Académique Documents
Professionnel Documents
Culture Documents
Section Editors: Armin J. Grau, MD, PhD, and George Howard, DrPH
Methods
References for this review were identified through a literature search
of the PubMed database through October 2013 by using the following search terms: coffee, tea, cocoa, chocolate, prospective study, cohort study, randomized trial, meta-analysis, review, stroke, cerebral
infarction, and cerebrovascular disease. Moreover, the reference lists
of pertinent publications were searched manually for further relevant
articles. Priority was given to systematic reviews and meta-analyses
published during the past 5 years. When >1 meta-analysis on the
same topic was available, the most recent publication was included
in the present review.
Coffee
Coffee is a complex beverage with hundreds of bioactive components
with potential adverse or beneficial effects on the cardiovascular system. The most abundant bioactive compounds in coffee are caffeine,
diterpenes (present in the oil), and polyphenols. The cardiovascular
effects of coffee drinking depend in part on coffee preparation method and individual characteristics (eg, hypertension and hyperlipidemia).13 There are 2 main methods of coffee preparation: filtered and
unfiltered. Filtered coffee, also known as drip-brewed coffee, is the
most common mode of preparation in the United States and involves
brewing the coffee through a paper filter. Unfiltered coffee, often
known as boiled coffee, do not use a filter and includes Scandinavian
boiled, French press, Turkish/Greek, and espresso coffees. Espresso
is often the base for other drinks, such as latte, cappuccino, macchiato, and caff Americano.
Caffeine is a stimulant that induces a transient increase in blood
pressure (BP). Findings from a meta-analysis of 5 randomized controlled trials (RCTs) of the acute effects of caffeine on BP in individuals with hypertension showed that intake of 200300 mg caffeine
(equivalent to 1.52 cups of coffee) produced a mean rise of 8.1
mmHg in systolic blood pressure and of 5.8 mmHg in diastolic blood
pressure (Table1).1 The increase in BP was observed in the first hour
after caffeine ingestion and lasted for 3 hours. However, a metaanalysis of 10 RCTs of the long-term effect of coffee consumption in
mainly healthy, normotensive individuals found no significant changes in systolic blood pressure or diastolic blood pressure (Table1).2
Prospective studies of habitual coffee consumption and risk of hypertension have yielded inconsistent results, with a positive association
found in 2 out of 4 studies.2 Tolerance to the effects of caffeine on BP
in some individuals may in part explain why the long-term effects
of coffee consumption differ from the short-term effects. Moreover,
other compounds present in coffee may counteract the BP-raising effect of caffeine. A study of 6 habitual and 9 nonhabitual coffee drinkers found that intravenous caffeine raised BP in both groups, whereas
coffee consumption increased BP in nonhabitual drinkers only.4
The diterpenes cafestol and kahweol have cholesterol-raising
properties.5 The diterpenes are extracted from the coffee beans by
hot water but are retained by a paper filter.5 Hence, unfiltered coffee,
particularly Scandinavian boiled and Turkish coffees, contains much
higher concentrations of diterpenes than filtered coffee, which only
contains negligible amounts.6 Espresso coffee contains intermediate
amounts.6 In a meta-analysis of 12 RCTs, including 1017 subjects,
consumption of unfiltered coffee significantly increased total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride
concentrations, whereas filtered coffee consumption produced a small
change in total cholesterol concentrations only (Table1).3 The metaanalysis further showed that those who had hyperlipidemia seemed to
be more sensitive to the cholesterol-raising effect of coffee.3
Coffee is rich in various polyphenols, most notably chlorogenic
acid (CGA), which possesses antioxidant activities in vitro.7 Studies
in animals have demonstrated that coffee and caffeic acid, a primary
CGA metabolite, can decrease lipid peroxidation, thus indicating
also an in vivo antioxidant activity.7 However, there is controversy on
whether chlorogenic acid and other polyphenols in coffee could suppress the oxidative modification of LDL particles in humans. Among
3 available studies on this topic, 2 studies reported a protective effect
of 1 cup of boiled8 or filtered coffee9 on LDL oxidation, whereas 1
study found neither short-term nor long-term effects of filtered coffee
consumption on lipid peroxidation.10 As opposed to caffeine, CGA
have been demonstrated to have antihypertensive effects,11,12 possibly
via nitric oxidemediated vasodilation.12 Results from an RCT of 23
healthy adults showed that CGA ingestion significantly reduced systolic blood pressure by 2.41 mmHg and diastolic blood pressure by
1.53 mmHg.11
From the Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
Correspondence to Susanna C. Larsson, PhD, Unit of Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Box 210,
SE-17177 Stockholm, Sweden. E-mail Susanna.Larsson@ki.se
(Stroke. 2014;45:309-314.)
2013 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.113.003131
310StrokeJanuary 2014
Table 1. Summary of Recent Meta-Analyses of RCTs of the Effects of Coffee or Caffeine Intake on Cardiometabolic Biomarkers
References
Interventions
Duration
Mesas et al,
20111
Coffee or caffeine
(200300 mg)
<60180 min
Steffen et al,
20122
Filtered, boiled,
instant, or
decaffeinated
coffee
416 wk
Filtered coffee
1479 d
Boiled/unfiltered
coffee
No. of
Trials
1479 d
Outcomes
Effects
Mean Change
(95% CI)
Heterogeneity
P Value
I2, %
SBP (mmHg)
0.99
DBP (mmHg)
0.57
10
SBP (mmHg)
<0.001
72
10
DBP (mmHg)
0.07
41
10
Total cholesterol
(mmol/L)*
0.52
LDL cholesterol
(mmol/L)*
0.35
10
Triglycerides
(mmol/L)*
0.43
12
Total cholesterol
(mmol/L)*
<0.0010
79
LDL cholesterol
(mmol/L)*
0.002
73
Triglycerides
(mg/dL)*
0.001
77
CI indicates confidence interval; DBP; diastolic blood pressure; LDL, low-density lipoprotein; RCTs, randomized controlled trials; and SBP; systolic blood pressure.
*Values were converted from mg/dL to mmol/L by dividing the levels of cholesterol (total, LDL, and HDL) by 38.67; triglyceride levels by 88.57; and glucose levels
by 18.02.
(Figure1).13 Compared with no coffee consumption, the overall relative risks (RRs; 95% CI) of total stroke were 0.87 (0.810.93) for 2,
0.84 (0.770.91) for 34, 0.88 (0.790.97) for 6, and 0.94 (0.801.10)
for 8 cups/d of coffee.13 Risk estimates were similar for ischemic and
hemorrhagic stroke and for men and women at lower levels of coffee
consumption (2 cups/d).13
Three prospective studies on coffee consumption and stroke1416 were
published since the meta-analysis. Two of them confirmed an inverse
association of moderate coffee consumption with stroke incidence14 or
mortality.15 Findings from a large prospective cohort of 229119 US
men and 173141 US women showed an inverse association between
moderate coffee consumption and stroke mortality.15 In men, the multivariable RRs (95% CI) of total stroke death were 0.99 (0.791.24) for
<1, 0.92 (0.731.15) for 1, 0.84 (0.681.02) for 23, 0.65 (0.510.84)
for 45, and 0.83 (0.611.14) for 6 cups/d compared with no coffee consumption (P for trend=0.003).15 In women, compared with no
coffee consumption, the RRs (95% CI) were 1.15 (0.911.45) for <1,
0.89 (0.701.13) for 1, 0.93 (0.751.15) for 23, 0.82 (0.621.09) for
45, and 0.84 (0.561.25) for 6 cups/d (P for trend=0.05).15 A prospective study of 82369 Japanese adults also observed an inverse association between moderate coffee consumption and stroke risk (RR,
1.1
1.00 (ref.)
0.94
0.92
0.9
0.91
0.88
0.87
0.84
0.85
0.84
0.8
0.7
Figure 1. Relative risks of stroke by coffee consumption in prospective studies. The relative risks were extracted from the metaanalysis by Larsson and Orsini.13
Duration
No. of
Trials
Outcomes
Effects
120 min4 wk
FMD (%)
Zheng et al,
201120
Green tea as a
beverage or green
tea extract
3 wk3 mo
14
Total cholesterol
(mmol/L)*
11
LDL cholesterol
(mmol/L)*
12
References
19
Hartley et al,
201321
Hartley et al,
201321
Zheng et al,
201323
Green tea as a
beverage or green
tea extract
36 mo
36 mo
4 wk3 mo
324 wk
Mean Change
(95% CI)
Heterogeneity
P Value
I2, %
<0.001
75.8
0.19 (0.21,
0.16)
0.35
0.06 (0.08,
0.03)
0.20
25
HDL cholesterol
(mmol/L)*
0.006 (0.02,
0.03)
0.27
18
SBP (mmHg)
3.18 (5.25,
1.11)
0.72
DBP (mmHg)
3.42 (4.54,
2.30)
0.39
Total cholesterol
(mmol/L)
0.62 (0.77,
0.46)
0.28
21
LDL cholesterol
(mmol/L)
0.64 (0.77,
0.52)
0.33
13
HDL cholesterol
(mmol/L)
0.18
39
Triglycerides
(mmol/L)
0.08 (0.24,
0.07)
0.41
SBP (mmHg)
1.85 (3.21,
0.48)
0.49
DBP (mmHg)
1.27 (3.06,
0.53)
0.53
Total cholesterol
(mmol/L)
NA
NA*
NA
84
LDL cholesterol
(mmol/L)
0.43 (0.56,
0.31)
0.22
33
HDL cholesterol
(mmol/L)
0.01 (0.06,
0.04)
0.20
36
Triglycerides
(mmol/L)
NA
NA*
NA
64
17
Fasting glucose
(mmol/L)
0.09 (0.15,
0.03)
0.73
13
Fasting insulin
(IU/mL)
1.16 (1.91,
0.40)
0.01
57
Hb A1c (%)
0.30 (0.37,
0.22)
0.10
44
HOMA-IR (units)
0.04 (0.67,
0.59)
0.13
44
22
Fasting glucose
(mmol/L)
0.08 (0.14,
0.02)
0.92
16
Fasting insulin
(U/mL)
0.35
Hb A1c (%)
0.04 (0.15,
0.08)
0.12
40
HOMA-IR (units)
0.05 (0.37,
0.26)
0.31
16
CI indicates confidence interval; DBP; diastolic blood pressure; FMD, flow-mediated dilation; Hb A1c, glycohemoglobin; HDL, high-density lipoprotein; HOMA-IR,
homeostatic model assessment index for insulin resistance; LDL, low-density lipoprotein; NA, not available; RCTs, randomized controlled trials; and SBP; systolic blood
pressure.
*Meta-analysis was not performed because of significant heterogeneity between the trials.
Values were converted from mg/dL to mmol/L by dividing by 38.67 for total cholesterol, LDL cholesterol, and HDL cholesterol; by 88.57 for triglycerides; and by
18.02 for glucose.
312StrokeJanuary 2014
Table 3. Summary of Recent Meta-Analyses of RCTs of the Effects of Cocoa or Chocolate Consumption on Cardiometabolic
Biomarkers
References
Ried et al, 2012
Hooper et al,
201228
27
Interventions
Duration
No. of
Trials
Outcomes
Effects
Dark or milk
chocolate or
flavanol-rich
cocoa powder
28 wk*
20
SBP (mmHg)
19
DBP (mmHg)
Dark or milk
chocolate, cocoa
drinks, or cocoa
supplements
18 wk
Mean Change
(95% CI)
Heterogeneity
P Value
I2, %
2.77 (4.72,
0.82)
<0.001
83
2.20 (3.46,
0.93)
<0.001
70
SBP (mmHg),
acute
1.75 (6.27,
2.77)
NA
85
23
SBP (mmHg),
chronic
1.50 (3.43,
0.43)
NA
NA
DBP (mmHg),
acute
1.38 (4.14,
1.38)
NA
79
22
DBP (mmHg),
chronic
1.60 (2.77,
0.43)
NA
52
MAP (mmHg),
chronic
1.64 (3.27,
0.01)
NA
11
<0.001
84
11
0.58
11
Fasting glucose
(mmol/L)
0.02 (0.22,
0.17)
0.02
54
Fasting insulin
(U/mL)
2.65 (4.65,
0.65)
0.50
Hb A1c (%)
NA
NA
HOMA-IR (units)
0.67 (0.98,
0.36)
0.61
21
Total cholesterol
(mmol/L)
0.04 (0.11,
0.03)
NA
NA
21
LDL cholesterol
(mmol/L)
0.07 (0.13,
0.00)
NA
NA
21
HDL cholesterol
(mmol/L)
NA
NA
22
Triglycerides
(mmol/L)
0.05 (0.09,
0.01)
NA
NA
10
C-reactive protein
(mg/L)
NA
NA
CI indicates confidence interval; DBP; diastolic blood pressure; FMD, flow-mediated dilation; Hb A1c, glycohemoglobin; HDL, high-density lipoprotein; HOMA-IR,
homeostatic model assessment index for insulin resistance; LDL, low-density lipoprotein; MAP, mean arterial pressure; NA, not available; RCTs, randomized controlled
trials; and SBP; systolic blood pressure.
*One trial was 18 wk.
Acute effect: studies of 90150 min duration; chronic effect: studies of <3, 36, or 726 wk duration.
concentrations but had no effect on high-density lipoprotein cholesterol.20 In another meta-analysis of RCTs of 3 months duration, both
green and black tea consumption reduced LDL cholesterol concentrations as well as BP.21 With regard to glucose and insulin, 2 metaanalyses of several RCTs found that green tea consumption decreased
fasting blood glucose concentrations, whereas results for insulin and
hemoglobin A1c concentrations were inconsistent.22,23
Cacao Products
Cacao products, such as chocolate, are rich sources of flavonoids,
mainly flavan-3-ols (also referred to as flavanols), which are potent
Figure 2. Relative risks (RRs) of stroke for the highest versus lowest category of chocolate consumption in prospective studies. Squares represent the
study-specific RRs (size of the square indicates the
study-specific statistical weight, that is, the inverse
of the variance); the horizontal lines represent
95% confidence intervals (CIs); and the diamond
represents the overall RR estimate with its 95%
CI. Study-specific RRs were combined by using
a random effects model. The RRs were extracted
from the meta-analysis by Larsson et al.33 Heterogeneity test: I2=0%; P=0.47. COSM indicates Cohort
of Swedish Men33; EPIC, European Prospective
Investigation into Cancer31; IWHS, Iowa Womens
Health Study34; SHEEP, Stockholm Heart Epidemiology Program35; and SMC, Swedish Mammography
Cohort.32
Summary
Current evidence from experimental studies in animals and
humans along with findings from prospective studies indicates
beneficial effects of green and black tea as well as chocolate
on cardiovascular health, and that tea and chocolate consumption may reduce the risk of stroke. The strongest evidence
exists for beneficial effects of tea and cocoa on endothelial
function, total and LDL cholesterol (tea only), and insulin
sensitivity (cocoa only). The majority of prospective studies
have reported a weak inverse association between moderate
consumption of coffee and risk of stroke. However, there are
yet no clear biological mechanisms whereby coffee might provide cardiovascular health benefits. Awaiting the results from
further long-term RCTs and prospective studies, moderate
consumption of filtered coffee, tea, and dark chocolate seems
prudent.
Disclosures
None.
References
1. Mesas AE, Leon-Muoz 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;94:11131126.
2. Steffen M, Kuhle C, Hensrud D, Erwin PJ, Murad MH. The effect of coffee consumption on blood pressure and the development of hypertension:
a systematic review and meta-analysis. J Hypertens. 2012;30:22452254.
3. 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;66:872877.
4. Corti R, Binggeli C, Sudano I, Spieker L, Hnseler E, Ruschitzka F, et al.
Coffee acutely increases sympathetic nerve activity and blood pressure
independently of caffeine content: role of habitual versus nonhabitual
drinking. Circulation. 2002;106:29352940.
5. Urgert R, Katan MB. The cholesterol-raising factor from coffee beans.
Annu Rev Nutr. 1997;17:305324.
6. Gross G, Jaccaud E, Huggett AC. Analysis of the content of the diterpenes cafestol and kahweol in coffee brews. Food Chem Toxicol.
1997;35:547554.
7. Bonita JS, Mandarano M, Shuta D, Vinson J. Coffee and cardiovascular
disease: in vitro, cellular, animal, and human studies. Pharmacol Res.
2007;55:187198.
8. Yukawa GS, Mune M, Otani H, Tone Y, Liang XM, Iwahashi H, et al.
Effects of coffee consumption on oxidative susceptibility of low-density
lipoproteins and serum lipid levels in humans. Biochemistry (Mosc).
2004;69:7074.
9. 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;86:604609.
10. Mursu J, Voutilainen S, Nurmi T, Alfthan G, Virtanen JK, Rissanen TH,
et al. The effects of coffee consumption on lipid peroxidation and plasma
314StrokeJanuary 2014
total homocysteine concentrations: a clinical trial. Free Radic Biol Med.
2005;38:527534.
11. Mubarak A, Bondonno CP, Liu AH, Considine MJ, Rich L, Mas E, et
al. Acute effects of chlorogenic acid on nitric oxide status, endothelial
function, and blood pressure in healthy volunteers: a randomized trial. J
Agric Food Chem. 2012;60:91309136.
12. Zhao Y, Wang J, Ballevre O, Luo H, Zhang W. Antihypertensive effects
and mechanisms of chlorogenic acids. Hypertens Res. 2012;35:370374.
13. Larsson SC, Orsini N. Coffee consumption and risk of stroke: a
dose-response meta-analysis of prospective studies. Am J Epidemiol.
2011;174:9931001.
14. Kokubo Y, Iso H, Saito I, Yamagishi K, Yatsuya H, Ishihara J, et al. The
impact of green tea and coffee consumption on the reduced risk of stroke
incidence in Japanese population: the Japan public health center-based
study cohort. Stroke. 2013;44:13691374.
15. Freedman ND, Park Y, Abnet CC, Hollenbeck AR, Sinha R. Association
of coffee drinking with total and cause-specific mortality. N Engl J Med.
2012;366:18911904.
16. Floegel A, Pischon T, Bergmann MM, Teucher B, Kaaks R, Boeing
H. Coffee consumption and risk of chronic disease in the European
Prospective Investigation into Cancer and Nutrition (EPIC)-Germany
study. Am J Clin Nutr. 2012;95:901908.
17. Hodgson JM, Croft KD. Tea flavonoids and cardiovascular health. Mol
Aspects Med. 2010;31:495502.
18. Moore RJ, Jackson KG, Minihane AM. Green tea (Camellia sinensis)
catechins and vascular function. Br J Nutr. 2009;102:17901802.
19. Ras RT, Zock PL, Draijer R. Tea consumption enhances endothelialdependent vasodilation; a meta-analysis. PLoS One. 2011;6:e16974.
20. Zheng XX, Xu YL, Li SH, Liu XX, Hui R, Huang XH. Green tea intake
lowers fasting serum total and LDL cholesterol in adults: a meta-analysis
of 14 randomized controlled trials. Am J Clin Nutr. 2011;94:601610.
21. Hartley L, Flowers N, Holmes J, Clarke A, Stranges S, Hooper L, et al.
Green and black tea for the primary prevention of cardiovascular disease.
Cochrane Database Syst Rev. 2013;6:CD009934.
22. Liu K, Zhou R, Wang B, Chen K, Shi LY, Zhu JD, et al. Effect of green
tea on glucose control and insulin sensitivity: a meta-analysis of 17 randomized controlled trials. Am J Clin Nutr. 2013;98:340348.
23. Zheng XX, Xu YL, Li SH, Hui R, Wu YJ, Huang XH. Effects of green tea
catechins with or without caffeine on glycemic control in adults: a metaanalysis of randomized controlled trials. Am J Clin Nutr. 2013;97:750762.
24. Shen L, Song LG, Ma H, Jin CN, Wang JA, Xiang MX. Tea consumption
and risk of stroke: a dose-response meta-analysis of prospective studies.
J Zhejiang Univ Sci B. 2012;13:652662.
25. Larsson SC, Virtamo J, Wolk A. Black tea consumption and risk of stroke
in women and men. Ann Epidemiol. 2013;23:157160.
26. Corti R, Flammer AJ, Hollenberg NK, Lscher TF. Cocoa and cardiovascular health. Circulation. 2009;119:14331441.
27. Ried K, Sullivan TR, Fakler P, Frank OR, Stocks NP. Effect of cocoa on
blood pressure. Cochrane Database Syst Rev. 2012;8:CD008893.
28. Hooper L, Kay C, Abdelhamid A, Kroon PA, Cohn JS, Rimm EB, et al.
Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health:
a systematic review and meta-analysis of randomized trials. Am J Clin
Nutr. 2012;95:740751.
29. Curtis PJ, Sampson M, Potter J, Dhatariya K, Kroon PA, Cassidy
A. Chronic ingestion of flavan-3-ols and isoflavones improves insulin sensitivity and lipoprotein status and attenuates estimated 10-year
CVD risk in medicated postmenopausal women with type 2 diabetes:
a 1-year, double-blind, randomized, controlled trial. Diabetes Care.
2012;35:226232.
30. Ostertag LM, OKennedy N, Kroon PA, Duthie GG, de Roos B. Impact of
dietary polyphenols on human platelet functiona critical review of controlled dietary intervention studies. Mol Nutr Food Res. 2010;54:6081.
31. Buijsse B, Weikert C, Drogan D, Bergmann M, Boeing H. Chocolate
consumption in relation to blood pressure and risk of cardiovascular disease in German adults. Eur Heart J. 2010;31:16161623.
32. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of
stroke in women. J Am Coll Cardiol. 2011;58:18281829.
33. Larsson SC, Virtamo J, Wolk A. Chocolate consumption and risk of
stroke: a prospective cohort of men and meta-analysis. Neurology.
2012;79:12231229.
34. Mink PJ, Scrafford CG, Barraj LM, Harnack L, Hong CP, Nettleton JA,
et al. Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women. Am J Clin Nutr. 2007;85:895909.
35. Janszky I, Mukamal KJ, Ljung R, Ahnve S, Ahlbom A, Hallqvist J.
Chocolate consumption and mortality following a first acute myocardial
infarction: the Stockholm Heart Epidemiology Program. J Intern Med.
2009;266:248257.
Key Words: cacao coffee diet flavonoids polyphenols risk
factors stroke tea
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/45/1/309
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/