Prof. Michael Bohm
Dr. Nicolas Werner
Epidemiological data concerning an association between coffee consumption and cardiovascular disease are contradictory. Here we review two recent studies demonstrating that slow caffeine metabolisers may have an increased risk for non-fatal myocardial infarction while a prospective cohort study in 44 005 men and 84 488 women did not find an association between caffeine intake and coronary heart disease.
The countries of the European Union and especially Scandinavia are worldwide leaders in coffee consumption. The major effector of coffee is caffeine which has been shown to be an antagonist at the adenosine receptor, increases blood pressure and homocysteine, stimulates fat oxidation and the release of free fatty acids, and decreases insulin sensitivity [1-3].
Nevertheless, coffee consists of a number of other compounds including antioxidants, potassium, niacin, and magnesium which may have a protective effect in the cardiovascular system . Caffeine is metabolised by cytochrome P4501A2 in the liver. Enzyme inducibility is influenced by mutations in the CYP1A2 gene and allows differentiation between “slow” and “rapid” caffeine metabolisers .
Epidemiological studies have demonstrated that coffee drinking and caffeine intake is associated with an increased risk of coronary heart disease (CHD) . However, prospective cohort studies have shown a lower risk in patients with increasing coffee consumption [6;7].
Reviewing the literature, the association between coffee consumption and an increased cardiovascular risk has mostly vanished after adjustment for conventional coronary risk factors and by a close correlation between coffee intake and an unhealthy lifestyle . However, a couple of studies have shown a protective role of coffee consumption in cardiovascular disease e.g. in diabetes mellitus [9;10]. Despite various large studies, data concerning coffee consumption and cardiovascular disease remain uncertain. Two large studies [2;4] have been recently published providing mechanistical insights and long-term follow-up concerning coffee consumption and heart disease.
In a recent prospective cohort study, Lopez-Garcia et al.  examined the association between coffee consumption and coronary heart disease. 44 005 men and 84 488 women were prospectively studied since 1986 and 1980, respectively. Patients had no history of cardiovascular or malignant disease. 1449 patients suffered from non-fatal myocardial infarction and 724 patients died due to cardiovascular reasons within the observational time frame. Coffee consumption was associated with an unhealthy lifestyle (e.g. more nicotine abuse, less exercise).
In an age-adjusted analysis, there was a positive association between coffee consumption (including caffeine derived from tea, cola beverages, and chocolate candies) and CHD in women but not in men. However, after adjustment for cardiovascular risk factors and especially smoking, the risk for CHD was not significantly increased with coffee consumption either in women or men. Further stratification according to recent coffee consumption or cardiovascular risk factors did not show a significant correlation within subgroups.
This large prospective cohort study demonstrates that coffee consumption is not associated with an increased risk for fatal and non-fatal myocardial infarction. There was no correlation between coffee consumption and the incidence of diabetes. Interestingly, the formerly proposed association between coffee consumption and arterial hypertension could not be confirmed in a recent study. Winkelmayer et al.  found no linear association between caffeine consumption and incident hypertension. Habitual coffee consumption was not associated with an increased risk of hypertension in contrast to consumption of sugared or diet cola which was associated with hypertension. It is tempting to speculate whether sugared coffee may be associated with incident hypertension.
The CYP1A2 is responsible for 95% of caffeine metabolism . Enzyme activity demonstrates a wide variability within individuals. Carriers of a mutation in the CYP1A2 gene (A->C substitution at position 734; CYP1A2*1F) identifies individuals with a decreased metabolization rate of caffeine (“slow” metabolizer) while individuals homozygous for the CYP1A2*1A allele are “rapid” metabolizer. To further elucidate the potential association between caffeine intake and nonfatal myocardial infarction, Cornelis et al.  genotyped 2014 patients in Costa Rica presenting with a first non-fatal myocardial infarction in a case-control study. 55% of cases and 54% of controls were slow metabolizers. Among slow metabolizers, the risk of a non-fatal myocardial infarction was increased in a logistic regression model correcting for cardiovascular risk factors (OR of MI 1.64, 95%CI 1.14-2.34) for 4 cups or more of coffee per day compared to 1 cup per day. This association was not present in fast metabolizers (OR 0.99, 95%CI 0.66-1.48). There was no association between caffeine intake and MI when looking at the total population or stratifying for gender or smokers.
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.
Various case-control studies have demonstrated that increased coffee intake is associated with an increased risk for cardiovascular disease. A recent meta-analysis of pooled case-control studies suggests a 60% increased risk for coronary heart disease for drinking 5 cups per day . However, most of the prospective cohort studies have not found the described correlation between coffee intake and CHD. This has been attributed in the past to a lack of studies investigating acute effects of caffeine, missing long-term follow-up studies, or a missing update of coffee intake in long term studies.
This lack of studies has been closed by the recent prospective study by Lopez-Garcia et al.  demonstrating that chronic and acute coffee consumption is not associated with an increased risk for MI. So, green light for the Europeans – world leaders in coffee consumption? It appears reasonable at present to sit back, relax, have a cup of coffee and wait for further studies bringing light into the dark.
1. Sudano I, Binggeli C, Spieker L, Luscher TF, Ruschitzka F, Noll G, Corti R. Cardiovascular effects of coffee: is it a risk factor? Prog Cardiovasc Nurs. 2005;20:65-69. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15886549&query_hl=2&itool=pubmed_docsum 2. Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, Stampfer MJ, Rexrode KM, Hu FB. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006;113:2045-2053. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16636169&query_hl=4&itool=pubmed_docsum 3. Winkelmayer WC, Stampfer MJ, Willett WC, Curhan GC. Habitual caffeine intake and the risk of hypertension in women. JAMA. 2005;294:2330-2335. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16278361&query_hl=6&itool=pubmed_docsum 4. Cornelis MC, El Sohemy A, Kabagambe EK, Campos H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA. 2006;295:1135-1141. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=16522833&query_hl=8&itool=pubmed_docsum 5. 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;72:269-275. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=7946780&query_hl=10&itool=pubmed_docsum 6. 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;160:3393-3400. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?CMD=search&DB=pubmed 7. 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;53:481-487. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=10562866&query_hl=13&itool=pubmed_docsum 8. Schreiber GB, Robins M, Maffeo CE, Masters MN, Bond AP, Morganstein D. Confounders contributing to the reported associations of coffee or caffeine with disease. Prev Med. 1988;17:295-309. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=3405986&query_hl=15&itool=pubmed_docsum 9. van Dam RM, Hu FB. Coffee consumption and risk of type 2 diabetes: a systematic review. JAMA. 2005;294:97-104. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=15998896&query_hl=17&itool=pubmed_docsum 10. van Dam RM, Feskens EJ. Coffee consumption and risk of type 2 diabetes mellitus. Lancet. 2002;360:1477-1478. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=12433517&query_hl=19&itool=pubmed_docsum 11. Butler MA, Iwasaki M, Guengerich FP, Kadlubar FF. Human cytochrome P-450PA (P-450IA2), the phenacetin O-deethylase, is primarily responsible for the hepatic 3-demethylation of caffeine and N-oxidation of carcinogenic arylamines. Proc Natl Acad Sci U S A. 1989;86:7696-7700. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=Abstract&list_uids=2813353&query_hl=21&itool=pubmed_docsum
N. Werner* and Prof. M. Böhm**
2 Klinik für Innere Medizin III Universitätsklinikum des Saarlandes 66421 Homburg-Saar
Correspondence: Nikos Werner, MD Medizinische Klinik und Poliklinik II Universitätsklinikum Bonn Sigmund-Freud-Str. 25 53105 Bonn phone +49-228-287-5217/5218 fax +49-228-287-6423 Email: firstname.lastname@example.org
Our mission: To reduce the burden of cardiovascular disease
© 2018 European Society of Cardiology. All rights reserved