1. Introduction
Hypertension is the leading risk factor for cardiovascular morbidity and mortality [
1]. Increased peripheral resistance due primarily to changes in vascular structure and function appear to be the fundamental hemodynamic abnormality in hypertension [
2]. These changes include endothelial dysfunction, arterial wall thickening and abnormal vascular tone, and are due to alterations in the biology of the arterial wall [
2]. Accordingly, an increased arterial stiffness is related to haemodynamic modifications at the level of the aorta, leading to a rise in cardiac afterload, a reduction in coronary perfusion and an over-stretch of the aortic wall [
3,
4]. The principal cause of increased systolic and pulse blood pressure (BP) is increased stiffness of the elastic arteries as a result of degeneration and hyperplasia of the arterial wall [
3,
4]. As stiffness increases, the reflected pulse wave amplitude increases and augments pressure in late systole, producing an increase in left ventricular afterload and myocardial oxygen demand. Current evidence reports that arterial stiffness should be recognized as a bidirectional interplay between the central and peripheral arteries. Specifically, the pressure pulse wave is not only transmitted forward to the periphery but also reflected backward to the central aorta. Consistent with this, also the pulse wave is composed of the forward and reverse components. Aortic stiffening and arteriolar remodeling due to hypertension not only augment the central pressure by increasing the wave reflection but may also alter the central bidirectional flow, inducing hemodynamic damage/dysfunction in target organs. Therefore, central hemodynamic monitoring has the potential to provide a diagnostic and therapeutic basis for preventing systemic target organ damage and for offering personalized therapy suitable for the arterial properties in each patient with hypertension [
3,
4,
5]. An increasing number of studies have indicated arterial stiffness and the amount of pulse wave reflections as independent predictors of cardiovascular events and cardiovascular mortality in patients with different co-morbidities and cardiovascular risk [
3,
4,
5]. Epidemiological studies have shown an inverse association between diets rich in flavonoids and cardiovascular disease [
6] as well as on specific flavonoid intake and vascular function [
7]. In this context, tea products account for a significant proportion of total flavonoid intake in different Western countries [
8,
9,
10]. Hodgson
et al. reported that regular ingestion of black tea over 6 months results in lower 24-h SBP and DBP [
11]. Accordingly, we performed a dose-finding study showing that black tea intake decreased office systolic (−2.6 mmHg) and diastolic (−2.2 mmHg) BP as well as peripheral arterial stiffness [
12].
However, a meal rich in fat has been reported to negatively affect BP and vascular function [
13,
14]. As most of the day is spent in the postprandial state, it is of interest to determine whether a fat-rich meal affects the postprandial BP and arterial haemodynamics. Further, the effect of treatment with black tea on vascular responses and on lipemia-induced impairment of arterial function has not been examined. Therefore, we aimed to investigate the effects of regular consumption of black tea, naturally rich in flavonoids, on wave reflections, systolic BP (SBP) and diastolic BP (DBP) before and after an oral fat load in untreated grade 1 hypertensive patients without additional cardiovascular risk factors.
4. Discussion
The novel finding of this study is that consumption of black tea, naturally rich in flavonoids, compared to a surrogate placebo resulted in significantly lower wave reflections and BP. Furthermore, the black tea counteracted or completely prevented the abnormalities in peripheral arterial haemodynamics and BP which were caused by a fat load in grade I hypertensive patients. These effects were observed with a tea dose of 2 cups per day, thus easily reachable in normal daily life.
The structural and functional changes in the arterial roundtrip travel time of the pressure and flow wave from the heart to the periphery and back is directly related to major reflecting site distance and inversely related to the pulse wave velocity [
2,
3]. Increased arterial stiffness causes an increase in transmission velocity of both forward and reflected waves, which, in turn, causes the reflected wave to arrive earlier in the central aorta with greater amplitude and duration. These changes in wave reflection characteristics augment pressure and decrease flow in late systole. These modifications in arterial effects and reflected wave characteristics cause an increase in systolic (and pulse) BP and left ventricular force generation, which cause a reduction in stroke output [
2,
3]. Similar changes occur in the shape of pressure and flow waves when the elastic arteries stiffen. The reflected wave arrives at the heart early during systole because of increased pulse wave velocity and decreased travel time of the reflected wave from the periphery (
Figure 5). The structural and functional changes in the arterial circulation provide disturbances in regional blood flow, progression of atherogenesis, and microvascular changes occurring during senescence and in the presence of cardiovascular risk factors [
2,
3,
18] (
Figure 5).
Figure 4.
Effect of 1 week placebo (white) and black tea (black) administration on baseline (square) values (Panel A and B) of diastolic blood pressure and acute effects without and with fat load (Panel A and B). Data are presented as LSmeans ± SE. In all panels vertical lines indicate SE and asterisks (*) indicate significant differences with respect the placebo phase (Panel A and B) while circles (°) indicate significant differences from baseline values (Panel A and B). Differences are considered significant when p < 0.05.
Figure 4.
Effect of 1 week placebo (white) and black tea (black) administration on baseline (square) values (Panel A and B) of diastolic blood pressure and acute effects without and with fat load (Panel A and B). Data are presented as LSmeans ± SE. In all panels vertical lines indicate SE and asterisks (*) indicate significant differences with respect the placebo phase (Panel A and B) while circles (°) indicate significant differences from baseline values (Panel A and B). Differences are considered significant when p < 0.05.
Table 4.
Effect of black tea on haemodynamic parameters after 8 days’ intervention measured in the postprandial state.
Table 4.
Effect of black tea on haemodynamic parameters after 8 days’ intervention measured in the postprandial state.
parameter | placebo | black tea | difference (95% CI) | Adj P-value |
---|
SBP (mmHg) | 146.7 ± 0.2 | 143.5 ± 0.2 | −3.2 (−4.2, −2.2) | <0.0001 |
DBP (mmHg) | 92.5 ± 0.2 | 90.5 ± 0.2 | −2.0 (−2.7,−1.2) | <0.0001 |
HR (bpm) | 71.4 ± 0.3 | 71.4 ± 0.3 | −0.0 (−1.2, 1.1) | n.s. |
PP (mmHg) | 54.3 ± 0.2 | 53.4 ± 0.2 | −1.0 (−2.0, 0.0) | n.s. |
PPT (ms) | 170 ± 2.3 | 203 ± 2.2 | 33.9 (24.6, 43.3) | <0.0001 |
RI (%) | 76.3 ± 0.7 | 70.4 ± 0.6 | −5.9 (−8.5, −3.3) | <0.0001 |
SI (m/s) | 9.8 ± 0.1 | 8.3 ± 0.1 | −1.5 (−1.8, −1.2) | <0.0001 |
Figure 5.
Arterial stiffness and wave reflections are known to play a fundamental role in cardiovascular health and disease. Indeed, in interplay with left ventricular ejection and the elastic properties of the aorta, wave reflections could specifically increase central pulse pressure, a recognized predictor of cardiovascular risk. These changes are attributed to the timing and amplitude of pulse wave reflections from peripheral reflecting sites, where high resistance arterioles are considered to be the major sites of wave reflection in the circulation.
Figure 5.
Arterial stiffness and wave reflections are known to play a fundamental role in cardiovascular health and disease. Indeed, in interplay with left ventricular ejection and the elastic properties of the aorta, wave reflections could specifically increase central pulse pressure, a recognized predictor of cardiovascular risk. These changes are attributed to the timing and amplitude of pulse wave reflections from peripheral reflecting sites, where high resistance arterioles are considered to be the major sites of wave reflection in the circulation.
Changes in wave reflection properties are associated with vascular disease and aging and cause an increase in left ventricular afterload, myocardial mass, and oxygen consumption [
3]. Hypertensive disease is associated with important structural alterations in the vasculature, such as large artery stiffening, small artery remodeling and microvascular rarefaction [
2,
3]. Recent basic research has revealed some of the molecular pathways involved in the remodelling of the cardiovascular system are under the influence of physical forces. Vasoactive drugs have little direct effect on large elastic arteries, but can markedly change wave reflection amplitude and augmentation index by altering stiffness of the muscular arteries and modifying transmission velocity of the reflected wave from the periphery to the heart [
2,
3,
4,
5]. Furthermore, arterial stiffening is the principal cause of increasing SBP with advancing years and in patients with arterial hypertension [
2,
3,
4,
5]. It is correlated with progressive arterial dilation as a consequence of arterial wall degeneration, probably due to repetitive cyclic mechanical stress [
2,
3,
4,
5]. The increased amplitude of the pressure wave generated by a given flow impulse from the heart, and indirectly by increasing wave velocity so that wave reflection from the periphery occurs earlier, and augments pressure in late systole. The first mechanism affects pressure in both the central and peripheral arteries, the second predominantly in the central arteries [
2,
3,
4,
5]. This study used DVP wave analysis to measure changes in vessel tone and wave reflections. The RI is an index of pressure wave reflection and vascular tone and SI of wave reflections and arterial stiffness [
17,
18]. Moreover, the marked changes that appear in RI in response to vasoconstrictors and vasodilators has been considered moderately correlated with pulse wave velocity (PWV) (
r = 0.65) [
18]. Although SI is a measure of wave reflections that increases with age, it has also been described to be sensitive to small changes in vascular tone induced by vasodilators [
17,
18]. Furthermore, although SI was found to be inappropriate as a surrogate of aortic PWV [
19], assessment of the SI derived by digital photoplethysmography has been considered an advantage in risk stratification of subjects with intermediate and high cardiovascular risk compared with the AIx [
20].
In this study, we observed that black tea ingestion decreased BP, SI and RI, and protected arterial haemodynamic alteration induced by a fat load. Overall, we showed decreased peripheral vascular tone and wave reflections, suggesting that tea consumption caused vasodilation of peripheral arteries indicating a decrease of vascular resistance, thus offering a putative mechanism for the reported effects in reducing BP. According to this, we may suppose that flavonoid-rich black tea was able to positively affect arterial function also by improving endothelial function [
12].
Loss of functional integrity of the vascular endothelium may be one of the initiating events in the etiology of atherosclerosis. Endothelial cells interact with blood components and the abluminal tissues, thus playing an active role in many aspects of vascular functions, such as permeability and vessel tone regulation. Endothelial cells are constantly exposed to nutrients which can modulate enzymes, receptors, transport molecules and various vasoactive mediators, resulting in significant functional changes of the endothelium and the underlying tissues [
21,
22]. There is evidence that individual nutrients or nutrient derivatives may either provoke or prevent metabolic and physiologic perturbations of the vascular endothelium [
21,
22,
23,
24]. Diets high in fat and/or calories are considered a risk factor for the development of atherosclerosis. Accordingly, certain diet-derived lipids and their derivatives can disrupt normal endothelial integrity, thus reducing the ability of the endothelium to act as a selectively permeable barrier to blood components [
21,
22,
23,
24]. Mechanisms underlying fatty acid-mediated endothelial cell dysfunction may be related to changes in fatty acid composition as well as to an increase in cellular oxidative stress [
21,
22,
23,
24]. Selective lipid accumulation and fatty acid changes in endothelial cells can modulate membrane fluidity, proteoglycan metabolism and signal transduction mechanisms. Most importantly, dietary fats rich in certain unsaturated fatty acids may be atherogenic by enhancing the formation of reactive oxygen intermediates. A subsequent imbalance in cellular oxidative stress/antioxidant status can activate oxidative stress-responsive transcription factors, which in turn may promote endothelial activation with expression of adhesion molecules on the surface of endothelial cells, and thus intensify an inflammatory response in atherosclerosis. Hypertriacylglycerolaemia in the postprandial state promotes the formation of small, dense low-density lipoproteins, as well as oxidative stress, inflammation, and endothelial dysfunction, all of which compound the risk of cardiovascular disease [
21,
22,
23,
24]. Because in normal subjects blood concentrations of glucose, lipids and insulin are increased after each meal, and postprandial changes last a long time after the meals, these changes might be of importance in the process of atherosclerosis initiation and development. These mechanisms may be involved in the development of atherosclerosis in normal subjects when food intake is chronically modified towards glucids and lipids with cumulative effects both on depression of endothelium dependent dilation and oxidative stress [
21,
22,
23,
24].
Impaired endothelium-dependent vasodilation due to decreased bioavailability of nitric oxide has been reported after a fat load in both healthy and obese individuals [
14,
23]. In particular, it has been observed that acute fat load administered orally or intravenously significantly increased BP, altered endothelial function, and activated the sympathetic nervous system by mechanisms not related to changes in leptin, glucose, and insulin levels [
14,
23]. Similarly, combined glucose and fat loads had additional deleterious impact on flow-mediated dilation and on nitric oxide bioavailability in hypertensive patients [
24]. Thus, fat load, independent of its source, has deleterious hemodynamic effects characterized by increased cardiovascular risk in hypertensive as well as in normal subjects [
14,
23,
24]. Our study was conducted in patients affected by EH and indicated that black tea is not only able to improve vascular function and BP, but also counteracts fat load induced transient vascular impairment resulting in a parallel increase in BP and wave reflection. From a public health point of view, avoiding to suggest black tea consumption as a ticket to consume high-fat diets, these findings may be of relevance: the tested tea dose of 1 (acute) or 2 cups (per day) was moderate and the intervention time relatively short. Moreover, the average energy intake in this study of 824 kcal mimicked a serving size typical for the main meal in Western diets [
25,
26]. The magnitude of wave reflection and arterial stiffness has been shown to have an independent predictive value for all cause mortality and cardiovascular morbidity, coronary events and strokes in hypertensive patients [
27]. Also, small changes in BP—for instance, due to dietary and lifestyle modificationmay have a significant impact on the prevalence of hypertension and risk of cardiovascular disease [
28].