Improvement In Vascular Function Research Articles

Chronic administration of sildenafil improves endothelial function in spontaneously hypertensive rats by decreasing COX-2 expression and oxidative stress

AimsSpontaneously hypertensive rats (SHR) exhibit impaired endothelial vasodilation and enhanced vasoconstriction. The phosphodiesterase 5 (PDE5) inhibitor sildenafil (Sild) potentiates the nitric oxide (NO)-mediated effects exerting antioxidative and anti-inflammatory actions. In the present study, we hypothesized that Sild could improve endothelial function in SHR. Materials and methodsMale rats were treated daily for 60 days by oral gavage with Sild (45 mg/kg) before the onset of the hypertensive state (pre-hypertensive protocol). The aortic relaxation to acetylcholine (ACh), sodium nitroprusside (SNP) and the phenylephrine (Phe)-induced contraction was evaluated in SHR. Protein expression of eNOS, p-eNOS, caveolin, COX-1, COX-2, ERK and p-ERK was measured by Western blot. Key findingsResting blood pressure was not modified by Sild administration. Treatment with Sild did not alter the relaxation response to SNP but improved the ACh-induced relaxation and reduced Phe-induced contraction in aortic rings from SHR. This protective effect of Sild could be attributed to reduced superoxide anions (O2−) generation, cyclooxygenase type 2 (COX-2) protein downregulation and increased NO bioavailability. SignificanceSild improves endothelial function in SHR aorta without affecting resting blood pressure values. These results indicate that PDE5 inhibition has a potential role in the improvement of vascular function and could be an adjuvant in the treatment of essential hypertension.

Differential effects of inhibition of interleukin 1 and 6 on myocardial, coronary and vascular function.

Anakinra, an interleukin-1 receptor antagonist and tocilizumab, an interleukin-6 receptor blocker, are used for the treatment of rheumatoid arthritis. We investigated the differential effects of anakinra and tocilizumab on myocardial and vascular function in an atherosclerosis model of patients with rheumatoid arthritis. 120 patients with rheumatoid arthritis were randomized to anakinra (n = 40), tocilizumab (n = 40) or prednisolone (n = 40) for 3 months. Primary outcome measure was the change of left ventricular longitudinal strain after 3months of treatment. Additionally, we measured coronary flow reserve, flow-mediated dilatation of the brachial artery, carotid-femoral pulse wave velocity, malondialdehyde and protein carbonyls as oxidative stress markers and C-reactive protein blood levels at baseline and post-treatment. At baseline, patients among the three treatment arms had similar age, sex, disease activity score and atherosclerotic risk factors. Compared with baseline, all patients had improved longitudinal strain (- 16% vs. - 17.8%), coronary flow reserve (2.56 vs. 2.9), malondialdehyde (2.0 vs. 1.5µM/L), protein carbonyls (0.0132 vs. 0.0115nmol/mg), and C-reactive protein post-treatment. In all patients, the percent decrease of malondialdehyde was correlated with percent increase of longitudinal strain (p < 0.001). Compared with tocilizumab and prednisolone, anakinra treatment resulted in a greater improvement of longitudinal strain (18.7% vs. 9.7% vs. 6%) and coronary flow reserve (29% vs. 13% vs. 1%), while pulse wave velocity and brachial blood pressure were improved only after tocilizumab treatment (11 ± 3 vs. 10.3 ± 2m/s p < 0.05 for all comparisons). Anakinra is associated with an improvement in cardiac function and tocilizumab with improvement in vascular function. URL: https:// http://www.clinicaltrials.gov . Unique identifier: NCT03288584.

Circulating Anthocyanin Metabolites Mediate Vascular Benefits of Blueberries: Insights From Randomized Controlled Trials, Metabolomics, and Nutrigenomics.

Potential health benefits of blueberries may be due to vascular effects of anthocyanins that predominantly circulate in blood as phenolic acid metabolites. We investigated which role blueberry anthocyanins and circulating metabolites play in mediating improvements in vascular function and explore potential mechanisms using metabolomics and nutrigenomics. Purified anthocyanins exerted a dose-dependent improvement of endothelial function in healthy humans, as measured by flow-mediated dilation. The effects were similar to those of wild blueberries containing similar amounts of anthocyanins, whereas control drinks containing fiber, minerals, or vitamins had no significant effect. Daily 1-month wild blueberry consumption increased flow-mediated dilation and lowered 24-hour ambulatory systolic blood pressure. Of the 63 anthocyanin plasma metabolites quantified, 14 and 21 correlated with acute and chronic flow-mediated dilation improvements, respectively. Injection of these metabolites improved flow-mediated dilation in mice. Daily wild blueberry consumption led to differential expression (>1.2-fold) of 608 genes and 3 microRNAs, with Mir-181c showing a 13-fold increase in peripheral blood mononuclear cells. Patterns of 13 metabolites were independent predictors of gene expression changes and pathway enrichment analysis revealed significantly modulated biological processes involved in cell adhesion, migration, immune response, and cell differentiation. Our results identify anthocyanin metabolites as major mediators of vascular bioactivities of blueberries and changes of cellular gene programs. Trial registration: NCT025208.

Vitamin D supplementation for the improvement of vascular function in patients with chronic kidney disease: a meta-analysis of randomized controlled trials

The efficacy of vitamin D on vascular function remains controversial in chronic kidney disease (CKD) patients. The aim of the present work was to perform a meta-analysis of randomized controlled trials to evaluate the efficacy of vitamin D on vascular function in CKD patients. We searched Medline, the Cochrane Central Register of Controlled Trials, Embase, the Science Citation Index, and clinical trial registries for randomized controlled trials comparing vitamin D with a placebo in CKD patients. We included seven trials. For flow-mediated dilation (FMD), there was no significant difference between the two groups (WMD 1.66%; 95% CI - 0.2 to 3.51, p = 0.08; with significant heterogeneity, p < 0.0001, I2 = 89%). We conducted a subgroup analysis. In the cholecalciferol group, compared with the placebo group, cholecalciferol significantly increased FMD (WMD 5.49%; 95% CI 4.36-6.62, p < 0.0001). In the 2ug paricalcitol group, compared with the placebo group, paricalcitol significantly increased FMD (WMD 2.09%; 95% CI 1.28-2.9, p < 0.0001; without significant heterogeneity, p = 0.47, I2 = 0%). In the 1 ug paricalcitol group, there was no significant difference between the two groups. For pulse wave velocity (PWV), vitamin D significantly decreased PWV compared with the placebo (WMD - 0.93m/s; 95% CI - 1.71 to - 0.15, p = 0.02; without significant heterogeneity, p = 0.14, I2 = 45%). For calcium (Ca) and parathyroid hormone (PTH), there was a significant difference between the vitamin D group and the placebo group. For 25-hydroxyvitamin D [25(OH)D], there was a significant difference between the inactive vitamin D group and the placebo group. For phosphorus (P), systolic blood pressure (SBP), and diastolic blood pressure (DBP), there were no significant differences between the two groups. We speculate that vitamin D might be able to improve vascular function in CKD patients. The effect of vitamin D might be associated with its doses and earlier stages of the disease might respond better to vitamin D. Furthermore, trials with larger populations and longer durations are needed in order to provide more reliable evidence.

The Effects of Nut Consumption on Vascular Function.

Vascular stiffness can be measured using numerous techniques including assessments of central haemodynamics, aortic arterial stiffness, and indices of aortic wave reflection and endothelial dilatation. Impaired vascular function is associated with increased risk of cardiovascular disease (CVD). Epidemiological studies indicate that regular nut consumption reduces CVD risk, with one of the proposed mechanisms being via improvements in vascular function. This narrative review summarizes the evidence from a systematic search of the literature of the effects of tree nut and peanut consumption on measures of vascular function excluding flow mediated dilatation. A total of 16 studies were identified, with a mix of acute controlled studies (n = 3), an uncontrolled pre/post chronic study (n = 1), chronic crossover (n = 7) and parallel studies (n = 5). Nut types tested included almonds, peanuts, pine nuts, pistachios and walnuts, with dose and length of supplementation varying greatly across studies. Most studies (n = 13) included individuals at risk for CVD, according to various criteria. Findings were inconsistent, with ten studies reporting no significant changes in vascular function and six studies (one acute and five chronic studies) reporting improvements in at least one measure of vascular function. In summary, nuts have the potential to improve vascular function and future studies should consider the population, dose and length of nut supplementation as well as suitability of the different vascular function techniques.

Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial

ABSTRACTBackgroundFlavanols are an important class of food bioactives that can improve vascular function even in healthy subjects. Cocoa flavanols (CFs) are composed principally of the monomer (−)-epicatechin (∼20%), with a degree of polymerisation (DP) of 1 (DP1), and oligomeric procyanidins (∼80%, DP2–10).ObjectiveOur objective was to investigate the relative contribution of procyanidins and (−)-epicatechin to CF intake–related improvements in vascular function in healthy volunteers.DesignIn a randomized, controlled, double-masked, parallel-group dietary intervention trial, 45 healthy men (aged 18–35 y) consumed the following once daily for 1 mo: 1) a DP1–10 cocoa extract containing 130 mg (−)-epicatechin and 560 mg procyanidins, 2) a DP2–10 cocoa extract containing 20 mg (−)-epicatechin and 540 mg procyanidins, or 3) a control capsule, which was flavanol-free but had identical micro- and macronutrient composition.ResultsConsumption of DP1–10, but not of either DP2–10 or the control capsule, significantly increased flow-mediated vasodilation (primary endpoint) and the concentration of structurally related (−)-epicatechin metabolites (SREMs) in the circulatory system while decreasing pulse wave velocity and blood pressure. Total cholesterol significantly decreased after daily intake of both DP1–10 and DP2–10 as compared with the control.ConclusionsCF-related improvements in vascular function are predominantly related to the intake of flavanol monomers and circulating SREMs in healthy humans but not to the more abundant procyanidins and gut microbiome–derived CF catabolites. Reduction in total cholesterol was linked to consumption of procyanidins but not necessarily to that of (−)-epicatechin. This trial was registered at clinicaltrials.gov as NCT02728466.

Comparison of the effects of exercise and anti-TNF treatment on cardiovascular health in rheumatoid arthritis: results from two controlled trials

People with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease (CVD). Both pharmacological treatment and exercise are suggested in the management of CVD risk in RA. This study explored the effects of exercise and anti-TNF treatment on CVD risk in RA. Twenty RA patients (70% female, 50 (10) years) completed a 3-month exercise intervention and 23 RA patients (65% female, 54 (15) years) started anti-TNF treatment. Markers of disease activity, CVD risk, and vascular function were assessed before and after 3-months of intervention/treatment. Both exercise and anti-TNF treatment improved functional ability and fatigue, anti-TNF treatment was more successful in improving inflammation, disease activity, functional ability and pain. Exercise induced a reduction in overall CVD risk and improvement in vascular function, which was significantly different from anti-TNF treatment where no such changes were found. These findings showed that exercise and anti-TNF had differential effects on CVD risk in RA, and should be combined for optimal CVD risk reduction. Whereas anti-TNF treatment is likely to impact on CVD risk through reducing the systemic inflammatory load, exercise should be recommended to people with RA as an effective self-management strategy to reduce CVD risk further. Once RA patients have responded successfully to anti-TNF treatment, increasing exercise should be encouraged to reduce the risk for CVD. Thus, supporting exercise programmes when the disease is controlled, is likely to enhance the uptake and the maintenance of exercise, which will result in additional benefits to cardiovascular health and wellbeing in people with RA.

P11 - Regulation of Heme Oxygenase-1 by Flavonoids: Mechanisms and Health Possibilities

Population studies have shown a strong association between dietary intake of polyphenols and reduced risk of cardiovascular disease. These associations have been confirmed to some extent by intervention studies which have shown improvements in vascular function and blood pressure with certain polyphenols or food extracts rich in polyphenols. The mechanism involved in the bioactivity of dietary polyphenols is still under active investigation. It is unlikely that polyphenols act as antioxidants in vivo. Evidence suggests that dietary polyphenols or their metabolites act as signalling molecules and can increase nitric oxide bioavailability and induce protective enzymes. This talk will outline some of the evidence that dietary polyphenols regulate Hmox-1 and that this is critical for vascular protection by these compounds. The structural features of polyphenols such as flavonoids or their metabolites that are responsible for induction of Hmox-1 will be discussed. This research is providing mechanistic insights into the action of dietary bioactive compounds and expands our understanding of the role of food bioactives in improving health.

Effects of Fragrance Components of Abies holophylla Max. on Stress Relief and Improvement of Vascular Function

Effects of Fragrance Components of Abies holophylla Max. on Stress Relief and Improvement of Vascular Function

A Pilot Trial to Examine the Changes in Carotid Arterial Inflammation in Renal Transplant Recipients as Assessed by 18F-Fluorodeoxyglucose (18F-FDG) Positron Emission Tomography Computed Tomography (PET/CT).

BackgroundInflammatory activity of the artery can be assessed by measuring 18F-fluorodeoxyglucose (18F-FDG) uptake with positron emission tomography computed tomography (PET/CT). Improvement in vascular function after renal transplantation has been reported, but no studies have used 18F-FDG PET/CT to examine the changes in vascular inflammation. This study investigated the changes in the inflammatory activity in the carotid artery after renal transplantation in patients with chronic kidney disease (CKD).Material/Methods18F-FDG PET/CT was performed before and at 4 months after transplantation. We quantified 18F-FDG uptake as the target-to-background ratio (TBR) in the carotid artery in 10 CKD patients. TBR was evaluated in the whole carotid artery (WH) and most-diseased segment (MDS), and the mean and maximum values were analyzed. The concentrations of inflammatory cytokines, including tumor necrosis factor-alpha, interleukin-6, plasminogen activator inhibitor-1, and endothelin-1, were measured.ResultsEight patients showed a decrease in mean or maximum TBR. The average mean or maximum TBRs in the WH and MDS of the right and left arteries were all reduced after transplantation. The average mean TBR for the right WH decreased significantly (% reduction [95% CI]) by −5.74% [−15.37, −0.02] (p=0.047). TBRs did not correlate significantly with cytokine concentrations. The changes in cytokine concentrations after transplantation varied.Conclusions18F-FDG uptake by the WH and MDS tended to reduce after renal transplantation. Therefore, renal transplantation may confer an anti-inflammatory effect on carotid atherosclerosis in patients with CKD; however, this effect is not large enough to be demonstrated in this study with small sample size.

Vascular Function Is Improved After an Environmental Enrichment Program: The Train the Brain-Mind the Vessel Study.

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01725178.

SGLT2 inhibition via dapagliflozin improves generalized vascular dysfunction and alters the gut microbiota in type 2 diabetic mice

BackgroundType 2 diabetes (T2D) is associated with generalized vascular dysfunction characterized by increases in large artery stiffness, endothelial dysfunction, and vascular smooth muscle dysfunction. Sodium glucose cotransporter 2 inhibitors (SGLT2i) represent the most recently approved class of oral medications for the treatment of T2D, and have been shown to reduce cardiovascular and overall mortality. Although it is currently unclear how SGLT2i decrease cardiovascular risk, an improvement in vascular function is one potential mechanism. The aim of the current study was to examine if dapagliflozin, a widely prescribed STLT2i, improves generalized vascular dysfunction in type 2 diabetic mice. In light of several studies demonstrating a bi-directional relation between orally ingested medications and the gut microbiota, a secondary aim was to determine the effects of dapagliflozin on the gut microbiota.MethodsMale diabetic mice (Db, n = 24) and control littermates (Con; n = 23) were randomized to receive either a standard diet or a standard diet containing dapagliflozin (60 mg dapagliflozin/kg diet; 0.006%) for 8 weeks. Arterial stiffness was assessed by aortic pulse wave velocity; endothelial function and vascular smooth muscle dysfunction were assessed by dilatory responses to acetylcholine and sodium nitroprusside, respectively.ResultsCompared to untreated diabetic mice, diabetic mice treated with dapagliflozin displayed significantly lower arterial stiffness (Db = 469 cm/s vs. Db + dapa = 435 cm/s, p < 0.05), and improvements in endothelial dysfunction (area under the curve [AUC] Db = 57.2 vs. Db + dapa = 117.0, p < 0.05) and vascular smooth muscle dysfunction (AUC, Db = 201.7 vs. Db + dapa = 285.5, p < 0.05). These vascular improvements were accompanied by reductions in hyperglycemia and circulating markers of inflammation. The microbiota of Db and Con mice were distinctly different, and dapagliflozin treatment was associated with minor alterations in gut microbiota composition, particularly in Db mice, although these effects did not conclusively mediate the improvements in vascular function.ConclusionsDapagliflozin treatment improves arterial stiffness, endothelial dysfunction and vascular smooth muscle dysfunction, and subtly alters microbiota composition in type 2 diabetic mice. Collectively, the improvements in generalized vascular function may represent an important mechanism underlying the cardiovascular benefits of SGLT2i treatment.

Polyphenols, Antioxidants and the Sympathetic Nervous System.

A high dietary intake of polyphenols has been associated with a reduced cardiovascular mortality, due to their antioxidant properties. However, growing evidence suggests that counteracting oxidative stress in cardiovascular disease might also reduce sympathetic nervous system overactivity. This article reviews the most commonly used techniques to measure sympathetic activity in humans; the role of sympathetic activation in the pathophysiology of cardiovascular diseases; current evidence demonstrating that oxidative stress is involved in the regulation of sympathetic activity and how antioxidants and polyphenols might counteract sympathetic overactivity, particularly focusing on preliminary data from human studies. The main mechanisms by which polyphenols are cardioprotective are related to the improvement of vascular function and their anti-atherogenic effect. Furthermore, a blood pressure-lowering effect was consistently demonstrated in randomized controlled trials in humans, when the effect of flavonoid-rich foods, such as tea and chocolate, was tested. More recent studies suggest that inhibition of sympathetic overactivity might be one of the mechanisms by which these substances exert their cardioprotective effects. Indeed, an increased adrenergic traffic to the vasculature is a major mechanism of disease in a number of cardiovascular and extra-cardiac diseases, including hypertension, obesity, metabolic syndrome and heart failure. A considerable body of evidence, mostly from experimental studies, support the hypothesis that reactive oxygen species might exert sympathoexcitatory effects both at the central and at the peripheral level. Accordingly, supplementation with antioxidants might reduce adrenergic overdrive to the vasculature and blunt cardiovascular reactivity to stress. While supplementation with "classical" antioxidants such as ROS-scavengers has many limitations, increasing the intake of polyphenol-rich foods seems to be a promising novel therapeutic strategy to reduce the deleterious effects of increased adrenergic tone, particularly in essential hypertension.

Blood Pressure and Vascular Function in Hypertensive Individuals: Partitioning cause and effect

IntroductionVascular dysfunction is a hallmark of hypertension and contributes to an increased risk of cardiovascular disease. Pharmacological interventions to treat hypertension generally result in improved blood pressure status and concomitant improvements in vascular function. However, recent findings have challenged this notion as vascular dysfunction appears to persist despite blood pressure control with antihypertensive medications. Importantly, medications differ in their vasoactive properties and may have direct effects on the vasculature independent of their impact on blood pressure. Therefore, it is difficult to discern if the potential improvements in vascular function are associated with lower blood pressure or a direct effect on vascular function. Utilizing the dietary approach of salt restriction this study examined the impact of reducing blood pressure on vascular function and peripheral hemodynamics in individuals with essential hypertension.MethodsHypertensive adults (male n=14, female n=8, 50±10 yr) completed two dietary phases: liberal sodium (LS) (200 mmol/d) followed by restricted sodium (RS) (10 mmol/day) diet for five days, respectively. Antihypertensive medications were withdrawn 2 weeks before the first intervention. Following each dietary phase, measurements of systolic (SBP), diastolic (DBP), and mean arterial blood pressure (MAP), arterial diameter and blood velocity (Doppler ultrasound) were assessed at rest, during brachial artery (BA) flow mediated dilation (FMD), and during progressive handgrip (HG) exercise performed at 15, 30 and 45% of maximal voluntary contraction (MVC).ResultsRS significantly lowered SBP (LS: 140±3, RS: 123±3 mmHg), DBP (LS: 85±2, RS: 79±2 mmHg) and MAP (LS: 103±2, RS: 94±2 mmHg) (all p&lt;0.05). Despite improvements in blood pressure, conduit artery function, as measured by FMD, was similar between conditions (LS: 4.6±0.4%; RS: 5.1±0.5%). Similarly, the hyperemic response during FMD, an assessment of microvascular function, was not different between conditions (LS: 548±43; RS: 615±44 ml). During HG exercise, MAP was lower at all exercise intensities during RS compared to LS (15% MVC; LS: 109±2 vs. RS: 102±2 mmHg; 30% MVC; LS: 113±2 vs. RS: 105±2 mmHg; 45% MVC; LS: 122±3 vs. RS: 112±3 mmHg) while vascular conductance and BA vasodilation were not different between LS and RS (p&gt;0.05).ConclusionDespite improvements in blood pressure at rest and during exercise, both conduit artery and microvascular function measured during FMD and HG exercise‐induced vasodilation were not improved. These findings support recent evidence that vascular dysfunction persists in individuals with hypertension independent of blood pressure status.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Passive mobilization‐induced vascular function adaptations in bedridden oldest‐old.

BackgroundWith aging, vascular function (VF) declines. Furthermore, a conspicuous number of oldest‐old individuals are in chronically bedridden, and literature indicates that chronic immobility exacerbates VF decline. Although studies have suggested that passive mobilization of the limbs (PM) may improve local VF, the effect of PM on nitric oxide (NO)‐mediated VF has not been studied yet.AimTo determine whether PM is effective to counteract VF worsening in bedridden oldest‐old. We hypothesized that bedridden patients who underwent a month of PM would have gained significant improvement in NO‐mediated VF.MethodsTwenty bedridden individuals (86±7 yrs) were randomly assigned to PM or control (CT) group, treated with standard therapies only. PM groups underwent a program of 30 min of passive knee (flexo‐extension) mobilization (4‐week, twice a day/5 days a week) in addition to their standard therapies. Ight before, right after and a month after the treatment, NO‐mediated VF was measured by means of single passive limb movement (sPLM) test.ResultsAll PM patients completed all sessions. Concerning sPLM test, right after the treatment PM group improved significantly sPLMpeak (+33%), ΔPLM (+55%), as well as Area Under the Curve (AUC, +200%). However, a month after the treatment, all the assessed parameters have returned close to basal levels. CT group did not exhibit any change in VF.ConclusionResults suggest that the reduction in VF exhibited in chronically bedridden oldest‐old individuals can be reversed by a PM program. Whether performed continously, PM seems to be an effective strategy to counteract the deleterious effects of bedridden on VF.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

A proposed staging system for CLN3 disease (juvenile Batten disease)

Major depression is associated with endothelial dysfunction and arterial stiffening, which may mediate development of hypertension and increased cardiovascular risk. The effect of response to antidepressant treatment on these vascular parameters has not been elucidated.We aimed to assess the net effect of antidepressant therapy on endothelial function and arterial stiffness in patients with psychotic depression.Thirty-seven patients with major psychotic depression, according to DSM-IV-TR, were treated with titrated citalopram 20–60 mg and risperidone 0.5–1 mg and were followed for 6 months. Twelve additional patients who denied treatment, or were non-compliant, were also followed for the same time period. Vascular function was assessed by flow-mediated dilatation (FMD), carotid-femoral pulse wave velocity (PWV) and augmentation index (AI), at baseline and at the end of follow-up.Aortic and peripheral blood pressure (BP), PWV, FMD and AI (p < 0.05 for all) were significantly improved in the group that received treatment. Overall, only responders to treatment (n = 24) presented significant improvements in all hemodynamic and vascular parameters (p < 0.05 for all), irrespectively of traditional cardiovascular risk factors (TRFs), vasoactive medication and BP lowering. In a secondary analysis, patients with psychotic depression presented worse endothelial function as compared to controls matched for TRFs.Non-randomized study.Patients who respond to therapy for major psychotic depression present sustained improvement in vascular function. Given that depressed patients are considered to be at high cardiovascular risk and are often non-compliant with treatment, further research to assess cardiovascular benefits of vigilant monitoring of antidepressant therapy is warranted.

The Effects of Chronic Aerobic Exercise on Cardiovascular Risk Factors in Persons with Diabetes Mellitus.

Aerobic exercise training is a component of diabetes mellitus (DM) care guidelines due to its favorable effects on glycemic control and cardiovascular disease (CVD) risk factors. The purpose of this review is to outline the recent evidence regarding the clinical effects of chronic aerobic exercise on CVD risk factors in persons with DM and to compare the effects of varying intensities and types of exercise. Among individuals with DM, all types of aerobic exercise training can impact positively on some traditional and non-traditional risk factors for CVD. Training programs with a higher volume or intensity induce greater improvements in vascular function, cardiorespiratory fitness (CRF), and lipid profiles. The beneficial outcomes of aerobic training include improvements in glycemic control, endothelial function, oxidative stress, dyslipidemia, myocardial function, adiposity, and CRF. Findings regarding markers of inflammation are discrepant and further research should focus on the role of exercise to impact upon the chronic inflammation associated with DM.

Cocoa, Blood Pressure, and Vascular Function.

Cardiovascular disease (CVD) represents the most common cause of death worldwide. The consumption of natural polyphenol-rich foods, and cocoa in particular, has been related to a reduced risk of CVD, including coronary heart disease and stroke. Intervention studies strongly suggest that cocoa exerts a beneficial impact on cardiovascular health, through the reduction of blood pressure (BP), improvement of vascular function, modulation of lipid and glucose metabolism, and reduction of platelet aggregation. These potentially beneficial effects have been shown in healthy subjects as well as in patients with risk factors (arterial hypertension, diabetes, and smoking) or established CVD (coronary heart disease or heart failure). Several potential mechanisms are supposed to be responsible for the positive effect of cocoa; among them activation of nitric oxide (NO) synthase, increased bioavailability of NO as well as antioxidant, and anti-inflammatory properties. It is the aim of this review to summarize the findings of cocoa and chocolate on BP and vascular function.

AGE-DEPENDENT INCREASE IN ENDOTHELIAL MICROPARTICLES IN HEALTHY SUBJECTS: IMPACT OF COCOA FLAVANOLS

Background: Clinical studies show that cocoa flavanols (CF) can decrease vascular stiffness and blood pressure and improve endothelial function even in healthy elderly subjects. We investigated whether age-dependent changes in circulating endothelial microparticles (EMPs) exist, whether these correlate with age-dependent vascular changes, and whether a CF-intervention also affects EMPs. Methods: EMPs were determined in 52 healthy subjects (22-75years) by flow cytometry. Endothelial function (flow-mediated-vasodilation; FMD), blood pressure, and wall-shear-stress (WSS) were measured. Using pulse-wave-analysis, pulse wave velocity (PWV) and aortic augmentation index (AIX) were measured. 22 young (<35yrs) and 20 elderly (50-80yrs) non-smoking healthy male consumed either CF-containing-drink [450mg] or nutrient-matched, CF-free-control BID for 14 days. Measurements were taken after overnight fasting before and 1h after the first drink on day 1 and day 14. Results: With increasing age, CD62e+ but not CD31+/41- and CD144+-EMPs, increased. Significant correlations were found between age and systolic blood pressure (SBP) and AIX. In elderly subjects, we observed an increased BA diameter and hence reduced WSS and FMD. CD62e+ correlated with SBP and inversely with FMD. Following 2 weeks of daily CF intake, FMD and PWV improved in young and elderly individuals. CF decreased AIX and thus SBP in elderly. CD62e+ and CD31+/41--MPs but not CD144+ significantly decreased in both groups. The decrease in CD62e+ correlated with decreases in SBP, AIX, and inversely with FMD improvements. Conclusion: In healthy humans, cardiovascular aging is associated with EMPs indicative of endothelial injury and can be modulated by dietary CFs along with improvements in vascular function.

Statin Therapy Does Not Significantly Alter Microvascular Function in Uncomplicated Hypertension

Objective Young patients with uncomplicated hypertension are frequently exempt from statin therapy as they generally fall below current treatment thresholds. This study examined whether there may be evidence of improved microvascular function in young patients with grade 1 hypertension after 12 weeks of statin therapy. Methods This was a randomized double-blind placebo-controlled crossover study in which 42 statin-naïve participants with grade 1 hypertension (mean systolic/diastolic blood pressure 142/92 mmHg) were randomized to receive either simvastatin 40 mg or a placebo for 12 weeks, followed by a 4-week washout period, after which the arms crossed for a further 12 weeks. Measures of vascular function were recorded at the beginning and end of each study period equating to four measures in total. The brachial artery was studied by flow-mediated dilatation (FMD) together with the resistive and pulsatility indices and mean velocity of flow. Results Statin therapy did not significantly alter the change in FMD seen in the brachial artery [standardized differential mean = 0.02 (0.23), confidence interval (CI) = −0.45 to 0.48, p = 0.932]. No significant changes were seen in the brachial artery mean velocity (CI = −9.68 to 11.51, p = 0.861), resistive index (CI = −0.11 to 0.12, p = 0.903), or pulsatility index (CI = −5.82 to 4.91, p = 0.864). Conclusion This study did not demonstrate any significant changes in established measures of microvascular function after treatment with a statin in a young hypertensive population with no antecedent cardiovascular disease. This may indicate that either the intervention was insufficiently vasoactive to produce a clinically detectable improvement in vascular function, or that the means used to assess the microvasculature were insufficiently sensitive to detect what may have been quite minor changes.