Montmorency tart cherries (MC) have been found to modulate indices of vascular function with interventions of varying duration. The objective of this preliminary study was to identify the chronic effects of MC supplementation on vascular function and the potential for urinary metabolomics to provide mechanistic evidence. We performed a placebo-controlled, double-blind, randomised study on 23 healthy individuals (18M, 7F) that consumed 30 ml MC or a placebo twice daily for 28 days. Whole body measures of vascular function and spot urine collections were taken at baseline and after supplementation. There were no significant changes to vascular function including blood pressure and arterial stiffness. Urinary metabolite profiling highlighted significant changes (P < 0⋅001) with putative discriminatory metabolites related to tryptophan and histidine metabolism. Overall, MC supplementation for 28 days does not improve indices of vascular function but changes to the urinary metabolome could be suggestive of potential mechanisms.

Whey protein (WP) has been heavily appreciated as a rich source of bioactive peptides, with potential benefits for cardiovascular health. This study constitutes a systematic review and meta-analysis summarising the effects of WP consumption on vascular reactivity, arterial stiffness and circulatory biomarkers of vascular function. We searched electronic databases, including PubMed, SCOPUS and Web of science for relevant articles from inception to July 2020. Original clinical trials published in English-language journals that investigated the effects of WP on vascular function were eligible. A total of 720 records were identified in the initial search; from these, sixteen were included in our systematic review and thirteen in meta-analysis. The pooled analysis of six studies showed a significant increase in flow-mediated dilation (FMD) after WP consumption (weighted mean differences (WMD): 1·09 %, 95 % CI: 0·17, 2·01, P= 0·01). Meta-analysis of available data did not show any significant reduction in arterial stiffness measures including augmentation index (effect sizes: 7, WMD: −0·29 %, 95 % CI: −1·58, 0·98, P= 0·64) and pulse wave velocity (effect sizes: 4, WMD: −0·72 m/s, 95 % CI: −1·47, 0·03, P= 0·06). Moreover, the pooled analysis of six effect sizes showed no significant effects on plasma levels of nitric oxide following WP supplementation (WMD: 0·42 μmol/l, 95 % CI: −0·52, 1·36, P= 0·38). The overall results provided evidence supporting a protective effect of WP on endothelial function measured by FMD, but not for arterial stiffness measures and circulatory biomarker of vascular function. Further research is required to substantiate the benefits of WP on vascular function.

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central haemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed cross-sectional analysis of 381 non-smoking healthy older adults (mean age 66·0 (sd 4·1) years; BMI, 26·4 (sd 4·41) kg/m2; 41 % male) recruited as part of the Australian Research Council Longevity Intervention study. Flavonoid intake (i.e. flavonols, flavones, flavanones, anthocyanins, isoflavones, flavan-3-ol monomers, proanthocyanidins, theaflavins/thearubigins and total consumption) was estimated from FFQ using the US Department of Agriculture food composition databases. Measures of central haemodynamics and arterial stiffness included systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean arterial pressure (cMAP) and augmentation index (cAIx). After adjusting for demographic and lifestyle confounders, each sd/d higher intake of anthocyanins ((sd 44·3) mg/d) was associated with significantly lower cDBP (−1·56 mmHg, 95 % CI −2·65, −0·48) and cMAP (−1·62 mmHg, 95 % CI −2·82, −0·41). Similarly, each sd/d higher intake of flavanones ((sd 19·5) mg/d) was associated with ~1 % lower cAIx (−0·93 %, 95 % CI −1·77, −0·09). These associations remained significant after additional adjustment for (1) a dietary quality score and (2) other major nutrients that may affect blood pressure or arterial stiffness (i.e. Na, K, Ca, Mg, n-3, total protein and fibre). This study suggests a possible benefit of dietary anthocyanin and flavanone intake on central haemodynamics and arterial stiffness; these findings require corroboration in further research.

Emerging CVD risk factors (e.g. HDL function and central haemodynamics) may account for residual CVD risk experienced by individuals who meet LDL-cholesterol and blood pressure (BP) targets. Recent evidence suggests that these emerging risk factors can be modified by polyphenol-rich interventions such as soya, but additional research is needed. This study was designed to investigate the effects of an isoflavone-containing soya protein isolate (delivering 25 and 50 g/d soya protein) on HDL function (i.e. ex vivo cholesterol efflux), macrovascular function and blood markers of CVD risk. Middle-aged adults (n 20; mean age=51·6 (sem 6·6) years) with moderately elevated brachial BP (mean systolic BP=129 (sem 9) mmHg; mean diastolic BP=82·5 (sem 8·4) mmHg) consumed 0 (control), 25 and 50 g/d soya protein in a randomised cross-over design. Soya and control powders were consumed for 6 weeks each with a 2-week compliance break between treatment periods. Blood samples and vascular function measures were obtained at baseline and following each supplementation period. Supplementation with 50 g/d soya protein significantly reduced brachial diastolic BP (−2·3 mmHg) compared with 25 g/d soya protein (Tukey-adjusted P=0·03) but not the control. Soya supplementation did not improve ex vivo cholesterol efflux, macrovascular function or other blood markers of CVD risk compared with the carbohydrate-matched control. Additional research is needed to clarify whether effects on these CVD risk factors depend on the relative health of participants and/or equol producing capacity.

The lower threshold plasma 25-hydroxy vitamin D (25(OH)D) level for optimal cardiovascular health is unclear, whereas the toxicity threshold is less clear. The aim of this study was to examine the cardiovascular–vitamin D dose–response curve in a normal rat model. Doses of cholecalciferol ranged from deficiency to toxic levels (equivalent to human doses of 0, 0·015, 0·25 and 3·75mg/d) for 4 weeks, and then cardiovascular health was examined using blood pressure telemetry and high-resolution ultrasound in normal male rats (n 16/group, 64 rats total). After 1 month, only the 0·25mg/d group had plasma 25(OH)D that was within current recommended range (100–125 nmol/l), and all groups failed to change plasma Ca or phosphate. Systolic blood pressure increased significantly (10–15 mmHg) in the rat groups with plasma 25(OH)D levels at both 30 and 561 nmol/l (groups fed 0 and 3·75mg/d) compared with the group fed the equivalent to 0·015mg/d (43 nmol/l 25(OH)D). Although not significant, the group fed the equivalent to 0·25mg/d (108 nmol/l 25(OH)D) also showed a 10 mmHg increase in systolic blood pressure. Carotid artery diameter was significantly smaller and wall thickness was larger, leading to higher peak carotid systolic blood velocity in these two groups. Despite these vascular changes, cardiac function did not differ among treatment groups. The key finding in this study is that arterial stiffness and systolic blood pressure both showed a U-shaped dose–response for vitamin D, with lowest values (best cardiovascular health) observed when plasma 25(OH)D levels were 43 nmol/l in normal male rats.

Whether supplemental Ca has similar effects to dietary Ca on vascular and bone markers is unknown. The present trial investigated the feasibility of applying dietary and supplemental interventions in a randomised-controlled trial (RCT) aiming to estimate the effect of supplemental Ca as compared with dietary Ca on vascular and bone markers in postmenopausal women. In total, thirteen participants were randomised to a Ca supplement group (CaSuppl) (750 mg Ca from CaCO3+450 mg Ca from food+20 µg vitamin D supplement) or a Ca diet group (CaDiet) (1200 mg Ca from food+10 µg vitamin D supplement). Participants were instructed on Ca consumption targets at baseline. Monthly telephone follow-ups were conducted to assess adherence to interventions (±20 % of target total Ca) using the multiple-pass 24-h recall method and reported pill count. Measurements of arterial stiffness, peripheral blood pressure and body composition were performed at baseline and after 6 and 12 months in all participants who completed the trial (n 9). Blood and serum biomarkers were measured at baseline and at 12 months. Both groups were compliant to trial interventions (±20 % of target total Ca intake; pill count ≥80 %). CaSuppl participants maintained a significantly lower average dietary Ca intake compared with CaDiet participants throughout the trial (453 (sd 187) mg/d v. 1241 (sd 319) mg/d; P<0·001). There were no significant differences in selected vascular outcomes between intervention groups over time. Our pilot trial demonstrated the feasibility of conducting a large-scale RCT to estimate the differential effects of supplemental and dietary Ca on vascular and bone health markers in healthy postmenopausal women.

Combined isometric exercise or metaboreflex activation (post-exercise muscle ischaemia (PEMI)) and cold pressor test (CPT) increase cardiac afterload, which may lead to adverse cardiovascular events. l-Citrulline supplementation (l-CIT) reduces systemic arterial stiffness (brachial-ankle pulse wave velocity (baPWV)) at rest and aortic haemodynamic responses to CPT. The aim of this study was to determine the effect of l-CIT on aortic haemodynamic and baPWV responses to PEMI+CPT. In all, sixteen healthy, overweight/obese males (age 24 (sem 6) years; BMI 29·3 (sem 4·0) kg/m2) were randomly assigned to placebo or l-CIT (6 g/d) for 14 d in a cross-over design. Brachial and aortic systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP), aortic augmented pressure (AP), augmentation index (AIx), baPWV, reflection timing (Tr) and heart rate (HR) were evaluated at rest and during isometric handgrip exercise (IHG), PEMI and PEMI+CPT at baseline and after 14 d. No significant effects were evident after l-CIT at rest. l-CIT attenuated the increases in aortic SBP and wave reflection (AP and AIx) during IHG, aortic DBP, MAP and AIx during PEMI, and aortic SBP, DBP, MAP, AP, AIx and baPWV during PEMI+CPT compared with placebo. HR and Tr were unaffected by l-CIT in all conditions. Our findings demonstrate that l-CIT attenuates aortic blood pressure and wave reflection responses to exercise-related metabolites. Moreover, l-CIT attenuates the exaggerated arterial stiffness response to combined metaboreflex activation and cold exposure, suggesting a protective effect against increased cardiac afterload during physical stress.

Specific gene polymorphisms are known to be associated with a different arterial physiology in the younger generation. The present study found that young Russians with the matrix metalloproteinase 3 6A/6A and γ-glutamyltransferase 1AA genotypes have lower levels of the cardio-ankle vascular index – a recent measure of arterial stiffness. This observation may serve as an additional tool for cardiovascular disease prevention in the young population.

The cardio-ankle vascular index is a measure of arterial stiffness, whereas oxidative stress underlies arterial pathology. This study aimed to investigate the association between the cardio-ankle vascular index and antioxidant-related gene polymorphisms in young Russians. A total of 89 patients (mean age, 21.6 years) were examined by the cardio-ankle vascular index and for 15 gene polymorphisms related to antioxidant enzymes including FMO3 (flavin-containing monooxygenase 3), GPX1 (glutathione peroxidase 1), and GPX4 (glutathione peroxidase 4). A higher cardio-ankle vascular index level was detected in carriers with the KK-genotype of FMO3 polymorphism rs2266782 than in those without (mean levels: 6.2 versus 5.6, respectively, p<0.05). Similarly, a higher cardio-ankle vascular index level was seen in carriers with the CC-genotype of GPX4 polymorphism rs713041 than in those without (6.0 versus 5.5, respectively, p<0.05). We did not observe significant associations between the cardio-ankle vascular index levels and the other gene polymorphisms. Although carriers with the LL-genotype of GPX1 polymorphism rs1050450 showed a higher diastolic blood pressure level than those without, the polymorphism did not affect the cardio-ankle vascular index level. This study showed a significant association between rs2266782 and rs713041 polymorphisms and arterial stiffness, as measured by the cardio-ankle vascular index, in young Russians. The pathways utilised by antioxidant enzymes may be responsible for early arterial stiffening in the Russian population.

Endothelial dysfunction and arterial stiffness are early predictors of CVD. Intervention studies have suggested that diet is related to vascular health, but most prior studies have tested individual foods or nutrients and relied on small samples of younger adults. The purpose of the present study was to examine the relationships between adherence to the 2010 Dietary Guidelines for Americans and vascular health in a large cross-sectional analysis. In 5887 adults in the Framingham Heart Study Offspring and Third Generation cohorts, diet quality was quantified with the 2010 Dietary Guidelines Adherence Index (DGAI-2010). Endothelial function was assessed via brachial artery ultrasound and arterial stiffness via arterial tonometry. In age-, sex- and cohort-adjusted analyses, a higher DGAI-2010 score (greater adherence) was modestly associated with a lower resting flow velocity, hyperaemic response, mean arterial pressure, carotid–femoral pulse wave velocity (PWV), and augmentation index, but not associated with resting arterial diameter or flow-mediated dilation (FMD). In multivariable models adjusting for cardiovascular risk factors, only the association of a higher DGAI-2010 score with a lower baseline flow velocity and augmentation index persisted (β = − 0·002, P= 0·003 and β = − 0·05 ± 0·02, P< 0·001, respectively). Age-stratified multivariate-adjusted analyses suggested that the relationship of higher DGAI-2010 scores with lower mean arterial pressure, PWV and augmentation index was more pronounced among adults younger than 50 years. Better adherence to the 2010 Dietary Guidelines for Americans, particularly in younger adults, is associated with a lower peripheral blood flow velocity and arterial wave reflection, but not FMD. The present results suggest a link between adherence to the Dietary Guidelines and favourable vascular health.

Studies on the associations of dietary Ca and vitamin D intakes with arterial stiffness are scarce. In the present study, these associations were evaluated in Japanese men. Data from a total of 535 eligible men, aged 35–69 years, who participated in the baseline survey of a cohort study in Tokushima Prefecture, Japan, and underwent brachial–ankle pulse wave velocity (ba-PWV) measurements were analysed. ba-PWV is a measure of arterial stiffness and is recognised as a marker of atherosclerotic vascular damage. Information regarding the cohort's lifestyle characteristics including dietary behaviour over the past year was obtained from a structured self-administered questionnaire. Dietary Ca and vitamin D intakes were adjusted for total energy intake using the residual method and divided into quartiles; the highest quartile was used as the reference. General linear models were used to evaluate the associations between dietary Ca and vitamin D intakes and ba-PWV values adjusted for probable covariates. The association between dietary Ca intake and ba-PWV was further evaluated using similar general linear models stratified by dietary vitamin D intake (median or below/above median). Dietary Ca intake was found to be significantly inversely associated with ba-PWV after adjusting for probable covariates (P for trend = 0·020). However, no such association was observed between dietary vitamin D intake and ba-PWV. The inverse association between dietary Ca intake and ba-PWV was striking in subjects with higher dietary vitamin D intake. However, no association was found in subjects with lower dietary vitamin D intake. These results indicate that adequate dietary Ca and vitamin D intakes may be protective against the development of arterial stiffness in Japanese men.

Recent studies have shown that a low birth weight is a risk factor for increased systemic blood pressure (BP) in adulthood. Further, systemic BP and arterial stiffness (AS) are reported to be increased in adolescents born prematurely. The purpose of this study was to characterize systemic BP and AS in young adults born preterm. Systemic BP was measured using an automated oscillometric device. AS was assessed by measuring the right carotid–radial pulse wave velocity (PWV) using a validated non-invasive automated method. Systemic BP, pulse pressure, and PWV [mean (confidence intervals)] were compared between 16 adults (age 21 years) born preterm (age at birth 32 weeks of gestation) with a birth weight (1710 g) appropriate for their gestational age and 15 adults (21 years) born at term (40 weeks of gestation) with a birth weight (3430 g) appropriate for their gestational age. Adults born preterm had a significantly higher systolic BP [122 mmHg (114–144) v. 112 (106–127)], mean BP [89 mmHg (86–98) v. 84 (81–91)], diastolic BP [69 mmHg (66–76) v. 65 (62–78)], pulse pressure [54 mmHg (47–72) v. 47 (42–60)], and PWV [7 m/s (6.3–8.6) v. 6.4 (5.8–8)] than did those born at term. Our findings suggest that young adults with a low birth weight due to preterm birth have increased systemic BP and AS. Accordingly, preterm birth may predispose individuals to cardiovascular diseases in adulthood due to increased AS.

The first Hungarian Twin Registry was established in Budapest in 1970 through the mandatory reporting of multiple-births. In the 1980s a second, volunteer adult registry was also founded. Unfortunately, both registries ceased to exist in the 1990s. Efforts started in 2006 to revive a Hungarian twin registry. The team spearheading this effort reports here on this progress. Currently, the voluntary Hungarian Twin Registry consists of 310 adult twin pairs and multiplets. Current research focuses on cardiovascular and respiratory health and yielded multiple awards and publications. Efforts are on the way to expand into social, psychological, and obesity studies.

We assessed vascular programming in genetically identical monochorionic twin pairs with twin-to-twin transfusion syndrome (TTTS) treated differently in utero by serial amnioreduction or fetal laser arterial photocoagulation. This case–control study re-assessed four twin groups at median 11 years comprising 20 pairs of monochorionic diamniotic twins: nine treated by amnioreduction (TTTS-amnio) and eleven by laser (TTTS-laser) with seven monochorionic and six dichorionic control pairs. Outcome measures were current blood pressure (BP), brachio-radial arterial stiffness derived from pulse wave velocity (PWV), resting microcirculation (Flux) and response to heating and post-occlusive reactive hyperaemia measured using laser Doppler. Potential confounders [PWV and BP at first study, current height, weight, heart rate and twin type (ex-recipient, ex-donor or heavier/lighter of pair)] were accounted for by Mixed Linear Models statistical methodology. PWV dichorionic > monochorionic (P = 0.024); systolic and diastolic BP dichorionic > TTTS-amnio and TTTS-laser (P = 0.004, P = 0.02 and P = 0.005, P = 0.02, respectively). Within-twin pair pattern of PWV discordance was similar in laser treated and dichorionic controls (heavier-born > lighter), opposite to TTTS-amnio and monochorionic controls. Flux monochorionic > dichorionic (P = 0.044) and heavier > lighter-born (P = 0.024). TTTS-laser and dichorionic diamniotic showed greatest hyperaemic responses (dichorionic > TTTS-amnio or monochorionic controls (P = 0.007, P = 0.025). Hyperaemic responses were slower in heavier-born twins (P = 0.005). In summary, monochorionic twins had lower BP, arterial stiffness and increased resting vasodilatation than dichorionic twins implying shared fetal circulation affects vascular development. Vascular responses in laser-TTTS were similar to dichorionic and opposite to TTTS-amnio suggesting a lasting effect of fetal therapy on vascular health.

Background: Our research group recently reported that aorto-radial (radial) and aorto-dorsalis-pedis (foot) pulse wave velocity (PWV) as proxies of arterial stiffness are substantially heritable in healthy youth. This article aimed at uncovering the genetic contributions of adhesion molecules, key members in the inflammatory process, to PWV in these young individuals. Methods: Radial and foot PWV were noninvasively measured with applanation tonometry in 702 black and white subjects (42% blacks, mean age 17.7 ± 3.3 years) from the Georgia Cardio vascular Twin Study. Eight functional polymorphisms from genes for E-selectin (SELE), P-selectin (SELP), intercellular adhesion molecules-1 (ICAM1), and vascular cell adhesion molecules-1 (VCAM1) were genotyped. Results: Youth with Ser290Asn or Asn290Asn genotype (SELP) compared to those with Ser290Ser had an increase in both radial and foot PWV (6.61 ± 0.07 vs. 6.41 ± 0.05 m/s, p = .026; 7.22 ± 0.05 vs. 7.04 ± 0.04 m/s, p = .007). TT homozygotes of rs2244529 (SELP) had higher foot PWV (7.28 ± 0.07 vs. 7.06 ± 0.03 m/s, p = .002) than CT heterozygotes and CC homozygotes. There appeared to be a decrease in foot PWV in youth with the 241Arg allele (ICAM1) as compared to those without (6.96 ± 0.08 vs. 7.14 ± 0.03 m/s, p = .005). For the Asp693Asp (C to T) polymorphism (VCAM1), CC genotype had higher foot PWV than CT and TT genotypes (7.18 ± 0.04 vs. 6.95 ± 0.06 m/s, p < .0001). There was an epistatic interaction between Ser290Asn, Gly241Arg, and Asp693Asp on foot PWV (p = .017), explaining 3.6% variance of the foot PWV. Conclusion: Genetic variation of adhesion molecules may be implicated in the development of arterial stiffness. Screening for adhesion molecule polymorphisms may help identify high-risk youth.

Fish oils, rich in long-chain n-3 PUFA, are known to reduce various risk factors for CVD. However, conclusive evidence regarding the benefits of n-3 on arterial stiffness, a risk factor for CVD, has not yet been established. Consequently, we conducted the first study aimed to quantify the effects of n-3 supplementation on arterial stiffness through meta-analysis. Multiple databases and clinical trial registries were systematically searched up until September 2010 for randomised and controlled adult human clinical trials to investigate the effects of long-chain n-3 fatty acids on arterial stiffness. No limits were set on dosage sizes or sample characteristics. A total of ten n-3 trials met the final inclusion criteria; four using pulse wave velocity (PWV) and six using arterial compliance, measured as capacitive compliance or systemic arterial compliance, as respective outcome measures. Meta-analysis revealed that n-3 was statistically significant in effectively improving both PWV (g = 0·33; 95 % CI 0·12, 0·56; P < 0·01) and arterial compliance (g = 0·48; 95 % CI 0·24, 0·72; P < 0·001). There was no evidence of heterogeneity or publication bias. Results were not influenced by changes in blood pressure, heart rate or BMI. The findings of the present study reveal that supplementation with n-3 offers a scientifically supported means of reducing arterial stiffness. Reduction in arterial stiffness by n-3 may account for some of its purported cardioprotective effects.

K-rich fruit and vegetables may lower blood pressure (BP) and improve vascular function. A randomised controlled trial (ISRCTN50011192) with a cross-over design was conducted in free-living participants with early stages of hypertension (diastolic BP>80 and < 100 mmHg, not receiving BP-lowering medication) to test this hypothesis. Following a 3-week run-in period on a control diet, each subject completed four dietary 6-week dietary interventions (control+placebo capsules, an additional 20 or 40 mmol K+/d from fruit and vegetables or 40 mmol potassium citrate capsules/d) using a Latin square design with a washout period ≥ 5 weeks between the treatment periods. Out of fifty-seven subjects who were randomised, twenty-three male and twenty-five female participants completed the study; compliance to the intervention was corroborated by food intake records and increased urinary K+ excretion; plasma lipids, vitamin C, folate and homocysteine concentrations, urinary Na excretion, and body weight remained were unchanged. On the control diet, mean ambulatory 24 h systolic/diastolic BP were 132·3 (sd 12·0)/81·9 (sd 7·9) mmHg, and changes (Bonferroni's adjusted 95 % CI) compared with the control on the diets providing 20 and 40 mmol K+/d as fruit and vegetables were 0·8 ( − 3·5, 5·3)/0·8 ( − 1·9, 3·5) and 1·7 ( − 3·0, 5·3)/1·5 ( − 1·5, 4·4), respectively, and were 1·8 ( − 2·1, 5·8)/1·4 ( − 1·6, 4·4) mmHg on the 40 mmol potassium citrate supplement, and were not statistically significant. Arterial stiffness, endothelial function, and urinary and plasma isoprostane and C-reactive protein (CRP) concentrations did not differ significantly between the diets. The present study provides no evidence to support dietary advice to increase K intake above usual UK intakes in the subjects with early stages of hypertension.