Next Article in Journal
Numerical Investigation of Fluid Flow and In-Cylinder Air Flow Characteristics for Higher Viscosity Fuel Applications
Next Article in Special Issue
Andrographis paniculata Extract Relieves Pain and Inflammation in Monosodium Iodoacetate-Induced Osteoarthritis and Acetic Acid-Induced Writhing in Animal Models
Previous Article in Journal
Infrared Infusion Monitor Based on Data Dimensionality Reduction and Logistics Classifier
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Processes
Volume 8
Issue 4
10.3390/pr8040438
processes-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Conflicting Effects of Coffee Consumption on Cardiovascular Diseases: Does Coffee Consumption Aggravate Pre-existing Risk Factors?

by
Dongwoo Lim
1,
Jiung Chang
1,
Jungyun Ahn
2 and
Jaieun Kim
1,*
1
Department of Pathology, College of Korean Medicine, Dongguk University, Goyang 10326, Korea
2
Department of Herbal Formula, College of Korean Medicine, Dongguk University, Goyang 10326, Korea
*
Author to whom correspondence should be addressed.
Processes 2020, 8(4), 438; https://doi.org/10.3390/pr8040438
Submission received: 15 March 2020 / Revised: 30 March 2020 / Accepted: 3 April 2020 / Published: 8 April 2020
(This article belongs to the Special Issue Pharmacodynamics Modeling of Anti-inflammatory Drugs)
Versions Notes

Abstract

:
Coffee is one of the most popular beverages worldwide. Its effect on health is generally regarded as beneficial in many studies. However, there are growing concerns about the adverse effect of coffee consumption on cardiovascular disease (CVD) due to the potential aggravating impact on the cardiovascular system attributed to various compounds within coffee. This review is focused on deteriorative effects of coffee consumption on CVDs with possible mechanisms. Patients with risk factors of CVDs should prudently consider heavy consumption of coffee as it may exacerbate hypertension, dyslipidemia, and atherosclerosis, and increase the odds of cardiovascular events. J-shaped or U-shaped dose-response graphs of coffee consumption and CVD parameters partially explain the inconsistency of conclusions between coffee studies on CVD, highlighting a moderate intake of coffee. Moreover, there are discrepancies in results from clinical studies elucidating considerable influences of confounding factors including gender and smoking status on outcomes of those conducted to reveal the actual impact of coffee consumption on CVDs. Physical features of subjects including genetic variations and body mass index (BMI) make it difficult to determine moderate intake of coffee for individuals in terms of caffeine metabolism. Further epidemiological studies with consideration about characteristics of the study population are needed to determine the exact effect of coffee consumption on CVD.

1. Introduction

Coffee is one of the most commonly consumed beverages worldwide [1]. According to a survey, the population number of coffee consumers has increased annually and approximately 65% of adults are taking coffee daily in South Korea [2]. To date, coffee consumption is regarded as beneficial to various health issues. For instance, the extract of coffee has been extensively investigated in various pathophysiological models in vitro and in vivo, showing prominent anti-inflammatory [3], anti-oxidant [4], anti-carcinogenic [5], and other potentials. Based on these findings, it is not very surprising that numerous coffee-related papers report the alleviating effects of coffee consumption on cardiovascular disease (CVD) [6,7,8] and even lowered all-cause mortality after 18 to 24 years of follow-ups [9]. From a pharmacognostic view, diverse physiological consequences of coffee intake on circulatory system are attributed to caffeine and other various bioactive phenolic compounds [10,11]. Results from a cross sectional study suggested that coffee consumption reduced inflammation and markers of endothelial activation in both healthy and diabetic women, which implies the beneficial effects of coffee on cardiovascular health [12]. These effects were independent of the presence or absence of caffeine in coffee, which means that the benefits of coffee are not limited by caffeine alone.
Notwithstanding those benefits of coffee as described above, coffee or caffeine intake should be discreetly considered in patients with CVDs since coffee has ambivalent influences on the circulatory system. An increasing number of papers are now reporting conflicting conclusions about the effects of coffee on CVDs. Some researchers have propounded the risk of acute coffee or caffeine consumption in populations with CVD-related risk factors, eminently increasing systolic and diastolic blood pressure [13,14,15]. In an analysis of a case control study, J-shaped association between coffee consumption and risk of acute coronary syndrome indicated that the amount of coffee intake should be in a consideration [16]. Moreover, coffee drinking turned out to be a significant forecaster of cardiovascular events for hypertensive patients especially in heavy drinkers [17].
The inconsistency over the effects of coffee consumption on cardiovascular health is assumed to be derived from various confounders [18], inadequacy of the study design or statistical analysis [19], and other unidentified reasons. However, what attracts our attention are the cases that coffee consumption aggravated risk factors in stratified group of patients with CVD in epidemiological studies. In these patients with cardiovascular risk factors, coffee consumption tends to aggravate already-existing cardiovascular risk factors [13,20].
Many previous review works have been conducted and present the adverse effects derived from consumption of coffee by analyzing epidemiological studies or randomized controlled trials (RCTs). In this review, we present some papers that considered coffee consumption to be related to the aggravation of CVD. We discuss the detrimental effects of coffee consumption on each risk factor of CVD with probable mechanisms. Then we scrutinize documents to find evidence that coffee consumption worsens preexisting risk factors of CVD in a vulnerable population.

2. Results

2.1. General Effects and Mechanisms of Coffee and Its Compounds on the Circulatory System

The major compound of coffee, caffeine, is a xanthine alkaloid which has structural similarities with adenosine and can act as a competitive inhibitor of adenosine receptor A1, A2a, and A2b [21] which leads to elevated adenosine levels in the plasma. Adenosine acts as a vasodilation factor in coronary arteries and different working modes of adenosine are largely dependent on the localization of adenosine receptor type (mostly A2a type with local vascular vasodilation effect) [22]. Caffeine can elevate intracellular cyclic adenosine monophosphate (cAMP) by inhibiting cAMP phosphodiesterase. Prolonged cAMP is known to accelerate heart function with positive inotropic effects [23]. In addition, caffeine may exert a cardioacceleratory effect and cause vagally-mediated bradycardia via baroreflex activation [24].
Chlorogenic acid is another major compound found in coffee. In addition to its favorable antioxidant properties [25], chlorogenic acid has fundamental influences on the circulatory system by activating the AMP activated protein kinase (AMPK) signaling pathway which is a key modulator of glucose and lipid metabolism [26]. Chlorogenic acid also restores diet-induced cardiovascular changes in vivo and inhibits platelet activation in vitro. Chlorogenic acid inhibits NAD(P)H oxidase activity to reduce superoxide production, and directly scavenges free radicals, and promotes NO production to support normal vascular function, and inhibits the angiotensin-converting enzyme in plasma [27]. Double-blinded randomized controlled crossover study performed with healthy volunteers revealed a decrease of mean systolic blood pressure (SBP) (−2.41 mmHg) and mean diastolic blood pressure (DBP) (−1.53 mmHg) by acute chlorogenic acid treatment [28].
Moreover, ferulic acid, a major metabolite of chlorogenic acid [27], also regulates the effects on blood pressure through inhibiting angiotensin-converting enzyme activity [29]. In a study, ferulic acid even decreased average blood pressure by 29.6% and improved endothelial function in hypertensive rats by mediating acetylcholine receptors [30]. A summary of coffee compounds and their effects is presented in Table 1.

2.2. Epidemiological Studies of CVDs Shed Light on Profound Influence of Coffee Consumption

Investigators have performed clinical studies targeting CVDs by scrutinizing the daily intake of coffee in subjects and recognized that coffee or caffeinated drinks may impact the outcomes of patients with CVDs. Epidemiological studies investigating the influence of undisclosed variates on CVDs have included coffee consumption as a covariate [34] or dietary confounding factor [35], implying its potential influence regardless of whether it is harmful or beneficial. A meta-analysis of 14 coffee consumption trials revealed a relationship between heavy coffee consumption and increased levels of serum cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol [20]. Results from studies concerning the efficacy of lipid-lowering drugs have also suggested that coffee consumption or caffeine intake may influence the results [36]. In addition, a guideline for hypertensive patients instructed patients to refrain from caffeine before measurement of systolic blood pressure as caffeine is recognized as a potential pressor agent [37]. The summarized result of representative studies investigating the effect of coffee consumption on parameters and risk factors of CVDs is presented in Table 2 and Table 3.

2.3. Coffee Consumption Exacerbates Hypertension in People Who Have Risk Factors

As previously studied, adenosine is a potent vasodilator in coronary arteries [45]. However, paraxanthine, a main metabolite of caffeine, has a pressor effect by exerting similar sympathomimetic action to caffeine; therefore it can increase serum epinephrine levels in healthy volunteers [46]. The reason why caffeine increases blood pressure can be explained with increased peripheral resistance, sympathetic tone, catecholamine, and renin secretion [22]. In addition, caffeinated coffee consumption can induce rapid increase in aortic systolic and diastolic pressure compared to decaffeinated coffee consumption in a double-blind study with healthy and young subjects [31]. A noteworthy point in the report is the pulse wave velocity (PWV) result, which increased significantly from 7.2 to 8.0 m/s at the end of 90 min after coffee ingestion, revealing evidences that caffeine intake can increase arterial stiffness.
Age, family history of hypertension, excess potassium or alcohol consumption, and obesity are well-known strong risk factors of hypertension [47]. Fifty-two healthy subjects having normal range blood pressure but with a family history of hypertension showed significant responses to caffeine consumption [38]. In detail, caffeine administration (3.3 mg/kg) caused an additional increase of systolic blood pressure and cortisol response to the stressor. In addition, analysis of controlled clinical and epidemiologic studies revealed that regular coffee ingestion may be harmful to hypertension-prone subjects [13]. Moreover, a cross-sectional study with 843 elderly volunteers aged 60–87 elucidated the positive relation of coffee intake and hypertension, especially in groups using anti-hypertensive drugs [48].

2.4. Lipid Profiles of Coffee Consumers with Underlying Risk Factors can Be Affected by Coffee Brewing Method

Although the doubt about caffeine’s property in increasing serum cholesterol level is now almost cleared [20], there are still remaining debates on other compounds of coffee. The effect of coffee drinking on lipid levels of subjects depends on the brewing method of coffee [49]. Cafestol and kahweol are abundant diterpenes in boiled Turkish or French press coffee. It has been reported that cafestol can increase serum cholesterol levels in a dose-dependent manner, with 1 mg/dL increase in cholesterol per 2 mg of cafestol consumption [50,51]. Similar results have been drawn after consumption of coffee oil containing 71.56 mg of cafestol and 52.96 mg of kahweol in daily dose (in Arabica coffee group) [39]. The mechanism of cafestol in increasing serum cholesterol levels includes suppressing both enzyme activity and gene expression of CYP7A1 by discouraging bile acid production, thus increasing hepatic free cholesterol [52]. Moreover, as an agonist ligand for both farnesoid-x-receptor (FXR) and pregnane-x-receptor (PXR), cafestol can modulates cholesterol levels [33]. Coffee consumption may have an inverse correlation with high density lipoprotein in men. The ratio of high density lipoprotein cholesterol to total cholesterol has been found to be lower in male coffee drinkers compared to those in male non-coffee drinkers, implying a deteriorating effect of coffee on lipid profile [53]. In a large cross-sectional study including 14,168 men and 14,859 women in Norway, serum total cholesterol level showed dose-response relation with coffee consumption per day [54]. In this study, investigators observed the strongest cholesterol-increasing effect in groups drinking boiled coffee.
Age, sex, obesity, diabetes sedentary lifestyle, alcohol use, smoking, and genetic factors [55,56,57] are considered to be related with the occurrence of dyslipidemia. Interestingly, a cross-sectional study carried out in Germany revealed a dose-related increment of serum total cholesterol was found only in young people [58], which is similar to those drawn from an Israeli study [59]. Hypertension and hyperlipidemia are frequently found as comorbidities [60] and the association has been proven in a cohort study [61]. A study investigated a group of 9043 hypertensive adults (during hypertension follow-up program), and found a positive association with coffee intake and serum cholesterol level [62]. Patients with hyperlipidemia tend to have higher cholesterol levels after coffee drinking than healthy subjects demonstrated by a meta-analysis review of 14 randomized clinical trials [20].

2.5. Coffee Consumption Potentially Worsens Vascular Health and Atherosclerosis

Coffee consumption is generally regarded as safe and advantageous to atherosclerosis with anti-oxidant properties because coffee contains phenols that can improve endothelial function [63]. However, there are still unfavorable effects of coffee intake on atherosclerosis progression and vascular health with some explainable mechanisms. Influence of caffeine ingestion on vascular wellness and hemodynamics has been determined by several parameters, including PWV, reflected wave, or carotid artery ultrasound in various studies. Acute or chronic coffee consumption increases arterial stiffness [31,64]. Arterial stiffness measured by carotid-femoral PWV is demonstrated to be positively associated with homocysteine level as an evident factor in atherosclerosis in a Chinese cross-sectional study [65]. It has been found that plasma homocysteine level, an independent risk factor of cardiovascular disease [66], was increased by caffeine (0.4 μmol/L) and coffee intake (0.9 μmol/L) in randomized controlled trials [67]. In addition, chlorogenic acid is known to be responsible for elevated homocysteine level in coffee consumers [68]. Homocysteine can provoke inflammation-driven endothelial dysfunction and generate excessive reactive oxygen species by inducing C-reactive protein which is critical to atherosclerotic progression [69] and can aggravate coronary artery calcium (CAC) [70]. Peripheral vascular resistance is also elevated by caffeine (3.3 mg/kg) [40], implying that coffee might play a role in the progression of atherosclerosis. Moreover, in a randomized, double blinded, cross-over study with 12 hypertensive patients, administration of 250 mg of caffeine showed significantly increased systolic blood pressure and PWV [71]. There is also additional evidence demonstrating relationships between moderate to heavy coffee consumption and increased inflammatory markers including interleukin (IL)-6, C-reactive protein, and serum amyloid-A [44]. Further, heavy coffee drinking of more than 4 cups/day is associated with increased inflammatory markers and impaired thrombosis/fibrinolysis in hypertensive smokers [72].
In a cross-sectional study conducted in Korea including 25,138 asymptomatic men and women, coffee consumption and coronary artery calcium score apparently showed a U-shaped relationship [73]. The authors focused on the point that CAC score ratio is lowest in groups drinking 3–5 cups of coffee/day. However, CAC score ratios of group drinking ≥5 cups of coffee/day showed higher CAC scores than 3–5 cups or even non-drinking groups, suggesting that high doses of coffee have detrimental effects.

2.6. Caffeine may Trigger Arrhythmia and Cardiovascular Events in Certain Populations

Coffee consumption should be considered carefully for patients with arrhythmia. Although many RCT studies concluded that the correlation between the occurrence of arrhythmia and intake of caffeine or coffee is not significant [74,75], there is evidence that coffee or caffeine can be associated with incidents of arrhythmia in populations with certain aggravation factors. Results from large-scale clinical studies have indicated that heavy consumption (more than 9 cups per day) can double the occurrence of premature ventricular complexes [76], particularly in certain subjects with risk factors [77]. By activating ryanodine receptor 2, caffeine may interfere with luminal calcium ion levels responsible for after-potential, thus inducing arrhythmia [78,79]. It has been reported that high coffee consumption increases the incidence of acute lone fibrillation [41].
A cohort study with a huge healthy Italian population revealed the coronary heart disease (CHD) hazard ratio is in direct proportion to the amount of coffee consumption ranging from 0 to 4 cups per day [80]. Meanwhile, an epidemiological study analyzing the etiology and prognosis of heart failure revealed higher odds ratio (OR = 1.11 as compared to non-consuming group) of heart failure in ordinary Swedish people taking more than 5 cups of coffee a day [42]. In another large cohort study conducted in the US, coffee consumption was associated with higher incidence of myocardial infarction with coinciding result of relative risk (RR) [81]. However, a recent meta-analysis demonstrated a J-shaped correlation between heart failure and coffee consumption, showing that the inverse-effect of coffee on relative risk of heart failure rebounded from more than 4 cups of coffee per day [82].

3. Discussion

The present study elucidated on the deteriorating effects of coffee consumption on CVDs with reasonable evidence. To the best of our knowledge, daily ingestion of caffeine less than 400 mg/day has no evident adverse effects in the general and healthy adult population [83]. Moderate coffee consumption itself has more benefits than harms for healthy population as supported by the majority of clinical works. Most published articles have reported that adverse effects of moderate coffee or caffeine consumption on CVDs are not evident in a healthy population without potential risk factors [84,85,86]. However, as we reviewed in this paper, for certain populations with risk factors, coffee consumption has remarkable deteriorating effects. Discrepancies of study results about coffee consumption can be explained by several reasons.
Consisting of various bioactive compounds, coffee consumption has both risks and benefits on cardiovascular disease due to varying intake amounts. In many papers, the relationship between coffee (or caffeine) intake and cardiovascular parameters showed J-shaped or U-shaped consequences with unfavorable effects on heavy consumers [16,64,73,87,88,89], implying a non-linear risk–benefit ratio; so it does seem to be a matter of the amount of coffee rather than whether it is consumed or not. “Moderate coffee consumption” whose benefit of consumption outweighs the risk, is often represented as 3–5 cups a day [90]. However, it is not easy to suggest a moderate amount for the entire population concerning individual characteristics. Genetic variation, especially CYP1A2 allele [91], can affect the clearance rate for caffeine among and within individuals and can vary up to 40-fold [92]. Females and non-smokers are reported to have lower activity of CYP1A2 [93], so more attention should be paid to these slow caffeine metabolizers in analyzing epidemiological data. Furthermore, the effect of coffee consumption can be modified by gender and obese status (body mass index, BMI) [94]; obese volunteers exhibited higher absorption rate, lower elimination rate, and longer half-life of caffeine in serum [95].
Confusing variables vary in many coffee studies with modification in criteria that requires delicate interpretation (Table 4). Particularly, as reviewed in many studies, both sex and smoking are two essential confounders in the study of coffee consumption and CVD [96]. Positive correlation between number of cigarettes smoked and amount of caffeine consumed was reported [97], deducing 2.3 times higher amount of coffee consumption in smokers as compared to non-smokers [96]. It has been found that smoking status can change the influence of coffee consumption on serum total cholesterol level [43]. As a significant cause and risk factor of CVD, smoking habits can confuse investigators from deducing appropriate results [98].
The differences in gender responses in cardiovascular parameters to caffeine were importantly considered by numerous studies which attribute the differences to steroid hormones and lifestyle [99,100,101]. As coffee or caffeine consumption is closely related with sex and smoking status, stratification by gender should be performed to eliminate gender bias. Social status and income levels affect various aspects of the health status of the group members, masking the true effect of coffee consumption on CVD.
To have consistency in clinical investigations, characteristics of subjects in clinical trials should be considered in designing the methodology, including ethnic variations in responsiveness to caffeine and different lifestyles. For instance, results of a Tromsø heart study with a Danish population characterized by highest servings of daily coffee per capita are different from those of an East Asian population in basal serum lipid levels and dose-response to coffee [102,103]. This raises the necessity of clinical investigations for each population according to their lifestyle to determine the precise effect of coffee on CVD. A retrospective investigation using the Framingham risk model determined the influence of coffee consumption on coronary heart disease risk in Korean society [104]. Another study reviewed the association between coffee consumption and stroke risk in a cross-sectional study in Korea [101]. Interestingly, results from both studies indicate that coffee only has beneficial effects in the female population (no significant association in males), attributing the result to lifestyle differences in both sexes. A similar trend was found in a study of Japanese, neighboring Korea, showing a significant inverse correlation of coffee with all mortality and CVD-related mortality only in women [105]. However, beneficial effects of coffee consumption on mortality and coronary morbidity in both sexes have been reported in a Scottish heart study [106] and the Tromsø heart study [102]. Their populations are clearly different from Asian ones.
Therefore, coffee consumption should be prudently considered in patients with high risk factors for cardiovascular events until concrete clinical evidences are established. Dosages of caffeine should be determined in medical context considering the unveiled influence of coffee on risk factors of CVDs and personal lifestyle of the subjects.

Author Contributions

D.L. designed the study and wrote the manuscript; J.C. designed the study and reviewed previous studies; J.A. revised the manuscript and wrote the manuscript; J.K. supervised the study and revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflicts of interest.

References

  1. Grigg, D. The worlds of tea and coffee: Patterns of consumption. GeoJournal 2002, 57, 283–294. [Google Scholar] [CrossRef]
  2. Je, Y.; Jeong, S.; Park, T. Coffee consumption patterns in Korean adults: The Korean National Health and Nutrition Examination Survey (2001–2011). Asia Pac. J. Clin. Nutr. 2014, 23, 691–702. [Google Scholar] [CrossRef] [PubMed]
  3. Jung, S.; Kim, M.H.; Park, J.H.; Jeong, Y.; Ko, K.S. Cellular Antioxidant and Anti-Inflammatory Effects of Coffee Extracts with Different Roasting Levels. J. Med. Food 2017, 20, 626–635. [Google Scholar] [CrossRef] [PubMed]
  4. Gomez-Ruiz, J.A.; Leake, D.S.; Ames, J.M. In vitro antioxidant activity of coffee compounds and their metabolites. J. Agric. Food Chem. 2007, 55, 6962–6969. [Google Scholar] [CrossRef] [PubMed]
  5. Tao, K.S.; Wang, W.; Wang, L.; Cao, D.Y.; Li, Y.Q.; Wu, S.X.; Dou, K.F. The multifaceted mechanisms for coffee’s anti-tumorigenic effect on liver. Med. Hypotheses 2008, 71, 730–736. [Google Scholar] [CrossRef]
  6. Bohn, S.K.; Ward, N.C.; Hodgson, J.M.; Croft, K.D. Effects of tea and coffee on cardiovascular disease risk. Food Funct. 2012, 3, 575–591. [Google Scholar] [CrossRef]
  7. Mattioli, A.V. Effects of caffeine and coffee consumption on cardiovascular disease and risk factors. Future Cardiol. 2007, 3, 203–212. [Google Scholar] [CrossRef]
  8. Chrysant, S.G. Coffee Consumption and Cardiovascular Health. Am. J. Cardiol. 2015, 116, 818–821. [Google Scholar] [CrossRef]
  9. Lopez-Garcia, E.; van Dam, R.M.; Li, T.Y.; Rodriguez-Artalejo, F.; Hu, F.B. The relationship of coffee consumption with mortality. Ann. Intern. Med. 2008, 148, 904–914. [Google Scholar] [CrossRef] [Green Version]
  10. Hoelzl, C.; Knasmuller, S.; Wagner, K.H.; Elbling, L.; Huber, W.; Kager, N.; Ferk, F.; Ehrlich, V.; Nersesyan, A.; Neubauer, O.; et al. Instant coffee with high chlorogenic acid levels protects humans against oxidative damage of macromolecules. Mol. Nutr. Food Res. 2010, 54, 1722–1733. [Google Scholar] [CrossRef]
  11. Nishitani, E.; Sagesaka, Y.M. Simultaneous determination of catechins, caffeine and other phenolic compounds in tea using new HPLC method. J. Food Compos. Anal. 2004, 17, 675–685. [Google Scholar] [CrossRef]
  12. Lopez-Garcia, E.; van Dam, R.M.; Qi, L.; Hu, F.B. Coffee consumption and markers of inflammation and endothelial dysfunction in healthy and diabetic women. Am. J. Clin. Nutr. 2006, 84, 888–893. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  13. Nurminen, M.L.; Niittynen, L.; Korpela, R.; Vapaatalo, H. Coffee, caffeine and blood pressure: A critical review. Eur. J. Clin. Nutr. 1999, 53, 831–839. [Google Scholar] [CrossRef] [Green Version]
  14. Mesas, A.E.; Leon-Munoz, L.M.; 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, 1113–1126. [Google Scholar] [CrossRef]
  15. Hartley, T.R.; Sung, B.H.; Pincomb, G.A.; Whitsett, T.L.; Wilson, M.F.; Lovallo, W.R. Hypertension risk status and effect of caffeine on blood pressure. Hypertension 2000, 36, 137–141. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  16. Panagiotakos, D.B.; Pitsavos, C.; Chrysohoou, C.; Kokkinos, P.; Toutouzas, P.; Stefanadis, C. The J-shaped effect of coffee consumption on the risk of developing acute coronary syndromes: The CARDIO2000 case-control study. J. Nutr. 2003, 133, 3228–3232. [Google Scholar] [CrossRef] [PubMed]
  17. Palatini, P.; Fania, C.; Mos, L.; Garavelli, G.; Mazzer, A.; Cozzio, S.; Saladini, F.; Casiglia, E. Coffee consumption and risk of cardiovascular events in hypertensive patients. Results from the HARVEST. Int. J. Cardiol. 2016, 212, 131–137. [Google Scholar] [CrossRef]
  18. Hamer, M. Coffee and health: Explaining conflicting results in hypertension. J. Hum. Hypertens. 2006, 20, 909–912. [Google Scholar] [CrossRef]
  19. De Giuseppe, R.; Di Napoli, I.; Granata, F.; Mottolese, A.; Cena, H. Caffeine and blood pressure: A critical review perspective. Nutr. Res. Rev. 2019, 32, 169–175. [Google Scholar] [CrossRef]
  20. Jee, S.H.; He, J.; Appel, L.J.; Whelton, P.K.; Suh, I.; Klag, M.J. Coffee consumption and serum lipids: A meta-analysis of randomized controlled clinical trials. Am. J. Epidemiol. 2001, 153, 353–362. [Google Scholar] [CrossRef]
  21. Muller, C.E.; Jacobson, K.A. Xanthines as adenosine receptor antagonists. In Methylxanthines; Springer: Berlin, Heidelberg, 2011. [Google Scholar] [CrossRef] [Green Version]
  22. Echeverri, D.; Montes, F.R.; Cabrera, M.; Galán, A.; Prieto, A. Caffeine’s vascular mechanisms of action. Int. J. Vasc. Med. 2010. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  23. Schmitz, W.; von der Leyen, H.; Meyer, W.; Neumann, J.; Scholz, H. Phosphodiesterase inhibition and positive inotropic effects. J. Cardiovasc. Pharmacol. 1989, 14 (Suppl. S3), S11–S14. [Google Scholar] [CrossRef] [PubMed]
  24. Suleman, A.; Siddiqui, N.H. Haemodynamic and cardiovascular effects of caffeine. Pharmacy On-Line, Int. J. Pharm. 2005. Available online: http://www.priory.com/pharmol/caffeine.htm (accessed on 8 April 2020).
  25. Tajik, N.; Tajik, M.; Mack, I.; Enck, P. The potential effects of chlorogenic acid, the main phenolic components in coffee, on health: A comprehensive review of the literature. Eur. J. Nutr. 2017. [Google Scholar] [CrossRef]
  26. Meng, S.; Cao, J.; Feng, Q.; Peng, J.; Hu, Y. Roles of chlorogenic Acid on regulating glucose and lipids metabolism: A review. Evid.-Based Complement. Altern. Med. 2013, 2013, 801457. [Google Scholar] [CrossRef] [PubMed]
  27. Zhao, Y.; Wang, J.; Ballevre, O.; Luo, H.; Zhang, W. Antihypertensive effects and mechanisms of chlorogenic acids. Hypertens. Res. 2012, 35, 370–374. [Google Scholar] [CrossRef] [Green Version]
  28. Mubarak, A.; Bondonno, C.P.; Liu, A.H.; Considine, M.J.; Rich, L.; Mas, E.; Croft, K.D.; Hodgson, J.M. 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, 9130–9136. [Google Scholar] [CrossRef]
  29. Ardiansyah; Ohsaki, Y.; Shirakawa, H.; Koseki, T.; Komai, M. Novel effects of a single administration of ferulic acid on the regulation of blood pressure and the hepatic lipid metabolic profile in stroke-prone spontaneously hypertensive rats. J. Agric. Food Chem. 2008, 56, 2825–2830. [Google Scholar] [CrossRef]
  30. Suzuki, A.; Kagawa, D.; Ochiai, R.; Tokimitsu, I.; Saito, I. Green coffee bean extract and its metabolites have a hypotensive effect in spontaneously hypertensive rats. Hypertens. Res. 2002, 25, 99–107. [Google Scholar] [CrossRef] [Green Version]
  31. Mahmud, A.; Feely, J. Acute effect of caffeine on arterial stiffness and aortic pressure waveform. Hypertension 2001, 38, 227–231. [Google Scholar] [CrossRef] [Green Version]
  32. Onrot, J.; Goldberg, M.R.; Biaggioni, I.; Hollister, A.S.; Kincaid, D.; Robertson, D.J. Hemodynamic and humoral effects of caffeine in autonomic failure: Therapeutic implications for postprandial hypotension. N. Engl. J. Med. 1985, 313, 549–554. [Google Scholar] [CrossRef]
  33. Ricketts, M.L.; Boekschoten, M.V.; Kreeft, A.J.; Hooiveld, G.J.; Moen, C.J.; Muller, M.; Frants, R.R.; Kasanmoentalib, S.; Post, S.M.; Princen, H.M.; et al. The cholesterol-raising factor from coffee beans, cafestol, as an agonist ligand for the farnesoid and pregnane X receptors. Mol. Endocrinol. 2007, 21, 1603–1616. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Chaput, J.P.; McNeil, J.; Despres, J.P.; Bouchard, C.; Tremblay, A. Seven to eight hours of sleep a night is associated with a lower prevalence of the metabolic syndrome and reduced overall cardiometabolic risk in adults. PLoS ONE 2013, 8, e72832. [Google Scholar] [CrossRef]
  35. Alkerwi, A.; Sauvageot, N.; Crichton, G.E.; Elias, M.F.; Stranges, S. Daily chocolate consumption is inversely associated with insulin resistance and liver enzymes in the Observation of Cardiovascular Risk Factors in Luxembourg study. Br. J. Nutr. 2016, 115, 1661–1668. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  36. Riksen, N.P.; Hausenloy, D.J.; Yellon, D.M. Wake up and smell the coffee: Yet another no go for cardiac patients? Editorial to “caffeinated coffee blunts the myocardial protective effects of statins against ischemia-reperfusion injury in the rat” by Ye et al. Cardiovasc. Drugs Ther. 2008, 22, 257–259. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  37. Craig, A.; Leonard, A.; Diane, C.; John, D.; Genevieve, G.; Jonathan, G.; Graeme, H.; Faline, H.; Les, L.; Arduino, M.; et al. Guideline for the Diagnosis and Management of Hypertension in Adults—2016; National Heart Foundation of Australia: Melbourne, Australia, 2016. [Google Scholar]
  38. Bennett, J.M.; Rodrigues, I.M.; Klein, L.C. Effects of caffeine and stress on biomarkers of cardiovascular disease in healthy men and women with a family history of hypertension. Stress Health 2013, 29, 401–409. [Google Scholar] [CrossRef]
  39. Mensink, R.P.; Lebbink, W.J.; Lobbezoo, I.E.; Weusten-Van der Wouw, M.P.; Zock, P.L.; Katan, M.B. Diterpene composition of oils from Arabica and Robusta coffee beans and their effects on serum lipids in man. J. Intern. Med. 1995, 237, 543–550. [Google Scholar] [CrossRef] [Green Version]
  40. Pincomb, G.A.; Lovallo, W.R.; Passey, R.B.; Whitsett, T.L.; Silverstein, S.M.; Wilson, M.F. Effects of caffeine on vascular resistance, cardiac output and myocardial contractility in young men. Am. J. Cardiol. 1985, 56, 119–122. [Google Scholar] [CrossRef]
  41. Mattioli, A.V.; Bonatti, S.; Zennaro, M.; Mattioli, G. The relationship between personality, socio-economic factors, acute life stress and the development, spontaneous conversion and recurrences of acute lone atrial fibrillation. EP Eur. 2005, 7, 211–220. [Google Scholar] [CrossRef]
  42. 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, 253–261. [Google Scholar] [CrossRef]
  43. Jossa, F.; Krogh, V.; Farinaro, E.; Panico, S.; Giumetti, D.; Galasso, R.; Celentano, E.; Mancini, M.; Trevisan, M. Coffee and serum lipids: Findings from the Olivetti Heart Study. Ann. Epidemiol. 1993, 3, 250–255. [Google Scholar] [CrossRef]
  44. Zampelas, A.; Panagiotakos, D.B.; Pitsavos, C.; Chrysohoou, C.; Stefanadis, C. Associations between coffee consumption and inflammatory markers in healthy persons: The ATTICA study. Am. J. Clin. Nutr. 2004, 80, 862–867. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Wilson, R.F.; Wyche, K.; Christensen, B.V.; Zimmer, S.; Laxson, D.D. Effects of adenosine on human coronary arterial circulation. Circulation 1990, 82, 1595–1606. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  46. Benowitz, N.L.; Jacob, P., 3rd; Mayan, H.; Denaro, C. Sympathomimetic effects of paraxanthine and caffeine in humans. Clin. Pharmacol. Ther. 1995, 58, 684–691. [Google Scholar] [CrossRef]
  47. Moon, B.-D.; Lee, S.-H.; Kwon, J.-I. Regional variations in risk factors for hypertension: Data analysis from the 6th Korea national health and nutrition examination survey. Korean J. Fam. Pract. 2017, 7, 25–29. [Google Scholar] [CrossRef]
  48. Burke, V.; Beilin, L.J.; German, R.; Grosskopf, S.; Ritchie, J.; Puddey, I.B.; Rogers, P. Association of lifestyle and personality characteristics with blood pressure and hypertension: A cross-sectional study in the elderly. J. Clin. Epidemiol. 1992, 45, 1061–1070. [Google Scholar] [CrossRef]
  49. Karabudak, E.; Türközü, D.; Köksal, E. Association between coffee consumption and serum lipid profile. Exp. Ther. Med. 2015, 9, 1841–1846. [Google Scholar] [CrossRef]
  50. Butt, M.S.; Sultan, M.T. Coffee and its consumption: Benefits and risks. Crit. Rev. Food Sci. Nutr. 2011, 51, 363–373. [Google Scholar] [CrossRef]
  51. Weusten-Van der Wouw, M.P.; Katan, M.B.; Viani, R.; Huggett, A.C.; Liardon, R.; Lund-Larsen, P.G.; Thelle, D.S.; Ahola, I.; Aro, A. Identity of the cholesterol-raising factor from boiled coffee and its effects on liver function enzymes. J. Lipid Res. 1994, 35, 721–733. [Google Scholar]
  52. Post, S.M.; de Roos, B.; Vermeulen, M.; Afman, L.; Jong, M.C.; Dahlmans, V.E.; Havekes, L.M.; Stellaard, F.; Katan, M.B.; Princen, H.M. Cafestol increases serum cholesterol levels in apolipoprotein E*3-Leiden transgenic mice by suppression of bile acid synthesis. Arterioscler. Thromb. Vasc. Biol. 2000, 20, 1551–1556. [Google Scholar] [CrossRef] [Green Version]
  53. Kark, J.D.; Friedlander, Y.; Kaufmann, N.A.; Stein, Y. Coffee, tea, and plasma cholesterol: The Jerusalem Lipid Research Clinic prevalence study. Br. Med. J. (Clin. Res. Ed.) 1985, 291, 699–704. [Google Scholar] [CrossRef] [Green Version]
  54. Stensvold, I.; Tverdal, A.; Foss, O.P. The effect of coffee on blood lipids and blood pressure. Results from a Norwegian cross-sectional study, men and women, 40–42 years. J. Clin. Epidemiol. 1989, 42, 877–884. [Google Scholar] [CrossRef]
  55. Opoku, S.; Gan, Y.; Fu, W.; Chen, D.; Addo-Yobo, E.; Trofimovitch, D.; Yue, W.; Yan, F.; Wang, Z.; Lu, Z. Prevalence and risk factors for dyslipidemia among adults in rural and urban China: Findings from the China National Stroke Screening and prevention project (CNSSPP). BMC Public Health 2019, 19, 1500. [Google Scholar] [CrossRef] [PubMed]
  56. Lusis, A.J. Genetic factors affecting blood lipoproteins: The candidate gene approach. J. Lipid Res. 1988, 29, 397–429. [Google Scholar] [PubMed]
  57. Rhee, E.-J.; Kim, H.C.; Kim, J.H.; Lee, E.Y.; Kim, B.J.; Kim, E.M.; Song, Y.; Lim, J.H.; Kim, H.J.; Choi, S.; et al. 2018 Guidelines for the Management of Dyslipidemia in Korea. J. Lipid Atheroscler. 2019, 8, 78–131. [Google Scholar] [CrossRef]
  58. Kohlmeier, L.; Mensink, G.; Kohlmeier, M. The relationship between coffee consumption and lipid levels in young and older people in the Heidelberg—Michelstadt—Berlin study. Eur. Heart J. 1991, 12, 869–874. [Google Scholar] [CrossRef] [Green Version]
  59. Green, M.S.; Jucha, E. Association of serum lipids with coffee, tea, and egg consumption in free-living subjects. J. Epidemiol. Community Health 1986, 40, 324–329. [Google Scholar] [CrossRef] [Green Version]
  60. Otsuka, T.; Takada, H.; Nishiyama, Y.; Kodani, E.; Saiki, Y.; Kato, K.; Kawada, T. Dyslipidemia and the Risk of Developing Hypertension in a Working-Age Male Population. J. Am. Heart Assoc. 2016, 5, e003053. [Google Scholar] [CrossRef] [Green Version]
  61. Halperin, R.O.; Sesso, H.D.; Ma, J.; Buring, J.E.; Stampfer, M.J.; Michael Gaziano, J. Dyslipidemia and the risk of incident hypertension in men. Hypertension 2006, 47, 45–50. [Google Scholar] [CrossRef] [Green Version]
  62. Davis, B.R.; Curb, J.D.; Borhani, N.O.; Prineas, R.J.; Molteni, A. Coffee consumption and serum cholesterol in the Hypertension Detection and Follow-up Program. Am. J. Epidemiol. 1988, 128, 124–136. [Google Scholar] [CrossRef]
  63. Bonita, J.S.; Mandarano, M.; Shuta, D.; Vinson, J. Coffee and cardiovascular disease: In vitro, cellular, animal, and human studies. Pharmacol. Res. 2007, 55, 187–198. [Google Scholar] [CrossRef]
  64. Vlachopoulos, C.; Panagiotakos, D.; Ioakeimidis, N.; Dima, I.; Stefanadis, C. Chronic coffee consumption has a detrimental effect on aortic stiffness and wave reflections. Am. J. Clin. Nutr. 2005, 81, 1307–1312. [Google Scholar] [CrossRef] [PubMed]
  65. Zhang, S.; Bai, Y.-Y.; Luo, L.-M.; Xiao, W.-K.; Wu, H.-M.; Ye, P. Association between serum homocysteine and arterial stiffness in elderly: A community-based study. J. Geriatr. Cardiol. 2014, 11, 32–38. [Google Scholar] [CrossRef] [PubMed]
  66. Ganguly, P.; Alam, S.F. Role of homocysteine in the development of cardiovascular disease. Nutr. J. 2015, 14, 6. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  67. Verhoef, P.; Pasman, W.J.; van Vliet, T.; Urgert, R.; Katan, M.B. Contribution of caffeine to the homocysteine-raising effect of coffee: A randomized controlled trial in humans. Am. J. Clin. Nutr. 2002, 76, 1244–1248. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  68. Olthof, M.R.; Hollman, P.C.; Zock, P.L.; Katan, M.B. Consumption of high doses of chlorogenic acid, present in coffee, or of black tea increases plasma total homocysteine concentrations in humans. Am. J. Clin. Nutr. 2001, 73, 532–538. [Google Scholar] [CrossRef]
  69. Savoia, C.; Schiffrin, E.L. Reduction of C-reactive protein and the use of anti-hypertensives. Vasc. Health Risk Manag. 2007, 3, 975–983. [Google Scholar]
  70. Kim, B.J.; Kim, B.S.; Kang, J.H. Plasma homocysteine and coronary artery calcification in Korean men. Eur. J. Prev. Cardiol. 2015, 22, 478–485. [Google Scholar] [CrossRef]
  71. Vlachopoulos, C.; Hirata, K.; Stefanadis, C.; Toutouzas, P.; O’Rourke, M.F. Caffeine increases aortic stiffness in hypertensive patients. Am. J. Hypertens. 2003, 16, 63–66. [Google Scholar] [CrossRef] [Green Version]
  72. Tsioufis, C.; Dimitriadis, K.; Vasiliadou, C.; Taxiarchou, E.; Vezali, E.; Tsiamis, E.; Stefanadis, C.; Kallikazaros, I. Heavy coffee consumption in conjunction with smoking is accompanied by increased inflammatory processes and impaired thrombosis/fibrinolysis system in essential hypertensive subjects. J. Hum. Hypertens. 2006, 20, 470–472. [Google Scholar] [CrossRef] [Green Version]
  73. Choi, Y.; Chang, Y.; Ryu, S.; Cho, J.; Rampal, S.; Zhang, Y.; Ahn, J.; Lima, J.A.; Shin, H.; Guallar, E. Coffee consumption and coronary artery calcium in young and middle-aged asymptomatic adults. Heart 2015, 101, 686–691. [Google Scholar] [CrossRef]
  74. Larsson, S.C.; Drca, N.; Jensen-Urstad, M.; Wolk, A. Coffee consumption is not associated with increased risk of atrial fibrillation: Results from two prospective cohorts and a meta-analysis. BMC Med. 2015, 13, 207. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  75. 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, 578–582. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  76. Prineas, R.J.; Jacobs, D.R., Jr.; Crow, R.S.; Blackburn, H. Coffee, tea and VPB. J. Chronic Dis. 1980, 33, 67–72. [Google Scholar] [CrossRef]
  77. Cannon, M.E.; Cooke, C.T.; McCarthy, J.S. Caffeine-induced cardiac arrhythmia: An unrecognised danger of healthfood products. Med. J. Aust. 2001, 174, 520–521. [Google Scholar] [CrossRef]
  78. Kong, H.; Jones, P.P.; Koop, A.; Zhang, L.; Duff, H.J.; Chen, S.R. Caffeine induces Ca2+ release by reducing the threshold for luminal Ca2+ activation of the ryanodine receptor. Biochem. J. 2008, 414, 441–452. [Google Scholar] [CrossRef] [Green Version]
  79. Patil, H.; Lavie, C.J.; O’Keefe, J.H. Cuppa joe: Friend or foe? Effects of chronic coffee consumption on cardiovascular and brain health. Mo. Med. 2011, 108, 431–438. [Google Scholar]
  80. Grioni, S.; Agnoli, C.; Sieri, S.; Pala, V.; Ricceri, F.; Masala, G.; Saieva, C.; Panico, S.; Mattiello, A.; Chiodini, P.; et al. Espresso coffee consumption and risk of coronary heart disease in a large Italian cohort. PLoS ONE 2015, 10, e0126550. [Google Scholar] [CrossRef]
  81. Klatsky, A.L.; Friedman, G.D.; Armstrong, M.A. Coffee use prior to myocardial infarction restudied: Heavier intake may increase the risk. Am. J. Epidemiol. 1990, 132, 479–488. [Google Scholar] [CrossRef]
  82. Mostofsky, E.; Rice, M.S.; Levitan, E.B.; Mittleman, M.A. Habitual coffee consumption and risk of heart failure: A dose-response meta-analysis. Circ. Heart Fail. 2012, 5, 401–405. [Google Scholar] [CrossRef] [Green Version]
  83. Heckman, M.A.; Weil, J.; Gonzalez de Mejia, E. Caffeine (1,3,7-trimethylxanthine) in foods: A comprehensive review on consumption, functionality, safety, and regulatory matters. J. Food Sci. 2010, 75, R77–R87. [Google Scholar] [CrossRef]
  84. Turnbull, D.; Rodricks, J.V.; Mariano, G.F.; Chowdhury, F. Caffeine and cardiovascular health. Regul. Toxicol. Pharmacol. 2017, 89, 165–185. [Google Scholar] [CrossRef] [PubMed]
  85. Pelchovitz, D.J.; Goldberger, J.J. Caffeine and cardiac arrhythmias: A review of the evidence. Am. J. Med. 2011, 124, 284–289. [Google Scholar] [CrossRef] [PubMed]
  86. Nawrot, P.; Jordan, S.; Eastwood, J.; Rotstein, J.; Hugenholtz, A.; Feeley, M. Effects of caffeine on human health. Food Addit. Contam. 2003, 20, 1–30. [Google Scholar] [CrossRef] [PubMed]
  87. De Koning Gans, J.M.; Uiterwaal, C.S.; van der Schouw, Y.T.; Boer, J.M.; Grobbee, D.E.; Verschuren, W.M.; Beulens, J.W. Tea and coffee consumption and cardiovascular morbidity and mortality. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 1665–1671. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  88. Crippa, A.; Discacciati, A.; Larsson, S.C.; Wolk, A.; Orsini, N. Coffee consumption and mortality from all causes, cardiovascular disease, and cancer: A dose-response meta-analysis. Am. J. Epidemiol. 2014, 180, 763–775. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  89. Zhao, Y.; Wu, K.; Zheng, J.; Zuo, R.; Li, D. Association of coffee drinking with all-cause mortality: A systematic review and meta-analysis. Public Health Nutr. 2015, 18, 1282–1291. [Google Scholar] [CrossRef]
  90. Ding, M.; Bhupathiraju, S.N.; Satija, A.; van Dam, R.M.; Hu, F.B. Long-term coffee consumption and risk of cardiovascular disease: A systematic review and a dose-response meta-analysis of prospective cohort studies. Circulation 2014, 129, 643–659. [Google Scholar] [CrossRef] [Green Version]
  91. Cornelis, M.C.; El-Sohemy, A.; Kabagambe, E.K.; Campos, H. Coffee, CYP1A2 genotype, and risk of myocardial infarction. JAMA 2006, 295, 1135–1141. [Google Scholar] [CrossRef] [Green Version]
  92. Kashuba, A.D.; Bertino, J.S., Jr.; Kearns, G.L.; Leeder, J.S.; James, A.W.; Gotschall, R.; Nafziger, A.N. Quantitation of three-month intraindividual variability and influence of sex and menstrual cycle phase on CYP1A2, N-acetyltransferase-2, and xanthine oxidase activity determined with caffeine phenotyping. Clin. Pharmacol. Ther. 1998, 63, 540–551. [Google Scholar] [CrossRef]
  93. Carrillo, J.A.; Benitez, J. CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine. Br. J. Clin. Pharmacol. 1996, 41, 605–608. [Google Scholar] [CrossRef] [Green Version]
  94. Gavrieli, A.; Fragopoulou, E.; Mantzoros, C.S.; Yannakoulia, M. Gender and body mass index modify the effect of increasing amounts of caffeinated coffee on postprandial glucose and insulin concentrations; a randomized, controlled, clinical trial. Metabolism 2013, 62, 1099–1106. [Google Scholar] [CrossRef]
  95. Kamimori, G.H.; Somani, S.M.; Knowlton, R.G.; Perkins, R.M. The effects of obesity and exercise on the pharmacokinetics of caffeine in lean and obese volunteers. Eur. J. Clin. Pharmacol. 1987, 31, 595–600. [Google Scholar] [CrossRef]
  96. Schreiber, G.B.; Robins, M.; Maffeo, C.E.; Masters, M.N.; Bond, A.P.; Morganstein, D. Confounders contributing to the reported associations of coffee or caffeine with disease. Prev. Med. 1988, 17, 295–309. [Google Scholar] [CrossRef]
  97. Hewlett, P.; Smith, A. Correlates of daily caffeine consumption. Appetite 2006, 46, 97–99. [Google Scholar] [CrossRef] [PubMed]
  98. Klatsky, A.L.; Koplik, S.; Kipp, H.; Friedman, G.D. The confounded relation of coffee drinking to coronary artery disease. Am. J. Cardiol. 2008, 101, 825–827. [Google Scholar] [CrossRef] [PubMed]
  99. Temple, J.L.; Ziegler, A.M. Gender Differences in Subjective and Physiological Responses to Caffeine and the Role of Steroid Hormones. J. Caffeine Res. 2011, 1, 41–48. [Google Scholar] [CrossRef] [Green Version]
  100. Temple, J.L.; Ziegler, A.M.; Graczyk, A.; Bendlin, A.; Sion, T.; Vattana, K. Cardiovascular responses to caffeine by gender and pubertal stage. Pediatrics 2014, 134, e112–e119. [Google Scholar] [CrossRef] [Green Version]
  101. Lee, J.; Lee, J.-E.; Kim, Y. Relationship between coffee consumption and stroke risk in Korean population: The Health Examinees (HEXA) Study. Nutr. J. 2017, 16, 7. [Google Scholar] [CrossRef] [Green Version]
  102. Thelle, D.S.; Arnesen, E.; Forde, O.H. The Tromso heart study. Does coffee raise serum cholesterol? N. Engl. J. Med. 1983, 308, 1454–1457. [Google Scholar] [CrossRef]
  103. Miyake, Y.; Kono, S.; Nishiwaki, M.; Hamada, H.; Nishikawa, H.; Koga, H.; Ogawa, S. Relationship of coffee consumption with serum lipids and lipoproteins in Japanese men. Ann. Epidemiol. 1999, 9, 121–126. [Google Scholar] [CrossRef]
  104. Noh, H.M.; Park, Y.S.; Kim, J.H. Coffee consumption and coronary heart disease risk using the Framingham risk score. Asia Pac. J. Clin. Nutr. 2017, 26, 931–938. [Google Scholar] [CrossRef] [PubMed]
  105. Sugiyama, K.; Kuriyama, S.; Akhter, M.; Kakizaki, M.; Nakaya, N.; Ohmori-Matsuda, K.; Shimazu, T.; Nagai, M.; Sugawara, Y.; Hozawa, A. Coffee consumption and mortality due to all causes, cardiovascular disease, and cancer in Japanese women. J. Nutr. 2010, 140, 1007–1013. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  106. 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. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  107. Wilson, P.W.; Garrison, R.J.; Kannel, W.B.; McGee, D.L.; Castelli, W.P. Is coffee consumption a contributor to cardiovascular disease? Insights from the Framingham Study. Arch. Intern. Med. 1989, 149, 1169–1172. [Google Scholar] [CrossRef]
Table
Table 1. General effects of major compounds derived from coffee on the circulatory system.
Table 1. General effects of major compounds derived from coffee on the circulatory system.
ComponentEffect on Circulatory SystemMechanismsReference
CaffeineVasodilation
Vasoconstriction
(Depending on adenosine receptor)		Increase serum adenosine[22]
Increase peripheral resistanceSympathetic stimulation[31]
Inotropic effectInhibiting cyclic adenosine monophosphate (cAMP) phosphodiesterase[22]
Cardioacceleratory effectBaroreflex activation[32]
Chlorogenic acidEndothelial dysfunctionIncrease inflammation
(via homocysteine)		[25]
Vascular protectionNAD(P)H inhibition
(Anti-oxidant)		[28]
Hypotensive effectAngiotensin converting enzyme inhibition[28]
Ferulic acidHypotensive effectAngiotensin converting enzyme inhibition[29]
CafestolCholesterol-increasing effectCYP7A1 suppression
farnesoid-x-receptor (FXR), pregnane-x-receptor
(PXR) agonist		[33]
Table
Table 2. Major parameters, clinical characteristics, and outcomes from random controlled trials investigating the influence of coffee consumption on cardiovascular disease (CVD) and risk factors reviewed in this work.
Table 2. Major parameters, clinical characteristics, and outcomes from random controlled trials investigating the influence of coffee consumption on cardiovascular disease (CVD) and risk factors reviewed in this work.
Study ModelSubjectsStudy DesignMeasured ParametersSignificant OutcomesReference
Randomized
Controlled
Trial		Healthy men and women with a family history of hypertension *
(n = 52)		0 mg/kg (placebo) or 3.3 mg/kg of anhydrous caffeine
single dose		Systolic BP
Diastolic BP
Heart rate
Cortisol
CRP		Both sexes showed significant additional increase in systolic BP and cortisol response to the stressor[38]
Randomized
Cross-over trial		Healthy men and women without glucosuria, proteinuria, and current drug administration
(n = 11)		Coffee oil (Arabica,
Robusta), 2 g per day
administered for
3 weeks		Total-C
LDL-C
HDL-C
Triglycerides
Thyroid hormones		Average serum cholesterol levels significantly rose by 13% on Arabica oil. Triglycerides levels significantly rose by 71% on Arabica oil and 61% on Robusta oil[39]
Randomized Controlled
Cross-over trial		Healthy men
without drug administration
(n = 15)		3.3 mg/kg caffeine sodium benzoate
2 days		Systolic BP
Diastolic BP
Heart rate
Stroke volume
System vascular resistance		Caffeine increased systolic and diastolic BP
and progressively increased systemic vascular resistance		[40]
* Having at least of parents (1) who has hypertension and currently taking or (2) had taken prescription with BP medication. Total-C: total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; BP: blood pressure; CRP: C-reactive protein.
Table
Table 3. Major parameters, clinical characteristics and outcomes from epidemiological studies investigating influence of coffee consumption on cardiovascular disease and its risk factors reviewed in this work.
Table 3. Major parameters, clinical characteristics and outcomes from epidemiological studies investigating influence of coffee consumption on cardiovascular disease and its risk factors reviewed in this work.
Study ModelPopulationClassification Variables and Clinical CharacteristicsSignificant OutcomesReference
Prospective Cohort StudyPatients with lone atrial fibrillation cardioverted within 48 h of the onset of arrhythmia
(n = 116)		Classified with atrial fibrillation and control group with daily coffee intake
(0, 1–3, >3 cups per day)		BMI
Coffee consumption
Stress
Type A personality *		Coffee intake (>3 cups of coffee/day) significantly increased risk of atrial fibrillation[41]
Retrospective
Cohort Study		Middle-aged adults
Swedish men
(n = 7495)		Classified all population with daily coffee intake
(0, 1–4, ≥5 cups per day)		Age
Myocardial infarction in brother and sister
Diabetes
Chest pain
Smoking
Alcohol abuse
BP
BMI		Significantly increased risk of heart failure in subjects who drank 5< cups of coffee per day compared to non-coffee drinkers[42]
Prospective Cohort StudyFactory employees
Italian men and women
(n = 900)		Classified all subject with daily coffee intake
(0, 1–2, 3–4, ≥5 cups per day)		Age
BMI
Total-C
LDL-C
Serum Triglycerides
HDL-C
Alcohol consumption
Cigarette smoking		After stratification for smoking status, significant linear trend between coffee consumption and total cholesterol only in smokers[43]
Cross-sectional StudyGreek men (n = 1514) and women (n = 1528)Classified all subject with daily coffee intake
(0, <200, 200–400, >400 mL)		Age
Education
Smoking
Physical activity
Obese
SBP DBP
Hypercholesterolemia
Diabetes mellitus
Family history of CHD		Coffee consumed >200 mL had higher IL-6, CRP, SAA, TNF-a, WBC count (all significant)[44]
* Following revised Minnesota Multiphasic Personality Inventory (MMPI-2) Type A scale. Total-C: total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; BMI: body mass index; BP: blood pressure; SAA: serum amyloid-A; CRP: C-reactive protein; CHD: coronary heart disease; IL-6: interleukin-6; TNF-αL tumor necrosis factor α; WBC: white blood cell.
Table
Table 4. Suspected confounding factors influencing the effect of coffee consumption on cardiovascular disease-related dependent variables in epidemiological clinical studies:
Table 4. Suspected confounding factors influencing the effect of coffee consumption on cardiovascular disease-related dependent variables in epidemiological clinical studies:
Independent
Variable		Variables (Confounding Factor)Dependent
Variable		Reference
Coffee consumption
(instant, brewed)		alcohol, BMI, hospital *, rank **, smoking, tea consumptionTotal-C
LDL-C
HDL-C
Triglycerides		[102]
Coffee consumption
(Turkish, instant)		age, BMI, daily total energy, food variates (fat, polyunsaturated fat, monounsaturated fat, omega 3, omega 6, carbohydrate and fiber intake, coffee consumption habit), sex, smoking, tea consumption, Total-C
LDL-C
HDL-C
VLDL-C
Triglycerides		[49]
Coffee and tea consumptionage, BMI, education ***, ethnic origin †, saturated fatty acid, season, smoking, sugar, tea consumptionTotal-C
LDL-C
HDL-C		[53]
Coffee and tea consumptionactivity at work, age, alcohol, BMI, BP, cotinine, housing tenure ††, leisure activity †††, smoking, occupational social class #, personality score ##, plasma fibrinogen, total-C, HDL-C, triglycerides, vitamin CCoronary risk factors
Coronary disease
All-cause mortality		[106]
Coffee consumptionage, alcohol, BMI, education ###, food variates (vegetable, fish, fruit, rice), history of HT, DM, smoking, walking hour,All-cause mortality
CVD mortality
Cancer mortality
Other causes mortality		[105]
Coffee consumptionageTotal-C
LDL-C
VLDL-C
HDL-C		[107]
age, BMI, BP, smoking, total-CCVD events
Coffee consumptionage, alcohol, BMI, number of cigarettes, smoking, physical activity, time since last meal &Total-C
HDL-C
Triglycerides		[102]
* According to three different visited hospitals for their examination; ** rank of subjects in military (low, middle, high); *** categorized as elementary, partial high school, high school, higher education; † according to country of birth (Israel, Europe, Asia, North Africa); †† categorized as owner occupier, renter; ††† categorized as active, average, inactive; # categorized as I~V level; ## according to Bortner score; ### categorized as years of education (~15 years, 16~18 years, 19~ years); & categorized as 5 grades, only in analysis of triglycerides. Total-C: total cholesterol; LDL-C: Low density lipoprotein cholesterol; HDL-C: high density lipoprotein cholesterol; VLDL-C: very-low density lipoprotein cholesterol; BMI: body mass index; BP: blood pressure; HT: hypertension; DM: diabetes mellitus.

Share and Cite

MDPI and ACS Style

Lim, D.; Chang, J.; Ahn, J.; Kim, J. Conflicting Effects of Coffee Consumption on Cardiovascular Diseases: Does Coffee Consumption Aggravate Pre-existing Risk Factors? Processes 2020, 8, 438. https://doi.org/10.3390/pr8040438

AMA Style

Lim D, Chang J, Ahn J, Kim J. Conflicting Effects of Coffee Consumption on Cardiovascular Diseases: Does Coffee Consumption Aggravate Pre-existing Risk Factors? Processes. 2020; 8(4):438. https://doi.org/10.3390/pr8040438

Chicago/Turabian Style

Lim, Dongwoo, Jiung Chang, Jungyun Ahn, and Jaieun Kim. 2020. "Conflicting Effects of Coffee Consumption on Cardiovascular Diseases: Does Coffee Consumption Aggravate Pre-existing Risk Factors?" Processes 8, no. 4: 438. https://doi.org/10.3390/pr8040438

APA Style

Lim, D., Chang, J., Ahn, J., & Kim, J. (2020). Conflicting Effects of Coffee Consumption on Cardiovascular Diseases: Does Coffee Consumption Aggravate Pre-existing Risk Factors? Processes, 8(4), 438. https://doi.org/10.3390/pr8040438

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop