Early and late response-to-injury in patients undergoing transradial coronary angiography: arterial remodeling in smokers.
ABSTRACT: OBJECTIVES:To investigate the effect of smoking on vascular response to transradial coronary angiography (TCA). BACKGROUND:Cigarette smoking is the most important modifiable cardiovascular risk factor associated with endothelial dysfunction. METHODS:Radial artery flow-mediated vasodilation (RA-FMD), local stiffness (fractional diameter change), intima-media thickness (IMT), luminal and external arterial diameter were measured in 40 current smokers (CS) and former smokers (FS) at 6-14 months at the site of previous TCA and contralateral control artery. Vascular regenerative capacity was studied as chemotactic cell migration in vitro and ex vivo (n=10) and the time course of endothelial functional recovery following RA-FMD up to 72 h after TCA (n=10). RESULTS:At 10 ± 3 months after TCA, subjects exhibited significant local stiffening and increased IMT as compared to the control arm. These late structural changes were significantly more pronounced in CS as compared to FS. IMT thickening correlated with packyears, number of daily cigarettes, and inversely with RA-FMD. Nitric oxide synthase (NOS)-dependent chemotaxis of CS' circulating angiogenic cells was impaired. Ex vivo incubation of endothelial cells with CS' plasma inhibited NOS-dependent endothelial wound closure and chemotaxis. In vivo, TCA acutely decreased RA-FMD. At 24 h, RA-FMD had recovered in FS but remained impaired at 24 h and only recovered at 48 h in CS. CONCLUSION:In active smokers, transradial coronary angiography is associated with delayed early recovery from transient endothelial dysfunction, decreased NOS-dependent vascular regeneration, and late arterial remodeling pointing towards potential harmful effects of transradial coronary angiography on vascular function in distinct subsets of patients.
Project description:BACKGROUND:Subclinical hypothyroidism (SHT) may increase the risk of cardiovascular disease. We compared endothelial function between SHT patients and euthyroid individuals, and evaluated the effects of levothyroxine therapy on endothelial function in the patients. MATERIALS AND METHODS:In a quasi-experimental study, flow-mediated dilatation (FMD) and intima-media thickness (IMT) were assessed in SHT patients and healthy controls (n = 25 in each group). Patients then received levothyroxine (50 ?g/day) for 2 months, and the FMD and IMT assessments were repeated. RESULTS:Patients and controls were similar in IMT (0.56 ± 0.09 vs. 0.58 ± 0.08 mm, P = 0.481), but FMD was lower in patients than in controls (4.95 ± 2.02 vs. 6.50 ± 2.57%, P = 0.011). A significant increase was observed in FMD (4.11 ± 2.37%, P = 0.001), but not in IMT (-0.004 ± 0.020 mm, P = 0.327), after levothyroxine therapy among the patients. CONCLUSIONS:Patients with SHT have endothelial dysfunction which responds to levothyroxine therapy. Randomized placebo-controlled trials are needed to confirm these findings.
Project description:OBJECTIVES:Impaired vascular pathophysiology and increased cardiovascular (CV) mortality are associated with rheumatoid arthritis (RA). To date, no genomic analysis of RA- and RA treatment-related vascular pathophysiology has been published. In this pilot study, we performed gene expression profiling in association with vascular pathophysiology in RA patients. METHODS:Sixteen and 19 biologic-naïve RA patients were included in study 1 and study 2, respectively. In study 1, genetic signatures determined by microarray were related to flow-mediated vasodilation (FMD), pulse-wave velocity (PWV), and common carotid intima-media thickness (IMT) of patients. In study 2, clinical response (cR) vs non-response (cNR) to 1-year etanercept (ETN) or certolizumab pegol (CZP) treatment, as well as "vascular" response (vR) vs non-response (vNR) to biologics, were also associated with genomic profiles. Multiple testing could not be performed due to the relatively small number of patients; therefore, our pilot study may lack power. RESULTS:In study 1, multiple genes were up- or downregulated in patients with abnormal vs normal FMD, IMT, and PWV. In study 2, there were 13 cR and 6 cNR anti-tumor necrosis factor (TNF)-treated patients. In addition, 10, 9, and 8 patients were FMD-20%, IMT-20%, and PWV-20% responders. Again, vascular responder status was associated with changes of the expression of various genes. The highest number of genes showing significant enrichment were involved in positive regulation of immune effector process, regulation of glucose transport, and Golgi vesicle budding. CONCLUSION:Differential expression of multiple genetic profiles may be associated with vascular pathophysiology associated with RA. Moreover, distinct genetic signatures may also be associated with clinical and vascular responses to 1-year anti-TNF treatment.
Project description:Endothelial dysfunction and intima-media thickness of common carotid arteries (IMT-CC) are considered subclinical markers of atherosclerotic cardiovascular disease (ASCVD). Advanced glycation end products (AGEs) are increased in type 2 diabetes mellitus (T2DM) patients, compared with non-diabetics, being implicated in micro- and macrovascular complications. Our aim was to compare serum AGEs levels and subclinical atherosclerotic markers between patients with established and newly diagnosed T2DM. Among 540 patients with T2DM and coronary heart disease from the CORDIOPREV study, 350 patients had established T2DM and 190 patients had newly diagnosed T2DM. Serum levels of AGEs (methylglyoxal (MG) and N-carboxymethyl lysine (CML)) and subclinical atherosclerotic markers (brachial flow-mediated vasodilation (FMD) and IMT-CC) were measured. AGEs levels (all p < 0.001) and IMT-CC (p = 0.025) were higher in patients with established vs. newly diagnosed T2DM, whereas FMD did not differ between the two groups. Patients with established T2DM and severe endothelial dysfunction (i.e., FMD < 2%) had higher serum MG levels, IMT-CC, HOMA-IR and fasting insulin levels than those with newly diagnosed T2DM and non-severe endothelial dysfunction (i.e., FMD ? 2%) (all p < 0.05). Serum CML levels were greater in patients with established vs. newly diagnosed T2DM, regardless of endothelial dysfunction severity. Serum AGEs levels and IMT-CC were significantly higher in patients with established vs. newly diagnosed T2DM, highlighting the progressively increased risk of ASCVD in the course of T2DM. Establishing therapeutic strategies to reduce AGEs production and delay the onset of cardiovascular complications in newly diagnosed T2DM patients or minimize ASCVD risk in established T2DM patients is needed.
Project description:BACKGROUND:Granulomatosis with polyangiitis (GPA) is a rare granulomatous vasculitis affecting small- and medium-sized blood vessels. In optimally treated patients with long-standing disease, the common cause of death is atherosclerosis even in the absence of typical risk factors. OBJECTIVE:To evaluate endothelial dysfunction in GPA patients. METHODS:44 patients (21 men and 23 women) diagnosed with GPA and 53 controls matched for age, sex, BMI and typical risk factors for cardiovascular diseases (22 men and 31 women) were enrolled in the study. We measured each participant's serum levels of vascular cell adhesion molecule-1 (VCAM-1), interleukin 6 (IL-6), and thrombomodulin. We also studied flow-mediated dilatation (FMD) of the brachial artery, intima-media thickness (IMT) of the common carotid artery and aortic stiffness using echocardiography. RESULTS:Patients with GPA showed a 15.9% increase in serum levels of VCAM-1 (p?=?0.01), 66% of IL-6 (p?<?0.001) and 50.9% of thrombomodulin (p?<?0.001) compared to controls. FMD% was 48.9% lower in patients with GPA in comparison to controls (p?<?0.001), after adjustment for potential confounders, with no differences regarding IMT or aortic stiffness. FMD% was negatively associated with duration of the disease (? = - 0.18 [95% CI: - 0.32 to - 0.04]), C-reactive protein (? = - 0.17 [95% CI: - 0.27 to - 0.07]), IL-6 (? = - 0.29 [95% CI: - 0.39 to - 0.19]), blood creatinine level (? = - 0.2 [95% CI: - 0.3 to - 0.1]), and IMT (? = - 0.14 (- 0.24 to - 0.04). In a multiple linear regression model, kidney function, IMT, pack-years of smoking, diabetes and level of VCAM-1 were independent predictors of lower FMD%. CONCLUSION:GPA is characterized by endothelial dysfunction. FMD is a useful tool for the detection of endothelial injury.
Project description:INTRODUCTION: Rheumatoid arthritis (RA) is an inflammatory disease associated with accelerated atherosclerosis and high risk of cardiovascular (CV) disease. Since genome-wide association studies demonstrated association between rs599839 polymorphism and coronary artery disease, in the present study we assessed the potential association of this polymorphism with endothelial dysfunction, an early step in atherogenesis. METHODS: A total of 128 RA patients without history of CV events were genotyped for rs599839 A/G polymorphism. The presence of endothelial dysfunction was assessed by brachial ultrasonography (brachial flow-mediated endothelium-dependent (FMD)). RESULTS: Patients carrying the allele G exhibited more severe endothelial dysfunction (FMD%: 4.61 ± 3.94%) than those carrying the wild allele A (FMD%: 6.01 ± 5.15%) (P = 0.08). Adjustment for gender, age at the time of study, follow-up time and classic CV risk factors disclosed a significant association between the rs599839 polymorphism and FMD (G vs. A: P = 0.0062). CONCLUSIONS: Our results confirm an association of the rs599839 polymorphism with endothelial dysfunction in RA.
Project description:Introduction:Epidemiological studies have shown increased morbidity and mortality in patients with coronary artery disease (CAD) and chronic obstructive pulmonary disease (COPD). We aimed to characterize the oxygen dependence of endothelial function in patients with CAD and coexisting COPD. Material and methods:In CAD patients with and without COPD (n = 33), we non-invasively measured flow-mediated dilation (FMD) and intima-media thickness (IMT) of the brachial artery (BA), forearm blood flow (FBF), and perfusion of the cutaneous microcirculation with laser Doppler perfusion imaging (LDPI). In an experimental setup, vascular function was assessed in healthy volunteers (n = 5) breathing 12% oxygen or 100% oxygen in comparison to room air. Results:COPD was associated with impaired FMD (3.4 ±0.5 vs. 4.2 ±0.6%; p < 0.001) and increased IMT (0.49 ±0.04 vs. 0.44 ±0.04 mm; p <0.01), indicating functional and structural alterations of the BA in COPD. Forearm blood flow and LDPI were comparable between the groups. Flow-mediated dilation correlated with capillary oxygen pressure (pO2, r = 0.608). Subgroup analysis in COPD patients with pO2 > 65 mm Hg and pO2 ? 65 mm Hg revealed even lower FMD in patients with lower pO2 (3.0 ±0.5 vs. 3.7 ±0.4%; p < 0.01). Multivariate analysis showed that pO2 was a predictor of FMD independent of the forced expiratory volume and pack years. Exposure to hypoxic air led to an acute decrease in FMD, whereby exposure to 100% oxygen did not change vascular function. Conclusions:Our data suggest that in CAD patients with COPD, decreased systemic oxygen levels lead to endothelial dysfunction, underlining the relevance of cardiopulmonary interaction and the potential importance of pulmonary treatment in secondary prevention of vascular disease.
Project description:Arterial stiffness (AS) is a well-accepted and reliable predictor of atherosclerotic diseases. Inflammation plays an important role in the development of AS.To evaluate local carotid stiffness (CS) together with fibrinogen and high-sensitivity C-reactive protein (hsCRP) levels in stable angina pectoris (SAP) patients.The study consisted of 353 consecutive patients with SAP. All underwent coronary angiography (CAG) after the evaluation of local CS parameters and carotid intima-media thickness (IMT) from both common carotid arteries by a real-time echo-tracking system. Baseline inflammatory biomarkers, serum hsCRP and fibrinogen levels were measured. Based on CAG findings, the patients were classified into 4 groups: control subjects with normal coronary arteries (group 1, n = 86), single-vessel disease (group 2, n = 104), double-vessel disease (group 3, n = 95) and triple-vessel disease (group 4, n = 68).The mean carotid pulse wave velocity (PWV) in patients with angiographically confirmed coronary artery disease (CAD) was significantly higher than that in patients with normal coronary arteries (7.82 ±1.76 vs. 6.51 ±0.85 cm/s, p = 0.001). The mean carotid IMT was detected to be significantly higher in group 4 patients compared to those in group 1 (p < 0.001) and group 2 (p = 0.001). Significant correlations were observed between both inflammatory biomarkers and the number of diseased vessels and carotid PWV. Using multi-variate analysis, carotid stiffness, carotid IMT, hsCRP and fibrinogen were independently associated with the presence and extent of CAD.Local CS, carotid IMT, hsCRP and fibrinogen levels are significant predictors of atherosclerotic burden and they may facilitate the identification of high-risk patients for the early diagnosis and prompt treatment of CAD.
Project description:Endothelial dysfunction has been detected in RA patients and seems to be reversed by control of inflammation. Low circulating endothelial progenitor cells (EPCs) have been described in many conditions associated with increased cardiovascular risk, including RA. The aim of this study was to investigate the effect of inhibition of TNF on EPCs in RA patients. Seventeen patients with moderate-severe RA and 12 sex and age-matched controls were evaluated. Endothelial biomarkers were tested at baseline and after 3 months. EPCs were identified from peripheral blood mononuclear cells by cytofluorimetry using anti-CD34 and anti-vascular endothelial growth factor-receptor 2. Asymmetric dimethylarginine (ADMA) was tested by ELISA and flow-mediated dilatation (FMD) by ultrasonography. Circulating EPCs were significantly lower in RA patients than in controls (P = 0.001). After 3 months EPCs increased significantly (P = 0.0006) while ADMA levels significantly decreased (P = 0.001). An inverse correlation between mean increase in EPCs number and mean decrease of DAS28 after treatment was observed (r = -0.56, P = 0.04). EPCs inversely correlated with ADMA (r = -0.41, P = 0.022). No improvement of FMD was detected. Short-term treatment with anti-TNF was able to increase circulating EPCs concurrently with a proportional decrease of disease activity suggesting that therapeutic intervention aimed at suppressing the inflammatory process might positively affect the endothelial function.
Project description:Endothelial dysfunction is the postulated link between coronary artery disease (CAD) and erectile dysfunction (ED). Brachial artery flow-mediated vasodilatation (FMD) is a non-invasive surrogate marker for endothelial function assessment. Despite Asian Indians representing a considerable global CAD burden, data on FMD and ED in these patients are lacking. Of the 225 patients undergoing coronary angiography, 72% had ED (assessed using the International Index of Erectile Function (IIEF-5) questionnaire); ED was moderate to severe in 61% of the patients. ED patients had a higher incidence of severe and diffuse angiographic CAD, a greater number of coronary vessels involved and a lower mean brachial artery FMD (6.40%±4.60% vs. 9.10%±4.87%, P<0.001) compared to non-ED patients. A progressive reduction in FMD was noted with increasing severity of ED. Impaired FMD (≤5.5%) was twice as common in ED patients (52% vs. 24% without ED). Patients with impaired FMD had higher ED prevalence (85% vs. 62%) and lower mean IIEF-5 scores compared to those with normal FMD. Impaired FMD was a significant ED predictor independent of other risk factors (odds ratio, 2.33; 95% confidence interval: 0.59-9.23; P=0.03). An inverse correlation between FMD and ED severity was observed (r=-0.22; P=0.004). ED is common among Asian Indians with angiographically documented CAD. Patients with ED have impaired FMD independent of other risk factors, suggesting that endothelial dysfunction is the underlying pathophysiology. Urologists and cardiologists need to be aware of the association between ED, CAD and endothelial dysfunction.
Project description:The determinants of HIV-associated cardiovascular disease (CVD) are not well understood. Periodontal disease (PD) has been linked to CVD but this connection has not been examined in HIV infection. We followed a cohort of HIV-infected adults to ascertain whether PD was associated with carotid artery intima media thickness (IMT) and brachial artery flow-mediated dilation (FMD). We performed a longitudinal observational study of HIV-infected adults on HAART for <2 years with no known heart disease. PD was characterized clinically and microbiologically. Cardiovascular disease was assessed by IMT/FMD. Linear mixed models assessed cross-sectional and longitudinal associations between PD and FMD/IMT. Forty three HIV(+) adults completed a median of 24 (6-44) months on the study. Defining delta to be the change in a variable between baseline and a follow-up time, longitudinally, on average and after adjusting for change in time, CVD-specific and HIV-specific potential confounding covariates, a 1-log(10) increase in delta Porphyromonas gingivalis was associated with a 0.013 mm increase in delta IMT (95% CI: 0.0006-0.0262; p=0.04). After adjusting for the same potential confounding covariates, a 10% increase in delta gingival recession was associated with a 2.3% increase in delta FMD (95% CI: 0.4-4.2; p=0.03). In a cohort of HIV-infected adults, an increase in subgingival Porphyromonas gingivalis, a known periodontal pathogen, was significantly associated with longitudinal increases in IMT, while increased gingival recession, which herein may represent PD resolution, was significantly associated with longitudinal improvement in FMD. In the context of HIV infection, PD may contribute to CVD risk. Intervention studies treating PD may help clarify this association.