Plasma oxyphytosterol concentrations are not associated with CVD status in Framingham Offspring Study participants.

Dietary plant sterols, such as campesterol and sitosterol, reduce plasma cholesterol concentrations, but any relationship to plaque development and CVD remains unclear. Some epidemiologic studies have suggested that elevated plasma plant sterol concentrations are atherogenic, including the Framingham Offspring Study that identified a positive association between plant sterol concentrations and CVD status. We hypothesized that this suggested atherogenicity relates to the oxidation status of plant sterols (i.e., concentrations of plasma oxyphytosterols). Therefore, in the Framingham Offspring Study cohort, we measured plasma oxyphytosterol concentrations in 144 patients with documented CVD and/or more than 50% carotid stenosis and 383 matched controls. We analyzed plasma oxyphytosterol concentrations by GC/MS/MS and performed conditional logistic regression analysis to determine associations between plasma plant sterol or oxyphytosterol concentrations and CVD status. We found that higher total cholesterol (TC)-standardized campesterol concentrations [odds ratio (OR): 2.36; 95% CI: 1.60, 3.50] and higher sitosterol concentrations (OR: 1.47; 95% CI: 1.09, 1.97) were significantly associated with increased CVD risk, as in the earlier study. However, the sum of absolute oxyphytosterol concentrations (OR: 0.99; 95% CI: 0.81, 1.21) and the sum of TC-standardized oxyphytosterol concentrations (OR: 0.98; 95% CI: 0.80, 1.19) were not associated with an increased CVD risk. Results were comparable for individual absolute and TC-standardized oxycampesterol and oxysitosterol concentrations. Plasma nonoxidized TC-standardized sitosterol and campesterol concentrations showed weak or no correlations with oxyphytosterol concentrations, while all individual plasma concentrations of oxyphytosterol correlated with each other. In conclusion, circulating plasma oxyphytosterols are not associated with CVD risk in the Framingham Offspring Study.

LDL-Cholesterol Lowering of Plant Sterols and Stanols-Which Factors Influence Their Efficacy?

The LDL-cholesterol (LDL-C) lowering effect of plant sterols/stanols (PSS) is summarized in several meta-analyses showing a dose-response relationship with intakes of 1.5 to 3 g/day lowering LDL-C by 7.5% to 12%. This review summarizes evidence for the impact of various factors potentially influencing the LDL-C-lowering efficacy of PSS. PSS are efficacious in all food formats and in food supplements. Some factors related to food format, e.g., solid vs. liquid foods, seem to impact efficacy, while there is no difference between free PSS and esters. Compared to multiple daily intakes, once-a-day intake of PSS, especially in the morning with light breakfast, leads to a sub-optimal LDL-C lowering. However, intake frequency seems influenced by intake occasion, i.e., with or without a meal, and time of day. Meal intake is a critical factor for an optimal LDL-C lowering efficacy of PSS. While age has no impact, gender is suggested to influence the LDL-C lowering effect of PSS with greater reductions reported for men than women; but overall evidence is inconclusive and larger studies show no gender by treatment interaction. In conclusion, PSS are efficacious in all foods and food supplements; for optimal efficacy they should be consumed with a (main) meal and twice daily.

Progress and perspectives in plant sterol and plant stanol research.

Current evidence indicates that foods with added plant sterols or stanols can lower serum levels of low-density lipoprotein cholesterol. This review summarizes the recent findings and deliberations of 31 experts in the field who participated in a scientific meeting in Winnipeg, Canada, on the health effects of plant sterols and stanols. Participants discussed issues including, but not limited to, the health benefits of plant sterols and stanols beyond cholesterol lowering, the role of plant sterols and stanols as adjuncts to diet and drugs, and the challenges involved in measuring plant sterols and stanols in biological samples. Variations in interindividual responses to plant sterols and stanols, as well as the personalization of lipid-lowering therapies, were addressed. Finally, the clinical aspects and treatment of sitosterolemia were reviewed. Although plant sterols and stanols continue to offer an efficacious and convenient dietary approach to cholesterol management, long-term clinical trials investigating the endpoints of cardiovascular disease are still lacking.

Consumer purchase behaviour of foods with added phytosterols in six European countries: Data from a post-launch monitoring survey.

A variety of foods with added phytosterols (plant sterols and stanols, PS) known to lower elevated blood cholesterol is available on the European market. This paper reports findings from a 2015 post-launch monitoring survey on consumer purchase behaviour of foods with added PS in UK, Germany, France, Netherlands, Belgium and Greece. Data from 80,825 households were included. Households were divided into categories depending on number of purchases, household size, age of primary shopper and presence of children <5 years. Penetration rates of households purchasing foods with added PS ranged between 3 and 34%. Of households purchasing PS, 34-61% purchased infrequently (≤2 times/year), 29-36% occasionally (

Plasma fat-soluble vitamin and carotenoid concentrations after plant sterol and plant stanol consumption: a meta-analysis of randomized controlled trials.

PURPOSE: Plant sterols and stanols interfere with intestinal cholesterol absorption, and it has been questioned whether absorption and plasma concentrations of fat-soluble vitamins and carotenoids are also affected. We conducted a meta-analysis to assess the effects of plant sterol and stanol consumption on plasma fat-soluble vitamin and carotenoid concentrations. METHODS: Forty-one randomized controlled trials involving 3306 subjects were included. Weighted absolute and relative changes of non-standardized and total cholesterol (TC)-standardized values (expressed as summary estimates and 95 % CIs) were calculated for three fat-soluble vitamins (α- and γ-tocopherol, retinol and vitamin D) and six carotenoids (ß-carotene, α-carotene, lycopene, lutein, zeaxanthin and ß-cryptoxanthin) using a random effects model. Heterogeneity was assessed using predefined subject and treatment characteristics. RESULTS: Average plant sterol or stanol intake was 2.5 g/d. Relative non-standardized and TC-standardized concentrations of ß-carotene decreased by, respectively, -16.3 % (95 % CI -18.3; -14.3) and -10.1 % (-12.3; -8.0), α-carotene by -14.4 % (-17.5; 11.3) and -7.8 % (-11.3; -4.3), and lycopene by -12.3 % (-14.6; -10.1) and -6.3 % (-8.6; -4.0). Lutein concentrations decreased by -7.4 % (-10.1; -4.8), while TC-standardized concentrations were not changed. For zeaxanthin, these values were -12.9 % (-18.9; -6.8) and -7.7 % (-13.8; -1.7) and for ß-cryptoxanthin -10.6 % (-14.3; -6.9) and -4.8 % (-8.7; -0.9). Non-standardized α-tocopherol concentrations decreased by -7.1 % (-8.0; -6.2) and γ-tocopherol by -6.9 % (-9.8; -3.9), while TC-standardized tocopherol concentrations were not changed. Non-standardized retinol and vitamin D concentrations were not affected. Results were not affected by baseline concentrations, dose, duration and type of plant sterols/stanols, except for significant effects of duration (≤4 vs. >4 weeks) on TC-standardized lutein concentrations (1.0 vs. -5.6 %) and type of plant sterol/stanol on TC-standardized ß-carotene concentrations (-8.9 vs. -14.2 %). CONCLUSIONS: Plant sterol and stanol intake lowers TC-standardized hydrocarbon carotenoid concentrations, differently affects TC-standardized oxygenated carotenoid concentrations, but does not affect TC-standardized tocopherol concentrations or absolute retinol and vitamin D concentrations. Observed concentrations remained within normal ranges.

Effects of phytosterols on markers of inflammation: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Regular intake of phytosterols (PS) is proven to dose-dependently lower LDL-cholesterol (LDL-C). Whether PS consumption can also impact low-grade inflammation is unclear. Considering the low feasibility of outcomes studies involving PS consumption, investigation of surrogate markers of atherosclerosis represents a valuable approach. This study assessed the anti-inflammatory effect of PS consumption, according to inflammatory biomarkers, mainly C-reactive protein (CRP). METHODS AND RESULTS: A systematic search of Medline, Cab Abstracts, and Food Science & Technology Abstracts was conducted through January 2015. Our study selection included randomized controlled trials (RCT), involving intake of PS-enriched foods as active treatment, and measurement of plasma inflammatory biomarkers. Random-effects meta-analyses were performed using average baseline and end-of-intervention concentrations and control-adjusted absolute changes in CRP and blood lipids. There were 20 eligible RCTs including a total of 1308 subjects. The absolute change of plasma CRP levels with PS consumption was -0.10 mg/L (95%CI -0.26; 0.05), a non-significant change, and heterogeneity had borderline significance (I(2) = 29.1; p-value = 0.073). The absolute reduction of LDL-C was -14.3 mg/dL (95%CI -17.3; -11.3). Meta-regression analyses showed that both the dose and duration of PS intake significantly influenced the absolute changes in plasma CRP (ß = -0.35, p = 0.0255 and ß = -0.03, p = 0.0209, respectively). CONCLUSIONS: In this meta-analysis, regular intake of PS-enriched foods did not significantly change CRP, whilst LDL-C concentrations were significantly reduced. Further studies with higher PS doses may provide more definite conclusions on a potential anti-inflammatory effect of PS intake.

The effect of plant sterols and different low doses of omega-3 fatty acids from fish oil on lipoprotein subclasses.

SCOPE: Consumption of a low-fat spread enriched with plant sterols (PS) and different low doses (<2 g/day) of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil reduces serum triglycerides (TGs) and low-density lipoprotein-cholesterol (LDL-Chol) and thus beneficially affects two blood lipid risk factors. Yet, their combined effects on TG and Chol in various lipoprotein subclasses have been investigated to a limited extent. METHODS AND RESULTS: In a randomized, double-blind, placebo-controlled, parallel study, we determined TG and Chol in 13 LP subclasses in fasting serum of 282 hypercholesterolemic subjects, who consumed either a placebo spread or one of the four spreads containing PS (2.5 g/day) and EPA+DHA (0.0, 0.9, 1.3, and 1.8 g/day) for 4 weeks. After PS treatment, total LDL-Chol was reduced, which was not further changed by EPA+DHA. No shift in the LDL-Chol particle distribution was observed. The addition of EPA+DHA to PS dose-dependently reduced VLDL-Chol and VLDL-TG mainly in larger particles. Furthermore, the two highest doses of EPA+DHA increased Chol and TG in the larger HDL particles, while these concentrations were decreased in the smallest HDL particles. CONCLUSION: The consumption of a low-fat spread enriched with both PS and EPA+DHA induced shifts in the lipoprotein distribution that may provide additional cardiovascular benefits over PS consumption alone.

The effect of a low-fat spread with added plant sterols on vascular function markers: results of the Investigating Vascular Function Effects of Plant Sterols (INVEST) study.

BACKGROUND: Plant sterols (PSs) lower LDL cholesterol, an established risk factor for coronary artery disease (CAD). No direct evidence is available supporting a reduced risk of CAD for foods with added PSs. Endothelial dysfunction is seen as an early indicator of atherosclerotic damage. OBJECTIVES: This study was primarily designed to investigate the effect of a low-fat spread with added PSs on brachial artery endothelial function as measured by flow-mediated dilation (FMD). Second, effects on arterial stiffness, blood pressure, serum lipids, and plasma PS concentrations were investigated. We hypothesized that PSs would not worsen FMD but would rather modestly improve FMD. DESIGN: This study had a double-blind, randomized, placebo-controlled, parallel design. After a 4-wk run-in period, 240 hypercholesterolemic but otherwise healthy men and women consumed 20 g/d of low-fat spread without (control) or with added PSs (3 g/d) during 12 wk. Pre- and postintervention, vascular function measurements and blood sampling were performed. RESULTS: In total, 232 participants completed the study period. For the primary endpoint FMD, 199 participants were included in the statistical analysis. PS intake did not affect FMD (+0.01 percentage points; 95% CI: -0.73, 0.75) compared with control. Measures of arterial stiffness (pulse wave velocity and augmentation index) and blood pressure were also not significantly changed compared with control. After PS intervention, LDL cholesterol significantly decreased on average by 0.26 mmol/L (95% CI: -0.40, -0.12) or 6.7% compared with control. Plasma sitosterol and campesterol concentrations significantly increased in the PS group up to on average 11.5 µmol/L and 13.9 µmol/L (expressed as geometric means), respectively. CONCLUSIONS: The intake of a low-fat spread with added PSs neither improved nor worsened FMD or other vascular function markers in hypercholesterolemic men and women. As expected, serum LDL cholesterol decreased, whereas plasma PSs increased after PS intake. This study was registered at clinicaltrials.gov as NCT01803178.

Intake of phytosterols from natural sources and risk of cardiovascular disease in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) population.

BACKGROUND: Phytosterols (PSs) are known to lower low-density lipoprotein cholesterol (LDL-C), an established risk factor for cardiovascular disease (CVD). Whether a high intake of PS reduces CVD risk is unknown. This observational study aimed to investigate the associations between intake of naturally occurring PSs, blood lipids and CVD risk. METHODS: The study included 35,597 Dutch men and women, participating in the European Prospective Investigation into Cancer and Nutrition-the Netherlands (EPIC-NL) study. At baseline, intakes of naturally occurring PSs were estimated with a validated food frequency questionnaire and non-fasting blood lipids were measured. Occurrence of CVD, coronary heart disease (CHD) and myocardial infarction (MI) was determined through linkage with registries. RESULTS: The average energy-adjusted PS intake at baseline was 296 mg/d (range: 83-966 mg/d). During 12.2 years of follow-up, 3047 CVD cases (8.6%) were documented. After adjustment for confounders, PS intake was not associated with risk of CVD, CHD or MI (p-value trend > 0.05); hazard ratios ranged from 0.90-0.99 for CVD, from 0.83-0.90 for CHD and from 0.80-0.95 for MI risk across quintiles of PS intake and were almost all non-significant. Higher PS intake was associated with lower total cholesterol (-0.06 mmol/l per 50 mg/d; p-value = 0.038) and lower LDL-C (-0.07 mmol/l; p-value = 0.007), particularly among men. In mediation analysis, LDL-C did not materially affect the association between PS intake and CVD risk. CONCLUSIONS: In this population with a relatively narrow range of low naturally occurring PS intakes, intake of PS was not associated with reduced CVD risk despite lower LDL-C concentrations in men.

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.

Low doses of eicosapentaenoic acid and docosahexaenoic acid from fish oil dose-dependently decrease serum triglyceride concentrations in the presence of plant sterols in hypercholesterolemic men and women.

Plant sterols (PSs) lower LDL cholesterol (LDL-C) concentrations, whereas the n-3 (ω-3) fish fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) lower triglyceride (TG) concentrations. Incorporating both PSs and EPA+DHA from fish oil (FO) in a single food format was expected to beneficially affect 2 blood lipid risk factors. The aim of this study was to investigate the dose-response relation between low doses (<2 g/d) of EPA+DHA from FO, incorporated in a low-fat PS-enriched spread, and TG concentrations. In addition, effects on LDL-C were investigated. The study was designed as a randomized, double-blind, placebo-controlled parallel study. After a 4-wk run-in period, subjects were randomly assigned to consume either a control (C) spread (no PSs, no FO) or 1 of 4 intervention spreads containing a fixed amount of PSs (2.5 g/d) and varying amounts of FO (0.0, 0.9, 1.3, and 1.8 g/d of EPA+DHA) for 4 wk. Before and after the intervention, fasting blood samples were drawn for measuring serum lipids and EPA and DHA in erythrocyte membranes. In total, 85 hypercholesterolemic men and 247 women with a mean age of 57.9 y (range: 25-74 y) were included. Eighteen subjects dropped out during the study. At baseline, mean TG and LDL-C concentrations were 1.09 and 4.00 mmol/L, respectively. After the intervention, a significant dose-response relation for the TG-lowering effect of EPA+DHA [ßln (TG) = -0.07 mmol/L per gram of EPA+DHA; P < 0.01] was found. Compared with the C group, TG concentrations were 9.3-16.2% lower in the different FO groups (P < 0.05 for all groups). LDL-C concentrations were 11.5-14.7% lower in the different PS groups than in the C group (P < 0.01 for all groups). EPA and DHA in erythrocyte membranes were dose-dependently higher after FO intake than after the C spread, indicating good compliance. Consumption of a low-fat spread enriched with PSs and different low doses of n-3 fatty acids from FO decreased TG concentrations in a dose-dependent manner and decreased LDL-C concentrations. This trial was registered at clinicaltrials.gov as NCT01313988.

LDL-cholesterol-lowering effect of plant sterols and stanols across different dose ranges: a meta-analysis of randomised controlled studies.

Phytosterols (PS, comprising plant sterols and plant stanols) have been proven to lower LDL-cholesterol concentrations. The dose-response relationship for this effect has been evaluated in several meta-analyses by calculating averages for different dose ranges or by applying continuous dose-response functions. Both approaches have advantages and disadvantages. So far, the calculation of averages for different dose ranges has not been done for plant sterols and stanols separately. The objective of the present meta-analysis was to investigate the combined and separate effects of plant sterols and stanols when classified into different dose ranges. Studies were searched and selected based on predefined criteria. Relevant data were extracted. Average LDL-cholesterol effects were calculated when studies were categorised by dose, according to random-effects models while using the variance as weighing factor. This was done for plant sterols and stanols combined and separately. In total, 124 studies (201 strata) were included. Plant sterols and stanols were administered in 129 and fifty-nine strata, respectively; the remaining used a mix of both. The average PS dose was 2.1 (range 0.2-9.0) g/d. PS intakes of 0.6-3.3 g/d were found to gradually reduce LDL-cholesterol concentrations by, on average, 6-12%. When plant sterols and stanols were analysed separately, clear and comparable dose-response relationships were observed. Studies carried out with PS doses exceeding 4 g/d were not pooled, as these were scarce and scattered across a wide range of doses. In conclusion, the LDL-cholesterol-lowering effect of both plant sterols and stanols continues to increase up to intakes of approximately 3 g/d to an average effect of 12%.

Consumption of plant sterol-enriched foods and effects on plasma plant sterol concentrations--a meta-analysis of randomized controlled studies.

OBJECTIVE: Intake of plant sterol (PS)-enriched foods effectively lowers plasma total- and LDL-cholesterol concentrations while increasing plasma PS concentrations. The magnitude of this increase has not been systematically assessed. This study aimed to investigate the effect of PS-enriched foods on plasma PS concentrations by performing a meta-analysis of randomized controlled studies. METHODS: Published PS intervention studies reporting plasma PS concentrations were searched through June 2012. Studies were selected that fulfilled pre-defined in- and exclusion criteria. Data were extracted, particularly on campesterol, sitosterol, total- and LDL-cholesterol. Random-effects models were used to calculate net effects while weighing each study by the inverse of its variance. Potential sources of heterogeneity were investigated. RESULTS: The meta-analysis included data from 41 studies (55 strata) with in total 2084 subjects. The average dose of PS from enriched foods was 1.6 g/d (range: 0.3-3.2 g/d). Plasma sitosterol and campesterol concentrations were increased by on average 2.24 µmol/L (31%) and 5.00 µmol/L (37%), respectively, compared to control. Total- and LDL-cholesterol were reduced by on average 0.36 mmol/L (5.9%) and 0.33 mmol/L (8.5%), respectively. The increase in sitosterol and campesterol was impacted by the dose of PS, the baseline PS concentration and the PS composition of the test products. In the highest PS dose category (2.0-3.2 g/d), increases in sitosterol and campesterol were on average 3.56 and 7.64 µmol/L, respectively. CONCLUSION: Intake of PS-enriched foods increases plasma sitosterol and campesterol concentrations. However, total PS remain below 1% of total sterols circulating in the blood.

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.

The effect of plant sterols on serum triglyceride concentrations is dependent on baseline concentrations: a pooled analysis of 12 randomised controlled trials.

PURPOSE: Plant sterols (PS) are well known for their low-density lipoprotein cholesterol-lowering effect. Until recently, they were believed to have little or no impact on blood triglycerides (TG). However, studies taken individually were possibly lacking statistical power to detect modest TG decreases. This study was performed to quantify the TG-lowering effect of PS by pooling individual subject data from 12 randomised controlled trials that investigated the effects of PS on blood lipids. METHODS: The main outcome variable was the control-adjusted PS effect on relative (%) and absolute (mmol/L) changes in TG. The relative and absolute changes in high-density lipoprotein cholesterol (HDL-C) were also assessed. Differences in changes of serum lipid concentrations between PS and control treatments were estimated by an ANCOVA using a random effect model which included PS intake (active or control), study and predefined subject characteristics. RESULTS: The twelve randomised controlled trials included in total 935 hypercholesterolaemic subjects not preselected based on their baseline TG concentrations. In most studies, the PS dose ranged between 1.6 and 2.5 g/day. PS intake significantly lowered serum TG by 6.0% (95% CI: -10.7, -1.2) or 0.12 mmol/L (95% CI: -0.20, -0.04). No significant interaction was observed between PS intake and baseline TG concentrations on relative changes, but, on absolute changes, interaction was significant with larger TG decreases observed with higher TG concentrations at baseline. No effects were observed on HDL-C concentrations. CONCLUSIONS: These results show that PS exert a modest TG-lowering effect which is dependent on baseline concentrations.

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.

Continuous dose-response relationship of the LDL-cholesterol-lowering effect of phytosterol intake.

Phytosterols (plant sterols and stanols) are well known for their LDL-cholesterol (LDL-C)-lowering effect. A meta-analysis of randomized controlled trials in adults was performed to establish a continuous dose-response relationship that would allow predicting the LDL-C-lowering efficacy of different phytosterol doses. Eighty-four trials including 141 trial arms were included. A nonlinear equation comprising 2 parameters (the maximal LDL-C lowering and an incremental dose step) was used to describe the dose-response curve. The overall pooled absolute (mmol/L) and relative (%) LDL-C-lowering effects of phytosterols were also assessed with a random effects model. The pooled LDL-C reduction was 0.34 mmol/L (95% CI: -0.36, -0.31) or 8.8% (95% CI: -9.4, -8.3) for a mean daily dose of 2.15 g phytosterols. The impacts of subject baseline characteristics, food formats, type of phytosterols, and study quality on the continuous dose-response curve were determined by regression or subgroup analyses. Higher baseline LDL-C concentrations resulted in greater absolute LDL-C reductions. No significant differences were found between dose-response curves established for plant sterols vs. stanols, fat-based vs. non fat-based food formats and dairy vs. nondairy foods. A larger effect was observed with solid foods than with liquid foods only at high phytosterol doses (>2 g/d). There was a strong tendency (P = 0.054) towards a slightly lower efficacy of single vs. multiple daily intakes of phytosterols. In conclusion, the dose-dependent LDL-C-lowering efficacy of phytosterols incorporated in various food formats was confirmed and equations of the continuous relationship were established to predict the effect of a given phytosterol dose. Further investigations are warranted to investigate the impact of solid vs. liquid food formats and frequency of intake on phytosterol efficacy.