Methodological Concerns Regarding the Meta-Analysis of Cranberry Consumption and Blood Pressure.

Background: Previous studies indicate cardiovascular health benefits of cranberry juice consumption. However, whether daily consumption of whole cranberries will have sustained vascular benefits in healthy individuals is currently unknown. Objective: To investigate the vascular effects of acute and daily consumption of freeze dried whole cranberry in healthy men and how effects relate to circulating cranberry (poly)phenol metabolites. Methods: A double-blind, parallel-group, randomized controlled trial was conducted in 45 healthy male adults randomly allocated to 1 month daily consumption of either cranberry (9 g powder solubilized in water equivalent to 100 g of fresh cranberries, 525 mg total (poly)phenols) or control (9 g powder, no (poly)phenols). Flow-mediated dilation (FMD, primary outcome), pulse wave velocity (PWV), aortic augmentation index (AIx), blood pressure, heart rate, blood lipids, and blood glucose were assessed at baseline and at 2 h on day 1 and after 1 month. Plasma and 24 h-urine were analyzed before and after treatment using targeted quantitative LC-MS methods including 137 (poly)phenol metabolites. Results: Cranberry consumption significantly increased FMD at 2 h and 1-month (1.1% (95% CI: 1.1%, 1.8%); ptreatment ≤ 0.001; ptreatment × time = 0.606) but not PWV, AIx, blood pressure, heart rate, blood lipids, and glucose. Of the 56 and 74 (poly)phenol metabolites quantified in plasma and urine, 13 plasma and 13 urinary metabolites significantly increased 2 h post-consumption and on day 1, respectively, while 4 plasma and 13 urinary metabolites were significantly higher after 1-month of cranberry consumption, in comparison with control. A multi-variable stepwise linear regression analysis showed that plasma cinnamic acid-4'-glucuronide, 4-hydroxybenzoic acid-3-sulfate, 2,5-dihydroxybenzoic acid, 3'-hydroxycinnamic acid, and 5-O-caffeoylquinic acid were significant independent predictors of 2 h FMD effects (R2 = 0.71), while 3'-hydroxycinnamic acid, 4-methoxycinnamic acid-3'-glucuronide, 3-(4'-methoxyphenyl)propanoic acid 3'-sulfate, and 3-(4'-methoxyphenyl)propanoic acid 3'-glucuronide predicted the 1-month FMD effects (R2 = 0.52). Conclusions: Acute and daily consumption of whole cranberry powder for 1 month improves vascular function in healthy men and this is linked with specific metabolite profiles in plasma. The National Institutes of Health (NIH)-randomized trial records held on the NIH ClinicalTrials.gov website (NCT02764749). https://clinicaltrials.gov/ct2/show/NCT02764749.

The aim of this paper, which includes a meta-analysis, is to elucidate the effects of cranberry consumption on systolic and diastolic blood pressure based on all relevant randomized controlled trials (RCTs). A systematic literature search was performed across the ISI Web of Science, PubMed, Embase, the Cochrane Library, and Google Scholar databases, encompassing trials published until December 2024. Weighted mean differences (WMD) were calculated using random or fixed-effects models. Between-study heterogeneity was evaluated using Cochrane's test and the I² index. This study's registration number in PROSPERO is CRD420251028424. A total of 1204 publications were reviewed, leading to the inclusion of 12 trials for qualitative synthesis and meta-analysis. The pooled effect size indicated statistically nonsignificant reductions of 1.31 mmHg for systolic blood pressure (SBP) (p = 0.19) and 1.31 mmHg for diastolic blood pressure (DBP) (p = 0.12). Stratified analysis showed that the reduction in SBP was statistically significant in studies where cranberry was provided in juice form, with a duration of 8 weeks or less, involving participants with a mean age of < 50 years, and predominantly in females. Furthermore, subgroup analysis indicated a significant reduction in DBP in studies that involved both genders, lasted more than 8 weeks, included participants with a normal body mass index, and had a mean age below 50 years. This systematic review and meta-analysis suggest that cranberry consumption was not effective in managing SBP and DBP.

Randomised controlled trials for the prevention of cognitive decline or dementia: A systematic review.

PurposeThe purpose of this paper with meta-analysis is to clarify the effects of cranberry consumption on features of the metabolic syndrome of interest of all relevant randomized controlled trials (RCTs).Design/methodology/approachA systematic literature search was conducted on ISI web of science, PubMed, Embase, the Cochrane library and Google Scholar databases, to include trials published up to March 2019. Weighted mean differences (WMD) were calculated from a random or fixed-effects models. Between‐study heterogeneity was assessed by Cochrane’s test and I2 index.FindingsTen RCTs were included in this review which involving a total of 371 subjects. Our meta-analysis showed that cranberry consumption had beneficial effects on waist circumference (WMD −0.49, 95% CI −0.96 to −0.036; p = 0.034). No significant effect of cranberry consumption on fasting blood glucose, high-density lipoprotein cholesterol, triglycerides and blood pressure was found in this meta-analysis.Originality/valueTo the best of the authors’ knowledge, this is the first systematic review with meta-analysis of RCTs that investigate the effect of cranberry consumption on features of the metabolic syndrome.

Cranberries are rich in potentially bioactive (poly)phenols. The aim of this paper was to investigate whether cranberry juice intake can improve vascular function in healthy men in a dose- and time-dependent manner, and to understand which of the circulating (poly)phenol metabolites correlate with vascular effects. A double-blind randomized controlled crossover trial was conducted in ten healthy males. Flow-mediated dilation (FMD), blood pressure, pulse wave velocity and augmentation index were investigated at baseline, 1, 2, 4, 6, and 8 h post-consumption of cranberry juices containing 409, 787, 1238, 1534, and 1910 mg of total cranberry (poly)phenols (TP), and a control drink. Plasma (poly)phenol metabolites were analyzed by UPLC-Q-TOF MS using authentic standards. We observed dose-dependent increases in FMD at 1, 2, 4, 6, and 8 h with a peak at 4 h and maximal effects with juice containing 1238 mg TP. A total of 60 metabolites were quantified in plasma after cranberry consumption. Twelve (poly)phenol metabolites significantly correlated with the increases in FMD, including ferulic and caffeic acid sulfates, quercetin-3-O-ß-D-glucuronide and a γ-valerolactone sulfate. (Poly)phenols in cranberry juice can improve vascular function in healthy males and this is linked to the presence of specific newly identified plasma metabolites.

Cranberries are high in polyphenols, and epidemiological studies have shown that a high-polyphenol diet may reduce risk factors for diabetes and CVD. The present study aimed to determine if short-term cranberry beverage consumption would improve insulin sensitivity and other cardiovascular risk factors. Thirty-five individuals with obesity and with elevated fasting glucose or impaired glucose tolerance participated in a randomised, double-blind, placebo-controlled, parallel-designed pilot trial. Participants consumed 450 ml of low-energy cranberry beverage or placebo daily for 8 weeks. Changes in insulin sensitivity and cardiovascular risk factors including vascular reactivity, blood pressure, RMR, glucose tolerance, lipid profiles and oxidative stress biomarkers were evaluated. Change in insulin sensitivity via hyperinsulinaemic-euglycaemic clamp was not different between the two groups. Levels of 8-isoprostane (biomarker of lipid peroxidation) decreased in the cranberry group but increased in the placebo group (-2·18 v. +20·81 pg/ml; P = 0·02). When stratified by baseline C-reactive protein (CRP) levels, participants with high CRP levels (>4 mg/l) benefited more from cranberry consumption. In this group, significant differences in the mean change from baseline between the cranberry (n 10) and the placebo groups (n 7) in levels of TAG (-13·75 v. +10·32 %; P = 0·04), nitrate (+3·26 v. -6·28 µmol/l; P = 0·02) and 8-isoprostane (+0·32 v. +30·8 pg/ml; P = 0·05) were observed. These findings indicate that 8 weeks of daily cranberry beverage consumption may not impact insulin sensitivity but may be helpful in lowering TAG and changing certain oxidative stress biomarkers in individuals with obesity and a proinflammatory state.

Arterial stiffness is a strong determinant of cardiovascular risk. Pulse wave velocity (PWV) is an index of arterial stiffness, and its prognostic value has been repeatedly emphasized. The purpose of the present study was to assess the effect of heart rate (HR) on PWV. Twenty-two subjects with a mean age of 77.8+/-8.4 (SD) years and permanent cardiac pacing were studied. In each subject, PWV was measured at 5 different pacing frequencies in the same session (60, 70, 80, 90, 100 bpm), the order of the various frequencies being randomly determined. Furthermore, to test the reproducibility, a repeat measurement of PWV was obtained in one randomly selected frequency. Blood pressure (BP) was measured by conventional means at each pacing frequency. PWV appeared fairly reproducible because no significant difference was disclosed between the 2 measurements obtained at the same HR level (P=0.5) and both measurements were strongly correlated (r=0.87, P<0.001). No significant BP variation was observed during pacing. There was a highly significant effect of HR on PWV estimated by a one-way, within-subjects analysis of variance (P=0.01). This study demonstrates that HR is an important factor in the intraindividual variation of PWV in elderly subjects. This raises methodological concern about the measurement of this parameter. Standardizing PWV for HR level seems mandatory if one wants to interpret PWV changes in clinical trials or in the follow-up of patients.

The epidemiological scale of the cardiometabolic continuum is established by two large-scale analyses anchored to the Global Burden of Disease 2021 dataset. Peng et al. quantify the fraction of hypertensive heart disease (HHD) mortality attributable to metabolic risk factors across 204 countries between 1990 and 2021, documenting a rise from 13.4% to 16.9% over three decades and identifying elevated systolic blood pressure and high BMI as the dominant drivers, with an excess burden concentrated in older women. Mapping the arterial periphery, Li et al. apply time-series modelling to GBD 2021 incidence data for lower-extremity peripheral arterial disease, projecting continued growth especially in lower-middle-income regions of South Asia and sub-Saharan Africaprecisely where diabetes and hypertension prevalence is accelerating. Together, these studies define the epidemiological urgency that frames the entire Research Topic.A coherent mechanistic thread links three of the contributions. Zhong, Tang, and Zhang demonstrate, in non-diabetic STEMI patients undergoing PCI, that subclinical insulin resistanceregardless the presence of T2DMindependently predicts impaired coronary microcirculatory function and increased major adverse cardiovascular events (MACE) during follow-up. This finding confirms the hypothesis that insulin resistance is a cardiovascular risk factor, independent of T2DM. Chen et al. reinforce this perspective with a systematic review of T2DM-mediated heart failure, tracing the cascade from chronic hyperglycaemia and advanced glycation end-product accumulation to diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF)a phenotype that frequently eludes conventional diagnostic algorithms. Complementing these mechanistic insights, Song et al. analyse a randomised trial using hierarchical composite endpoints to evaluate intensive glycaemic control and kidney disease risk, illustrating the complex trade-off between microvascular protection and hypoglycaemia hazard that clinicians must navigate when individualising glucose targets.The non-linear amplification of risk when multiple cardiometabolic conditions coexist is examined from complementary angles. Wu, Huang, and Liu present a systematic review and meta-analysis confirming that the relationship between BMI and cardiometabolic multimorbidity begins in the overweight range (25-30 kg/m²), well before obesity thresholds are reached, with each incremental BMI unit carrying additional risk. Chehal et al. extend this observation to a socially vulnerable population, documenting rising multimorbidity prevalence among non-elderly enrolled between 2018 and 2022, highlighting equity dimensions that aggregate statistics often obscure. At the other end of the age spectrum, Fangman et al. report that Type D personalitycharacterised by negative affectivity and social inhibitionis associated with early markers of vascular dysfunction in adolescents, underscoring that the cardiovascular continuum begins to take shape long before clinical risk factors manifest. The conceptual apex of this section is the perspective by López-Gil, Abellán-Huerta, and Abellán-Alemán, who introduce the Gulliver syndrome: a framework to capture the clinically significant yet systematically overlooked risk conferred by the simultaneous presence of at least four borderline risk factorseach sub-threshold by conventional guidelines, yet collectively imposing a cardiovascular burden analogous to established disease. The metaphor, drawn from Swift's protagonist restrained by countless small threads, elegantly frames the problem of therapeutic inertia in patients who fall below every single action threshold. Unlike the metabolic syndrome, the Gulliver syndrome does not require central obesity as a defining feature, making it applicable to a wider range of phenotypes.Two methodologically oriented contributions address the tools we use to measure and act upon cardiovascular risk in T2DM. Guo and Wu compare cardiovascular risk stratification protocols in a real-world diabetic cohort, finding that protocol choice substantially alters patient classification and that simultaneous attainment of blood pressure, HbA1c, and LDL-cholesterol targets remains the exception rather than the rulea stark reminder of the implementation gap between guidelines and practice. Van Bruggen and Luijendijk raise an important methodological concern: the use of type 2 myocardial infarction (demand-supply mismatch rather than plaque rupture) as an efficacy endpoint in cardiovascular trials may conflate mechanistically distinct events and distort treatment effect estimates, with downstream consequences for guideline recommendations.Taken as a whole, the eleven articles assembled in this Research Topic articulate a compelling and consistent message: hypertension, T2DM, and CVD are facets of a single, temporally extended pathological process. Acting on this continuum requires moving beyond singledisease, single-threshold logicintegrating psychosocial determinants, early-life exposures, and cumulative sub-threshold risk into a genuinely unified clinical approach. The Editors hope that these contributions will stimulate both further research and the translation of this integrative framework into everyday cardiovascular prevention practice.

Hypertension is a risk factor for stroke, a leading cause of death in North America. A reduction in systolic blood pressure of only 3 mm Hg reduces the incidence of cerebrovascular disease. Vascular integrity is altered in hypertension, characterized by arterial inflammation, oxidative stress and vasoconstriction. American cranberries (Vaccinium macrocarpon) contain polyphenols which have been shown to act as antioxidants and anti‐inflammatory agents in biological systems. We hypothesized that feeding cranberry‐enriched diets (CBD) to spontaneously hypertensive stroke prone rats (SHRSP) would reduce hypertension and incidence of stroke mortalities. Eight‐week‐old SHRSP and Wistar rats (n=10) were fed one of two diets: 3% cranberry + 4% NaCl or 4% NaCl, mixed into commercial chow. SHRSP eating CBD experienced a 10–20 mm Hg reduction in systolic blood pressure by week 6. This hypotensive effect may be due to a reduction in vasoconstriction as SHRSP eating CBD had significantly higher nitrite levels in their urine after 6 wks (p=0.034), suggestive of higher levels of NO release. SHRSP fed control diet had signs of oxidative stress, with elevated F2 isoprostane excretion in the urine. Feeding cranberry reduced urinary isoprostane excretion in SHRSP rats (p=0.01). Overall, SHRSP on CBD lived 40% longer than control rats (51.3 ± 3.8 days vs 70.5 ± 9.9 days, p= 0.039). These data suggest that cranberry supplementation reduces oxidative stress and vasoconstriction, resulting in lower blood pressure and increased longevity. Funded by NSERC &amp; Atlantic Innovation Fund.

Impact of Cranberries on Gut Microbiota and Cardiometabolic Health: Proceedings of the Cranberry Health Research Conference 2015