European Cardiovascular Disease Statistics 2008, European Heart Network, Brussels

European Cardiovascular Disease Statistics 2008

European Heart Network, Brussels

This is the third edition of European cardiovascular disease statistics published by the European Heart Network. European cardiovascular disease statistics is designed for policy makers, health professionals, medical researchers and anyone else with an interest in cardiovascular disease (CVD). It provides the most recent statistics related to the incidence, prevalence, causes and effects of the disease.

The aim of European cardiovascular disease statistics is to show:

(i) the extent to which CVD is a major health problem in Europe;
(ii) where, in Europe, this problem is greatest;
(iii) the variability in efforts to treat and prevent CVD across Europe as shown by differences
in levels of treatment and in levels of risk factors for the disease;
(iv) the economic costs of CVD in the European Union;
(v) trends in CVD mortality, morbidity, treatment and risk factors over time.

European cardiovascular disease statistics is divided into 12 sections. The first two sections on mortality and morbidity deal with the burden of CVD in Europe. Next there is a section on
treatment. Then there are four sections on the main aspects of lifestyle which affect the risk of the disease: smoking, diet, physical activity and alcohol consumption. These are followed by four sections on the main pathophysiological risk factors for the disease: raised blood pressure, raised blood cholesterol, overweight/obesity and diabetes. The final section provides information about the economic costs of CVD in the European Union (EU)1. Each section contains a set of tables and graphs and a brief description of the data presented.

In European cardiovascular disease statistics we aim only to describe and not to explain. So,
although there may be relationships between the various geographical and temporal patterns observed, we have made no attempt to draw any conclusions about the strength of these relationships or about causality.

Petersen S, Peto V, Rayner M, Leal J, Luengo-Fernandez R, Gray A. European cardiovascular disease statistics. BHF: London; 2005.

BHF: London; 2005

European cardiovascular disease statistics

Petersen S, Peto V, Rayner M, Leal J, Luengo-Fernandez R, Gray A.

This is the second edition of European cardiovascular disease statistics published by the British Heart Foundation and the European Heart Network. European cardiovascular disease statistics is designed for policy makers, health professionals, medical researchers and anyone else with an interest in cardiovascular disease (CVD). It provides the most recent statistics related to the incidence, prevalence, causes and effects of the disease.

The aim of European cardiovascular disease statistics is to show:

(i) the extent to which CVD is a major health problem in Europe;
(ii) where, in Europe, this problem is greatest;
(iii) the variability in efforts to treat and prevent CVD across Europe as shown by differences
in levels of treatment and in levels of risk factors for the disease;
(iv) trends in CVD mortality, morbidity, treatment and risk factors over time;
(vi) the economic costs of CVD in the European Union.

European cardiovascular disease statistics is divided into 12 sections. The first two sections on mortality and morbidity deal with the burden of CVD in Europe. Next there is a section on
treatment. Then there are four sections on the main aspects of lifestyle which affect the risk of the disease: smoking, diet, physical activity and alcohol consumption. These are followed by four sections on the main pathophysiological risk factors for the disease: raised blood pressure, raised blood cholesterol, overweight/obesity and diabetes. The fi nal section, new to this edition, provides information about the economic costs of CVD in the European Union (EU)1. Each section contains a set of tables and graphs and a brief description of the data presented. In European cardiovascular disease statistics we aim only to describe and not to explain. So, although there may be relationships between the various geographical and temporal patterns observed, we have made no attempt to draw any conclusions about the strength of these relationships or about causality.

BHF (2010), Economic costs of CVD in Europe, Coronary Heart Disease Statistics, Chapter 6

Wu J. et al. Coffee consumption and the risk of coronary heart disease: a meta-analysis of 21 prospective cohort studies. Int. J. Cardiology, 137, 216-225, 2009.

Int. J. Cardiology, 137, 216-225, 2009.

Coffee consumption and the risk of coronary heart disease: a meta-analysis of 21 prospective cohort studies.

Wu J. et al.

Background: A large amount of cohort studies addressed coffee consumption and risk of coronary heart disease (CHD) and yielded inconsistent results. We conducted a meta-analysis to estimate the pooling effects.

Methods: We searched for all published English articles indexed in MEDLINE or PubMed from January 1966 to January 2008. Twenty-one independent prospective cohort studies, which tested CHD risk by coffee consumption, were identified. A general variance-based method was used to pool the relative risks (RR). 15,599 cases from 407,806 participants were included in pooling the overall effects.

Results: As compared to the light coffee consumption (or=7 cups/d) categories of coffee consumption (all p>0.05); Moderate coffee consumption showed significantly lower CHD RR (95% CI) of 0.82 (0.73-0.92) (p
Conclusion: Our findings do not support the hypothesis that coffee consumption increases the long-term risk of coronary heart disease. Habitual moderate coffee drinking was associated with a lower risk of CHD in women.

de Koning Gans J.M. et al. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler Thromb Vasc Biol., 30, xx-xx, 2010.

Arterioscler Thromb Vasc Biol., 30, xx-xx, 2010.

Tea and coffee consumption and cardiovascular morbidity and mortality

de Koning Gans J.M. et al.

Objective: To examine the associations of coffee and tea consumption with risk of morbidity and mortality of stroke and coronary heart disease (CHD) and with all-cause mortality

Methods and Results: Coffee and tea consumption were assessed with a validated food-frequency questionnaire, and 37 514 participants were observed for 13 years for the occurrence of cardiovascular morbidity and mortality. A U-shaped association between coffee and CHD was found, with the lowest hazard ratio (HR [95% CI]) for 2.1 to 3.0 cups per day (0.79 [0.65 to 0.96]; P(trend)=0.01). Tea was inversely associated with CHD, with the lowest HR (95% CI) for more than 6.0 cups per day (0.64 [0.46 to 0.90]; P(trend)=0.02). No associations between tea or coffee and stroke were found (P(trend)=0.63 and P(trend)=0.32, respectively). Although not significant, coffee slightly reduced the risk for CHD mortality (HR, 0.64; 95% CI, 0.37 to 1.11; P(trend)=0.12) for 3.1 to 6.0 cups per day. A U-shaped association between tea and CHD mortality was observed, with an HR of 0.55 (95% CI, 0.31 to 0.97; P(trend)=0.03) for 3.1 to 6.0 cups per day. Neither coffee nor tea was associated with stroke (P(trend)=0.22 and P(trend)=0.74, respectively) and all-cause mortality (P(trend)=0.33 and P(trend)=0.43, respectively).

Conclusions: High tea consumption is associated with a reduced risk of CHD mortality. Our results suggest a slight risk reduction for CHD mortality with moderate coffee consumption and strengthen the evidence on the lower risk of CHD with coffee and tea consumption.

Sugiyama K. et al. Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women. J. Nutrtion, doi: 10.3945/jn.109.109314.

J. Nutrtion, doi: 10.3945/jn.109.109314

Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women.

Sugiyama K. et al.

Coffee contains various compounds that have recently been reported to exert beneficial health effects. However, the conclusion of its relation with mortality has not yet been reached. In this study, we aimed to investigate the associations between coffee consumption and all-cause and cause-specific mortality in Japan. We included 37,742 participants (18,287 men and 19,455 women) aged 40–64 y without a history of cancer, myocardial infarction, or stroke at baseline in our analysis, based on the Miyagi Cohort Study initiated in 1990. The outcomes were mortality due to all causes, cardiovascular disease (CVD), and cancer. During the 10.3 y of follow-up, 2454 participants died, including 426 due to CVD and 724 due to cancer. In women, the multivariate hazard ratios (HR) (95% CI) for all-cause mortality in participants who drank coffee never, occasionally, 1–2 cups (150–300 mL)/d, and ≥3 cups/d were 1.00, 0.88 (0.73–1.06), 0.82 (0.66–1.02), and 0.75 (0.53–1.05), respectively (P-trend = 0.04). For CVD mortality in women, the multivariate HR (95% CI) were 1.00, 0.56 (0.36–0.86), 0.48 (0.29–0.80), and 0.45 (0.20–1.03), respectively (P-trend = 0.006). Of the specific CVD diseases, there was a strong inverse association between coffee consumption and mortality due to coronary heart disease (CHD) in women (P-trend = 0.02) but not in men. Death due to cancer was not associated with coffee consumption in either men or women, except for colorectal cancer in women. Our results suggest that coffee may have favorable effects on morality due to all causes and to CVD, especially CHD, in women.

Ahmed H.N. et al. Coffee consumption and risk of heart failure in men: an analysis from the cohort of Swedish men. Am. Heart J, 158, 667-72, 2009.

Am. Heart J, 158, 667-72, 2009.

Coffee consumption and risk of heart failure in men: an analysis from the cohort of Swedish men.

Ahmed H.N. et al.

Background: A previous study found that consuming 5 or more cups of coffee per day was associated with increased incidence of heart failure (HF). We sought to evaluate this association in a larger population.

Methods: We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HF. They were observed for HF hospitalization or mortality from January 1, 1998, until December 31, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs).
RESULTS: For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank or=5 cups/d (P for trend in RR = .61).

Conclusions: This study did not support the hypothesis that high coffee consumption is associated with increased rates of HF hospitalization or mortality.

Nilson L.M. et al. Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction: a nested case/referent study. Nutr Metabol & Cardiovasc Diseases, doi: 10.1016/j.numecd.2009.05.004.

Nutr Metabol & Cardiovasc Diseases, doi: 10.1016/j.numecd.2009.05.004.

Consumption of filtered and boiled coffee and the risk of first acute myocardial infarction: a nested case/referent study.

Nilson L.M. et al.

Background and Aim: In northern Sweden, consumption of both filtered and boiled coffee is common. Boiled coffee, especially popular in rural areas, is known to raise blood lipids, a risk factor for acute myocardial infarction (MI). To our knowledge, only one epidemiological study, a case-control study from Sweden, has investigated boiled coffee in MI, noting an increased risk at high consumption levels in men, and no association in women. The aim of the present nested case-referent study was to relate consumption of filtered and boiled coffee to the risk of first MI.

Methods: We measured coffee consumption using food frequency questionnaires among 37,315 men without history of myocardial infarction, diabetes, or HF. They were observed for HF hospitalization or mortality from January 1, 1998, until December 31, 2006, using record linkage to the Swedish inpatient and cause of death registries. Cox proportional hazards models adjusted for age, dietary, and demographic factors were used to calculate incidence rate ratios (RR) and 95% confidence intervals (CIs).
RESULTS: For 9 years of follow-up, 784 men experienced an HF event. Compared to men who drank or=5 cups/d (P for trend in RR = .61).

Methods and Results: The study subjects were 375 cases (303 men, 72 women) and 1293 matched referents from the population-based Northern Sweden Health and Disease Study. Coffee consumption was assessed by food frequency questionnaire. Risk estimates were calculated by conditional logistic regression. A statistically significant positive association was found between consumption of filtered coffee and MI risk in men [odds ratio for consumption > or = 4 times/day versus < or = 1 time/day 1.73 (95% CI 1.05-2.84)]. In women, a similar association was observed, but for boiled coffee [odds ratio 2.51 (95% CI 1.08-5.86)]. After adjustment for current smoking, postsecondary education, hypertension, and sedentary lifestyle, the results for women were no longer statistically significant.

Conclusion: Consumption of filtered coffee was positively associated with the risk of a first MI in men. A similar tendency was observed for boiled coffee in women, but the result was not statistically significant in multivariate analysis. Further investigation in a larger study is warranted.

Lopez-Garcia E. et al. Coffee consumption and risk of stroke in women. Circulation, doi: 10.1161/circulationnaha.108.826164. Volume 119, 1116-1123

Circulation, doi: 10.1161/circulationnaha.108.826164. Volume 119, 1116-1123

Coffee consumption and risk of stroke in women.

Lopez-Garcia E. et al.

Background: Data on the association between coffee consumption and risk of stroke are sparse. We assessed the association between coffee consumption and the risk of stroke over 24 years of follow-up in women.

Methods and Results: We analyzed data from a prospective cohort of 83,076 women in the Nurses’ Health Study without history of stroke, coronary heart disease, diabetes, or cancer at baseline. Coffee consumption was assessed first in 1980 and then repeatedly every 2 to 4 years, with follow-up through 2004. We documented 2280 strokes, of which 426 were hemorrhagic, 1224 were ischemic, and 630 were undetermined. In multivariable Cox regression models with adjustment for age, smoking status, body mass index, physical activity, alcohol intake, menopausal status, hormone replacement therapy, aspirin use, and dietary factors, the relative risks (RRs) of stroke across categories of coffee consumption (or=4 per day) were 1, 0.98 (95% CI, 0.84 to 1.15), 0.88 (95% CI, 0.77 to 1.02), 0.81 (95% CI, 0.70 to 0.95), and 0.80 (95% CI, 0.64 to 0.98) (P for trend=0.003). After further adjustment for high blood pressure, hypercholesterolemia, and type 2 diabetes, the inverse association remained significant. The association was stronger among never and past smokers (RR for >or=4 cups a day versusor=4 cups a day versusor=2 cups a day versus

Conclusions: Long-term coffee consumption was not associated with an increased risk of stroke in women. In contrast, our data suggest that coffee consumption may modestly reduce risk of stroke.

Conen D. et al. Caffeine consumption and incident atrial fibrillation in women. Am J Clin Nutr, doi: 103945/ajcn.2010.29627.

Am J Clin Nutr, doi: 103945/ajcn.2010.29627.

Caffeine consumption and incident atrial fibrillation in women.

Conen D. et al.

Background: It is somewhat controversial whether caffeine consumption is associated with an increased risk of developing atrial fibrillation (AF).
Objective: We prospectively assessed the relation between caffeine intake and incident AF.
Design: A total of 33,638 initially healthy women who participated in the Women’s Health Study and who were >45 y of age and free of cardiovascular disease and AF at baseline were prospectively followed for incident AF from 1993 to 2 March 2009. All women provided information on caffeine intake via food-frequency questionnaires at baseline and in 2004.

Results: During a median follow-up of 14.4 y (interquartile range: 13.8–14.8 y), 945 AF events occurred. Median caffeine intakes across increasing quintiles of caffeine intake were 22, 135, 285, 402, and 656 mg/d, respectively. Age-adjusted incidence rates of AF across increasing quintiles of caffeine intake were 2.15, 1.89, 2.01, 2.24, and 2.04 events, respectively, per 1000 person-years of follow-up. In Cox proportional hazards models updated in 2004 by using time-varying covariates, the corresponding multivariable-adjusted hazard ratios (95% CI) were 1.0, 0.88 (0.72, 1.06), 0.78 (0.64, 0.95), 0.96 (0.79, 1.16), and 0.89 (0.73, 1.09) (P for linear trend: 0.45). None of the individual components of caffeine intake (coffee, tea, cola, and chocolate) were significantly associated with incident AF.

Conclusions: In this large cohort of initially healthy women, elevated caffeine consumption was not associated with an increased risk of incident AF. Therefore, our data suggest that elevated caffeine consumption does not contribute to the increasing burden of AF in the population. This trial was registered at clinicaltrials.gov as NCT00000479.

Frost L & Vestergaard P. Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer and Health Study. Am J Clin Nutr 2005:81:578-82.

Am J Clin Nutr 2005:81:578-82.

Caffeine and risk of atrial fibrillation or flutter: the Danish Diet, Cancer and Health Study.

Frost L & Vestergaard P.

Background: It is not known whether the consumption of caffeine is associated with excess risk of atrial fibrillation.

Objective: We evaluated the risk of atrial fibrillation or flutter in association with daily consumption of caffeine from coffee, tea, cola, cocoa, and chocolate.

Design: We prospectively examined the association between the amount of caffeine consumed per day and the risk of atrial fibrillation or flutter among 47 949 participants ( age: 56 y) in the Danish Diet, Cancer, and Health Study. Subjects were followed in the Danish National Registry of Patients and in the Danish Civil Registration System. The consumption of caffeine was analyzed by quintiles with Cox proportional-hazard models.

Results: During follow-up ( : 5.7 y), atrial fibrillation or flutter developed in 555 subjects (373 men and 182 women). When the lowest quintile of caffeine consumption was used as a reference, the adjusted hazard ratios (95% CIs) in quintiles 2, 3, 4, and 5 were 1.12 (0.87, 1.44), 0.85 (0.65, 1.12), 0.92 (0.71, 1.20), and 0.91 (0.70, 1.19), respectively.
Conclusion: Consumption of caffeine was not associated with risk of atrial fibrillation or flutter.

Geleijnse J.M. Habitual coffee consumption and blood pressure: An epidemiological perspective. Vasc Health Risk Man. 4(5), 963-970, 2008.

Vasc Health Risk Man. 4(5), 963-970, 2008.

Habitual coffee consumption and blood pressure: An epidemiological perspective.

Geleijnse J.M.

This paper summarizes the current epidemiological evidence on coffee consumption in relation to blood pressure (BP) and risk of hypertension. Data from crosssectional studies suggest an inverse linear or U-shaped association of habitual coffee use with BP in different populations. Prospective studies suggest a protective effect of high coffee intake (4 or more cups per day) against hypertension, mainly in women. Furthermore, the risk of hypertension may be lower in coffee abstainers. Randomized controlled trials, which are mostly of short duration (1–12 weeks), have shown that coffee intake around 5 cups per day causes a small elevation in BP (∼2/1 mmHg) when compared to abstinence or use of decaffeinated coffee. With regard to underlying biological mechanisms, most research has been devoted to BP-raising effects of caffeine. However, there are many other substances in coffee, such as polyphenols, soluble fi bre and potassium, which could exert a beneficial effect in the cardiovascular system. Although the precise nature of the relation between coffee and BP is still unclear, most evidence suggests that regular intake of caffeinated coffee does not increase the risk of hypertension.

Urgert R& Katan MB. The cholesterol-raising factor from coffee beans. J R Med, 1996,89(11), 618-623

J R Med, 1996,89(11), 618-623

The cholesterol-raising factor from coffee beans.

Urgert R& Katan MB.

Some coffee brewing techniques raise the serum concentration of total and low-density-lipoprotein cholesterol in humans, whereas others do not. The responsible factors are the diterpene lipids cafestol and kahweol, which make up about 1% (wt:wt) of coffee beans. Diterpenes are extracted by hot water but are retained by a paper filter. This explains why filtered coffee does not affect cholesterol, whereas Scandinavian “boiled,” cafetiere, and Turkish coffees do. We describe the identification of the cholesterol-raising factors, their effects on blood levels of lipids and liver function enzymes, and their impact on public health, based on papers published up to December 1996.

Jee S.H. et al. Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials. Am j Epidemiol, 153, 353-62, 2001.

Am j Epidemiol, 153, 353-62, 2001.

Coffee consumption and serum lipids: a meta-analysis of randomized controlled clinical trials.

Jee S.H. et al.

Coffee drinking has been associated with increased serum cholesterol levels in some, but not all, studies. A Medline search of the English-language literature published prior to December 1998, a bibliography review, and consultations with experts were performed to identify 14 published trials of coffee consumption. Information was abstracted independently by two reviewers using a standardized protocol. With a random-effects model, treatment effects were estimated by pooling results from individual trials after weighting the results by the inverse of total variance. A dose-response relation between coffee consumption and both total cholesterol and LDL cholesterol was identified (p < 0.01). Increases in serum lipids were greater in studies of patients with hyperlipidemia and in trials of caffeinated or boiled coffee. Trials using filtered coffee demonstrated very little increase in serum cholesterol. Consumption of unfiltered, but not filtered, coffee increases serum levels of total and LDL cholesterol.

Kempf K. et al. Effects of coffee consumption on subclinical inflammation and other risk factors for type-2 diabetes: a clinical trial. Am J Clin Nutr, 91, 950-7, 2010.

Am J Clin Nutr, 91, 950-7, 2010.

Effects of coffee consumption on subclinical inflammation and other risk factors for type-2 diabetes: a clinical trial.

Kempf K. et al.

Background: Coffee consumption is associated with a decreased risk of type 2 diabetes. Suggested mechanisms underlying the association have included attenuation of subclinical inflammation and a reduction in oxidative stress.
Objective: The aim was to investigate the effects of daily coffee consumption on biomarkers of coffee intake, subclinical inflammation, oxidative stress, glucose, and lipid metabolism.

Design: Habitual coffee drinkers (n = 47) refrained for 1 mo from coffee drinking; in the second month they consumed 4 cups of filtered coffee/d and in the third month 8 cups of filtered coffee/d (150 mL/cup). Blood samples were analyzed by gas chromatography–mass spectrometry, bead-based multiplex technology, enzyme-linked immunosorbent assay, or immunonephelometry.

Results: Coffee consumption led to an increase in coffee-derived compounds, mainly serum caffeine, chlorogenic acid, and caffeic acid metabolites. Significant changes were also observed for serum concentrations of interleukin-18, 8-isoprostane, and adiponectin (medians: –8%, −16%, and 6%, respectively; consumption of 8 compared with 0 cups coffee/d). Serum concentrations of total cholesterol, HDL cholesterol, and apolipoprotein A-I increased significantly by 12%, 7%, and 4%, respectively, whereas the ratios of LDL to HDL cholesterol and of apolipoprotein B to apolipoprotein A-I decreased significantly by 8% and 9%, respectively (8 compared with 0 cups coffee/d). No changes were seen for markers of glucose metabolism in an oral-glucose-tolerance test.

Conclusions: Coffee consumption appears to have beneficial effects on subclinical inflammation and HDL cholesterol, whereas no changes in glucose metabolism were found in our study. Furthermore, many coffee-derived methylxanthines and caffeic acid metabolites appear to be useful as biomarkers of coffee intake.

Nystad T. et al. The effect of coffee consumption on serum total cholesterol in the Sami & Norwegian populations. Public Health Nutrition, doi: 10.1017/S1368980010000376.

Public Health Nutrition, doi: 10.1017/S1368980010000376.

The effect of coffee consumption on serum total cholesterol in the Sami & Norwegian populations.

Nystad T. et al.

Objective: To assess coffee consumption in the Sami and Norwegian populations and to investigate the impact of unfiltered boiled coffee consumption on serum cholesterol concentrations.

Design: A cross-sectional study. Information was collected by self-administrated questionnaires and total serum cholesterol was analysed. Participants were divided into three ethnic groups: Sami I (Sami used as home language in the last three generations), Sami II (at least one Sami identity marker) and Norwegian.

Setting: In an area with Sami, Kven/Finnish and Norwegian populations, the SAMINOR study, 2003-2004.

Subjects: A total of 5647 men and 6347 women aged 36-79 years.

Results: More than 90 % of the study populations were coffee drinkers. Only 22 % were unfiltered coffee consumers. Sami I had the highest proportion of participants who consumed nine or more cups of unfiltered coffee per day, although the number of participants was limited. Total coffee consumption was associated with increased total cholesterol for men (P < 0•01) and women (P < 0•0001). For those who drank only unfiltered coffee, a significant association was found only in Norwegian men, adjusted for physical activity in leisure time, BMI and smoking habits (P < 0•001). From the lowest (less than five cups) to the highest (nine or more cups) unfiltered coffee consumption category, the mean total cholesterol levels increased by 0•29 mmol/l in Norwegian men.

Conclusions: Unfiltered coffee consumption was lower in the present study compared to previous reports. In general, total coffee consumption was positively associated with total cholesterol levels. However, for unfiltered coffee consumption, an association was found only in Norwegian men.

Buscemi S. et al. Acute effects of coffee on endothelial function in healthy subjects. Eur J Clin Nutrit, 2010.

Eur J Clin Nutrit, 2010, doi: 10.1038/ejcn.2009.51

Acute effects of coffee on endothelial function in healthy subjects.

Buscemi S. et al.

Background/Objectives: Coffee is the most widely consumed beverage in the world, but its effect on the cardiovascular system has not been fully understood. Coffee contains caffeine and antioxidants, which may influence endothelial function, both of which have not yet been investigated. The objective of this study was to investigate the acute effects of coffee on endothelial function measured by brachial artery flow-mediated dilation (FMD).

Subjects/Methods: A total of 20 (10 males and 10 females) healthy non-obese subjects underwent a double-blind, crossover study. Subjects ingested one cup of caffeinated (CC) and one cup of decaffeinated (DC) Italian espresso coffee in random order at 5- to 7-day intervals.

Results: Following CC ingestion, FMD decreased progressively and significantly (mean+/-s.e.m.: 0 min, 7.7+/-0.6; 30 min, 6.3+/-0.7; 60 min, 6.0+/-0.8%; ANOVA (analysis of variance), P

Conclusions: CC acutely induced unfavorable cardiovascular effects, especially on endothelial function. In the fasting state, insulin secretion is also likely reduced after CC ingestion. Future studies will determine whether CC has detrimental clinically relevant effects, especially in unhealthy subjects.

Buscemi S. et al. Coffee and endothelial function: a battle between caffeine and antioxidants. Eur J Clin Nutrit, 2010, doi: 10.1038/ejcn.2010.9.

Eur J Clin Nutrit, 2010, doi: 10.1038/ejcn.2010.9.

Coffee and endothelial function: a battle between caffeine and antioxidants.

Buscemi S. et al.

Although coffee is largely consumed by adults in Western countries, controversy exists about its impact on the cardiovascular system. We recently demonstrated that caffeinated and decaffeinated espresso coffee have different acute effects on endothelial function in healthy subjects, measured using flow-mediated dilation (FMD) of the brachial artery. In this study, we measured the anti-oxidant capacity of two coffee substances in terms of free stable radical 2,2-diphenyl-1-picryl-hydrazyl 50% inhibition (I50 DPPH). The caffeinated coffee had a slightly higher anti-oxidant capacity than decaffeinated espresso coffee (I50 DPPH: 1.13±0.02 vs 1.30±0.03 μl; P

Refsum H et al, The Hordaland Homocysteine Study: a community based study of homocysteine, its determinants, and associations with disease. Journal of Nutrition, 2006; 136 (6suppl):17731S-1740S

Journal of Nutrition, 2006; 136 (6suppl):17731S-1740S

The Hordaland Homocysteine Study: a community based study of homocysteine, its determinants, and associations with disease.

Refsum H et al.

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992–93, when the subjects were aged 40–67 y. In 1997–99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels >15 µmol/L, but for most conditions, there is a continuous concentration–response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Refsum H et al, The Hordaland Homocysteine Study: a community based study of homocysteine, its determinants, and associations with disease. Journal of Nutrition, 2006; 136 (6suppl):17731S-1740S

Journal of Nutrition, 2006; 136 (6suppl):17731S-1740S

The Hordaland Homocysteine Study: a community based study of homocysteine, its determinants, and associations with disease.

Refsum H et al.

The Hordaland Homocysteine Study (HHS) is a population-based study of more than 18,000 men and women in the county of Hordaland in Western Norway. The first investigation (HHS-I) took place in 1992–93, when the subjects were aged 40–67 y. In 1997–99, a follow-up study (HHS-II) of 7,053 subjects was carried out. In this large population, plasma levels of total homocysteine (tHcy) are associated with several physiologic and lifestyle factors and common diseases. Increasing age, male sex, smoking, coffee consumption, high blood pressure, unfavorable lipid profile, high creatinine, and the MTHFR 677C > T polymorphism are among the factors associated with increased tHcy levels; physical activity, moderate alcohol consumption, and a good folate or vitamin B-12 status are associated with lower tHcy levels. Subjects with raised tHcy levels have increased risk of cardiovascular morbidity, cardiovascular and noncardiovascular mortality, and are more likely to suffer from depression and from cognitive deficit (elderly). Among women, raised tHcy levels are associated with decreased bone mineral density and increased risk of osteoporosis. Women with raised tHcy levels also have an increased risk of having suffered from pregnancy complications and an adverse pregnancy outcome. Significant associations between tHcy and clinical outcomes are usually observed for tHcy levels >15 µmol/L, but for most conditions, there is a continuous concentration–response relation with no apparent threshold concentration. Overall, the findings from HHS indicate that a raised tHcy level is associated with multiple clinical conditions, whereas a low tHcy level is associated with better physical and mental health.

Henkey G J & Eikelboom J W, Homocysteine and Vascular Disease. Lancet, 1999: 354; 407-413

Lancet, 1999: 354; 407-413

Homocysteine and Vascular Disease.

Henkey G J & Eikelboom J W.

For more than 20 years, moderately raised concentrations of total homocysteine (tHcy) have been associated with an increased risk of atherothrombotic vascular events but only recently has evidence mounted to suggest that the association may be causal. The association is independent of other factors, it is fairly consistent across many studies, it is strong and dose-related, and it is biologically plausible. However, the evidence needs to be strengthened by a systematic review of all comparable studies and the demonstration, in randomised trials, that lowering tHcy is followed by a significant reduction in atherothrombotic vascular disease. In addition, the measurement of tHcy needs to be standardised. If these can be achieved then tHcy measurement will become another useful marker of vascular risk, multivitamin therapy will be another therapeutic option for people at risk of atherothrombotic vascular disease, and fortification of food with folic acid will rise high on the political and public health agenda.

Folsom A R et al, Prospective study of coronary heart disease incidence in relation to fasting homocysteine, related polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 1998: 98; 204-210

Circulation. 1998: 98; 204-210

Prospective study of coronary heart disease incidence in relation to fasting homocysteine, related polymorphisms, and B vitamins: the Atherosclerosis Risk in Communities (ARIC) study.

Folsom A R et al.

Background: Elevated plasma total homocysteine (tHcy), low B-vitamin intake, and genetic polymorphisms related to tHcy metabolism may play roles in coronary heart disease (CHD). More prospective studies are needed.

Methods and Results: We used a prospective case-cohort design to determine whether tHcy-related factors are associated with incidence of CHD over an average of 3.3 years of follow-up in a biracial sample of middle-aged men and women. Age-, race-, and field center-adjusted CHD incidence was associated positively (P

Conclusions: Our prospective findings add uncertainty to conclusions derived mostly from cross-sectional studies that tHcy is a major, independent, causative risk factor for CHD. Our findings point more strongly to the possibility that vitamin B6 offers independent protection. Randomized trials, some of which are under way, are needed to better clarify the interrelationships of tHcy, B vitamins, and cardiovascular disease.

Fallon U B et al, Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow-up. Heart 2001: 85; 153-158.

Heart 2001: 85; 153-158.

Homocysteine and coronary heart disease in the Caerphilly cohort: a 10 year follow-up.

Fallon U B et al.

Objective: Prospective assessment of the risk of coronary heart disease associated with total serum homocyst(e)ine (homocysteine) concentration.

Design: Nested case-control study.

Setting: Caerphilly and surrounding villages in south Wales, UK.

Participants: 2290 men who participated in phase II of the study in 1984. After a mean follow up of 10 years, 312 men developed coronary heart disease and were compared with 1248 randomly selected, age frequency matched controls.
Main Outcome Measure: Acute myocardial infarction or death from coronary heart disease.

Results: The geometric mean serum homocysteine concentration was higher in cases (12.2 μmol/l, 95% confidence interval (CI) 11.8 to 12.6 μmol/l) than in controls (11.8 μmol/l, 95% CI 11.3 to 12.5 μmol/l) (p = 0.09). There was a graded increase in the odds ratio of coronary heart disease across quintiles of the homocysteine concentration distribution compared with the first (p = 0.04), which was attenuated when adjusted for confounding variables (p = 0.4). There was a small but non-significant increase in the adjusted odds ratio of coronary heart disease per standard deviation change in the log distribution of homocysteine concentration (OR = 1.07 (95% CI .93 to 1.24), p = 0.34). Comparing the top quintile of the homocysteine concentration with the remaining 80%, the adjusted odds ratio of coronary heart disease was 1.03 (95% CI 0.73 to 1.45) (p = 0.8) and comparing the top 5% with the remaining 95% it was 1.05 (95% CI 0.56 to 1.95) (p = 0.9).

Conclusions: These findings do not support the hypothesis that a raised homocysteine concentration is a strong independent risk factor for coronary heart disease. Randomised controlled trials of homocysteine lowering treatment such as folic acid are needed before generalising the early positive results of observational studies.

Higdon J V & Frei B, Coffee and Health: A Review of Recent Human Research. Critical Reviews Food Science and Nutrition, 2006; 46: 101-123

Critical Reviews Food Science and Nutrition, 2006; 46: 101-123

Coffee and Health: A Review of Recent Human Research.

Higdon J V & Frei B.

Coffee is a complex mixture of chemicals that provides significant amounts of chlorogenic acid and caffeine. Unfiltered coffee is a significant source of cafestol and kahweol, which are diterpenes that have been implicated in the cholesterol raising effects of coffee. The results of epidemiological research suggest that coffee consumption may help prevent several chronic diseases, including type 2 diabetes mellitus, Parkinson’s disease and liver disease (cirrhosis and hepatocellular carcinoma). Most prospective cohort studies have not found coffee consumption to be associated with significantly increased cardiovascular disease risk. However, coffee consumption is associated with increases in several cardiovascular disease risk factors, including blood pressure and plasma homocysteine. At present, there is little evidence that coffee consumption increases the risk of cancer. For adults consuming moderate amounts of coffee (3–4 cups/d providing 300–400 mg/d of caffeine), there is little evidence of health risks and some evidence of health benefits. However, some groups, including people with hypertension, children, adolescents, and the elderly, may be more vulnerable to the adverse effects of caffeine.
In addition, currently available evidence suggests that it may be prudent for pregnant women to limit coffee consumption to 3 cups/d providing no more than 300 mg/d of caffeine to exclude any increased probability of spontaneous abortion or impaired fetal growth.

Grubben M J et al, Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial. American Journal of Clinical Nutrition, 2000: 71; 448-484.

American Journal of Clinical Nutrition, 2000: 71; 448-484.

Unfiltered coffee increases plasma homocysteine concentrations in healthy volunteers: a randomized trial.

Grubben M J et al.

Background: An elevated plasma homocysteine concentration is a putative risk factor for cardiovascular disease. Observational studies have reported an association between coffee consumption and plasma homocysteine concentrations.

Objective: We studied the effect of coffee consumption on plasma homocysteine in a crossover trial. We used unfiltered coffee so as to include the possible effects of coffee diterpenes, which are removed by filtering.

Design: Sixty-four healthy volunteers (31 men and 33 women) with a mean (±SD) age of 43 ± 11 y were randomly assigned to 2 groups. One group (n = 30) drank 1 L unfiltered cafetière (French press) coffee daily for 2 wk. Such coffee is rich in the cholesterol-raising diterpenes kahweol and cafestol. The other group (n = 34) received water, milk, broth, tea, and chocolate drinks instead of coffee. After a washout period of 8 wk, both groups received the alternate intervention for another 2 wk.

Conclusions: Unfiltered coffee increases plasma homocysteine concentrations in volunteers with normal initial concentrations. It is unclear whether the effect is caused by the cholesterol-raising diterpenes present exclusively in unfiltered coffee or by factors that are also present in filtered coffee.

Urgert R A et al, Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers. American Journal of Clinical Nutrition, 2000: 72; 1107-1110

American Journal of Clinical Nutrition, 2000: 72; 1107-1110

Heavy coffee consumption and plasma homocysteine: a randomized controlled trial in healthy volunteers.

Urgert R A et al.

Background: An elevated plasma concentration of total homocysteine is considered to be a strong risk factor for cardiovascular disease. Heavy coffee drinking has been related to high homocysteine concentrations in epidemiologic studies and in one experiment in which healthy subjects drank unfiltered, boiled coffee.

Objective: Our goal was to determine whether daily consumption of paper-filtered coffee raises plasma concentrations of total homocysteine in healthy subjects.

Design: Twenty-six volunteers (18–53 y of age) consumed 1 L/d of paper-filtered coffee brewed with 70 g regular ground beans or no coffee for 4 wk each in a randomized, crossover design.

Results: The mean (±SD) plasma concentration of total homocysteine in fasting blood was 8.1 ± 1.8 µmol/L after abstention from coffee and 9.6 ± 2.9 µmol/L after 3–4 wk of coffee drinking, a difference of 1.5 µmol/L (95% CI: 0.9, 2.1 µmol/L) or 18% (P < 0.001). Coffee increased homocysteine concentrations in 24 of 26 individuals. Circulating concentrations of vitamin B-6, vitamin B-12, and folate were unaffected.

Verhoef P et al, Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans. American Journal of Clinical Nutrition, 2002;76:1244-1248

Verhoef P et al,

Contribution of caffeine to the homocysteine-raising effect of coffee: a randomized controlled trial in humans.

American Journal of Clinical Nutrition, 2002;76:1244-1248

Background: A high plasma total homocysteine concentration is associated with increased risk of cardiovascular disease. Consumption of unfiltered or filtered coffee raises total homocysteine concentrations in healthy volunteers. The responsible compound, however, is unknown.

Objective: The objective was to determine whether caffeine explains the homocysteine-raising effect of coffee.

Design: Forty-eight subjects aged 19–65 y completed this randomized crossover study with 3 treatments, each lasting 2 wk. Subjects consumed 6 capsules providing 870 mg caffeine/d (test treatment), 0.9 L paper-filtered coffee providing ≈870 mg caffeine/d, or 6 placebo capsules. Blood samples were drawn fasting and 4 h after consumption of 0.45 L coffee or 3 capsules.

Results: The mean fasting plasma homocysteine concentration after the placebo treatment was 9.6 ± 3.1 µmol/L. The caffeine and coffee treatments increased fasting homocysteine by 0.4 µmol/L (95% CI: 0.1, 0.7; P = 0.04), or 5%, and by 0.9 µmol/L (95% CI: 0.6, 1.2; P = 0.0001), or 11%, respectively, compared with placebo. The increase in homocysteine concentrations 4 h after consumption of 0.45 L coffee relative to consumption of 3 placebo capsules was 19% (P = 0.0001). Caffeine treatment had a much weaker acute effect on homocysteine (4%; P = 0.09). Effects of caffeine were stronger in women than in men, but the effects of coffee did not differ significantly between men and women.

Conclusions: Caffeine is partly responsible for the homocysteine-raising effect of coffee. Coffee, but not caffeine, affects homocysteine metabolism within hours after intake, although the effect is still substantial after an overnight fast.

Olthof M R et al, Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. American Journal of Clinical Nutrition, 2001;7 737;532-538

American Journal of Clinical Nutrition, 2001;7 737;532-538

Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans.

Olthof M R et al,

Background: In population studies, high intakes of coffee are associated with raised concentrations of plasma homocysteine, a predictor of risk of cardiovascular disease. Chlorogenic acid is a major polyphenol in coffee; coffee drinkers consume up to 1 g chlorogenic acid/d.

Objective: We studied whether chlorogenic acid affects plasma total homocysteine concentrations in humans. For comparison we also studied the effects of black tea rich in polyphenols and of quercetin-3-rutinoside, a major flavonol in tea and apples.

Design: In this crossover study, 20 healthy men and women ingested 2 g (5.5 mmol) chlorogenic acid, 4 g black tea solids containing ≈4.3 mmol polyphenols and comparable to ≈2 L strong black tea, 440 mg (0.7 mmol) quercetin-3-rutinoside, or a placebo daily. Each subject received each of the 4 treatments for 7 d, in random order.

Results: Total homocysteine in plasma collected 4–5 h after supplement intake was 12% (1.2 µmol/L; 95% CI: 0.6, 1.7) higher after chlorogenic acid and 11% (1.1 µmol/L; 95% CI: 0.6, 1.5) higher after black tea than after placebo. Total homocysteine in fasting plasma collected 20 h after supplement intake was 4% (0.4 µmol/L; 95% CI: 0.0, 0.8) higher after chlorogenic acid and 5% (0.5 µmol/L; 95% CI: 0.0, 0.9) higher after black tea than after placebo. Quercetin-3-rutinoside did not significantly affect homocysteine concentrations.
Conclusions: Chlorogenic acid, a compound in coffee, and black tea raise total homocysteine concentrations in plasma. Chlorogenic acid could be partly responsible for the higher homocysteine concentrations observed in coffee drinkers. Whether these effects on homocysteine influence cardiovascular disease risk remains to be established. Am J Clin Nutr 2001;73:532–8.

Zhang W. et al. Coffee consumption and risk of cardiovascular disease and all-cause mortality among men with type 2 diabetes. Diabetes Care, 32, 1043-1045, 2009.

Diabetes Care, 32, 1043-1045, 2009.

Coffee consumption and risk of cardiovascular disease and all-cause mortality among men with type 2 diabetes.

Zhang W. et al.

Objective: Coffee consumption has been linked to detrimental acute metabolic and hemodynamic effects. We investigated coffee consumption in relation to risk of CVDs and mortality in diabetic men.
Research Design and Methods: We conducted a prospective cohort study including 3,497 diabetic men without CVD at baseline.

Results: After adjustment for age, smoking, and other cardiovascular risk factors, relative risks (RRs) were 0.88 (95% CI 0.50–1.57) for CVDs (P for trend = 0.29) and 0.80 (0.41–1.54) for all-cause mortality (P for trend = 0.45) for the consumption of ≥4 cups/day of caffeinated coffee compared with those for non–coffee drinkers. Stratification by smoking and duration of diabetes yielded similar results. RRs for caffeine intake for the highest compared with the lowest quintile were 1.02 (0.70–1.47; P for trend = 0.96) for CVDs and 0.96 (0.64–1.44; P for trend = 0.69) for mortality.

Conclusions:These data indicate that regular coffee consumption is not associated with increased risk for CVDs or mortality in diabetic men.

Mukanal K.J. et al. Coffee consumption and mortality after acute myocardial infarction: the Stockholm Heart Epidemiology Program. Am Heart J., 157, 495-501, 2009.

Am Heart J., 157, 495-501, 2009.

Coffee consumption and mortality after acute myocardial infarction: the Stockholm Heart Epidemiology Program.

Mukanal K.J. et al.

Background: Cohort studies have suggested little effect of coffee consumption on risk of acute myocardial infarction. The effect of coffee consumption on prognosis after myocardial infarction is uncertain.

Methods: In a population-based inception cohort study, we followed 1,369 patients hospitalized with a confirmed first acute myocardial infarction between 1992 and 1994 in Stockholm County, Sweden, as part of the Stockholm Heart Epidemiology Program. Participants reported usual coffee consumption over the preceding year with a standardized questionnaire distributed during hospitalization and underwent a health examination 3 months after discharge. Participants were followed for hospitalizations and mortality with national registers through November 2001.

Results: A total of 289 patients died during follow-up. Compared with intake of

Conclusions: Self-reported coffee consumption at the time of hospitalization for myocardial infarction was inversely associated with subsequent postinfarction mortality in this population with broad coffee intake. If confirmed in other settings, identification of relevant mechanisms could lead to an improved prognosis for survivors of acute myocardial infarction.

Palatini P. et al. CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension. J Hypertension, 2009, doi: 10.1097/HJH.0b013e32832ba850.

J Hypertension, 2009, doi: 10.1097/HJH.0b013e32832ba850.

CYP1A2 genotype modifies the association between coffee intake and the risk of hypertension.

Palatini P. et al.

Objectives: The longitudinal relationship between coffee use and hypertension is still controversial. Cytochrome P450 1A2 (CYP1A2) is the main responsible enzyme for the metabolism of caffeine. The aim of the present study was to investigate the effect of coffee intake on the risk of developing hypertension needing antihypertensive treatment in individuals stratified by CYP1A2 genotype.

Design: We assessed prospectively 553 young White individuals screened for stage 1 hypertension. Coffee intake was ascertained from regularly administered questionnaires. Incident physician-diagnosed hypertension was the outcome measure. Genotyping of CYP1A2 SNP was performed by real time PCR.

Results: During a median follow-up of 8.2 years, 323 individuals developed hypertension. For carriers of the slow *1F allele (59%), hazard ratios of hypertension from multivariable Cox analysis were 1.00 in abstainers (reference), 1.72 (95%CI, 1.21-2.44) in moderate coffee drinkers (P = 0.03), and 3.00 (1.53-5.90) in heavy drinkers (P = 0.001). In contrast, hazard ratios for coffee drinkers with the rapid *1A/*1A genotype were 0.80 (0.52-1.23, P = 0.29) for moderate drinkers and 0.36 (0.14-0.89, P = 0.026) for heavy drinkers. In a two-way ANCOVA, a gene × coffee interactive effect was found on follow-up changes in systolic (P = 0.000) and diastolic (P = 0.007) blood pressure. Urinary epinephrine was higher in coffee drinkers than abstainers but only among individuals with slow *1F allele (P = 0.001).
Conclusion: These data show that the risk of hypertension associated with coffee intake varies according to CYP1A2 genotype. Carriers of slow *1F allele are at increased risk and should thus abstain from coffee, whereas individuals with *1A/*1A genotype can safely drink coffee.

Richardson T. et al. Ramdoized control trials investigating the influence of coffee on heart rate variability in patients with ST-segment elevation myocardial infarction. Q J Med, doi: 10.1093/qjmed/hcp072.

Q J Med, doi: 10.1093/qjmed/hcp072.

Ramdoized control trials investigating the influence of coffee on heart rate variability in patients with ST-segment elevation myocardial infarction.

Richardson T. et al.

Background: Cardiac autonomic dysfunction post ST-segment elevation myocardial infarction (STEMI) has been linked to an excess risk of premature cardiovascular morbidity and mortality above those with normal autonomic function post-STEMI.

Aim: The aim of this study was to evaluate the effect of acute ingestion of coffee on autonomic function and cardiovascular outcomes in patients with acute STEMI.

Design: Randomized control trial.

Methods: We randomized 103 patients with acute STEMI, admitted to our Coronary Care Unit, to receive regular coffee (caffeinated) or de-caffeinated coffee using a randomized controlled double-blinded design. Heart rate variability was assessed 5 days post-STEMI to assess the effect of caffeine on autonomic function.

Results: In the group randomized to regular coffee, parasympathetic activity increased by up to 96% (P = 0.04) after 5 days. There was no detrimental effect of regular coffee on cardiac rhythm post-STEMI.
Conclusion: Coffee ingestion is associated with an increase in parasympathetic autonomic function immediately post-STEMI. Coffee was found to be safe and not associated with any adverse cardiovascular outcomes in the short term.

Namdar M. et al. Caffeine impairs myocardial blood flow response to physical exercise in patients with artery disease as well as in age-matched controls. PloS ONE, 4(5), e5665, 2009.

PloS ONE, 4(5), e5665, 2009.

Caffeine impairs myocardial blood flow response to physical exercise in patients with artery disease as well as in age-matched controls.

Namdar M. et al.

Background: Caffeine is one of the most widely consumed pharmacologically active substances. Its acute effect on myocardial blood flow is widely unknown. Our aim was to assess the acute effect of caffeine in a dose corresponding to two cups of coffee on myocardial blood flow (MBF) in coronary artery disease (CAD).

Methodology/Principal Findings: MBF was measured with 15O-labelled H2O and Positron Emission Tomography (PET) at rest and after supine bicycle exercise in controls (n = 15, mean age 58±13 years) and in CAD patients (n = 15, mean age 61±9 years). In the latter, regional MBF was assessed in segments subtended by stenotic and remote coronary arteries. All measurements were repeated fifty minutes after oral caffeine ingestion (200 mg). Myocardial perfusion reserve (MPR) was calculated as ratio of MBF during bicycle stress divided by MBF at rest. Resting MBF was not affected by caffeine in both groups. Exercise-induced MBF response decreased significantly after caffeine in controls (2.26±0.56 vs. 2.02±0.56, P

Conclusions: We conclude that caffeine impairs exercise-induced hyperaemic MBF response in patients with CAD to a greater degree than age-matched controls.