Richard Draijer

Flow-mediated dilation and cardiovascular risk prediction: A systematic review with meta-analysis

BACKGROUND Flow-mediated dilation (FMD) is an accepted technique to quantify endothelial function and has shown to have prognostic value for future cardiovascular disease (CVD). The predictive strength of FMD in CVD patients compared to populations not diagnosed for CVD warrants further investigation. We systematically reviewed prospective studies that investigated the association between brachial FMD and future cardiovascular events, with particular focus on the role of underlying health status. METHODS To obtain eligible studies, several literature databases were systematically searched through March 2011. Pooled overall risk estimates were calculated separately for continuous risk estimates for CVD (per 1% higher FMD) and for categorical risk estimates for CVD (having high vs. low FMD), based on random-effects models. RESULTS A total of 23 studies including 14,753 subjects were eligible for inclusion in the meta-analysis. For studies reporting continuous risk estimates, the pooled overall CVD risk was 0.92 (95%CI: 0.88; 0.95) per 1% higher FMD. The observed association seemed stronger (P-value<0.01) in diseased populations than in asymptomatic populations (0.87 (95%CI: 0.83; 0.92) and 0.96 (95%CI: 0.92; 1.00) per 1% higher FMD, respectively). For studies reporting categorical risk estimates, the pooled overall CVD risk for high vs. low FMD was similar in both types of populations, on average 0.49 (95%CI: 0.39; 0.62). CONCLUSIONS Our findings show that brachial FMD is inversely associated with future CVD events, with some indications for a stronger relation in diseased populations. Endothelial dysfunction may be considered relevant for classifying subjects in terms of CVD risk.

Tea Consumption Enhances Endothelial-Dependent Vasodilation; a Meta-Analysis

Background Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association. Objective We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk. Methods Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical Abstracts and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity. Results In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6% of the arterial diameter (95% CI: 1.8-3.3%; P-value <0.001) for a median daily dose of 500 mL of tea (2–3 cups). This is a relative increase of approximately 40% compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value <0.001) that might partly be explained by the cuff position either distal or proximal to the area of FMD measurement. No indication for publication bias was found. Conclusion Moderate consumption of tea substantially enhances endothelial-dependent vasodilation. This may provide a mechanistic explanation for the reduced risk of cardiovascular events and stroke observed among tea drinkers.

Black tea consumption dose-dependently improves flow-mediated dilation in healthy males.

Objectives Flavonoids may protect against cardiovascular disease. Tea is a major source of dietary flavonoids. Studies indicate black tea improves endothelial function but data on arterial haemodynamics, blood pressure (BP) and insulin resistance are equivocal. Inconsistency may be due to flaws in study design or flavonoid doses tested. Further, no study has evaluated the dose–response curve. Our study aimed to test the effects of various doses of black tea on vascular function, BP and insulin resistance. Methods According to a randomized, double-blind, controlled, cross-over design, 19 healthy men were assigned to receive either five treatments with a twice daily intake of black tea (0, 100, 200, 400 and 800 mg tea flvanoids/day) in five periods lasting 1 week each. Results Black tea dose dependently increased flow-mediated dilation (FMD) from 7.8% (control) to 9.0, 9.1, 9.6 and 10.3% after the different flavonoid doses, respectively (P = 0.0001). Already 100 mg/day (less than 1 cup of tea) increased FMD compared with control (P = 0.0113). FMD improvement after 800 mg/day was significant compared with control (P < 0.0001) but also to 100 mg/day (P = 0.0121) and 200 mg/day (P = 0.0275). Black tea intake decreased office systolic (−2.6 mmHg, P = 0.0007) and diastolic (−2.2 mmHg, P = 0.006) BP as well as stiffness index (P = 0.0159) without changes in other parameters studied. Conclusion Our study is the first showing black tea ingestion dose dependently improved FMD and decreased peripheral arterial stiffness in healthy volunteers. Our data suggest that worldwide all tea drinkers could benefit from protective cardiovascular effects exerted by tea.

Grape Polyphenols Do Not Affect Vascular Function in Healthy Men

Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors. Grape and wine contain high amounts of polyphenols, but effects of these polyphenols have hardly been investigated in isolation in randomized controlled studies. Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation (FMD). Blood pressure and other vascular function measures, platelet function, and blood lipids were secondary outcomes. Thirty-five healthy males were randomized in a double-blind, placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods. The test products, containing 800 mg of polyphenols, were consumed as capsules. At the end of each intervention period, effects were measured after consumption of a low-fat breakfast (~751 kJ, 25% fat) and a high-fat lunch (~3136 kJ, 78% fat). After the low-fat breakfast, the treatments did not significantly affect FMD. The absolute difference after the wine grape solid treatment was -0.4% (95% CI = -1.8 to 0.9; P = 0.77) and after grape seed solids, 0.2% (95% CI = -1.2 to 1.5; P = 0.94) compared with after the placebo treatment. FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment. In conclusion, consumption of grape polyphenols has no major impact on FMD in healthy men. Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in populations with increased cardiovascular risk.

Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension.

Dietary polyphenols, such as those from grape products, may exert beneficial effects on cardiovascular health, including anti-hypertensive effects. We investigated the effect of a specific grape seed extract (GSE) rich in low-molecular-weight polyphenolic compounds on ambulatory blood pressure (ABP) in untreated subjects with pre- and stage I hypertension. In addition, potential mechanisms that could underlie the hypothesised effect of GSE on blood pressure (BP), and platelet aggregation, were explored. The study was designed as a double-blind, placebo-controlled, randomised, parallel-group intervention study including seventy healthy subjects with systolic BP between 120 and 159 mmHg. A 1-week run-in period was followed by an 8-week intervention period, during which subjects consumed capsules containing either 300 mg/d of GSE or a placebo (microcrystalline cellulose). Before and after the intervention, daytime ABP readings, 24 h urine samples and fasting and non-fasting blood samples were taken. The mean baseline systolic BP was 135.8 (SE 1.3) mmHg and diastolic BP was 81.5 (SE 0.9) mmHg. BP values were modestly, but not significantly, affected by the polyphenol-rich GSE treatment v. placebo with an effect of - 3.0 mmHg for systolic BP (95% CI - 6.5, 0.5) and - 1.4 mmHg for diastolic BP (95% CI - 3.5, 0.6). Vasoactive markers including endothelin-1, NO metabolites and asymmetric dimethylarginine, plasma renin activity and platelet aggregation were not affected by the GSE intervention. Our findings show that consumption of polyphenol-rich GSE does not significantly lower ABP in untreated subjects with pre- and stage I hypertension.

Red wine polyphenols do not lower peripheral or central blood pressure in high normal blood pressure and hypertension.

BACKGROUND Epidemiological data suggest that modest red wine consumption may reduce cardiovascular disease risk. Red wine polyphenols improved human endothelial vascular function and reduced blood pressure (BP) in animal studies, but the results of human intervention studies investigating the effect of red wine polyphenols on BP are inconsistent. The objective was to investigate whether polyphenols extracted from red wine reduce peripheral and central BP in subjects with high-normal BP or grade 1 hypertension. METHODS In a double-blind, placebo-controlled three-period crossover trial, we assigned 61 subjects (mean age 61.4 ± 8.4 years) with office systolic BP 135 ± 9 mm Hg and diastolic BP 82 ± 8 mm Hg to dairy drinks containing either placebo, 280 mg red wine polyphenols, or 560 mg red wine polyphenols. After each 4-week intervention period, office and 24-h ambulatory BP measurements, and central hemodynamic measurements derived from continuous finger BP recordings were assessed. RESULTS Polyphenol treatment did not significantly affect 24-h BP: systolic/diastolic BP was 143 ± 2/84 ± 1 mm Hg after placebo, 143 ± 2/84 ± 1 mm Hg after 280 mg/day of red wine polyphenols, and 142 ± 2/83 ± 1 mm Hg after 560 mg/day. Neither dose of polyphenol treatment changed office or central BP, aortic augmentation index (AIx) or pulse wave reflection index. CONCLUSIONS Intake of red wine polyphenols in two different dosages for 4 weeks did not decrease peripheral or central BP in subjects with a high normal or grade 1 hypertension. Our findings do not support the hypothesis that polyphenols account for the suggested cardiovascular benefits of red wine consumption by lowering BP.

Consumption of a Polyphenol-Rich Grape-Wine Extract Lowers Ambulatory Blood Pressure in Mildly Hypertensive Subjects

Polyphenols in grape and wine have been suggested to contribute to the cardiovascular health benefits of the Mediterranean lifestyle. The reported effects of grape products on blood pressure (BP) remain, however, equivocal. In a double-blind placebo controlled crossover study, the effect of two grape extracts on BP and vascular function was assessed in 60 untreated, mildly hypertensive subjects after four weeks intervention. Both extracts (grape-red wine and grape alone) had high concentrations of anthocyanins and flavonols, but the grape alone was relatively poor in catechins and procyanidins. Parameters measured included ambulatory and office BP, flow-mediated vasodilation, arterial distensibility, platelet function and plasma lipoproteins. Results showed that 24-hour ambulatory systolic/diastolic BPs were significantly lower in the grape-wine extract intervention (135.9 ± 1.3/84.7 ± 0.8 mmHg; mean ± SEM) compared to placebo (138.9 ± 1.3/86.6 ± 1.2 mmHg), predominantly during daytime. Plasma concentrations of the vasoconstrictor endothelin-1 decreased by 10%, but other measures of vascular function were not affected. Grape juice extract alone had no effect on BP or any measures of vascular function. Polyphenol-rich food products, and may be specifically catechins and procyanidins, may thus help sustain a healthy BP and contribute to the healthy Mediterranean lifestyle.

The Effect of Black Tea on Blood Pressure: A Systematic Review with Meta-Analysis of Randomized Controlled Trials

Objective Epidemiological evidence has linked consumption of black tea, produced from Camellia sinensis, with a reduced risk of cardiovascular diseases. However, intervention studies on the effects of tea consumption on blood pressure (BP) have reported inconsistent results. Our objective was to conduct a systematic literature review with meta-analysis of controlled human intervention studies examining the effect of tea consumption on BP. Methods We systematically searched Medline, Biosis, Chemical Abstracts and EMBASE databases through July 2013. For inclusion, studies had to meet the following pre-defined criteria: 1) placebo controlled design in human adults, 2) minimum of 1 week black tea consumption as the sole intervention, 3) reported effects on systolic BP (SBP) or diastolic BP (DBP) or both. A random effects model was used to calculate the pooled overall effect of black tea on BP. Results Eleven studies (12 intervention arms, 378 subjects, dose of 4–5 cups of tea) met our inclusion criteria. The pooled mean effect of regular tea ingestion was −1.8 mmHg (95% CI: −2.8, −0.7; P = 0.0013) for SBP and −1.3 mmHg (95% CI: −1.8, −0.8; P<0.0001) for DBP. In covariate analyses, we found that the method of tea preparation (tea extract powders versus leaf tea), baseline SBP and DBP, and the quality score of the study affected the effect size of the tea intervention (all P<0.05). No evidence of publication bias could be detected. Conclusions Our meta-analysis indicates that regular consumption of black tea can reduce BP. Although the effect is small, such effects could be important for cardiovascular health at population level.

The effect of black tea and caffeine on regional cerebral blood flow measured with arterial spin labeling

Black tea consumption has been shown to improve peripheral vascular function. Its effect on brain vasculature is unknown, though tea contains small amounts of caffeine, a psychoactive substance known to influence cerebral blood flow (CBF). We investigated the effects on CBF due to the intake of tea components in 20 healthy men in a double-blinded, randomized, placebo-controlled study. On separate days, subjects received a single dose of 184 mg caffeine (equivalent to one strong espresso coffee), 2,820 mg black tea solids containing 184 mg caffeine (equivalent to 6 cups of tea), 2,820 mg decaffeinated black tea solids, or placebo. The CBF and cerebrovascular reactivity (CVR) to hypercapnia were measured with arterial spin labeled magnetic resonance imaging (MRI) before and 2 hours after administration. We found a significant global reduction with caffeine (20%) and tea (21%) in gray matter CBF, with no effect of decaffeinated tea, suggesting that only caffeine influences CBF acutely. Voxelwise analysis revealed the effect of caffeine to be regionally specific. None of the interventions had an effect on CVR. Additional research is required to conclude on the physiologic relevance of these findings and the chronic effects of caffeine and tea intake on CBF.

Black tea lowers blood pressure and wave reflections in fasted and postprandial conditions in hypertensive patients: a randomised study.

Hypertension and arterial stiffening are independent predictors of cardiovascular mortality. Flavonoids may exert some vascular protection. We investigated the effects of black tea on blood pressure (BP) and wave reflections before and after fat load in hypertensives. According to a randomized, double-blind, controlled, cross-over design, 19 patients were assigned to consume black tea (129 mg flavonoids) or placebo twice a day for eight days (13 day wash-out period). Digital volume pulse and BP were measured before and 1, 2, 3 and 4 h after tea consumption. Measurements were performed in a fasted state and after a fat load. Compared to placebo, reflection index and stiffness index decreased after tea consumption (p < 0.0001). Fat challenge increased wave reflection, which was counteracted by tea consumption (p < 0.0001). Black tea decreased systolic and diastolic BP (−3.2 mmHg, p < 0.005 and −2.6 mmHg, p < 0.0001; respectively) and prevented BP increase after a fat load (p < 0.0001). Black tea consumption lowers wave reflections and BP in the fasting state, and during the challenging haemodynamic conditions after a fat load in hypertensives. Considering lipemia-induced impairment of arterial function may occur frequently during the day, our findings suggest regular consumption of black tea may be relevant for cardiovascular protection.