Habitual coffee and caffeinated beverages consumption is inversely associated with arterial stiffness and central and peripheral blood pressure

Abstract

The effects of chronic coffee consumption on the cardiovascular system are still under debate. Aortic stiffness, wave reflections, and central and peripheral blood pressure (BP) are milestone indicators of cardiovascular-risk. We sought to investigate the association between coffee and caffeine consumption, arterial stiffness, and central/peripheral BP. Aortic stiffness was evaluated via pulse wave velocity (PWV); wave reflections with the augmentation index (AIx);peripheral systolic BP (SBP), diastolic BP (DBP), and central BP (cSBP/cDBP) were non-invasively assessed. Coffee and caffeine consumption was ascertained using a questionnaire. A linear inverse relationship between coffee and caffeine consumption and arterial stiffness and central and peripheral BP was found.Light coffee and caffeine consumers showed β-coefficients for PWV–0.15, SBP–3.61, DBP–2.48, cSBP–3.21, and cDBP-2.18 (all p values < 0.05).Present findings suggest that coffee and caffeine consumption is inversely associated with arterial stiffness and central and peripheral BP in a large population sample. Interventional prospective studies are needed to demonstrate the causal association

Keywords:

• Coffee consumption
• arterial stiffness
• pulse wave velocity
• central systolic blood pressure
• central diastolic blood pressure

Background

Several dietary compounds and lifestyle factors are related to arterial stiffness and blood pressure (BP). Physical activity, being overweight, excessive salt consumption, and low potassium intake represent the most investigated and the best understood factors among them (LaRocca et al. 2017; Greer et al. 2020).

Beverages represent key elements in the daily diet, and coffee, which is one of the most widely available and consumed beverages worldwide, contains many elements such as antioxidants, some minerals (e.g. magnesium and potassium), and polyphenols (de Melo Pereira et al. 2020). For its composition and considering its wide use, several studies have previously investigated its association with various pathological conditions (e.g. inflammatory diseases, liver dysfunction, and diabetes), as well as its effects on systemic hemodynamic parameters (van Dam et al. 2020).

Even though the acute pressor effect of caffeine seems to be clearly established, in contrast, the long-term effects of the chronic habitual intake of coffee on peripheral and central BP, as well as on arterial stiffness, are less well elucidated.

A recent summary of epidemiological evidence which investigated the associations between coffee and caffeine consumption and several non-communicable diseases including cancer and cardiovascular diseases, highlighted the potential beneficial effect of coffee, indicating its consumption as part of a healthy diet (Grosso et al. 2017). Nevertheless, previous investigations exploring the relationship between coffee consumption and hemodynamic parameters and arterial stiffness have produced conflicting results, ranging from a linear relationship to an inverse association or a lack of association (Hamer 2006; Riksen et al. 2009; Mesas et al. 2011; De Giuseppe et al. 2019).

In relation to the peripheral blood pressure (BP), overall, most of the observational data scarcely support a chronic effect of coffee on raising BP, except for an immediate BP elevation shortly after coffee intake (Geleijnse 2008; Lopez-Garcia et al. 2016). Large prospective population-based studies, seem to indicate an inverse relationship between chronic coffee intake and the risk of developing hypertension (Rhee et al. 2016; Miranda et al. 2020). Moreover, recently, a dose–response meta-analysis of cohort studies exploring the risk of hypertension and coffee consumption has found that chronic moderate coffee intake is inversely associated with hypertension (Grosso et al. 2017).

However, a very limited number of studies have investigated the role of coffee on central blood pressure, with findings to date limited to only clarifying the acute increase of central BP after caffeine intake (Karatzis et al. 2005; Waring et al. 2003).

Regarding the effect of coffee intake on arterial stiffness, even if previous findings have indicated that caffeine acutely increases arterial stiffness and wave reflections, a limited number of studies have explored the effect of habitual intake. Moreover, conflicting results have been obtained, with some studies indicating a detrimental effect on aortic stiffness, and others indicating an inverse relationship (Vlachopoulos et al. 2005; Uemura et al. 2013).

In the present study, we aimed to explore, in an extensive and comprehensive way, the association between habitual coffee consumption and arterial stiffness and central and peripheral blood pressure in a large unselected sample of subjects in Southern Switzerland.

Methods

Study participants

The Present secondary analysis was based on the TEST study (Ticino epidemiological stiffness) performed in Switzerland between the years 2017 and 2018, and described elsewhere (Del Giorno et al. 2021). Briefly, it was an observational population-based study of adults aged ≥18 years, residents in the Italian-speaking part of Switzerland. The study was conducted at the research unit of the Regional hospital of Bellinzona and Valli. The primary objective of the study was to explore the cardiovascular factors affecting arterial stiffness. Participants were recruited in a random sampling method on the basis of a list provided by the Swiss Federal Statistical Department. Inclusion criteria were: i) age ≥18 years; ii) residence in the Italian speaking region of Switzerland iii) ability to understand the study procedures and to provide adequate informed consent iv) ability to fill out questionnaires provided during study visits v) ability to collect urine within 24 h. Exclusion criteria were i) inability to understand the study or to answer the questionnaire (language problems); ii) inability to perform a 24 h urine collection; iii) age <18 years; iv) institutionalisation. A total of 1202 subjects participated in the study, of which 107 individuals were excluded on the basis of incomplete data in their 24 h ambulatory BP monitoring (ABPM) or questionnaire. The results were, therefore, based on 1095 individuals. All participants provided written informed consent. The study was carried out in accordance with the Declaration of Helsinki, and the Swiss ethics committee approved the study protocol (CE 3050). The data are presented in accordance with the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (von Elm et al. 2007).

Data collection

In accordance with the study protocol, each study participant performed two consecutive study-visits at the research unit of the regional hospital of Bellinzona (Switzerland). As mentioned above participants were recruited from the general population without limitations for selected comorbidities. Information on demographics, anthropometry, medication use, comorbidities, and traditional CVD risk factors was collected by healthcare professionals. Blood drawn under fasting conditions was also collected, in which fasting blood glucose, total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and creatinine levels were assessed. Twenty-four-hour urine collections were performed, in which sodium and potassium concentrations were measured. At the second visit participants filled in a questionnaire about behavioural, lifestyle factors and selected dietary habits. Information on smoking (current, never, former), alcohol consumption (number of standard glasses/day), fruit and vegetable intake (number of servings/day), salt intake (dose, awareness of consumption) and physical activity (type; time/day/week) were collected by questionnaire. Each participant was asked to provide their average daily use of coffee and caffeinated beverages over the last month, and the following possible answers were collected: never or <1 cup/day, 1–3 cups/day, 4–6 cups/day, and >6 cups/day. The question for coffee use was phrased as follows: How many cups of beverages containing caffeine do you usually drink each day? (e.g. coffee, tea, cola beverages, other types of beverages containing caffeine). We classified participants into three categories according to the number of caffeine drinking (0, 1–3, ≥4 units per day). Smoking status was classified as current smoker versus non-smoker. The questionnaire was previously widely used in other studies to assess the salt consumption and associated lifestyle factors in Switzerland (Schoen et al 2013).

Peripheral and Central blood pressure and arterial stiffness assessment

Each participant performed 24 h ambulatory BP monitoring (ABPM). Peripheral and central blood pressure values were non-invasively obtained using the ABPM device (Mobil-O-Graph, IEM; Stolberg, Germany), programmed to perform BP measurements every 30 min during the daytime and every hour during the night-time. The device was a brachial cuff-based oscillometric monitor, able to calculate the aortic pulse waveform after a process of calibration based on the brachial systolic blood pressure (SBP) and diastolic blood pressure (DBP) through a generalised transfer function algorithm (ARC Solver). The algorithm for the oscillometric central BP estimation was previously investigated and the central parameters provided by the device have been validated in comparison with both non-invasive and invasive intra-aortic devices (Wassertheurer et al. 2010; Hametner et al. 2013).

Briefly, the assessment of central BP was based on the oscillometric BP measurements using the calculated pulse waves. First, after the assessment of the peripheral BP, the cuff of the device reinflated, recording the central BP at diastolic pressure levels for 10 s. The central aortic pressure was therefore calculated from the brachial BP using a transfer function and the central aortic waveform, decomposed (forward and reflected waves) using an uncalibrated triangular aortic flow waveform.

Thus, from the time difference between the derived forward and reflected waves, the pulse wave velocity was estimated. Arterial stiffness was therefore determined based on the analysis of a gold standard parameter: The pulse wave velocity (PWV), noninvasively assessed, using the above described device.

The following central and peripheral hemodynamic and stiffness parameters were recorded and analysed (more than 75% of readings): Systolic blood pressure (SBP), diastolic blood pressure (DBP), central systolic blood pressure (cSBP), central diastolic blood pressure (cDBP), augmentation index standardised to a heart rate of 75 bpm (AIx75), pulse pressure (PP), and pulse wave velocity (PWV).

Statistical analysis

The variables are expressed as mean ± SD or as a percentage. According to their coffee and caffeine consumption, participants were categorised into groups: coffee and caffeine non-drinkers, i.e. < 1 cup/day; coffee and caffeine light drinkers, i.e. 1–3 cups/day; coffee and caffeine moderate drinkers, i.e. >3 cups/day. The lowest consumption group was used as the reference in the analysis. Differences in arterial stiffness and peripheral blood pressure parameters, based on gender, among groups of coffee consumption were also explored. The χ² test was used to compare the categorical variables across groups of coffee and caffeine consumption. Analysis of variance (ANOVA) for multiple comparisons and post-hoc testing (Tukey’s or Games–Howell test) were used for the comparison of arterial stiffness parameters and central and peripheral BP among the three groups of coffee consumption.

The association of coffee consumption with arterial stiffness and central/peripheral BP was explored using cSBP, cDBP, PP, SBP, DBP, PWV, and AIx as the dependent variables. Adjusted linear regression models were constructed to examine potential confounding effects. Several cardiovascular (CV) risk factors and variables potentially affecting the dependent variables were used in the multivariate analyses: sex, age, body mass index, diabetes, hypertension, hypercholesterolaemia, personal history of CVD, current smoking, consumption of vegetables and fruit, alcohol consumption, waist circumference, heart rate, cardiac output, mean arterial blood pressure, peripheral resistance, augmentation pressure, coefficient of reflection, total body water, cholesterol LDL and HDL, triglycerides, creatinine, and urine potassium and sodium; the β-coefficient and confidence interval (CI) are shown. The regression models were examined for multicollinearity using the variance inflation factor (VIF) statistic; VIF > 4.0 was considered an indicator of multicollinearity. Covariates in adjusted models were detailed in tables’ legends and appropriately selected for each outcome, in order to avoid multicollinearity. For linear regression models, predicted probability (P-P) plots of the residuals were performed to check the assumption of normality. For PWV a leptokurtic distribution of residuals, very close to normality, was observed. Considering the high R² of the linear model (94%), and the absence of substantial differences in parameter estimates with a more complex generalised linear model, for consistency with other dependent variables analysed, estimates of the linear regression were provided. All statistical analyses were conducted using SPSS (version 18.0, SPSS Inc, IBM, USA). A p value ≤ 0.05 was considered statistically significant; all p values were two-tailed.

Results

A sample of 1095 subjects (mean age 53.2 ± 13.6 years, female 56%, and males 44%) was analysed. The participants’ characteristics, stratified by daily coffee and caffeine consumption (i.e. non-drinkers, light drinkers, and moderate drinkers), are presented in Table 1. Coffee and caffeine drinkers, both light and moderate, were more frequently older, male, and smokers compared to coffee non-drinkers (p < 0.001). No differences in the prevalence of hypertension and diabetes were found among the groups. Potassium levels in the urine significantly increased as coffee consumption increased (p ≤ 0.001). No significant differences in the other parameters were found when comparing the baseline characteristics among the three groups.

Table 1. Participant’s characteristics stratified by self-reported daily coffee and caffeine consumption (n.1095).

	Overall polpulation	No coffee and caffeine drinkers (n.110)	Light coffee and caffeine drinkers (n.778)	Moderate coffee and caffeine drinkers (n.207)	p Value
Demographics
Age, years	56.2 ± 13.2	49.1 ± 14.7	53.9 ± 13.8	52.3 ± 11.9	<0.001
Males (%)	478 (43.7)	38 (34.5)	330 (42.4)	110 (53.1)	<0.001
Clinical Characteristics
BMI, kg/m^2	25.1 ± 4.3	23.6 ± 3.9	25.1 ± 4.3	25.8 ± 4.3	<0.001
Waist, cm	89.2 ± 12.8	84.9 ± 13.5	89.2 ± 12.6	91.7 ± 12.6	<0.001
Heart reate, beats/min	68.7 ± 10.7	68.8 ± 10.9	68.3 ± 10.9	69.4 ± 9.9	0.437
TBW, L/m	23.0 ± 4.1	21.6 ± 3.5	22.9 ± 4.2	24.1 ± 4.2	<0.001
Current smoking, (%)	212 (19.4)	12 (10.9)	133 (17.2)	67 (32.5)	<0.001
Diabetes, (%)	21 (1.9)	2 (1.8)	15 (1.9)	4 (1.9)	0.997
Hypertension, (%)	178 (16.3)	13 (11.8)	136 (17.5)	29 (14.0)	0.200
Hypercolesterolemia (%)	161 (14.7)	10 (9.1)	130 (16.7)	21 (10.1)	0.013
Laboratory parametrs
Fasting blood glucose, mmol/L	5.9 ± 0.77	5.8 ± 0.90	5.9 ± 0.74	5.9 ± 0.83	0.175
Magnesium, mmol/L	0.83 ± 0.06	0.82 ± 0.09	0.84 ± 0.06	0.83 ± 0.062	0.133
Total cholesterol, mmol/L	5.3 ± 1.1	5.2 ± 1.17	5.4 ± 1.07	5.4 ± 0.98	0.199
HDL, mmol/L	1.6 ± 0.42	1.63 ± 0.43	1.59 ± 0.43	1.52 ± 0.40	0.037
LDL,mmol/L	3.6 ± 1.03	3.4 ± 1.10	3.6 ± 1.04	3.7 ± 0.99	0.126
Triglycerides, mmol/L	1.12 ± 0.81	1.01 ± 0.66	1.13 ± 0.87	1.14 ± 0.69	0.314
Creatinine, µmol/L	75.6 ± 16.6	74.5 ± 17.12	75.6 ± 16.32	76.1 ± 17.3	0.719
Sodium excretion 24 h, mmol	178.4 ± 88.9	169.8 ± 78.24	181.4 ± 92.4	171.9 ± 80.30	0.246
Potassium excrection, mmol	61.7 ± 21.4	55.7 ± 18.9	61.1 ± 21.5	66.9 ± 21.5	<0.001

BMI: body mass index; HDL: high density lipoprotein; LDL: low density lipoprotein; TBW: total body water. p Value from χ² test or ANOVA.

A comparison of arterial stiffness and central and peripheral BP parameters by coffee and caffeine consumption is shown in Table 2. Significantly different values of PWV were found across the groups of coffee and caffeine consumption (p ≤ 0.001), and moderate coffee and caffeine drinkers showed significantly lower PWV compared to light coffee consumers. Moreover, light and moderate coffee and caffeine drinkers showed significantly lower AIx75 values (p = 0.028). When considering peripheral BP parameters, no differences across the groups of coffee and caffeine consumption were found, and no significant differences were found in terms of central blood pressure among the groups. Arterial stiffness and central and peripheral BP parameters differences by coffee and caffeine consumption in men and women separately were shown in Supplementary Table 1. Differences in PWV were more evident in men compared with women and in coffee and caffeine consumers comparing with non-consumers. In non-coffee and caffeine drinkers, no differences in PWV values were found, whilst significant differences in light consumers were detected based on gender (7.6 ± 1.8 in males vs. 7.3 ± 1.8 in females, p value 0.01). No significant differences were found in comparisons separating males and females.

Table 2. Comparison of Arterial Stiffness, central and peripheral BP parameters by coffee consumption.

Arterial stiffness and central aortic pressure parameters	No-coffee and caffeine drinkers	Light coffee and caffeine drinkers	Moderate coffee and caffeine drinkers	F/χ2	p Value
PWV	6.9 ± 1.8^¥	7.4 ± 1.8^¥	7.1 ± 1.5^¥	3.15	0.001
AIx (HR75)	24.4 ± 8.3	24.9 ± 8.1^¥	23.3 ± 7.5^¥	3.60	0.028
cSBP	110.2 ± 12.2	110.2 ± 11.1	110.0 ± 11.7	0.023	0.977
cDBP	76.2 ± 9.8	75.7 ± 8.9	76.3 ± 9.2	0.494	0.610
Pheripheral blood Pressure
Systolic BP	118.4 ± 12.4	119.2 ± 11.6	119.0 ± 12.1	0.202	0.817
Diastolic BP	74.1 ± 9.4	74.1 ± 8.6	74.7 ± 8.9	0.394	0.674
MAP	94.4 ± 10.1	94.7 ± 9.4	94.9 ± 9.9	0.140	0.869
PP	44.4 ± 7.8	45.1 ± 7.6	44.3 ± 7.4	1.128	0.324

PWV: Pulse Wave Velocity; Alx (HR75): augmentation index; cSBP: central systolic blood pressure; cDBP: central diastolic blood pressure; SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; PP: pulse pressure; MAP: Mean Arterial Pressure.

^¥p Value <0.05 according to post hoc testing comparisons No-Coffee Drinkers vs Light Coffee Drinkers and Light Coffee Drinkers vs Moderate Coffee Drinkers.

Differences in parameters under analysis among groups of coffee consumption were explored also mixing gender and age groups (younger than 50 and older than 50 years, i.e. the mean age of the study population), Supplementary Table 2. Differences in PWV in men, among groups of coffee consumption (no coffee vs. light coffee vs. moderate coffee drinkers), were evident only in the group older than 50 years (8.6 ± 1.4; 8.5 ± 1.5; 7.9 ± 1.4; p value 0.039). No other significant differences were found by age-gender groups.

The associations between coffee and caffeine consumption and the arterial stiffness parameters were explored in multivariate linear regression models (Table 3). The parameters of arterial stiffness were significantly inversely associated with coffee and caffeine consumption. The linear associations between coffee and caffeine consumption (in reference to coffee non-consumption) and the arterial stiffness parameters were investigated. Significant associations were found for PWV; light and moderate coffee and caffeine consumption levels were each associated with a significant decrease in PWV, though this decrease was more pronounced for moderate coffee and caffeine consumers. More specifically, light coffee and caffeine consumers showed a decrease in PWV (β-coefficient and CI) of −0.15 (–0.26 to −0.04; p < 0.001), while moderate coffee and caffeine consumers showed a decrease of −0.11 (–0.19 to −0.02; p = 0.018).

Table 3. Linear regression exploring the correlation between coffee consumption and arterial stiffness parameters and central hemodynamics.

	β-coefficient	Confidence interval	p Value
PWV
No coffee and caffeine drinkers	Reference
Light coffee and caffeine drinkers	−0.15	−0.26 to −0.04	<0.001
Moderate coffee and caffeine drinkers	−0.11	−0.19 to −0.02	0.018
AI
No coffee and caffeine drinkers	Reference
Light coffee and caffeine drinkers	−0.81	−1.27 to 0.36	0.277
Moderate coffee and caffeine drinkers	−0.45	−1.77 to 0.15	0.100

PWV: pulse wave velocity; AI: augmentation index. Multivariate models were adjusted according to: sex, age, body mass index, diabetes, hypertension, hypercholesterolaemia, personal history of CVD, current smoking, consumption of vegetables and fruit, alcohol consumption, waist circumference, heart rate, cardiac output, mean arterial blood pressure, peripheral resistance, augmentation pressure, coefficient of reflection, total body water, cholesterol LDL and HDL, triglycerides, creatinine, and urinary potassium and sodium.

Linear associations between coffee and caffeine consumption and peripheral and central blood pressure were also investigated (with coffee coffee and caffeine non-consumption used as a reference). An inverse linear association was found for both the peripheral and central blood pressure parameters (Table 4). In particular, a significant decrease in peripheral systolic blood pressure was found in light and moderate coffee consumers, with respective β-coefficients of −3.61 (CI: 5.91 to −1.32; p < 0.001) and −2.80 (CI: −4.75 to −0.84; p < 0.001). A significant inverse association was also found for diastolic blood pressure, though for light coffee and caffeine consumers (–2.48; −4.16 to −0.80; p < 0.001) and moderate consumers (−1.68; −3.11 to −0.26; p value = 0.021). A similar significant inverse trend was confirmed for MAP (light coffee and caffeine consumers: −3.00, −4.79 to −1.21, p < 0.001; moderate coffee and caffeine consumers: −2.18, −3.70 to −0.65, p < 0.001).

A significant inverse trend was found between coffee and caffeine consumption and central blood pressure for both systolic and diastolic blood pressure. Light coffee and caffeine consumers showed a decrease in cSBP (–3.21; −5.09 to −1.32; p < 0.001), as did moderate coffee coffee and caffeine consumers (–4.28; −6.25 to −1.81; p < 0.001). A significant inverse association was also found for central DBP for both light and moderate consumers.

Discussion

The present study showed that coffee coffee and caffeine consumption was significantly inversely associated with the parameters of arterial stiffness and with peripheral and central blood pressure in a large sample of the general population in Switzerland.

Coffee represents one of the most widely consumed beverages worldwide, and due to its stimulating effect, several reservations persist from a clinician's perspective in considering it a healthy drink [Institute for Scientific Information on Coffee (ISIC) Roundtable Report 2020].

However, in recent years, several studies have highlighted the various positive effects of coffee on the different biological systems and mechanisms in humans (Godos et al. 2014; Loftfield et al. 2015).

The potential beneficial effects of coffee consumption on the cardiovascular system are probably related to its compounds, considering that it is one of the major dietary sources of antioxidants (Farah and Donangelo 2006, Yashin et al. 2013).

Nevertheless, to date, a very limited number of studies have investigated the associations between coffee consumption and arterial stiffness, and among them, a smaller proportion have investigated this relationship from an epidemiological perspective.

Table 4. Linear regression exploring the correlation between coffee and caffeine consumption and Peripheral and Central Blood Pressure Parameters.

	β-coefficient	Confidence interval	p Value
Pheripheral BP parameters
SBP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−3.61	−5.91 to −1.32	<0.001
Moderate coffee and caffeine drinkers	−2.80	−4.75 to −0.84	<0.001
DBP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−2.48	−4.16 to −0.80	<0.001
Moderate coffee and caffeine drinkers	−1.68	−3.11 to −0.26	0.021
MAP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−3.00	−4.79 to −1.21	<0.001
Moderate coffee and caffeine drinkers	−2.18	−3.70 to −0.65	<0.001
PP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−1.10	−2.55 to 0.36	0.141
Moderate coffee and caffeine drinkers	−1.18	−2.89 to 0.53	0.177
Central BP parameters
cSBP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−3.21	−5.09- to −1.32	<0.001
Moderate coffee and caffeine drinkers	−4.28	−6.25 to −1.81	<0.001
cDBP
No coffee and caffeine drinkers	reference
Light coffee and caffeine drinkers	−2.18	−3.67 to −0.69	<0.001
Moderate coffee and caffeine drinkers	−3.00	−4.75 to −1.26	<0.001

SBP: Systolic Blood Pressure; DBP: Diastolic Blood Pressure; PP: pulse pressure; MAP: Mean Arterial Pressure cSBP: central systolic blood pressure; cDBP: central diastolic blood pressure. Multivariate models were adjusted according to: sex, age, body mass index, diabetes, hypertension, hypercholesterolaemia, personal history of CVD, current smoking, consumption of vegetables and fruit, alcohol consumption, waist circumference, heart rate, cardiac output, peripheral resistance, augmentation pressure, coefficient of reflection, total body water, cholesterol LDL and HDL, triglycerides, creatinine, and urinary potassium and sodium.

Our results are in line with some of the previous evidence in other populations, indicating an inverse relationship between chronic coffee consumption and arterial stiffness. In a previous study in Japanese men, Uemura et al. showed an inverse association between arterial stiffness and coffee consumption, underlining that this association is partially mediated by triglycerides (Uemura et al. 2013). A possible effect of coffee in ameliorating the components of metabolic syndrome is supported by the findings of several previous studies and is hypothesised as a possible mechanism mediating the relationship with arterial stiffness (Suliga et al. 2017).

These findings were later confirmed in an elegant study conducted by Ponte et al., in which, in an unselected sample population of men and women in Switzerland, an inverse relationship between urinary caffeine and arterial stiffness was found (Ponte et al. 2018).

A recent meta-analysis aimed at exploring the effect of coffee on endothelial function and arterial stiffness suggested a beneficial effect of coffee intake on endothelial function, but it was unable to draw firm conclusions on the long-term effects of coffee on arterial stiffness. Considering the large study heterogeneity; additional studies with larger sample populations were advocated in order to better clarify the long-term effects of coffee on arterial stiffness (Azad et al. 2020).

Herein, we corroborated, in an extensive way and in a large sample population, some previous evidence suggesting a potential beneficial relationship between coffee and arterial stiffness. Moreover, as a measure of arterial stiffness, we used the gold standard parameter PWV, as well as the augmentation index. Both parameters were found to be inversely related to coffee consumption, highlighting a consistency in the relationship between arterial stiffness and coffee consumption. We note that in our study, the association found was investigated in both sexes and in an unselected population of hypertensive and non-hypertensive subjects, suggesting that the inverse association between arterial stiffness and coffee consumption is independent of BP levels.

We believe it important to point out that the associations between coffee consumption and CVD, which remains a leading cause of death worldwide to date, remain controversial, and even though PWV represents a well-established independent CV risk factor (Kim and Kim 2019), we cannot affirm that the inverse relationship between coffee consumption and arterial stiffness likewise applies to incident CV risk.

Interestingly, in the present study, we strove to elucidate the relationship between habitual coffee consumption and blood pressure, and both the peripheral and central BP parameters were investigated.

Current evidence of this relationship is contrasting, and even though the acute pressor effect of caffeine on blood pressure is well established, the long-term effects on BP still remain unclear. A recent meta-analysis provided quantitative proof that coffee consumption, in a dose–response manner, is inversely associated with the risk of hypertension (Xie et al. 2018).

Careful interventional prospective studies could be helpful to determine the long term CV effect of coffee. As recently underlined, moderate chronic intake of caffeine up to 400 mg/day is tolerable and safe in healthy adults (of concern is the rate of caffeine intake in vulnerable populations such as pregnant/lactating women, children, adolescents, young adults, and people with CV disease or other health conditions) (Temple et al.2017).

There are two main mechanisms hypothesised to underlie the positive long-term effects of coffee consumption on BP:

The first is related to a “tolerance” in habitual coffee consumers to caffeine, and the second one is related to the positive effect of other substances present in coffee (i.e. phenolic compounds, minerals, and antioxidants such as chlorogenic acid) able to limit the pro-hypertensive effects of caffeine (Godos et al. 2014). Moreover, anti-inflammatory effects of caffeine have been demonstrated, which can be partially related to the anti-hypertensive effect of chronic coffee consumption (Muqaku et al. 2016).

Overall, we believe it is important to underline that the CV effects of coffee are still debated, and the mechanisms by which coffee exerts its action on the CV system is still not completely clear. If on one hand several effects of coffee are caffeine-related, other substances, such as polyphenols contained in coffee, could also be pharmacologically active (Ferruzzi MG 2010). The caffeine-induced effects are mainly represented by the antagonisation of adenosine receptors (Ribeiro and Sebastiao 2010); inhibition of phosphodiesterases (Ribeiro and Sebastiao 2010) and hence accumulation of cyclic AMP with exacerbation of the catecholamine effects (Robertson et al 1978).

On the other hand the coffee poliphenols are able to contrast the oxidative stress present in many CV diseases (Tangney and Rasmussen 2013; Daneshzad et al. 2019). To note that dietary sources of polyphenol and flavonoids (mostly fruit and beverages including coffee and, to a lesser extent vegetables, dry legumes and cereals) are the most important sources of dietary antioxidants (Daneshzad et al. 2019) and the diet antioxidant capacity (i.e. the cumulative measure of total antioxidants present in a diet) is used as a parameter of diet quality (Mozaffari et al. 2018).

Several epidemiological and experimental studies have found an inverse association between blood pressure levels and the diet antioxidants capacity and different mechanisms underlying this association have been postulated. Some findings have suggested that the phenolic compounds (as well as their metabolites) have the capacity to improve endothelial dysfunction, through a direct action on nitric oxide synthase (Hügel et al. 2016) as well as through a reduction of vasoconstriction modulated by ACE and angiotensin II receptor activity (Clark et al. 2015). Moreover, the overall beneficial CV protective effects of many phenolic compounds, was found related to an anti-inflammatory capacity, globally mediated via inhibition of NF-κB (de Pascual-Teresa et al. 2010). Nevertheless, the association of blood pressure and dietary flavonoids (in particular g.e. anthocyanins) needs to be more extensively investigated.

Last but not least a large variability exists in chronic effects of coffee consumption on CV system. Part of this variability is explained by the action of confounding factors ranging from the type of studies, population age, gender, frequency of coffee drinking and smoking, to the types of coffee blend or preparations used. However, it also known that a large part of the CV phenotypic variability consequent to the chronic coffee consumption could have a genetic explanation (Renda et al. 2012).

Several genetic variants in different genes implicated in caffeine metabolism (such as CYP1A2) but also in adrenergic receptors ADRA1A and ADRA2B or in AMP deaminase, are under investigation as responsible for different cardiovascular responses to coffee consumption (De Caterina and El-Sohemy 2016).

It is important to note that to the best of our knowledge, this study is the first to explore the association between habitual coffee consumption and central BP. A previous study explored the acute effect of caffeine administration on central BP and its ability to provoke an acute pressor response, predominantly affecting central BP (Waring et al. 2003). Herein, we found an inverse association between coffee consumption and both systolic and diastolic central BP. The findings in the present study appear to be in line with the inverse association, here found, between coffee consumption and arterial stiffness. A large decrease in artery stiffness causes a slowing waveform reflection from the peripheries, thereby reducing central pressure.

Some limitations of our study should be acknowledged. First, the study was conducted in a general population in Switzerland and may not be directly extendable to other population groups. Coffee consumption was assessed on the basis of the subjects’ self-reports; therefore, their actual consumption levels could be over- or under-estimated. The cross-sectional design of the study means that we were unable to establish causality; however, our results suggest an association between habitual coffee intake and arterial stiffness and central/peripheral BP, providing evidence for further investigation.

A further limitation is that the study population was quite healthy, and we cannot exclude the possibility that the effects of coffee (e.g. in raising central/peripheral BP) may be different in individuals with higher CV risk, such as diabetic patients or multimorbid aged patients; therefore, our findings require confirmation in these groups. However, in these groups of patients concerns exist about safe and tolerable doses of caffeine. Last but not least, we have to acknowledge, as a limitation of the present study that dietary information, including coffee intake, was not collected via a standardised and detailed food-frequency questionnaire, and therefore we cannot exclude the possibility that dietary information could be incomplete and/or imprecise. Coffee and caffeinated beverages were included in the same questions on coffee consumption. Therefore we were unable to analyse the types of caffeinated beverages consumed separately. Furthermore, since caffeinated beverages are not equal to coffee, the association of caffeinated beverages with arterial stiffness should not be equated with that of caffeine. However, a clear distinction between coffee drinkers and non drinkers exists and our findings indicate a potential favourable relationship with arterial stiffness and central hemodynamic parameters in consumers. Regardless, we believe that these observational findings could become a trigger to generate hypothesis to be confirmed in perspective and experimental studies.

To conclude, the influence of regular caffeine intake on the parameters of CV risk such as arterial stiffness and peripheral and central BP remains controversial, and several confounding factors could influence the association. Our findings suggest an observational inverse association between chronic caffeine intake and arterial stiffness and central and peripheral BP. Further works are required to confirm this association and to elucidate the potential mechanisms through which caffeine influences central BP and arterial stiffness.

Conclusions

The findings of the present study suggest potential beneficial relationship between habitual coffee consumption and arterial stiffness and central and peripheral blood pressure in a large sample of the population. Regular light and moderate coffee consumers showed decreased arterial stiffness parameter values, as well as of central and peripheral BP, when compared to non-habitual coffee drinkers, even after adjusting for several CV risk factors. The present results corroborate those in the literature that have highlighted the positive effect of habitual coffee consumption on arterial stiffness and hemodynamic parameters, suggesting the importance of controlling for this dietary habit in studies exploring this topic. We recommend further efforts to explore whether the decrease in arterial stiffness and BP via caffeine intake could represent a mechanism of the long-term effect of coffee on cardiovascular diseases.

Acknowledgements

We would like to thank the participants in the TEST study for their valuable and active contribution and Dr. Giorgio Merlani of the Department of Public Health of the Ticino canton, for his valuable support. We would like also to thank the study nurse Natasa Bettosini for her support in the data collection, Ms. Irene Menghini e her staff for data entry.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

We gratefully acknowledge for the financial support the Error! Hyperlink reference not valid. for Clinical Research (Locarno, Switzerland). The funding source had no role in study design, data collection, data analysis, data interpretation, or writing of the report.