Impaired Flow-mediated Dilation Research Articles

Fetal Growth and Preterm Birth Influence Cardiovascular Risk Factors and Arterial Health in Young Adults

Impaired fetal growth is associated with cardiovascular disease in adulthood. The mechanisms of this association remain poorly described. We aimed to determine the associations of impaired fetal growth and preterm birth with cardiovascular risk factors and arterial health in a large cohort of young adults. Carotid intima-media thickness, brachial flow-mediated dilatation and cardiovascular risk factors were compared between young adults (24-45 years) born at term with impaired fetal growth (birth weight <10th percentile; n=207), born preterm (<37 weeks' gestation; n=253), and a control group born at term with normal fetal growth (birth weight 50-90th percentile; n=835), in the Cardiovascular Risk in Young Finns study. Compared with controls, those with impaired fetal growth had elevated triglycerides (P=0.006), C-reactive protein (P=0.004), low-density lipoprotein cholesterol, systolic blood pressure (both P=0.06), and intima-media thickness and impaired flow-mediated dilatation (both P=0.02), the latter partially mediated by systolic blood pressure, C-reactive protein, and triglycerides. Those born preterm had higher intima-media thickness (P=0.005) and lower flow-mediated dilatation (P=0.03) compared with controls, although this was restricted to those with concurrent fetal growth restriction. Impaired fetal growth is associated with impaired endothelial function and elevated preclinical atherosclerosis in young adults, partly mediated by inflammation, blood pressure, and triglycerides. This association is most marked for those also born preterm.

Plasma aldosterone levels and aldosterone-to-renin ratios are associated with endothelial dysfunction in young to middle-aged subjects

ObjectiveSmall clinical studies suggested a role for aldosterone in the development of endothelial dysfunction. We investigated whether the plasma aldosterone concentration (PAC) or the aldosterone-to-renin ratio (ARR) were associated with decreased endothelial function as measured by flow-mediated dilation (FMD) of the brachial artery in the general population. MethodsOur study population comprised 972 participants from the Study of Health in Pomerania, who were not treated with antihypertensive medication. We performed age-stratified (<50 and ≥50 years) ordinal logistic regression analyses. FMD was categorised as decreased (1st quintile), moderate (2nd–4th quintile), or increased (5th quintile). PAC and ARR were divided into low, moderate, and high values according to age- and sex-specific tertiles. All models were re-calculated for 871 subjects with PAC and ARR within the study-specific reference ranges. Odds ratios (OR) and 95% confidence intervals (CI) are presented. ResultsSubjects <50 years with high PAC (OR 1.60; 95% CI 1.07–2.38) or ARR (OR 1.81; 95% CI 1.21–2.73) had higher odds for decreased FMD than subjects with low PAC or ARR, respectively. Similar results were obtained in analyses restricted to subjects with PAC and ARR within the reference range. High-normal PAC (OR 1.62; 95% CI 1.07–2.47) or ARR (OR 1.62; 95% CI 1.05–2.50) was associated with higher odds for decreased FMD when compared with low-normal PAC or ARR, respectively. These associations were not observed in subjects ≥50 years. ConclusionsHigh and high-normal PAC or ARR contribute to an impaired FMD and subsequently the progression of subclinical atherosclerosis in young to middle-aged subjects.

DHA-rich fish oil reverses the detrimental effects of saturated fatty acids on postprandial vascular reactivity

Experimental elevation of nonesterified fatty acids (NEFAs) impairs endothelial function, but the effect of NEFA composition is unknown. The objective was to test the effect of acute elevation of NEFAs enriched with either saturated fatty acids (SFAs) or SFAs with long-chain (LC) n-3 (omega-3) PUFAs on vascular function measured via flow-mediated dilatation (FMD), laser Doppler iontophoresis (LDI), and digital volume pulse (DVP). In 59 subjects (30 men and 29 women), repeated oral fat feeding of either palm stearin (SFA) or palm stearin with DHA-rich fish oil (SFA + LC n-3 PUFA) was performed on 2 separate occasions with continuous heparin infusion to elevate NEFAs for a duration of 60 to 240 min. Vascular function was measured at baseline and at the end of NEFA elevation; venous blood was collected for measurement of lipids and circulating markers of endothelial function. NEFA elevation during consumption of the SFA-rich drinks was associated with a marked impairment of FMD, whereas consumption of SFAs + LC n-3 PUFAs improved FMD response, with a mean (±SEM) difference of 2.06 ± 0.29% (P < 0.001). Positive correlations were found with percentage weight of LC n-3 PUFAs in circulating NEFAs and change in FMD response [Spearman's rho (r(s)) = 0.460, P < 0.001]. LDI measures increased during both treatments (P ≤ 0.026), and there was no change in DVP indexes. The composition of NEFAs can acutely affect FMD. The beneficial effect of LC n-3 PUFAs on postprandial vascular function warrants further investigation but may be mediated by nitric oxide-independent mechanisms. This trial is registered at clinicaltrials.gov as NCT01351324.

Effect of moderate-to-severe chronic kidney disease on flow-mediated dilation and progenitor cells

A reduction in progenitor cell populations that help preserve vascular continuity and induce vascularization may accentuate endothelial cell apoptosis and dysfunction, ultimately contributing to organ failure and increased cardiovascular disease in chronic kidney disease (CKD). We hypothesized that CD45+ myeloid and CD34+ hematopoietic circulating progenitor cell (CPC) subpopulations would be reduced, peripheral blood mononuclear cell (PBMNC) colony-forming units (CFU) would be impaired, and flow-mediated dilation (FMD) would be impaired in patients with moderate-to-severe CKD as compared with healthy controls. Eleven moderate-to-severe CKD patients (mean estimated glomerular filtration rate [eGFR]: 36 ± 5) and 14 healthy controls were studied; blood was drawn and FMD was assessed by brachial artery FMD. CPCs were quantified via flow cytometry, and isolated PBMNCs were cultured for the colony-forming assay. CKD patients had significantly impaired FMD; lower CD34+, CD34+/KDR+, CD34+/CD45- and CD34+/KDR+/CD45- hematopoietic CPCs; lower CD45+, CD45+/KDR+, CD34+/CD45+ and CD34+/KDR+/CD45+ myeloid CPCs; and impaired CFUs as compared with healthy controls. Regression analysis revealed that CD34+, CD34+/KDR+ and CD34+/CD45- hematopoietic CPCs were associated positively with eGFR and negatively with blood urea nitrogen and serum creatinine. The CD45+/KDR+ myeloid CPCs also were associated positively with eGFR and negatively with serum creatinine. CD34+ hematopoietic CPCs and CD45+/KDR+ as well as CD34+/CD45+ myeloid CPCs were associated positively with FMD. In conclusion, myeloid and hematopoietic CPCs are reduced and associated with renal function as well as FMD in CKD. Therefore, reductions in CPCs may be a potential mechanism by which vascular integrity is compromised, increasing cardiovascular disease risk and contributing to renal disease progression in CKD.

Non traditional risk factors of carotid atherosclerosis in rheumatoid arthritis

IntroductionCardiovascular events are markedly increased in rheumatoid arthritis, and they remain poorly understood. Aim of workTo investigate inflammatory markers, markers of endothelial dysfunction, antioxidant vitamins and rheumatoid arthritis-related factors as non traditional risk factors for occurrence of carotid atherosclerosis in rheumatoid arthritis patients. Patients and methodsThirty RA patients were included in this study. All of them were females and their ages ranged from 23 to 62 years with a mean of 43.95±7.2 years. All of them were subjected to full history taking, thorough clinical examination, laboratory investigations, disease activity assessment, bone erosion assessment by Modified Larsen score and functional assessment by health assessment questionnaire (HAQ) score. Carotid Duplex was done to measure the intima-media thickness (IMT) and carotid plaques. The patients who proved to have carotid atherosclerosis by ultrasound were subjected to ultrasound examination of brachial artery flow mediated dilatation (FMD) to confirm presence of endothelial dysfunction in those patients. ResultsTen out of 30 RA patients (33.3%) had carotid atherosclerosis in whom there was impaired FMD denoting endothelial dysfunction. Among those patients, the risk factors that associated with occurrence of carotid atherosclerosis included higher levels of inflammatory markers (CRP, ESR and IL-6) and VCAM-1 (a marker of endothelial dysfunction), lower levels of antioxidant vitamins A and E, and RA-related factors as longer duration of disease, increased RF titer, increased HAQ-score, bone erosion, duration of prednisone use and prednisone cumulative dose. ConclusionThe prevalence of carotid atherosclerosis in rheumatoid arthritis patients was 33.3%. Among those patients, a statistically significant association was found between occurrence of carotid atherosclerosis and inflammatory markers, endothelial dysfunction, antioxidant vitamins and rheumatoid arthritis related factors.

Rhesus macaques develop metabolic syndrome with reversible vascular dysfunction responsive to pioglitazone.

The metabolic syndrome (MetS) is a constellation of clinical features that include central obesity, hypertension, atherogenic dyslipidemia, and insulin resistance. However, the concept remains controversial; it has been debated whether MetS represents nothing more than simultaneous co-occurrence of individual risk factors or whether there are common shared pathophysiological mechanisms that link the individual components. To investigate the emergence of metabolic and cardiovascular components during the development of MetS, we identified MetS-predisposed animals (n=35) in a large population of rhesus macaques (Macaca mulatta, 12.7±2.9 years old, n=408), acclimated them to standardized conditions, and monitored the progression of individual component features over 18 months. In 18 MetS animals with recently developed fasting hyperinsulinemia, central obesity, hypertension, and atherogenic dyslipidemia, we found that individual metabolic and cardiovascular components track together during the transition from pre-MetS to onset of MetS; MetS was associated with a 60% impairment of flow-mediated dilation, establishing the mechanistic link with vascular dysfunction. Pioglitazone treatment (3 mg/kg body weight/d for 6 weeks), a peroxisome proliferator-activated receptor γ agonist, reversibly improved atherogenic dyslipidemia and insulin resistance and fully restored flow-mediated dilation with persistent benefits. Coemergence of metabolic and cardiovascular components during MetS progression and complete normalization of vascular dysfunction with peroxisome proliferator-activated receptor γ agonists suggest shared underlying mechanisms rather than separate processes, arguing for the benefit of early intervention of MetS components. Predictive nonhuman primate (NHP) models of MetS should be highly valuable in mechanistic and translational studies on the pathogenesis of MetS in relation to cardiovascular disease and diabetes mellitus.

Relationships between vascular dysfunction, circulating endothelial progenitor cells, and psychological status in healthy subjects

Although the mechanisms remain unclear, depression and mental stress are associated with endothelial dysfunction and increases risk of cardiovascular disease (CVD). Recent studies suggest that circulating endothelial progenitor cells (EPC) play an important role in endothelial repair and correlate with endothelial function. We studied the relationship between the level of circulating CD34/KDR(+) EPCs and CD133/KDR(+) EPCs, brachial artery flow-mediated dilation (FMD), Depression Anxiety Stress Scales in 129 normal individuals (54 ± 10 years, 54 men) without prior CVD or diabetes. Their median depression score (DS) and stress score (SS) was 4 (range 0-34) and 6 (range 0-32), respectively. As defined by the ≥75th percentile, 41 subjects (32%) had high DS (≥8) and 31 (24%) had high SS (≥14). Subjects with high DS had significantly lower FMD (5.4 ± 2.7 versus 8.0 ± 4.0%, P<0.001) and percentage of CD34/KDR(+) EPC (1.2 ± 1.3 versus 2.0 ± 2.4%, P = 0.037), but not CD133/KDR(+) EPC (0.56 ± 0.42 versus 0.68 ± 0.76%, P = 0.44), than those with normal DS. In contrast, there were no significant difference in FMD (6.8 ± 3.5 versus 7.3 ± 3.9%, P = 0.46), percentages of circulating CD34/KDR(+) EPC (1.20 ± 1.28 versus 1.95 ± 2.34%, P = 0.052) and CD133/KDR(+) EPC (0.55 ± 0.41 versus 0.67 ± 0.73%, P = 0.52) between subjects with high and normal SS. Multivariate regression analysis revealed that high DS (OR 1.08, 95% CI: 1.02-1.15, P = 0.010) and old age (OR 1.05, 95% CI: 1.01-1.10, P = 0.019), but not SS or percentage of circulating EPC, were independent predictors for decreased FMD. Our results demonstrated that, in subjects without significant CVD, a high DS was associated with impaired brachial FMD and depletion of circulating EPC. However, only DS, but not SS or EPC count, was an independent predictor for impaired brachial FMD.

The metabolic and vascular phenotype of men who father pregnancies affected by fetal growth restriction

BackgroundLow birth weight is associated with an increased risk of developing type-2 diabetes in later life. The fathers of low birth weight offspring are themselves more likely to have type-2...

Idiopathic deep venous thrombosis and arterial endothelial dysfunction in the elderly

Arterial and venous thrombosis have always been regarded as different pathologies and epidemiological studies have examined the association between venous thrombosis and indicators of atherosclerosis and/or arterial thromboembolic events. We measured the flow-mediated dilation (FMD), a well-known marker of arterial endothelial dysfunction, in young-middle-aged and old-aged patients with and without unprovoked deep venous thrombosis (DVT). The aim of this study was to investigate whether DVT was a significant predictor for impaired FMD, considering all the patients and young-middle-aged (age < 65 years) and old-aged (age ≥ 65 years) patients separately. FMD was measured in the brachial artery on a population of 120 subjects with the same atherosclerosis risk factors, 68 male and 52 female, 70 young-middle-aged subjects (mean age ± SD 49.5 ± 10.5 years) and 50 old-aged subjects (76.2 ± 7.7 years). Patients with DVT showed a significant decrease of FMD compared to patients without DVT (6.8 ± 5.5% vs. 10.9 ± 3.5%, p < 0.001). Moreover, old-aged patients showed a significant decrease of FMD compared to the young-middle-aged subjects (7.4 ± 4.1% vs. 9.8 ± 5.3%, p = 0.005). In the whole study population, DVT was strongly associated with FMD (risk factors adjusted β = -4.14, p < 0.001). A significant interaction between age and the presence of DVT on predicting FMD was found (p = 0.003) suggesting a differential behavior of DVT as predictor of FMD. In young-middle-aged group, multivariate model confirmed that DVT was the most significant predictor of continuous FMD (β = -6.06, p < 0.001). On the contrary, DVT was no more a predictor of FMD in the old age group (β = -0.73, p = 0.556). Furthermore, old-aged patients without DVT showed a statistically significant decrease of FMD compared to the young-middle-aged subjects without DVT (8.2 ± 2.1% vs. 12.6 ± 2.7%, p<0.001) and old-aged patients with DVT showed a not statistically significant decrease of the FMD compared to the young-middle-aged patients with DVT (6.7 ± 5.3% vs. 6.8 ± 5.7%, p = 0.932). In conclusion, young-middle-aged patients with spontaneous DVT show an impaired FMD, whereas this impairment in old-aged subjects is evident independently from the presence or absence of DVT. Aging per se may be associated with physiologic abnormalities in the systemic arteries and with endothelial dysfunction.

Non-dipping pattern relates to endothelial dysfunction in patients with uncontrolled resistant hypertension

Resistant hypertension (RHTN) includes both patients whose blood pressure (BP) is uncontrolled on three or more medications (uncontrolled RHTN (UCRH)) and patients whose BP is controlled with use of four or more drugs (controlled RHTN (CRH)). It is unknown whether endothelial function and nocturnal drop demonstrate a similar pattern in patients with CRH and UCRH. We examined circadian BP patterns and vascular function in these patients. In all, 40 CRH and 26 UCRH patients, and 25 normotensives underwent biochemical testing, ambulatory BP monitoring, determination of brachial artery responses to endothelial-dependent (flow-mediated; dilation (FMD)) and independent (nitroglycerin mediated) stimuli. The nighttime drop in systolic BP (SBP) and diastolic BP (DBP) was less pronounced in UCRH than in CRH (SBP, 1.9±1.6 versus 4.9±1.7%; DBP, 7.5±1.8 versus 10.9±1.8%, UCRH and CRH, respectively; P<0.05). FMD was greater in control group compared with RHTN patients. Patients with UCRH had significantly impaired FMD compared with CRH (5.9±2.3% versus 7.1±5.1%; P<0.0001). Therefore, UCRH patients have less nocturnal dipping and a more impaired endothelial response compared with CRH patients. These findings suggest that important differences among patients with RHTN may allow identify subgroups with increased cardiovascular risk.

Noninvasive assessment of endothelial dysfunction in essential hypertension: Comparison of the forearm microvascular reactivity with flow-mediated dilatation of the brachial artery

Endothelial dysfunction is detectable both in the forearm skin microcirculation by laser Doppler flowmetry and in the brachial artery by Duplex Ultrasound. The aim of the study was to evaluate whether endothelium-dependent vasodilation in the forearm microcirculation is related to endothelium-dependent flow mediated dilation (FMD) of the brachial artery. In 22 treated male essential hypertensive patients (EHT) who had impaired FMD of the brachial artery, and in 11 male normotensive subjects (NT) we measured first the postocclusive reactive hyperemic response (PORH), then the effect of two doses of acetylcholine (ACh) and sodium nitroprusside (SNP) on the forearm skin microcirculation. FMD resulted from forearm reactive hyperemia induced by 5 minutes of ischaemia and the vasodilation induced by sublingual nitroglycerine (GTN) were also measured. Responses were calculated as the maximal percent increase above baseline. PORH and the responses to ACh were significantly (p < 0.05, p <0.01) reduced in EHT (272 ± 180, 177 ± 194, 463 ± 302) as compared to NT (409 ± 123, 470 ± 467, 805 ± 603). Response to SNP was similar. FMD was significantly (p < 0.001) reduced in EHT as compared to NT (3.98 ± 2.2 vs 9.3 ± 2.88), while response to GTN was similar. There was no significant relationship (p = n.s.) either between maximal response to ACh and FMD (r = 0.28), or between PORH and FMD (r = −0.01). Endothelial dysfunction was detectable with both methods in EHT. Our results show that endothelium-dependent vasodilation in forearm microcirculation is not related to FMD of the brachial artery. This can be explained by the differences in vascular beds and mechanism involved in the hyperemic response.

Impaired flow-mediated dilatation response in uncomplicated Type 1 diabetes mellitus: influence of shear stress and microvascular reactivity

Impaired FMD (flow-mediated dilatation) has traditionally been recognized as an indirect marker of NO bioactivity, occurring in disease states such as DM (diabetes mellitus). Endothelium-dependent FMD is a homoeostatic response to short-term increases in local shear stress. Microvascular dysfunction in DM influences blood flow velocity patterns. We explored the determinants of the FMD response in relation to evoked DSS (diastolic shear stress) and forearm microcirculation haemodynamics by quantifying changes in Doppler flow velocity waveforms between groups. Forty patients with uncomplicated Type1 DM and 32 controls underwent B-mode and Doppler ultrasound scanning to interrogate the brachial artery. Postischaemic Doppler velocity spectral envelopes were recorded and a wavelet-based time-frequency spectral analysis method was employed to track change in distal microcirculatory haemodynamics. No difference in baseline brachial artery diameter was evident between the groups (4.15 compared with 3.94 mm, P=0.23). FMD was significantly impaired in patients with Type1 DM (3.95 compared with 7.75%, P<0.001). Endothelium-independent dilatation in response to GTN (glyceryl trinitrate) was also significantly impaired (12.07 compared with 18.77%, P<0.001). DSS (dyn/cm2) was significantly reduced in the patient group (mean 20.19 compared with 29.5, P=0.001). Wavelet interrogation of postischaemic flow velocity waveforms identified significant differences between groups. In conclusion, DSS, microcirculatory function and endothelium-independent vasodilatation in response to GTN are important determinants that impact on the magnitude of FMD response and are impaired in patients with Type1 DM. Impaired FMD response is multifactorial in origin and cannot be attributed solely to a diminished NO bioavailability.

Endothelium-dependent But Not Endothelium-independent Flow-mediated Dilation Is Significantly Reduced in Patients with Systemic Lupus Erythematosus without Vascular Events: A Metaanalysis and Metaregression

To assess whether endothelium-dependent and endothelium-independent flow-mediated dilation (FMD) are impaired in patients with systemic lupus erythematosus (SLE) with no history of vascular event; and to determine factors moderating impaired FMD in SLE. Electronic databases were searched for case-control studies that compared endothelium-dependent and/or endothelium-independent FMD at the brachial artery between SLE patients who were naive for vascular events and matched healthy controls. Effect size as standardized mean difference (SMD) and 95% confidence intervals of FMD between SLE patients and controls was pooled using the inverse variance method. Mixed-model metaregression was performed to identify potential demographic and clinical factors associated with the effect size. Thirteen relevant studies involving 580 patients and 381 matched healthy controls were included. Endothelium-dependent FMD was significantly lower in SLE patients than in controls (SMD -0.832, 95% CI -1.172 to -0.492, p < 0.001). Endothelium-independent FMD, however, did not differ between the 2 groups (SMD -0.179, 95% CI -0.433 to 0.075, p = 0.167). Metaregression revealed that increasing age (r = 0.047, p = 0.037) and duration of SLE (r = 0.008, p = 0.024) at the time of FMD measurement significantly narrowed the difference of endothelium-dependent FMD between patients and controls; whereas sex, smoking, menopause, diabetes mellitus, body mass index, blood pressure, fasting lipid profile, C-reactive protein, and prednisolone use did not. Endothelium-dependent, but not endothelium-independent FMD is significantly impaired in lupus patients who are naive for vascular events. Increasing age and longer disease duration may limit the potential of endothelial reactivity as an indicator of early atherosclerosis in SLE.

Predictive value of serial assessment of endothelial function in chronic heart failure

BackgroundIt remains undefined whether reversibility of endothelial dysfunction after optimized therapies for heart failure (HF) provides prognostic information in patients with HF. This study examined whether changes in endothelial vasomotor function after therapies for HF may predict future outcomes in patients with stable HF. MethodsThis study included 245 patients with stable chronic ischemic HF and an impaired flow-mediated dilation (FMD) of the brachial artery (FMD <5.5%). Measurement of FMD was repeated after 6months for individualized and optimized therapy for HF and atherosclerotic risk factors. Patients were followed for 36months or until the occurrence of cardiac death or hospitalization with decompensated HF. ResultsFMD was persistently impaired (<5.5%) in 130 (53%) patients after 6months of the optimized therapy, whereas it improved (FMD ≥5.5%) in the remaining 115 (47%) patients. During follow-up, an event occurred in 26 (20%) patients with persistently impaired FMD and in 7 (6%) patients with improved FMD (p<0.01). Multivariate Cox hazards analysis showed that persistent impairment of FMD was an independent predictor of cardiac events (hazard ratio 3.0, 95% CI 1.3–6.9, p=0.013). Persistently impaired FMD had a significantly incremental effect on the predictability of brain natriuretic peptide levels for cardiac events. Baseline FMD before the therapy for HF and atherosclerotic risk factors had no significant prognostic information. ConclusionsPersistent endothelial vasomotor dysfunction despite therapies for HF and atherosclerotic risk factors was a predictor of cardiac events in patients with chronic ischemic HF.

Role of carbon monoxide in impaired endothelial function mediated by acute second-hand tobacco, incense, and candle smoke exposures

The aim of this study was to determine if carbon monoxide (CO) is responsible for acute adverse cardiovascular effects of different sources of smoke: second-hand tobacco smoke (SHS), incense and candle smoke. Endothelial function was tested using flow-mediated dilation (FMD) in pigs and was shown to be sensitive to nitric oxide synthase blockade. Subsequent experiments showed that FMD was significantly impaired compared to sham-exposed pigs at 30 min after a 30-min exposure to all three sources of smoke. In contrast, SHS significantly increased systolic, diastolic and pulse pressures compared to sham-exposure, while both incense and candle smoke exposure had no effect. The FMD impairment correlated well with CO levels in the exposure chamber, but not total particulates or venous CO–hemoglobin. Therefore, this study suggests a gas phase component of smoke that accompanies CO, but not CO itself, is responsible for acute endothelial dysfunction after SHS, incense or candle smoke exposure.

Association of vascular health and neurocognitive performance in overweight adults with high blood pressure

The relationship between vascular health—including flow-mediated dilation (FMD) and intima medial thickness (IMT)—and neurocognitive performance was examined in a sample of 124 sedentary, middle-aged adults with high blood pressure (systolic blood pressure, SBP, 130–159 mmHg or diastolic blood pressure, DBP, 85–99 mmHg) who were overweight or obese (body mass index 25.0–39.99 kg/m2). Patients completed a neuropsychological test battery, including measures of executive function and psychomotor speed, and measures of IMT and FMD were obtained. Hierarchical multiple regression analyses were used to investigate the association between vascular measures and neurocognitive performance after controlling for demographic factors and cerebrovascular risk factors. Higher levels of FMD predicted better executive function (b = 0.90, p = .045). Greater IMT tended to be associated with slower psychomotor speed (b = −0.82, p = .084), with the effect attenuated after controlling for FMD. Impaired FMD is associated with worse neurocognitive functioning among overweight adults with high blood pressure.

Improved Endothelial Function in Patients with Atrial Fibrillation through Maintenance of Sinus Rhythm by Successful Catheter Ablation

Although atrial fibrillation (AF) is a risk factor for endothelial dysfunction (ED), the effect of catheter ablation (CA) on AF-associated ED has not been evaluated. The aims of this study are to determine if the degree of ED predicts the outcome of AF ablation and to evaluate whether ED can be improved through restoring sinus rhythm (SR) by successful CA. This study prospectively enrolled 80 subjects who underwent CA for AF (paroxysmal AF = 61, persistent AF = 19). Eighty subjects with no history of AF were enrolled as controls, all of whom were matched by age, gender, body mass index, and atherosclerotic risk factor distribution. Brachial artery flow-mediated dilatation (FMD) was measured at baseline, and at 1 month and 6 months post CA in AF subjects who remained in SR. Among controls, FMD was measured at baseline and at 6 months. We used high sensitivity C-reactive protein (hs-CRP), interleukin-6, soluble E- or P-selectin, and endothelin-1 as biomarker indices for inflammation and/or ED. Compared with controls, AF subjects had lower FMD at baseline (FMD(baseline), P < 0.001). After successful CA, FMD was significantly improved at 1 month and 6 months, nearly approaching control levels. A multivariate analysis revealed that FMD(baseline), hs-CRP, and left atrial volume (LAV) were independent predictors for arrhythmia recurrence after CA. Other biomarkers were not related to rhythm outcome. AF subjects have significantly impaired FMD, which can be reversed through maintenance of SR by successful CA. FMD(baseline), hs-CRP, and LAV are important predictors for AF recurrence after CA.

Relation of flow-mediated dilation to global arterial load: Impact of hypertension and additional cardiovascular risk factors

BackgroundEndothelial dysfunction may be related to increased left ventricular (LV) mass due to an association between endothelial dysfunction with increased arterial load. Therefore, we evaluated whether brachial artery flow-mediated dilation (FMD) is related to global arterial load. MethodsPulse pressure/stroke index (PP/SVi, global arterial stiffness, prognostically validated), stroke volume/PP (SV/PP, global arterial compliance), and % of the predicted SV/PP by heart rate, age and body weight (confounder-adjusted global compliance, prognostically validated) were used as LV geometry-related indices of global arterial load. ResultsCompared to normotensive participants (NT, n=50), those with hypertension (HTN, n=51) had lower FMD (8.3%±5.4 vs. 12.8%±6.5), higher PP/SVi (1.24±0.34 vs. 1.04±0.28mmHg m2/ml), higher LV mass and higher relative wall thickness (all p<0.01); in contrast, SV/PP and % of predicted SV/PP did not differ between NT and HTN (all p>0.1). Impaired FMD was 3–4-fold more prevalent than LV hypertrophy or increased arterial load both in NT and in HTN. Within NT and HTN separately, PP/SVi, SV/PP and % of predicted SV/PP were comparable among tertiles of FMD. Only in NT, lower FMD was associated with higher peak exercise systolic BP (p<0.05). In multivariable regression models, FMD was not associated with indices of arterial load independently (all p>0.1). ConclusionsIn young-to-middle-age subjects with cardiovascular risk factors, impaired FMD is more prevalent than traditional preclinical manifestation of cardiovascular disease, and may exist independent to increased arterial load. Thus, endothelial dysfunction assessment may refine cardiovascular risk profile and risk-reduction strategies based on detection of traditional target organ damage.

Effect of pioglitazone on endothelial function in impaired glucose tolerance

Flow-mediated dilation (FMD) is a surrogate marker of endothelial function, which has been proposed as a barometer of vascular health. Impaired microvascular response to reactive hyperaemia is thought to be the mechanism behind reduced shear stress and subsequently impaired FMD, which has been associated with cardiovascular events. This study aims to assess the effect of pioglitazone on the vasculature of patients with impaired glucose tolerance (IGT). Forty IGT patients with no cardiovascular disease were compared with 24 healthy age- and sex-matched controls. Endothelial function was assessed using FMD of the brachial artery. Adiponectin (ADN) levels were measured and insulin sensitivity was calculated using homeostasis model assessment of insulin resistance (HOMA-IR). A randomised double-blind placebo-controlled trial of the IGT subjects was then performed, with subjects receiving either pioglitazone 30 mg od or matched placebo for 12 weeks before the measurements were repeated. The IGT subjects had a significantly impaired FMD compared with the controls (p < 0.001). Diastolic shear stress (DSS) was also significantly reduced in IGT (p = 0.04). High molecular weight (HMW) ADN was significantly lower in the IGT group than in controls (p = 0.03). On analysis of the IGT group after 12 weeks treatment, FMD was significantly increased in the pioglitazone group compared with placebo (p = 0.03) as was endothelium-independent dilation (EID) (p = 0.03). A significant increase in total ADN (p < 0.001), HMW ADN (p < 0.001) and HMW/total ratio (p = 0.001) occurred in the pioglitazone group compared with placebo. Pioglitazone improved endothelial function in IGT. Treatment with pioglitazone may reduce the risk of cardiovascular disease in this patient group.

Is there an association between non-functioning adrenal adenoma and endothelial dysfunction?

Subtle changes in hypothalamic- pituitary-adrenal (HPA) axis of subjects with nonfunctioning adrenal adenoma may be associated with endothelial alterations. We sought to investigate endothelial function, visceral adiposity and osteoprotegerin (OPG) and interleukin- 18 (IL-18) levels in subjects with non-functioning adrenal adenomas. The adenoma group included 40 subjects without clinical and subclinical findings of hypercortisolism or other adrenal gland disorders. Twenty-two body mass index-matched controls were also enroled. The patients and control subjects underwent hormonal evaluation and assessment of anthropometric and metabolic parameters. Endothelial function was assessed with flowmediated dilatation (FMD) of the brachial artery and intima media thickness (IMT) of common carotid arteries. Visceral adipose tissue area was measured by computed tomography. Plasma OPG and serum IL-18 levels were also measured. When compared with healthy controls, the adenoma group had elevated systolic blood pressure, post-dexamethasone suppression test cortisol and reduced DHEAS. Visceral adipose tissue area and IMT of common carotid arteries were comparable. In the adenoma group, FMD of the brachial artery was significantly impaired and IL-18 level was significantly elevated. Visceral adipose tissue area was independently related with FMD. Homeostasis model assessment (HOMA) was the independent factor associated with visceral adipose tissue area. Cortisol, DHEAS and visceral adipose tissue area were independently associated with HOMA. We achieved evidence that could be attributable to endothelial alterations in subjects with non-functioning adrenal adenomas. Impaired FMD appeared to be a consequence of subtle changes in HPA axis in terms of elevated cortisol and reduced DHEAS as these conditions were known to disturb endothelial-dependent vasodilatation.