND CARDIOVASCULAR DISEASE
TABLE 41.1 Summary of Epidemiologic Studies Relating Coffee Consumption to Coronary Heart Disease (CHD) Risk—cont’d References
Study
Exposure
Outcome
Summary
Cornelis5
Slow caffeine metabolizer
Coffee intake ≥4 cups/day vs <1 cup/day
First acute nonfatal MI
Increased MI risk only in subjects with impaired caffeine metabolism
Sofi13
13 case–control studies + 10 cohort studies, meta-analysis
Coffee intake ≥4 cups/ day vs none
CHD
Coffee consumption is not associated with an increased risk of CHD
Wu14
21 prospective cohort studies, Coffee consumption <1 cup/day meta-analysis (United States) or ≤2 cups/day (Europe) vs ≥6 or ≥7 cups/day
CHD
No long-term increased CHD risk
Moderate coffee consumption Floegel9
European Prospective Investigation into Cancer and Nutrition (EPIC-Germany)
Caffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Lower CHD risk in moderate coffee drinker women MI
No association between coffee consumption and MI
Decaffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Table modified from Ref. 8, Table 2, with permission from Elsevier.
recently, in a nested case/referent study, men drinking filtered coffee four or more times per day showed an increased MI risk (OR 1.73, 95% CI 1.05–2.84), compared to those drinking filtered coffee one or no times per day. In women, a positive association was observed for boiled coffee (OR 2.51, 95% CI 1.08–5.86) in univariate analysis only.26 Results from a recent meta-analysis of randomized controlled trials suggest that drinking unfiltered coffee significantly increases, in a positive dose–response relationship, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels.27 Interestingly, Weggemans and colleagues28 observed increased LDL-cholesterol levels in response to cafestol, but only in homozygous carriers of the C allele of the ApoA1 83 genotype. Years later, Cornelis et al. observed, for the first time, an increased risk of nonfatal MI in slow caffeine metabolizers, thus putting forward a role of caffeine in the development of this disease.5 However, a nonlinear dose–response relationship between coffee (and caffeine) intake and CHD risk may explain the heterogeneous findings from different studies, which typically investigated the role of coffee at various doses, and, partly, the null findings of meta-analyses. de Koning Gans and colleagues observed a U-shaped relationship between CHD morbidity and coffee consumption with a hazard ratio (HR) of 0.79 (95% CI 0.65– 0.96) in healthy men and women drinking between 2.1 and 6 cups of coffee per day.29 A “J-shaped” relationship between acute coronary syndrome (ACS) and coffee was already observed in a previous study of Panagiotakos et al.30 In particular, they found a lower coronary risk for
moderate coffee consumption (<300 ml coffee/day; OR 0.69, 95% CI 0.50–0.86) and a significant increased risk for heavy or very heavy consumption (>300 ml coffee/ day; OR 3.10, 95% CI 1.82–5.26).30 These findings indeed suggest that more accurate quantitative reviews of the literature that consider the “J- or U-shaped” relationship between coffee and CHD risk are warranted, to clarify this issue.
41.3 COFFEE AND STROKE RISK As for CHD, studies examining the association between coffee consumption and risk of stroke have produced inconsistent findings (Table 41.2). Indeed, coffee may exert protective effects on stroke, for instance, by positively affecting the risk of atherosclerosis,31,32 although this potential health effect could be counterbalanced by slight acute rise in BP after coffee consumption.32 Two recent meta-analyses, one comprising 941 and one 11 prospective studies,40 have been published with the aim to clarify the relationship between coffee consumption and risk of stroke. In particular, in their dose– response meta-analysis of 10,003 stroke cases and 479,689 participants, Larsson and Orsini40 found a significant evidence of a nonlinear association between coffee consumption and risk of stroke. The strongest inverse association was observed in moderate consumers drinking 3–4 cups of coffee per day (RR 0.83, 95% CI 0.74–0.92) compared to nonconsumers (Figure 41.2).40 The associations did not differ in men and women, across geographic regions, years of follow-up, and for ischemic
II. EFFECTS OF COFFEE CONSUMPTION
381
41.3 Coffee and Stroke Risk
TABLE 41.2 Summary of Epidemiologic Studies Relating Coffee Consumption to Stroke Risk References Grobbee
de15
Study
Exposure
Outcome
Summary
The Health Professional Follow-up Study
Total coffee consumption ≥4 cups/ day vs none
Fatal and nonfatal stroke
No increase in stroke risk according to caffeine and caffeinated coffee intake
Stroke subtypes
Inverse association between coffee and ischemic stroke
Caffeinated coffee consumption ≥4 cups/day vs none Decaffeinated coffee consumption ≥4 cups/day vs none Larsson33
α-Tocopherol, β-Carotene Cancer Prevention Study, prospective study: male smokers
Coffee consumption ≥8 cups/day vs <2 cups/day
Cerebral infarction Intracerebral hemorrhages Subarachnoid hemorrhages
Lopez-Garcia34
Nurses’ Health Study
Coffee consumption >4 cups/day vs <1 cup/month
Nonfatal and fatal stoke
Cohort study
Lack of association between coffee and intracerebral or subarachnoid hemorrhage
Long-term coffee consumption is not associated with stroke risk Modest reduced risk of stroke according to coffee consumption
Mukamal35
Stockholm Heart Epidemiology Program
Coffee consumption >7 cups/day vs <1 cup/day
Nonfatal stroke
No association
Sugiyama36
Miyagi cohort study: Japanese men and women
Total coffee consumption ≥1 cups/ day vs never
Fatal strokes
No association between coffee consumption and stroke mortality
Mostofsky37
Stroke onset study, multicenter case-crossover study
Coffee drinkers vs non drinkers
Stroke in subjects with acute ischemic stroke
Increased ischemic stroke risk onset in infrequent coffee drinkers
1 h after 1 serving of coffee 1 h after 1 serving of caffeinated coffee in subjects drinking ≤1 cup/ day
Larsson38
Swedish Mammography Cohort: Finnish women
Coffee consumption >5 cups/day vs <1 cup/day
Nonfatal stroke
Low or no coffee consumption associated with increased stroke risk in women
Mineharu39
Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study)
Coffee consumption ≥3 cups/day vs <1 cup/week
Fatal stroke
Coffee consumption associated with stroke mortality reduction in men
Larsson40
Dose–response meta-analysis Coffee consumption ≥8 cups/day of 11 prospective studies vs none
Stroke
Moderate coffee consumption weakly inversely associated with stroke risk
Floegel9
European Prospective Investigation into Cancer and Nutrition (EPIC-Germany)
Stroke
No association between coffee consumption and stroke
Caffeinated coffee consumption ≥4 cups/day vs <1 cup/day Decaffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Table modified from Ref. 8, Table 2, with permission from Elsevier.
stroke versus hemorrhagic stroke, although statistically significant only for the former.40 These results are indeed largely comparable to those of a meta-analysis published 1 year later by Kim and colleagues.41 In particular, in their pooled analysis of nine prospective studies, the authors found that drinking ≥4 cups of coffee per day was associated with a 17% decreased risk of stroke. In a by-country
subgroup analysis, the authors found a nonstatistically significant RR of 0.86 (95% CI 0.73–1.02) in Americans, as opposed to a significant protective effect of increased coffee drinking on stroke risk (RR 0.82, 95% CI 0.74–0.92) in Europeans. Furthermore, in the latter subgroup, the authors observed a lower risk in women (RR 0.81, 95% CI 0.70–0.93); in those drinking ≥4 cups of coffee per day
II. EFFECTS OF COFFEE CONSUMPTION
382
41. COFFEE AND CARDIOVASCULAR DISEASE
FIGURE 41.2 Adjusted relative risk of stroke associated with coffee consumption in a meta-analysis of published studies, 1966–2011. Coffee consumption was modeled with restricted cubic splines in a multivariate random-effects dose–response model. The lowest value of zero was used to estimate all relative risks. The vertical axis is on a log scale. Taken from Ref. 40. By permission of Oxford University Press (OUP) on behalf of The Johns Hopkins Bloomberg School of Public Health.
(RR 0.83, 95% CI 0.75–0.91), and for ischemic stroke (RR 0.80, 95% CI 0.71–0.90) only.41 However, results from the recently published prospective cohort study EPICGermany that was not included in the latter meta-analysis could not confirm a significant association between coffee consumption and risk of stroke.9 There is, indeed, some evidence that coffee may exert different effects depending on the stroke subtypes.38 Results from the Swedish Mammography Cohort38 suggested a lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage, but not intracerebral hemorrhage strokes in women drinking ≥1 cups of coffee per day versus those drinking ≤1 cup. The protective effect of coffee seemed particularly strong for subarachnoid hemorrhagic strokes, whereas consumption of alcohol, smoking, body mass index, and history of diabetes or hypertension did not modify the observed association between coffee consumption and risk of cerebral infarction.38 Furthermore, in a cohort of 26,556 Finnish male smokers,33 drinking ≥8 cups of coffee per day was inversely related to the risk of cerebral infarction (RR 0.77, 95% CI 0.66–0.90) but not intracerebral or subarachnoid hemorrhage. Further studies, however, could not finally clarify whether there were differences in the impact of coffee consumption to the risk of fatal or nonfatal stroke subtypes.36,42 There are only a few studies supporting a possible harmful effect of coffee on the development of stroke. Mineharu and colleagues39 observed a higher risk of fatal stroke in women drinking at least 3 cups of coffee per day compared to noncoffee drinkers, but not in
men.39 However, as for CHD, there is indication of an acute effect of coffee on the risk of stroke.37 Interestingly, Mostofsky and colleagues observed a two-fold increased risk of ischemic stroke in the first hour after drinking 1 cup of coffee, or less, but not in those drinking coffee more regularly.37These findings are, somehow, in line with those of a very recent study in which the authors found a 20% reduced risk of all strokes in consumers drinking 1, 2, or more cups of coffee per day compared to seldom drinkers.37 Besides, an inverse association between coffee consumption and cerebral infarction was also observed.37 Thus, taking the whole state of research into account, these findings seem to suggest that coffee does not apparently exert any adverse effect on the risk of stroke. However, coffee is rather likely to be protective at moderate consumption, although the observed reduction in risk is small. Indeed, further studies are warranted to better understand which coffee compounds may protect against stroke.
41.4 COFFEE AND HEART FAILURE RISK Heart failure (HF) is a complex clinical syndrome that represents a growing public health problem with a tremendous potential for morbidity43 and mortality.44 Furthermore, HF is a disease with various entities, distinguished by function (diastolic vs systolic), location (left vs right), or disease progression (chronic vs acute), and triggered by prior conditions such as hypertension, obesity, and diabetes, along with a whole series of cardiovascular disorders. At the beginning of the 2000s, Wilhelmsen and colleagues published the results from the Swedish Multifactor Primary Prevention Study suggesting that, in men, atrial fibrillation, stroke, and especially MI were common antecedent or concomitant morbidities in the onset of HF.43 Thus, behind this background, it is not surprising that observational studies have been mostly focused on the contribution of coffee to the risk of CHD, stroke, and CVD mortality, rather than to the risk of HF. Indeed, these authors were also the first mentioning the association between coffee and the risk of HF.43 In their study, a trend toward an increased HF risk was observed in consumers drinking 5 cups of coffee per day, although the increased risk was small (OR 1.17, 95% CI 1.05– 1.30).43 Since then, further publications followed from other northern European populations, especially from Sweden.35,45–47 However, the increased HF risk observed in coffee drinkers by Wilhelmsen and colleagues43 could not be replicated by any of these studies. Rather, most studies showed a protective effect of coffee, although not statistically significant.48 Results from a dose–response meta-analysis of five prospective studies, showed a
II. EFFECTS OF COFFEE CONSUMPTION
383
41.6 Concluding Remarks
TABLE 41.3 Summary of Epidemiologic Studies Relating Coffee Consumption to Heart Failure (HF) Risk References
Study
Exposure
Outcome
Summary
Wilhelmsen43
Swedish multifactor primary prevention study
Coffee consumption >5 cups/day vs none
HF
Weak positive association between coffee consumption and HF risk
Ahmed45
Prospective cohort study in Swedish men
Coffee consumption ≥5 cups/day vs <1 cup/day
HF hospitalization or mortality
High coffee consumption is not associated with increased rates of HF hospitalization or mortality
Mukamal35
Stockholm Heart Epidemiology Program, cohort study
Coffee consumption 5–7 cups/day vs 1–3 cups/ day
Mortality after acute MI
Coffee intake is not associated with hospitalization for congestive heart failure or stroke
Levitan46
Swedish Mammography Coffee consumption Cohort ≥5 cups/day vs <1 cup/day
HF hospitalization or death from HF
No association between coffee consumption and incidence of HF events
Wang47
FINRISK study, cohort study
Coffee consumption ≥10 cups/day vs none
HF
Coffee consumption does not increase HF risk
Mostofsky48
Dose–response metaanalysis of prospective studies
Coffee consumption ≥11 cups/day vs none
HF
Significant J-shaped relationship between coffee consumption and HF risk; strongest inverse association for 4 servings/day
significant J-shaped relationship between coffee consumption and HF risk.48 The strongest inverse association was observed for a moderate consumption of 4 or 5 servings per day (pooled RR 0.89, 95% CI 0.81–0.99), after which the curve reached a plateau and reverted at higher levels of consumption.48 Although these findings seem to suggest no detrimental effects of coffee consumption on the risk of HF, until now evidence in this field is limited to Scandinavian studies. Perhaps, the relationship between coffee and HF might differ by region. Thus, to provide a more complete picture, further studies with different cultural and geographic backgrounds, or with different HF entities (such as diastolic and systolic), are warranted (Table 41.3).
41.5 COFFEE AND CVD MORTALITY Besides the detrimental effects attributed to caffeine and diterpene alcohols in raising the cardiovascular risk, coffee contains antioxidant compounds that could contribute to a reduction in CVD mortality.4 Although an early meta-analysis on coffee consumption and coronary death showed inconclusive results,11 later and more recent epidemiologic studies have shown a U-shaped relationship between coffee consumption and CVD mortality.18,29,34,39,49,50 At the beginning of the 2000s, in a Finnish population, men not drinking coffee showed a risk ratio for CHD mortality of 1.88 (95% CI 1.20–2.95) compared to habitual consumers.18 The relationship was J-shaped in the age-adjusted analysis, but it changed when smoking status, serum cholesterol level, BP, and previous MI were added to the model. The authors therefore concluded
that not only was coffee drinking not harmful, but also the slight increased CHD mortality observed in heavy coffee drinkers was largely explained by the effects of smoking and high serum cholesterol level.18 Furthermore, they put forward that the increased CHD mortality, observed in men not drinking coffee might have been attributed to some underlying diseases that led to a reduction in coffee consumption.18 Recently, de Koning Gans and colleagues29 observed a U-shaped association between coffee consumption and CHD mortality for 3–6 cups/day with an HR of 0.64, although the association did not reach the customary level of statistical significance. Nevertheless, a dose– response relationship with CVD mortality was already observed in the Iowa Women’s Health Study whose results suggested a 24% decreased CVD mortality in people drinking 1–3 cups of coffee per day.49 Furthermore, in two large cohort studies, the inverse association between coffee consumption and all-cause mortality observed in both men and women was independent of caffeine intake and mainly explained by a reduction in CVD mortality.34 All in all, these findings seem to suggest that coffee drinking is harmless, although it cannot be ruled out the possibility that in both men and women excessive coffee consumption might increase the risk of mortality from CVD.
41.6 CONCLUDING REMARKS Lifestyle changes may have a key role in the prevention of CVD. Although regular consumption of moderate quantities of coffee seems to be associated with a small protection against CVD, results from
II. EFFECTS OF COFFEE CONSUMPTION
384
41. COFFEE AND CARDIOVASCULAR DISEASE
epidemiologic studies are conflicting. A nonlinear dose– response relationship between coffee intake and CVD risk may explain the heterogeneity in findings. In fact, the American Heart Association so far suggests that a moderate consumption of 1–2 cups of coffee per day does not seem to be harmful for the cardiovascular system (http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/HealthyDietGoals/Caffeine-and -Heart-Disease_UCM_305888_Article.jsp), rather “possibly” useful (http://newsroom.heart.org/news/regu lar-moderate-coffee-drinking-235549). In contrast, the effect of high caffeine intake on the risk of CHD is still under debate. Thus, moderation seems to be the keyword that may simplify this controversial topic. In fact, the possible health effects of coffee on both CVD morbidity and mortality have been observed at moderate intake, whereas they disappear at heavy or very heavy consumption.
41.7 SUMMARY POINTS • A decreased risk of both CVDs morbidity and mortality has been observed at moderate intake of coffee. • Possible health effects disappear at heavy or very heavy coffee consumption. • Slow caffeine metabolizers may be at increased risk of nonfatal MI. • A nonlinear dose–response relationship between coffee and caffeine intake and CHD risk may explain the heterogeneous findings. • Coffee consumption does not apparently exert any adverse effect on the risk of stroke or HF.
Acknowledgments We thank Lisa Eggebrecht for help with systematic literature research. We are indebted to the Oxford University Press (OUP), to the Johns Hopkins Bloomberg School of Public Health, and to the authors of the paper Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose–response meta-analysis of prospective studies. Am J Epidemiol 2011;174:993–1001 in allowing us to reproduce Figure 41.2. We are indebted to Elsevier Publisher in allowing us to reproduce and modify Table 41.2 from: “Di Castelnuovo A, di Giuseppe R, Iacoviello L, de Gaetano G. Consumption of cocoa, tea and coffee and risk of cardiovascular disease. Eur J Intern Med 2012;23:15–25.
References 1. Yanagimoto K, Ochi H, Lee KG, Shibamoto T. Antioxidative activities of fractions obtained from brewed coffee. J Agric Food Chem 2004;52:592–6. 2. Spiller MA. The chemical components of coffee. Prog Clin Biol Res 1984;158:91–147. 3. Urgert R, Katan MB. The cholesterol-raising factor from coffee beans. Annu Rev Nutr 1997;17:305–24.
4. Cornelis MC, El-Sohemy A. Coffee, caffeine, and coronary heart disease. Curr Opin Clin Nutr Metab Care 2007;10:745–51. 5. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 2006;295:1135–41. 6. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, et al. Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21–181. 7. Paul O, Lepper MH, Phelan WH, Dupertuis GW, Macmillan A, et al. A longitudinal study of coronary heart disease. Circulation 1963;28:20–31. 8. Di Castelnuovo A, di Giuseppe R, Iacoviello L, de Gaetano G. Consumption of cocoa, tea and coffee and risk of cardiovascular disease. Eur J Intern Med 2012;23:15–25. 9. Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, et al. Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)Germany study. Am J Clin Nutr 2012;95:901–8. 10. Myers MG, Basinski A. Coffee and coronary heart disease. Arch Intern Med 1992;152:1767–72. 11. Greenland S. A meta-analysis of coffee, myocardial infarction, and coronary death. Epidemiology 1993;4:366–74. 12. Kawachi I, Colditz GA, Stone CB. Does coffee drinking increase the risk of coronary heart disease? Results from a meta-analysis. Br Heart J 1994;72:269–75. 13. Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A, et al. Coffee consumption and risk of coronary heart disease: a meta-analysis. Nutr Metab Cardiovasc Dis 2007;17:209–23. 14. Wu JN, Ho SC, Zhou C, Ling WH, Chen WQ, et al. Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21 prospective cohort studies. Int J Cardiol 2009;137:216–25. 15. Grobbee DE, Rimm EB, Giovannucci E, Colditz G, Stampfer M, et al. Coffee, caffeine, and cardiovascular disease in men. N Engl J Med 1990;323:1026–32. 16. Willett WC, Stampfer MJ, Manson JE, Colditz GA, Rosner BA, et al. Coffee consumption and coronary heart disease in women. A tenyear follow-up. JAMA 1996;275:458–62. 17. Woodward M, Tunstall-Pedoe H. Coffee and tea consumption in the Scottish Heart Health Study follow up: conflicting relations with coronary risk factors, coronary disease, and all cause mortality. J Epidemiol Community Health 1999;53:481–7. 18. Kleemola P, Jousilahti P, Pietinen P, Vartiainen E, Tuomilehto J. Coffee consumption and the risk of coronary heart disease and death. Arch Intern Med 2000;160:3393–400. 19. Hammar N, Andersson T, Alfredsson L, Reuterwall C, Nilsson T, et al. Association of boiled and filtered coffee with incidence of first nonfatal myocardial infarction: the SHEEP and the VHEEP study. J Intern Med 2003;253:653–9. 20. Happonen P, Voutilainen S, Salonen JT. Coffee drinking is dosedependently related to the risk of acute coronary events in middleaged men. J Nutr 2004;134:2381–6. 21. Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045–53. 22. Azevedo A, Barros H. Coffee and myocardial infarction: heterogeneity of an association in Portuguese men. Eur J Cardiovasc Prev Rehabil 2006;13:268–73. 23. 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;17:506–11. 24. Corti R, Binggeli C, Sudano I, Spieker L, Hanseler E, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 2002;106:2935–40.
II. EFFECTS OF COFFEE CONSUMPTION
References
25. Ranheim T, Halvorsen B. Coffee consumption and human health– beneficial or detrimental?–Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus. Mol Nutr Food Res 2005;49:274–84. 26. Nilsson LM, Wennberg M, Lindahl B, Eliasson M, Jansson JH, et al. Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction; a nested case/referent study. Nutr Metab Cardiovasc Dis 2010;20:527–35. 27. Cai L, Ma D, Zhang Y, Liu Z, Wang P. The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 2012;66:872–7. 28. Weggemans RM, Zock PL, Ordovas JM, Ramos-Galluzzi J, Katan MB. Genetic polymorphisms and lipid response to dietary changes in humans. Eur J Clin Invest 2001;31:950–7. 29. de Koning Gans JM, Uiterwaal CS, van der Schouw YT, Boer JM, Grobbee DE, et al. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler Thromb Vasc Biol 2010;30: 1665–71. 30. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kokkinos P, Toutouzas P, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228–32. 31. Natella F, Nardini M, Belelli F, Scaccini C. Coffee drinking induces incorporation of phenolic acids into LDL and increases the resistance of LDL to ex vivo oxidation in humans. Am J Clin Nutr 2007;86:604–9. 32. Riksen NP, Rongen GA, Smits P. Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol Ther 2009;121:185–91. 33. Larsson SC, Mannisto S, Virtanen MJ, Kontto J, Albanes D, et al. Coffee and tea consumption and risk of stroke subtypes in male smokers. Stroke 2008;39:1681–7. 34. Lopez-Garcia E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB. The relationship of coffee consumption with mortality. Ann Intern Med 2008;148:904–14. 35. Mukamal KJ, Hallqvist J, Hammar N, Ljung R, Gemes K, et al. Coffee consumption and mortality after acute myocardial infarction: the Stockholm Heart Epidemiology Program. Am Heart J 2009;157:495–501. 36. Sugiyama K, Kuriyama S, Akhter M, Kakizaki M, Nakaya N, et al. Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women. J Nutr 2010;140:1007–13.
385
37. Mostofsky E, Schlaug G, Mukamal KJ, Rosamond WD, Mittleman MA. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 2010;75:1583–8. 38. Larsson SC, Virtamo J, Wolk A. Coffee consumption and risk of stroke in women. Stroke 2011;42:908–12. 39. Mineharu Y, Koizumi A, Wada Y, Iso H, Watanabe Y, et al. Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women. J Epidemiol Community Health 2011;65:230–40. 40. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol 2011;174:993–1001. 41. Kim B, Nam Y, Kim J, Choi H, Won C. Coffee consumption and stroke risk: a meta-analysis of epidemiologic studies. Korean J Fam Med 2012;33:356–65. 42. Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode KM, Logroscino G, Hu FB, et al. Coffee consumption and risk of stroke in women. Circulation 2009;119:1116–23. 43. Wilhelmsen L, Rosengren A, Eriksson H, Lappas G. Heart failure in the general population of men–morbidity, risk factors and prognosis. J Intern Med 2001;249:253–61. 44. Fitzgibbons TP, Meyer TE, Aurigemma GP. Mortality in diastolic heart failure: an update. Cardiol Rev 2009;17:51–5. 45. Ahmed HN, Levitan EB, Wolk A, Mittleman MA. Coffee consumption and risk of heart failure in men: an analysis from the Cohort of Swedish Men. Am Heart J 2009;158:667–72. 46. Levitan EB, Ahmed HN, Mittleman MA, Wolk A. Coffee consumption and incidence of heart failure in women. Circ Heart Fail 2011;4:414–8. 47. Wang Y, Tuomilehto J, Jousilahti P, Antikainen R, Mahonen M, et al. Coffee consumption and the risk of heart failure in Finnish men and women. Heart 2011;97:44–8. 48. Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure: a dose-response metaanalysis. Circ Heart Fail 2012;5:401–5. 49. Andersen LF, Jacobs Jr DR, Carlsen MH, Blomhoff R. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. Am J Clin Nutr 2006;83:1039–46. 50. Bidel S, Hu G, Qiao Q, Jousilahti P, Antikainen R, et al. Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes. Diabetologia 2006;49:2618–26.
II. EFFECTS OF COFFEE CONSUMPTION
41
Coffee and Risk of Cardiovascular Disease: An Overview of Epidemiologic Studies Romina di Giuseppe*, Janine Wirth*, Cornelia Weikert Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
List of Abbreviations AMI Acute myocardial infarction ACS Acute coronary syndrome BP Blood pressure CI Confidence interval CHD Coronary heart disease CVD Cardiovascular disease EPIC European Prospective Investigation into Cancer and Nutrition HF Heart failure HR Hazard ratio MI Myocardial infarction MSA Muscle sympathetic nervous activity OR Odds ratio RR Relative risk
41.1 INTRODUCTION Coffee, one of the most popular (brewed) beverages, is prepared from the roasted coffee beans of the homonymous plant. Its particular and intense taste, flavor and chemical properties make it the most consumed nonalcoholic drink worldwide. Indeed, coffee is particularly appreciated for its stimulatory effects, mainly attributed to the caffeine content, which may help consumers to feel more alert and awake. In fact, coffee helps us to wake up in the morning or to get regenerated during a break from daily work activities. Also, social rituals make coffee particularly pleasant, for instance, by simply sharing a relaxing cup of “espresso” with friends. But, apart from being the main source of caffeine, coffee also contains several other compounds, some with antioxidant properties,1 such as chlorogenic acid, flavonoids, melanoidins, furans, pyrroles, and maltol, to name a few.2 However, some coffee bean compounds, the diterpenoid cafestol and kahweol, have * Both
been accused of raising serum cholesterol levels, thus posing possible cardiovascular health threats.3 In contrast, being a high source of antioxidant, coffee may contribute to a lower risk of coronary heart disease (CHD), at least in moderate drinkers4 who quickly metabolize caffeine.5 Nevertheless, braced by a long history, coffee has generated a plethora of controversial research findings, particularly when they encompass the cardiovascular diseases (CVDs).4 CVDs are the most common cause of morbidity and mortality in developed countries, with CHD, stroke, and heart failure being the familiar contributors.6 Thus, considering the global burden of CVD along with the popularity of coffee, even small health effects of coffee could have substantial public health impact. With the aim to provide the state-of-the-art compilations of current knowledge of the relationship between coffee and risk of major CVD endpoints, this chapter presents an overview of epidemiologic evidence.
41.2 COFFEE AND CHD RISK It was in 1963 that, for the first time, coffee came into the limelight because of its negative effect on human health.7 In particular, in their pioneering study, Paul and colleagues7 observed a positive relationship between coffee consumption and CHD development. However, although some studies found a link between coffee consumption and CHD risk, later epidemiologic studies did not provide any significant evidence.3 Indeed, a major flaw of these early observational studies is the inadequate adjustment for confounding, as already highlighted by others.4
authors contributed equally to this work.
Coffee in Health and Disease Prevention http://dx.doi.org/10.1016/B978-0-12-409517-5.00041-3
377
© 2015 Elsevier Inc. All rights reserved.
378
41. COFFEE AND CARDIOVASCULAR DISEASE
FIGURE 41.1 Confounding diagram of smoking on the relationship between coffee drinking and risk of CHD. The figure shows that the relationship between coffee drinking (exposure) and CHD (outcome) is noncausal but mediated by smoking (confounding factor).
As shown in Figure 41.1, smoking—among others— is a clear confounder in the association between coffee drinking and CHD, as heavy drinkers are also more likely to smoke. And, certainly, this figure may also explain the original finding of Paul et al.7 In fact, in more recent studies taking into account potential confounding risk factors, a moderate coffee consumption did not significantly increase the risk of CHD, especially when only prospective studies were reviewed.8 This concept has been recently supported by the findings from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Germany study, in which no significant association was observed between caffeinated coffee consumption and risk of myocardial infarction (MI).9 However, large discrepancies exist when results from case–control studies are compared to those from prospective studies (for a summary of these studies and relative references, please refer to Table 41.1), as confirmed by early10–12 and more recent meta-analyses.13,14 At the beginning of the 1990s, three comprehensive meta-analyses investigating coffee consumption in relation to CHD10–12 were published with conflicting results. Myers et al.10 observed a nonsignificant pooled relative risk (RR) of 1.09 (95% confidence interval (CI) 0.97–1.22) for the association between coffee consumption (4–6 and ≥6 cups/day vs ≥1 cup/day) and CHD, when results from 11 cohort studies were considered. One year later, Greenland et al.11 in a meta-analysis of eight case– control and 14 cohort studies, found an increased CHD risk among coffee consumers drinking 5 cups/day versus nonconsumers, but only in case–control studies. These findings were confirmed in a meta-analysis of eight case–control and 15 cohort studies published by Kawachi et al., where an increased CHD risk was observed in case–control data (pooled odds ratio (OR) 1.63, 95% CI 1.50–1.78; pooled cohort study RR 1.05, 95% CI 0.99–1.12).12 Two more recent meta-analyses of, respectively, 1013 and 21 prospective cohort studies14 have indeed confirmed these previous findings. Interestingly, Wu et al.14 instead found a lower CHD risk in both men (RR 0.87, 95% CI 0.80–0.86) and women
(RR 0.82, 95% CI 0.73–0.92) regularly indulging in a moderate coffee consumption (1–3 or 3–4 cups/day).14 As highlighted by Sofi and colleagues,13 the disagreement between case–control and cohort studies could be attributed to systematic errors such as recall bias (i.e., cases are more likely to overreport coffee intake than healthy controls) or to the lack of inclusion of fatal events in case–control studies, which likely contributes to differences among outcome measures.13 However, it cannot be ruled out that coffee may have a transient (acute) effect on CHD, thus making the preservation of the temporal relationship in longitudinal studies particularly weak. Results from a case-crossover study suggested that coffee may act as a trigger of a first MI, with an RR of 1.49 (95% CI 1.17–1.89) in the hour after coffee intake.23 This risk seemed to be particularly strong in occasional coffee drinkers (≤1 cup/day, RR 4.14, 95% CI 2.03–8.42), in sedentary patients (RR 1.72, 95% CI 1.30–2.30), or in patients with three or more risk factors (RR 2.10, 95% CI 1.30–3.39).23 Yet, several other factors should be taken into account when coffee consumption is investigated in relation to CHD, such as the caffeine content of coffee beverages, coffee preparation and metabolism, and the doses of consumption. In a study conducted in six habitual and nine nonhabitual coffee drinkers, the authors observed in the latter group an acute increase in both blood pressure (BP) and muscle sympathetic nervous activity (MSA) after coffee and caffeine intake.24 Because decaffeinated coffee also increased BP and MSA in nonhabitual drinkers, the authors put forward that other compounds present in coffee, other than caffeine, may boost cardiovascular risk.24 Although not confirmed in other studies, Floegel and colleagues found a positive association between decaffeinated coffee consumption and risk of MI.9 However, this association was no longer significant after the authors excluded all MI cases occurred during the first 2 years of follow-up, thus speculating that reverse causation might have been responsible for the observed association. Several lines of evidence suggest that boiled coffee raises cholesterol levels,4 an effect mainly attributed to the diterpene lipids cafestol and kahweol.3 Indeed, the use of a paper filter during coffee preparation seems sufficient to limit the content of these “hypercholesterolemic” compounds,4 thus making a moderate filtered coffee consumption a harmless heart habit.25 Results from the SHEEP and the VHEEP study,19 a population-based case–control study, showed a 1.4 times higher incidence of first nonfatal MI in men drinking boiled coffee versus those drinking filtered coffee, with an even higher risk for women (RR 1.63, 95% CI 1.04–2.56) (Table 41.1). More
II. EFFECTS OF COFFEE CONSUMPTION
379
41.2 Coffee and CHD Risk
TABLE 41.1 Summary of Epidemiologic Studies Relating Coffee Consumption to Coronary Heart Disease (CHD) Risk References
Study
Exposure
Outcome
Summary
Grobbee15
The Health Professional Follow-up Study, longitudinal study
Total coffee consumption ≥4 cups/ day vs none
Nonfatal myocardial infarction (MI) and CHD eath Total CHD
No increase in CHD according to caffeine and caffeinated coffee intake
Caffeinated coffee consumption ≥4 cups/day vs none Decaffeinated coffee consumption ≥4 cups/day vs none
Moderate CHD risk increase for decaffeinated coffee
Myers10
11 prospective studies, meta-analysis
Coffee intake, ≥6 cups/ day vs ≤1 cup/day
Coronary events
No association between coffee consumption and CHD
Greenland11
8 case–control studies + 14 cohort studies, meta-analysis
Coffee intake 5 cups/ day vs none
MI
Weak increase in CHD risk for heavy coffee consumption in cohort studies
Kawachi12
8 case–control and 15 cohort studies, meta-analysis
Coffee drinking, ≥5 cups/ day vs none
CHD
Increased CHD risk in heavy drinkers Weak increased CHD risk in habitual coffee drinkers
Willet16
Prospective cohort study
Coffee intake ≥6 cups/day vs none
CHD
No association between caffeinated and decaffeinated coffee and caffeine consumption and CHD risk
Woodward17
Scottish Heart Health Study, cohort study
Coffee consumption ≥5 vs none
CHD
Moderate benefit from coffee consumption
Kleemola18
Finnish men and women
Coffee consumption >7 cups/ day vs 1–34 cups/day
Non fatal MI
No association between coffee drinking and CHD risk
Hammar19
The SHEEP and the VHEEP study, population-based case–control study
Consumption >9 dl filtered coffee/ day vs ≤3 dl/day
First nonfatal MI
In men drinking boiled coffee incidence of first nonfatal MI 1.4 times higher vs men drinking filtered coffee, with an even higher risk for women
Consumption >9 dl mixed coffee/day vs ≤3 dl/day Consumption >9 dl boiled coffee/day vs ≤3 dl/day Boiled vs filtered coffee
Happonen20
The Kuopio Ischemic Heart Disease Risk Factor Study, prospective study
Boiled coffee increases the occurrence of first nonfatal MI
Moderate drinkers vs heavy drinkers (≥814 ml/day)
Acute coronary events Heavy coffee drinking (MI or coronary raises the risk of acute MI or death) coronary death
Lopez-Garcia21 Prospective cohort study
Coffee intake, ≥6 cups/day vs <1 cup/month
CHD
No indication that coffee (or caffeine) intake increases CHD
Azevedo22
Community-based case–control study
Regular ever coffee drinkers
Acute myocardial infarction (AMI)
Significant decreased MI risk in men with no family history of AMI; nonsignificant increased MI risk in men with family history of AMI
Baylin23
Costa Rica, case-crossover design
Habitual coffee consumption
Nonfatal MI, 1 h after coffee drinking
Coffee intake probably triggers MI risk
≤1 cup/day 2–3 cups/day ≥4 cups/day
Continued
II. EFFECTS OF COFFEE CONSUMPTION
380
41. COFFEE AND CARDIOVASCULAR DISEASE
TABLE 41.1 Summary of Epidemiologic Studies Relating Coffee Consumption to Coronary Heart Disease (CHD) Risk—cont’d References
Study
Exposure
Outcome
Summary
Cornelis5
Slow caffeine metabolizer
Coffee intake ≥4 cups/day vs <1 cup/day
First acute nonfatal MI
Increased MI risk only in subjects with impaired caffeine metabolism
Sofi13
13 case–control studies + 10 cohort studies, meta-analysis
Coffee intake ≥4 cups/ day vs none
CHD
Coffee consumption is not associated with an increased risk of CHD
Wu14
21 prospective cohort studies, Coffee consumption <1 cup/day meta-analysis (United States) or ≤2 cups/day (Europe) vs ≥6 or ≥7 cups/day
CHD
No long-term increased CHD risk
Moderate coffee consumption Floegel9
European Prospective Investigation into Cancer and Nutrition (EPIC-Germany)
Caffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Lower CHD risk in moderate coffee drinker women MI
No association between coffee consumption and MI
Decaffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Table modified from Ref. 8, Table 2, with permission from Elsevier.
recently, in a nested case/referent study, men drinking filtered coffee four or more times per day showed an increased MI risk (OR 1.73, 95% CI 1.05–2.84), compared to those drinking filtered coffee one or no times per day. In women, a positive association was observed for boiled coffee (OR 2.51, 95% CI 1.08–5.86) in univariate analysis only.26 Results from a recent meta-analysis of randomized controlled trials suggest that drinking unfiltered coffee significantly increases, in a positive dose–response relationship, total cholesterol, low-density lipoprotein (LDL)-cholesterol, and triglyceride levels.27 Interestingly, Weggemans and colleagues28 observed increased LDL-cholesterol levels in response to cafestol, but only in homozygous carriers of the C allele of the ApoA1 83 genotype. Years later, Cornelis et al. observed, for the first time, an increased risk of nonfatal MI in slow caffeine metabolizers, thus putting forward a role of caffeine in the development of this disease.5 However, a nonlinear dose–response relationship between coffee (and caffeine) intake and CHD risk may explain the heterogeneous findings from different studies, which typically investigated the role of coffee at various doses, and, partly, the null findings of meta-analyses. de Koning Gans and colleagues observed a U-shaped relationship between CHD morbidity and coffee consumption with a hazard ratio (HR) of 0.79 (95% CI 0.65– 0.96) in healthy men and women drinking between 2.1 and 6 cups of coffee per day.29 A “J-shaped” relationship between acute coronary syndrome (ACS) and coffee was already observed in a previous study of Panagiotakos et al.30 In particular, they found a lower coronary risk for
moderate coffee consumption (<300 ml coffee/day; OR 0.69, 95% CI 0.50–0.86) and a significant increased risk for heavy or very heavy consumption (>300 ml coffee/ day; OR 3.10, 95% CI 1.82–5.26).30 These findings indeed suggest that more accurate quantitative reviews of the literature that consider the “J- or U-shaped” relationship between coffee and CHD risk are warranted, to clarify this issue.
41.3 COFFEE AND STROKE RISK As for CHD, studies examining the association between coffee consumption and risk of stroke have produced inconsistent findings (Table 41.2). Indeed, coffee may exert protective effects on stroke, for instance, by positively affecting the risk of atherosclerosis,31,32 although this potential health effect could be counterbalanced by slight acute rise in BP after coffee consumption.32 Two recent meta-analyses, one comprising 941 and one 11 prospective studies,40 have been published with the aim to clarify the relationship between coffee consumption and risk of stroke. In particular, in their dose– response meta-analysis of 10,003 stroke cases and 479,689 participants, Larsson and Orsini40 found a significant evidence of a nonlinear association between coffee consumption and risk of stroke. The strongest inverse association was observed in moderate consumers drinking 3–4 cups of coffee per day (RR 0.83, 95% CI 0.74–0.92) compared to nonconsumers (Figure 41.2).40 The associations did not differ in men and women, across geographic regions, years of follow-up, and for ischemic
II. EFFECTS OF COFFEE CONSUMPTION
381
41.3 Coffee and Stroke Risk
TABLE 41.2 Summary of Epidemiologic Studies Relating Coffee Consumption to Stroke Risk References Grobbee
de15
Study
Exposure
Outcome
Summary
The Health Professional Follow-up Study
Total coffee consumption ≥4 cups/ day vs none
Fatal and nonfatal stroke
No increase in stroke risk according to caffeine and caffeinated coffee intake
Stroke subtypes
Inverse association between coffee and ischemic stroke
Caffeinated coffee consumption ≥4 cups/day vs none Decaffeinated coffee consumption ≥4 cups/day vs none Larsson33
α-Tocopherol, β-Carotene Cancer Prevention Study, prospective study: male smokers
Coffee consumption ≥8 cups/day vs <2 cups/day
Cerebral infarction Intracerebral hemorrhages Subarachnoid hemorrhages
Lopez-Garcia34
Nurses’ Health Study
Coffee consumption >4 cups/day vs <1 cup/month
Nonfatal and fatal stoke
Cohort study
Lack of association between coffee and intracerebral or subarachnoid hemorrhage
Long-term coffee consumption is not associated with stroke risk Modest reduced risk of stroke according to coffee consumption
Mukamal35
Stockholm Heart Epidemiology Program
Coffee consumption >7 cups/day vs <1 cup/day
Nonfatal stroke
No association
Sugiyama36
Miyagi cohort study: Japanese men and women
Total coffee consumption ≥1 cups/ day vs never
Fatal strokes
No association between coffee consumption and stroke mortality
Mostofsky37
Stroke onset study, multicenter case-crossover study
Coffee drinkers vs non drinkers
Stroke in subjects with acute ischemic stroke
Increased ischemic stroke risk onset in infrequent coffee drinkers
1 h after 1 serving of coffee 1 h after 1 serving of caffeinated coffee in subjects drinking ≤1 cup/ day
Larsson38
Swedish Mammography Cohort: Finnish women
Coffee consumption >5 cups/day vs <1 cup/day
Nonfatal stroke
Low or no coffee consumption associated with increased stroke risk in women
Mineharu39
Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study)
Coffee consumption ≥3 cups/day vs <1 cup/week
Fatal stroke
Coffee consumption associated with stroke mortality reduction in men
Larsson40
Dose–response meta-analysis Coffee consumption ≥8 cups/day of 11 prospective studies vs none
Stroke
Moderate coffee consumption weakly inversely associated with stroke risk
Floegel9
European Prospective Investigation into Cancer and Nutrition (EPIC-Germany)
Stroke
No association between coffee consumption and stroke
Caffeinated coffee consumption ≥4 cups/day vs <1 cup/day Decaffeinated coffee consumption ≥4 cups/day vs <1 cup/day
Table modified from Ref. 8, Table 2, with permission from Elsevier.
stroke versus hemorrhagic stroke, although statistically significant only for the former.40 These results are indeed largely comparable to those of a meta-analysis published 1 year later by Kim and colleagues.41 In particular, in their pooled analysis of nine prospective studies, the authors found that drinking ≥4 cups of coffee per day was associated with a 17% decreased risk of stroke. In a by-country
subgroup analysis, the authors found a nonstatistically significant RR of 0.86 (95% CI 0.73–1.02) in Americans, as opposed to a significant protective effect of increased coffee drinking on stroke risk (RR 0.82, 95% CI 0.74–0.92) in Europeans. Furthermore, in the latter subgroup, the authors observed a lower risk in women (RR 0.81, 95% CI 0.70–0.93); in those drinking ≥4 cups of coffee per day
II. EFFECTS OF COFFEE CONSUMPTION
382
41. COFFEE AND CARDIOVASCULAR DISEASE
FIGURE 41.2 Adjusted relative risk of stroke associated with coffee consumption in a meta-analysis of published studies, 1966–2011. Coffee consumption was modeled with restricted cubic splines in a multivariate random-effects dose–response model. The lowest value of zero was used to estimate all relative risks. The vertical axis is on a log scale. Taken from Ref. 40. By permission of Oxford University Press (OUP) on behalf of The Johns Hopkins Bloomberg School of Public Health.
(RR 0.83, 95% CI 0.75–0.91), and for ischemic stroke (RR 0.80, 95% CI 0.71–0.90) only.41 However, results from the recently published prospective cohort study EPICGermany that was not included in the latter meta-analysis could not confirm a significant association between coffee consumption and risk of stroke.9 There is, indeed, some evidence that coffee may exert different effects depending on the stroke subtypes.38 Results from the Swedish Mammography Cohort38 suggested a lower risk of total stroke, cerebral infarction, and subarachnoid hemorrhage, but not intracerebral hemorrhage strokes in women drinking ≥1 cups of coffee per day versus those drinking ≤1 cup. The protective effect of coffee seemed particularly strong for subarachnoid hemorrhagic strokes, whereas consumption of alcohol, smoking, body mass index, and history of diabetes or hypertension did not modify the observed association between coffee consumption and risk of cerebral infarction.38 Furthermore, in a cohort of 26,556 Finnish male smokers,33 drinking ≥8 cups of coffee per day was inversely related to the risk of cerebral infarction (RR 0.77, 95% CI 0.66–0.90) but not intracerebral or subarachnoid hemorrhage. Further studies, however, could not finally clarify whether there were differences in the impact of coffee consumption to the risk of fatal or nonfatal stroke subtypes.36,42 There are only a few studies supporting a possible harmful effect of coffee on the development of stroke. Mineharu and colleagues39 observed a higher risk of fatal stroke in women drinking at least 3 cups of coffee per day compared to noncoffee drinkers, but not in
men.39 However, as for CHD, there is indication of an acute effect of coffee on the risk of stroke.37 Interestingly, Mostofsky and colleagues observed a two-fold increased risk of ischemic stroke in the first hour after drinking 1 cup of coffee, or less, but not in those drinking coffee more regularly.37These findings are, somehow, in line with those of a very recent study in which the authors found a 20% reduced risk of all strokes in consumers drinking 1, 2, or more cups of coffee per day compared to seldom drinkers.37 Besides, an inverse association between coffee consumption and cerebral infarction was also observed.37 Thus, taking the whole state of research into account, these findings seem to suggest that coffee does not apparently exert any adverse effect on the risk of stroke. However, coffee is rather likely to be protective at moderate consumption, although the observed reduction in risk is small. Indeed, further studies are warranted to better understand which coffee compounds may protect against stroke.
41.4 COFFEE AND HEART FAILURE RISK Heart failure (HF) is a complex clinical syndrome that represents a growing public health problem with a tremendous potential for morbidity43 and mortality.44 Furthermore, HF is a disease with various entities, distinguished by function (diastolic vs systolic), location (left vs right), or disease progression (chronic vs acute), and triggered by prior conditions such as hypertension, obesity, and diabetes, along with a whole series of cardiovascular disorders. At the beginning of the 2000s, Wilhelmsen and colleagues published the results from the Swedish Multifactor Primary Prevention Study suggesting that, in men, atrial fibrillation, stroke, and especially MI were common antecedent or concomitant morbidities in the onset of HF.43 Thus, behind this background, it is not surprising that observational studies have been mostly focused on the contribution of coffee to the risk of CHD, stroke, and CVD mortality, rather than to the risk of HF. Indeed, these authors were also the first mentioning the association between coffee and the risk of HF.43 In their study, a trend toward an increased HF risk was observed in consumers drinking 5 cups of coffee per day, although the increased risk was small (OR 1.17, 95% CI 1.05– 1.30).43 Since then, further publications followed from other northern European populations, especially from Sweden.35,45–47 However, the increased HF risk observed in coffee drinkers by Wilhelmsen and colleagues43 could not be replicated by any of these studies. Rather, most studies showed a protective effect of coffee, although not statistically significant.48 Results from a dose–response meta-analysis of five prospective studies, showed a
II. EFFECTS OF COFFEE CONSUMPTION
383
41.6 Concluding Remarks
TABLE 41.3 Summary of Epidemiologic Studies Relating Coffee Consumption to Heart Failure (HF) Risk References
Study
Exposure
Outcome
Summary
Wilhelmsen43
Swedish multifactor primary prevention study
Coffee consumption >5 cups/day vs none
HF
Weak positive association between coffee consumption and HF risk
Ahmed45
Prospective cohort study in Swedish men
Coffee consumption ≥5 cups/day vs <1 cup/day
HF hospitalization or mortality
High coffee consumption is not associated with increased rates of HF hospitalization or mortality
Mukamal35
Stockholm Heart Epidemiology Program, cohort study
Coffee consumption 5–7 cups/day vs 1–3 cups/ day
Mortality after acute MI
Coffee intake is not associated with hospitalization for congestive heart failure or stroke
Levitan46
Swedish Mammography Coffee consumption Cohort ≥5 cups/day vs <1 cup/day
HF hospitalization or death from HF
No association between coffee consumption and incidence of HF events
Wang47
FINRISK study, cohort study
Coffee consumption ≥10 cups/day vs none
HF
Coffee consumption does not increase HF risk
Mostofsky48
Dose–response metaanalysis of prospective studies
Coffee consumption ≥11 cups/day vs none
HF
Significant J-shaped relationship between coffee consumption and HF risk; strongest inverse association for 4 servings/day
significant J-shaped relationship between coffee consumption and HF risk.48 The strongest inverse association was observed for a moderate consumption of 4 or 5 servings per day (pooled RR 0.89, 95% CI 0.81–0.99), after which the curve reached a plateau and reverted at higher levels of consumption.48 Although these findings seem to suggest no detrimental effects of coffee consumption on the risk of HF, until now evidence in this field is limited to Scandinavian studies. Perhaps, the relationship between coffee and HF might differ by region. Thus, to provide a more complete picture, further studies with different cultural and geographic backgrounds, or with different HF entities (such as diastolic and systolic), are warranted (Table 41.3).
41.5 COFFEE AND CVD MORTALITY Besides the detrimental effects attributed to caffeine and diterpene alcohols in raising the cardiovascular risk, coffee contains antioxidant compounds that could contribute to a reduction in CVD mortality.4 Although an early meta-analysis on coffee consumption and coronary death showed inconclusive results,11 later and more recent epidemiologic studies have shown a U-shaped relationship between coffee consumption and CVD mortality.18,29,34,39,49,50 At the beginning of the 2000s, in a Finnish population, men not drinking coffee showed a risk ratio for CHD mortality of 1.88 (95% CI 1.20–2.95) compared to habitual consumers.18 The relationship was J-shaped in the age-adjusted analysis, but it changed when smoking status, serum cholesterol level, BP, and previous MI were added to the model. The authors therefore concluded
that not only was coffee drinking not harmful, but also the slight increased CHD mortality observed in heavy coffee drinkers was largely explained by the effects of smoking and high serum cholesterol level.18 Furthermore, they put forward that the increased CHD mortality, observed in men not drinking coffee might have been attributed to some underlying diseases that led to a reduction in coffee consumption.18 Recently, de Koning Gans and colleagues29 observed a U-shaped association between coffee consumption and CHD mortality for 3–6 cups/day with an HR of 0.64, although the association did not reach the customary level of statistical significance. Nevertheless, a dose– response relationship with CVD mortality was already observed in the Iowa Women’s Health Study whose results suggested a 24% decreased CVD mortality in people drinking 1–3 cups of coffee per day.49 Furthermore, in two large cohort studies, the inverse association between coffee consumption and all-cause mortality observed in both men and women was independent of caffeine intake and mainly explained by a reduction in CVD mortality.34 All in all, these findings seem to suggest that coffee drinking is harmless, although it cannot be ruled out the possibility that in both men and women excessive coffee consumption might increase the risk of mortality from CVD.
41.6 CONCLUDING REMARKS Lifestyle changes may have a key role in the prevention of CVD. Although regular consumption of moderate quantities of coffee seems to be associated with a small protection against CVD, results from
II. EFFECTS OF COFFEE CONSUMPTION
384
41. COFFEE AND CARDIOVASCULAR DISEASE
epidemiologic studies are conflicting. A nonlinear dose– response relationship between coffee intake and CVD risk may explain the heterogeneity in findings. In fact, the American Heart Association so far suggests that a moderate consumption of 1–2 cups of coffee per day does not seem to be harmful for the cardiovascular system (http://www.heart.org/HEARTORG/GettingHealthy/NutritionCenter/HealthyDietGoals/Caffeine-and -Heart-Disease_UCM_305888_Article.jsp), rather “possibly” useful (http://newsroom.heart.org/news/regu lar-moderate-coffee-drinking-235549). In contrast, the effect of high caffeine intake on the risk of CHD is still under debate. Thus, moderation seems to be the keyword that may simplify this controversial topic. In fact, the possible health effects of coffee on both CVD morbidity and mortality have been observed at moderate intake, whereas they disappear at heavy or very heavy consumption.
41.7 SUMMARY POINTS • A decreased risk of both CVDs morbidity and mortality has been observed at moderate intake of coffee. • Possible health effects disappear at heavy or very heavy coffee consumption. • Slow caffeine metabolizers may be at increased risk of nonfatal MI. • A nonlinear dose–response relationship between coffee and caffeine intake and CHD risk may explain the heterogeneous findings. • Coffee consumption does not apparently exert any adverse effect on the risk of stroke or HF.
Acknowledgments We thank Lisa Eggebrecht for help with systematic literature research. We are indebted to the Oxford University Press (OUP), to the Johns Hopkins Bloomberg School of Public Health, and to the authors of the paper Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose–response meta-analysis of prospective studies. Am J Epidemiol 2011;174:993–1001 in allowing us to reproduce Figure 41.2. We are indebted to Elsevier Publisher in allowing us to reproduce and modify Table 41.2 from: “Di Castelnuovo A, di Giuseppe R, Iacoviello L, de Gaetano G. Consumption of cocoa, tea and coffee and risk of cardiovascular disease. Eur J Intern Med 2012;23:15–25.
References 1. Yanagimoto K, Ochi H, Lee KG, Shibamoto T. Antioxidative activities of fractions obtained from brewed coffee. J Agric Food Chem 2004;52:592–6. 2. Spiller MA. The chemical components of coffee. Prog Clin Biol Res 1984;158:91–147. 3. Urgert R, Katan MB. The cholesterol-raising factor from coffee beans. Annu Rev Nutr 1997;17:305–24.
4. Cornelis MC, El-Sohemy A. Coffee, caffeine, and coronary heart disease. Curr Opin Clin Nutr Metab Care 2007;10:745–51. 5. Cornelis MC, El-Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 2006;295:1135–41. 6. Lloyd-Jones D, Adams R, Carnethon M, De Simone G, Ferguson TB, et al. Heart disease and stroke statistics–2009 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 2009;119:e21–181. 7. Paul O, Lepper MH, Phelan WH, Dupertuis GW, Macmillan A, et al. A longitudinal study of coronary heart disease. Circulation 1963;28:20–31. 8. Di Castelnuovo A, di Giuseppe R, Iacoviello L, de Gaetano G. Consumption of cocoa, tea and coffee and risk of cardiovascular disease. Eur J Intern Med 2012;23:15–25. 9. Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, et al. Coffee consumption and risk of chronic disease in the European Prospective Investigation into Cancer and Nutrition (EPIC)Germany study. Am J Clin Nutr 2012;95:901–8. 10. Myers MG, Basinski A. Coffee and coronary heart disease. Arch Intern Med 1992;152:1767–72. 11. Greenland S. A meta-analysis of coffee, myocardial infarction, and coronary death. Epidemiology 1993;4:366–74. 12. Kawachi I, Colditz GA, Stone CB. Does coffee drinking increase the risk of coronary heart disease? Results from a meta-analysis. Br Heart J 1994;72:269–75. 13. Sofi F, Conti AA, Gori AM, Eliana Luisi ML, Casini A, et al. Coffee consumption and risk of coronary heart disease: a meta-analysis. Nutr Metab Cardiovasc Dis 2007;17:209–23. 14. Wu JN, Ho SC, Zhou C, Ling WH, Chen WQ, et al. Coffee consumption and risk of coronary heart diseases: a meta-analysis of 21 prospective cohort studies. Int J Cardiol 2009;137:216–25. 15. Grobbee DE, Rimm EB, Giovannucci E, Colditz G, Stampfer M, et al. Coffee, caffeine, and cardiovascular disease in men. N Engl J Med 1990;323:1026–32. 16. Willett WC, Stampfer MJ, Manson JE, Colditz GA, Rosner BA, et al. Coffee consumption and coronary heart disease in women. A tenyear follow-up. JAMA 1996;275:458–62. 17. Woodward M, Tunstall-Pedoe H. Coffee and tea consumption in the Scottish Heart Health Study follow up: conflicting relations with coronary risk factors, coronary disease, and all cause mortality. J Epidemiol Community Health 1999;53:481–7. 18. Kleemola P, Jousilahti P, Pietinen P, Vartiainen E, Tuomilehto J. Coffee consumption and the risk of coronary heart disease and death. Arch Intern Med 2000;160:3393–400. 19. Hammar N, Andersson T, Alfredsson L, Reuterwall C, Nilsson T, et al. Association of boiled and filtered coffee with incidence of first nonfatal myocardial infarction: the SHEEP and the VHEEP study. J Intern Med 2003;253:653–9. 20. Happonen P, Voutilainen S, Salonen JT. Coffee drinking is dosedependently related to the risk of acute coronary events in middleaged men. J Nutr 2004;134:2381–6. 21. Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation 2006;113:2045–53. 22. Azevedo A, Barros H. Coffee and myocardial infarction: heterogeneity of an association in Portuguese men. Eur J Cardiovasc Prev Rehabil 2006;13:268–73. 23. 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;17:506–11. 24. Corti R, Binggeli C, Sudano I, Spieker L, Hanseler E, et al. Coffee acutely increases sympathetic nerve activity and blood pressure independently of caffeine content: role of habitual versus nonhabitual drinking. Circulation 2002;106:2935–40.
II. EFFECTS OF COFFEE CONSUMPTION
References
25. Ranheim T, Halvorsen B. Coffee consumption and human health– beneficial or detrimental?–Mechanisms for effects of coffee consumption on different risk factors for cardiovascular disease and type 2 diabetes mellitus. Mol Nutr Food Res 2005;49:274–84. 26. Nilsson LM, Wennberg M, Lindahl B, Eliasson M, Jansson JH, et al. Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction; a nested case/referent study. Nutr Metab Cardiovasc Dis 2010;20:527–35. 27. Cai L, Ma D, Zhang Y, Liu Z, Wang P. The effect of coffee consumption on serum lipids: a meta-analysis of randomized controlled trials. Eur J Clin Nutr 2012;66:872–7. 28. Weggemans RM, Zock PL, Ordovas JM, Ramos-Galluzzi J, Katan MB. Genetic polymorphisms and lipid response to dietary changes in humans. Eur J Clin Invest 2001;31:950–7. 29. de Koning Gans JM, Uiterwaal CS, van der Schouw YT, Boer JM, Grobbee DE, et al. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler Thromb Vasc Biol 2010;30: 1665–71. 30. Panagiotakos DB, Pitsavos C, Chrysohoou C, Kokkinos P, Toutouzas P, et al. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: the CARDIO2000 case-control study. J Nutr 2003;133:3228–32. 31. Natella F, Nardini M, Belelli F, Scaccini C. Coffee drinking induces incorporation of phenolic acids into LDL and increases the resistance of LDL to ex vivo oxidation in humans. Am J Clin Nutr 2007;86:604–9. 32. Riksen NP, Rongen GA, Smits P. Acute and long-term cardiovascular effects of coffee: implications for coronary heart disease. Pharmacol Ther 2009;121:185–91. 33. Larsson SC, Mannisto S, Virtanen MJ, Kontto J, Albanes D, et al. Coffee and tea consumption and risk of stroke subtypes in male smokers. Stroke 2008;39:1681–7. 34. Lopez-Garcia E, van Dam RM, Li TY, Rodriguez-Artalejo F, Hu FB. The relationship of coffee consumption with mortality. Ann Intern Med 2008;148:904–14. 35. Mukamal KJ, Hallqvist J, Hammar N, Ljung R, Gemes K, et al. Coffee consumption and mortality after acute myocardial infarction: the Stockholm Heart Epidemiology Program. Am Heart J 2009;157:495–501. 36. Sugiyama K, Kuriyama S, Akhter M, Kakizaki M, Nakaya N, et al. Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women. J Nutr 2010;140:1007–13.
385
37. Mostofsky E, Schlaug G, Mukamal KJ, Rosamond WD, Mittleman MA. Coffee and acute ischemic stroke onset: the Stroke Onset Study. Neurology 2010;75:1583–8. 38. Larsson SC, Virtamo J, Wolk A. Coffee consumption and risk of stroke in women. Stroke 2011;42:908–12. 39. Mineharu Y, Koizumi A, Wada Y, Iso H, Watanabe Y, et al. Coffee, green tea, black tea and oolong tea consumption and risk of mortality from cardiovascular disease in Japanese men and women. J Epidemiol Community Health 2011;65:230–40. 40. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a dose-response meta-analysis of prospective studies. Am J Epidemiol 2011;174:993–1001. 41. Kim B, Nam Y, Kim J, Choi H, Won C. Coffee consumption and stroke risk: a meta-analysis of epidemiologic studies. Korean J Fam Med 2012;33:356–65. 42. Lopez-Garcia E, Rodriguez-Artalejo F, Rexrode KM, Logroscino G, Hu FB, et al. Coffee consumption and risk of stroke in women. Circulation 2009;119:1116–23. 43. Wilhelmsen L, Rosengren A, Eriksson H, Lappas G. Heart failure in the general population of men–morbidity, risk factors and prognosis. J Intern Med 2001;249:253–61. 44. Fitzgibbons TP, Meyer TE, Aurigemma GP. Mortality in diastolic heart failure: an update. Cardiol Rev 2009;17:51–5. 45. Ahmed HN, Levitan EB, Wolk A, Mittleman MA. Coffee consumption and risk of heart failure in men: an analysis from the Cohort of Swedish Men. Am Heart J 2009;158:667–72. 46. Levitan EB, Ahmed HN, Mittleman MA, Wolk A. Coffee consumption and incidence of heart failure in women. Circ Heart Fail 2011;4:414–8. 47. Wang Y, Tuomilehto J, Jousilahti P, Antikainen R, Mahonen M, et al. Coffee consumption and the risk of heart failure in Finnish men and women. Heart 2011;97:44–8. 48. Mostofsky E, Rice MS, Levitan EB, Mittleman MA. Habitual coffee consumption and risk of heart failure: a dose-response metaanalysis. Circ Heart Fail 2012;5:401–5. 49. Andersen LF, Jacobs Jr DR, Carlsen MH, Blomhoff R. Consumption of coffee is associated with reduced risk of death attributed to inflammatory and cardiovascular diseases in the Iowa Women’s Health Study. Am J Clin Nutr 2006;83:1039–46. 50. Bidel S, Hu G, Qiao Q, Jousilahti P, Antikainen R, et al. Coffee consumption and risk of total and cardiovascular mortality among patients with type 2 diabetes. Diabetologia 2006;49:2618–26.
II. EFFECTS OF COFFEE CONSUMPTION