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1.
Vasa ; 52(2): 81-85, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36734252

RESUMEN

Tobacco consumption is one of the most important risk factors for cardiovascular disease. Despite all efforts to curb any form of smoking, the number of e-cigarette users is still rising more than tabacco smoking decreases. E-cigarettes are often advertised as less harmful than regular cigarettes and helpful for smoking cessation. But e-cigarettes are not risk-free and their use causes vascular damage. There is concern about long-term health risks of e-cigarettes or when non-smokers use them as first nicotine contact. Furthermore, their use for smoking cessation is discussed controversially. To optimize treatment and medical counselling of current smokers and e-cigarette users, we present an evidence-based overview of the most important issues of e-cigarette use from a vascular medicine point of view. The key messages are presented as a position statement of the German Society of Vascular Medicine and endorsed by the European Society of Vascular Medicine.


Asunto(s)
Sistemas Electrónicos de Liberación de Nicotina , Cese del Hábito de Fumar , Humanos , Fumar/efectos adversos , Factores de Riesgo
2.
Vasa ; 51(3): 121-137, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35418243

RESUMEN

With an increasing global burden of patients with chronic peripheral artery disease (PAD) the safe and effective provision of lower limb revascularisation is a growing medical need. Endovascular procedures for the treatment of PAD have become a crucial cornerstone of modern vascular medicine, and the first line revascularisation approach if technically feasible and taking patient choice into consideration. With the increasing age of patients with PAD and the increasing number of comorbidities open vascular surgery is also often not feasible. We outline a framework of key messages, endorsed by the board of the European Society of Vascular Medicine for pre-, peri- and post procedural management of patients requiring endovascular arterial procedures of the lower limbs. These key messages emphasize the important and increasing role of interventional vascular physicians.


Asunto(s)
Cardiología , Procedimientos Endovasculares , Enfermedad Arterial Periférica , Procedimientos Endovasculares/efectos adversos , Procedimientos Endovasculares/métodos , Humanos , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/cirugía , Factores de Riesgo , Resultado del Tratamiento
3.
Vasa ; 50(6): 462-467, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34743586

RESUMEN

Background: There is limited information regarding the effects of air pollutants, such as nitrogen oxides (NOx), nitric oxide (NO2), nitrous oxide (NO) and particulate matter with a diameter smaller than 10 µm (PM10), on acute limb ischaemia (ALI), a peripheral arterial disease (PAD) often with a poor clinical outcome. Patients and methods: We conducted an 18-year retrospective cohort study using routinely collected healthcare records from Ninewells Hospital, Dundee, and Perth Royal Infirmary, in Tayside, Scotland, UK from 2000 to 2017. ALI hospitalisation events and deaths were linked to daily NOx, NO2, NO and PM10 levels extracted from publicly available data over this same time period. Distributed lag models were used to estimate risk ratios for ALI hospitalisation and for ALI mortality, adjusting for temperature, humidity, day of the week, month and public holiday. Results: 5,608 hospital admissions in 2,697 patients were identified over the study period (mean age 71.2 years, ±11.1). NOx and NO were associated with an increase of ALI hospital admissions on days of exposure to pollutant (p=.018), while PM10 was associated with a cumulative (lag 0-9 days) increase (p=.027) of ALI hospital admissions in our study. There was no increase of ALI mortality associated with pollution levels. Conclusions: ALI hospital admissions were positively associated with ambient NOx and NO on day of high measured pollution levels and a cumulative effect was seen with PM10.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Anciano , Contaminantes Atmosféricos/análisis , Contaminantes Atmosféricos/toxicidad , Contaminación del Aire/análisis , Contaminación del Aire/estadística & datos numéricos , Humanos , Isquemia/diagnóstico , Isquemia/epidemiología , Material Particulado/análisis , Material Particulado/toxicidad , Estudios Retrospectivos
4.
Vasa ; 50(6): 401-411, 2021 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-34743585

RESUMEN

Patients with peripheral arterial disease (PAD) are at very high risk of cardiovascular events, but risk factor management is usually suboptimal. This Joint Task Force from the European Atherosclerosis Society and the European Society of Vascular Medicine has updated evidence on the management on dyslipidaemia and thrombotic factors in patients with PAD. Guidelines recommend a low-density lipoprotein cholesterol (LDLC) goal of more than 50% reduction from baseline and <1.4 mmol/L (<55 mg/dL) in PAD patients. As demonstrated by randomized controlled trials, lowering LDL-C not only reduces cardiovascular events but also major adverse limb events (MALE), including amputations, of the order of 25%. Addition of ezetimibe or a PCSK9 inhibitor further decreases the risk of cardiovascular events, and PCSK9 inhibition has also been associated with reduction in the risk of MALE by up to 40%. Furthermore, statin- based treatment improved walking performance, including maximum walking distance, and pain-free walking distance and duration. This Task Force recommends strategies for managing statin-associated muscle symptoms to ensure that PAD patients benefit from lipid-lowering therapy. Antiplatelet therapy, either daily clopidogrel 75 mg or the combination of aspirin 100 mg and rivaroxaban (2×2.5 mg) is also indicated to prevent cardiovascular events. Dual pathway inhibition (aspirin and rivaroxaban) may be considered following revascularization, taking into account bleeding risk. This Joint Task Force believes that adherence with these recommendations for lipid-lowering and antithrombotic therapy will improve the morbidity and mortality in patients with PAD.


Asunto(s)
Inhibidores de Hidroximetilglutaril-CoA Reductasas , Enfermedad Arterial Periférica , LDL-Colesterol , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/efectos adversos , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/tratamiento farmacológico , Proproteína Convertasa 9 , Resultado del Tratamiento
5.
Int J Mol Sci ; 22(16)2021 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-34445361

RESUMEN

Inflammation promotes endothelial dysfunction, but the underlying mechanisms remain poorly defined in vivo. Using translational vascular function testing in myocardial infarction patients, a situation where inflammation is prevalent, and knock-out (KO) mouse models we demonstrate a role for mitogen-activated-protein-kinases (MAPKs) in endothelial dysfunction. Myocardial infarction significantly lowers mitogen and stress kinase 1/2 (MSK1/2) expression in peripheral blood mononuclear cells and diminished endothelial function. To further understand the role of MSK1/2 in vascular function we developed in vivo animal models to assess vascular responses to vasoactive drugs using laser Doppler imaging. Genetic deficiency of MSK1/2 in mice increased plasma levels of pro-inflammatory cytokines and promoted endothelial dysfunction, through attenuated production of nitric oxide (NO), which were further exacerbated by cholesterol feeding. MSK1/2 are activated by toll-like receptors through MyD88. MyD88 KO mice showed preserved endothelial function and reduced plasma cytokine expression, despite significant hypercholesterolemia. MSK1/2 kinases interact with MAPK-activated proteins 2/3 (MAPKAP2/3), which limit cytokine synthesis. Cholesterol-fed MAPKAP2/3 KO mice showed reduced plasma cytokine expression and preservation of endothelial function. MSK1/2 plays a significant role in the development of endothelial dysfunction and may provide a novel target for intervention to reduce vascular inflammation. Activation of MSK1/2 could reduce pro-inflammatory responses and preserve endothelial vasodilator function before development of significant vascular disease.


Asunto(s)
Proteínas Quinasas S6 Ribosómicas 90-kDa/fisiología , Enfermedades Vasculares/genética , Adulto , Anciano , Animales , Estudios de Casos y Controles , Células Cultivadas , Estudios de Cohortes , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Persona de Mediana Edad , Proteínas Quinasas S6 Ribosómicas 90-kDa/genética , Transducción de Señal/fisiología , Enfermedades Vasculares/fisiopatología , Adulto Joven
6.
BMC Med ; 18(1): 300, 2020 11 09.
Artículo en Inglés | MEDLINE | ID: mdl-33161898

RESUMEN

BACKGROUND: Chronic kidney disease has emerged as a strong cardiovascular risk factor, and in many current guidelines, it is already considered as a coronary heart disease (CHD) equivalent. Routinely, creatinine has been used as the main marker of renal function, but recently, cystatin C emerged as a more promising marker. The aim of this study was to assess the comparative cardiovascular and mortality risk of chronic kidney disease (CKD) using cystatin C-based and creatinine-based equations of the estimated glomerular filtration rate (eGFR) in participants of population-based and disease cohorts. METHODS: The present study has been conducted within the BiomarCaRE project, with harmonized data from 20 population-based cohorts (n = 76,954) from 6 European countries and 3 cardiovascular disease (CVD) cohorts (n = 4982) from Germany. Cox proportional hazards models were used to assess hazard ratios (HRs) for the various CKD definitions with adverse outcomes and mortality after adjustment for the Systematic COronary Risk Evaluation (SCORE) variables and study center. Main outcome measures were cardiovascular diseases, cardiovascular death, and all-cause mortality. RESULTS: The overall prevalence of CKD stage 3-5 by creatinine- and cystatin C-based eGFR, respectively, was 3.3% and 7.4% in the population-based cohorts and 13.9% and 14.4% in the disease cohorts. CKD was an important independent risk factor for subsequent CVD events and mortality. For example, in the population-based cohorts, the HR for CVD mortality was 1.72 (95% CI 1.53 to 1.92) with creatinine-based CKD and it was 2.14 (95% CI 1.90 to 2.40) based on cystatin-based CKD compared to participants without CKD. In general, the HRs were higher for cystatin C-based CKD compared to creatinine-based CKD, for all three outcomes and risk increased clearly below the conventional threshold for CKD, also in older adults. Net reclassification indices were larger for a cystatin-C based CKD definition. Differences in HRs (between the two CKD measures) in the disease cohorts were less pronounced than in the population-based cohorts. CONCLUSION: CKD is an important risk factor for subsequent CVD events and total mortality. However, point estimates of creatinine- and cystatin C-based CKD differed considerably between low- and high-risk populations. Especially in low-risk settings, the use of cystatin C-based CKD may result in more accurate risk estimates and have better prognostic value.


Asunto(s)
Enfermedad Coronaria/etiología , Creatinina/metabolismo , Cistatina C/metabolismo , Factores de Riesgo de Enfermedad Cardiaca , Enfermedades Cardiovasculares/mortalidad , Enfermedad Coronaria/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Medición de Riesgo
7.
Radiology ; 287(3): 795-804, 2018 06.
Artículo en Inglés | MEDLINE | ID: mdl-29714681

RESUMEN

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.


Asunto(s)
Aterosclerosis/diagnóstico por imagen , Aterosclerosis/epidemiología , Angiografía por Resonancia Magnética/métodos , Imagen de Cuerpo Entero/métodos , Adulto , Anciano , Anciano de 80 o más Años , Medios de Contraste , Femenino , Humanos , Aumento de la Imagen/métodos , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Riesgo , Escocia/epidemiología
8.
J Cardiovasc Magn Reson ; 20(1): 7, 2018 01 30.
Artículo en Inglés | MEDLINE | ID: mdl-29382349

RESUMEN

BACKGROUND: Arteriosclerosis (arterial stiffening) is associated with future cardiovascular events, with this effect postulated to be due to its effect on cardiac afterload, atherosclerosis (plaque formation) progression or both, but with limited evidence examining these early in disease formation. The aim of the current study is to examine the association between arteriosclerosis, atherosclerosis and ventricular remodelling in a population at low-intermediate cardiovascular risk. METHODS: One thousand six hundred fifty-one subjects free of clinical cardiovascular disease and with a < 20% 10 year cardiovascular risk score underwent a cardiovascular magnetic resonance (CMR) study and whole body CMR angiogram. Arteriosclerosis was measured using total arterial compliance (TAC) - calculated as the indexed stroke volume divided by the pulse pressure. Atherosclerosis was quantified using a standardised atheroma score (SAS) which was calculated by scoring 30 arterial segments within the body based on the degree of stenosis, summating these scores and normalising it to the number of assessable segments. Left ventricular remodelling was measured using left ventricular mass to volume ratio (LVMVR). RESULTS: One thousand five hundred fifteen (38% male, 53.8 ± 8.2 years old) completed the study. On univariate analysis TAC was associated with SAS but this was lost after accounting for cardiovascular risk factors in both males (B = - 0.001 (- 0.004-0.002),p = 0.62) and females (B = 0.000(95%CI -0.002--0.002),p = 0.78). In contrast compliance correlated with LVMVR after accounting for cardiovascular risk factors (B = - 0.12(95%CI -0.16--0.091),p < 0.001 in males; B = - 0.12(95%CI -0.15--0.086),p < 0.001 in females). CONCLUSION: Systemic arteriosclerosis is associated with left ventricular remodelling but not atherosclerosis. Future efforts in cardiovascular risk prevention should thus seek to address both arteriosclerosis and atherosclerosis individually.


Asunto(s)
Arteriosclerosis/diagnóstico por imagen , Cardiopatías/diagnóstico por imagen , Angiografía por Resonancia Magnética , Imagen por Resonancia Cinemagnética , Enfermedad Arterial Periférica/diagnóstico por imagen , Rigidez Vascular , Función Ventricular Izquierda , Remodelación Ventricular , Arteriosclerosis/fisiopatología , Estudios de Casos y Controles , Femenino , Cardiopatías/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/fisiopatología , Placa Aterosclerótica , Valor Predictivo de las Pruebas , Pronóstico , Imagen de Cuerpo Entero
9.
BMC Cardiovasc Disord ; 18(1): 31, 2018 02 13.
Artículo en Inglés | MEDLINE | ID: mdl-29433433

RESUMEN

BACKGROUND: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. METHODS: One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. RESULTS: EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.001; group 3 EAT 15.1 ± 4.3 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.024). EAT was independently associated with IL-6 (beta 0.2, p = 0.019). When added to clinical variables, both EAT (beta 0.16, p = 0.035) and IL-6 (beta 0.26, p = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. CONCLUSIONS: In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.


Asunto(s)
Tejido Adiposo/fisiopatología , Adiposidad , Enfermedades Cardiovasculares/fisiopatología , Diabetes Mellitus Tipo 2/fisiopatología , Inflamación/fisiopatología , Rigidez Vascular , Tejido Adiposo/diagnóstico por imagen , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Femenino , Humanos , Inflamación/diagnóstico , Inflamación/epidemiología , Imagen por Resonancia Cinemagnética , Masculino , Persona de Mediana Edad , Pericardio , Análisis de la Onda del Pulso , Factores de Riesgo , Escocia/epidemiología
10.
BMC Med Imaging ; 16: 18, 2016 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-26923316

RESUMEN

BACKGROUND: The aim of this study was to use whole body cardiovascular magnetic resonance imaging (WB CVMR) to assess the heart and arterial network in a single examination, so as to describe the burden of atherosclerosis and subclinical disease in participants with symptomatic single site vascular disease. METHODS: 64 patients with a history of symptomatic single site vascular disease (38 coronary artery disease (CAD), 9 cerebrovascular disease, 17 peripheral arterial disease (PAD)) underwent whole body angiogram and cardiac MR in a 3 T scanner. The arterial tree was subdivided into 31 segments and each scored according to the degree of stenosis. From this a standardised atheroma score (SAS) was calculated. Cine and late gadolinium enhancement images of the left ventricle were obtained. RESULTS: Asymptomatic atherosclerotic disease with greater than 50% stenosis in arteries other than that responsible for their presenting complain was detected in 37% of CAD, 33% of cerebrovascular and 47% of PAD patients. Unrecognised myocardial infarcts were observed in 29% of PAD patients. SAS was significantly higher in PAD patients 24 (17.5-30.5) compared to CAD 4 (2-11.25) or cerebrovascular disease patients 6 (2-10) (ANCOVA p < 0.001). Standardised atheroma score positively correlated with age (ß 0.36 p = 0.002), smoking status (ß 0.34 p = 0.002), and LV mass (ß -0.61 p = 0.001) on multiple linear regression. CONCLUSION: WB CVMR is an effective method for the stratification of cardiovascular disease. The high prevalence of asymptomatic arterial disease, and silent myocardial infarctions, particularly in the peripheral arterial disease group, demonstrates the importance of a systematic approach to the assessment of cardiovascular disease.


Asunto(s)
Aterosclerosis/diagnóstico , Enfermedades Cardiovasculares/complicaciones , Imagen por Resonancia Magnética/métodos , Imagen de Cuerpo Entero/métodos , Factores de Edad , Anciano , Aterosclerosis/epidemiología , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de Riesgo
12.
J Cardiovasc Nurs ; 31(4): 323-30, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27299758

RESUMEN

The purpose of this study was to investigate the effects of 2 types of transcutaneous electrical nerve stimulation (TENS) on walking distance and measures of pain in patients with peripheral arterial disease (PAD) and intermittent claudication (IC). In a phase 2a study, 40 participants with PAD and IC completed a graded treadmill test on 2 separate testing occasions. Active TENS was applied to the lower limb on the first occasion; and placebo TENS, on the second. The participants were divided into 2 experimental groups. One group received high-frequency TENS; and the other, low-frequency TENS. Measures taken were initial claudication distance, functional claudication distance, and absolute claudication distance. The McGill Pain Questionnaire (MPQ) vocabulary was completed at the end of the intervention, and the MPQ-Pain Rating Index score was calculated. Four participants were excluded from the final analysis because of noncompletion of the experimental procedure. Median walking distance increased with high-frequency TENS for all measures (P < .05, Wilcoxon signed rank test, all measures). Only absolute claudication distance increased significantly with low-frequency TENS compared with placebo (median, 179-228; Ws = 39; z = 2.025; P = .043; r = 0.48). No difference was observed between reported median MPQ-Pain Rating Index scores: 21.5 with placebo TENS and 21.5 with active TENS (P = .41). Transcutaneous electrical nerve stimulation applied to the lower limb of the patients with PAD and IC was associated with increased walking distance on a treadmill but not with any reduction in pain. Transcutaneous electrical nerve stimulation may be a useful adjunctive intervention to help increase walking performance in patients with IC.


Asunto(s)
Claudicación Intermitente/terapia , Estimulación Eléctrica Transcutánea del Nervio , Caminata , Humanos , Dimensión del Dolor , Enfermedad Arterial Periférica
15.
Microvasc Res ; 85: 86-92, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23123637

RESUMEN

Endothelial dysfunction is associated with early development of cardiovascular disease, making longitudinal measurements desirable. We devised a protocol using laser Doppler imaging (LDI) and iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) to assess the skin microcirculation longitudinally in mice every 4 weeks for 24 weeks in two groups of C57BL/6 mice, chow versus high-cholesterol diet(known to induce endothelial dysfunction). LDI measurements were compared with vascular function (isometric tension) measured using wire myography in the tail artery in response to ACh and SNP. Microvascular responses to ACh were significantly reduced in cholesterol-fed versus chow-fed mice from week 4 onwards (P<0.005, ANOVA). Pre-treatment with N(G)-nitro-L-arginine methyl-ester-hydrochloride (L-NAME) showed a significant reduction in ACh response compared with vehicle-treated animals (P<0.05) at baseline and at 12 weeks. In cholesterol-fed mice, ACh responses were 226 ± 21 and 180 ± 21 AU (P=0.03) before and after L-NAME, respectively. A reduction in ex-vivo ACh response was detected in the tail artery in cholesterol-fed mice, and a significant correlation found between peak microvascular ACh response and maximum ACh response in the tail artery (r=0.699, P=0.017). No changes were found in SNP responses in the microvasculature or tail artery. Using this protocol, we have shown longitudinal decreases in microvascular endothelial function to cholesterol feeding. L-NAME studies confirm that the reduced vasodilatation to ACh in cholesterol-fed mice was mediated partly through reduced NO bioavailability. Wire myography of tail arteries confirmed that in-vivo measurements of microvascular function reflect ex-vivo vascular function in other beds. Longitudinal assessments of skin microvascular function in mice could provide a useful translatable model for assessing early endothelial dysfunction.


Asunto(s)
Endotelio Vascular/patología , Acetilcolina/metabolismo , Animales , Aorta/patología , Arterias/patología , Peso Corporal , Colesterol/metabolismo , Progresión de la Enfermedad , Relación Dosis-Respuesta a Droga , Endotelio Vascular/metabolismo , Flujometría por Láser-Doppler/métodos , Lípidos/química , Masculino , Ratones , Ratones Endogámicos C57BL , Microcirculación , NG-Nitroarginina Metil Éster/farmacología , Óxido Nítrico/química , Nitroprusiato/farmacología
16.
Circulation ; 124(16): 1765-73, 2011 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-21947297

RESUMEN

BACKGROUND: Hypoxia-inducible factor-1α (HIF-1α) is a transcriptional regulatory factor that orchestrates cellular responses to hypoxia. It increases collateral vessel growth and blood flow in models of hind-limb ischemia. This study tested whether intramuscular administration of Ad2/HIF-1α/VP16, an engineered recombinant type 2 adenovirus vector encoding constitutively active HIF-1α, improves walking time in patients with peripheral artery disease and intermittent claudication. METHODS AND RESULTS: Two hundred eighty-nine patients with claudication were randomized in a double-blind manner to 1 of 3 doses of Ad2/HIF-1α/VP16 (2×10(9), 2×10(10), or 2×10(11) viral particles) or placebo, administered by 20 intramuscular injections to each leg. Graded treadmill tests were performed at baseline and then 3, 6, and 12 months after treatment. The primary end point was the change in peak walking time from baseline to 6 months. The secondary end point was change in claudication onset time, and tertiary end points included changes in ankle-brachial index and quality-of-life assessments. Median peak walking time increased by 0.82 minutes (interquartile range, -0.05-1.93 minutes) in the placebo group and by 0.82 minutes (interquartile range, -0.07-2.12 minutes), 0.28 minutes (interquartile range, -0.37-1.70 minutes), and 0.78 minutes (interquartile range, -0.02-2.10 minutes) in the HIF-1α 2×10(9), 2×10(10), and 2×10(11) viral particle groups, respectively (P=NS between placebo and each HIF-1α treatment group). There were no significant differences in claudication onset time, ankle-brachial index, or quality-of-life measurements between the placebo and each HIF-1α group. CONCLUSIONS: Gene therapy with intramuscular administration of Ad2/HIF-1α/VP16 is not an effective treatment for patients with intermittent claudication. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00117650.


Asunto(s)
Terapia Genética/métodos , Subunidad alfa del Factor 1 Inducible por Hipoxia/administración & dosificación , Claudicación Intermitente/terapia , Caminata , Adenoviridae/genética , Adulto , Anciano , Anciano de 80 o más Años , Método Doble Ciego , Prueba de Esfuerzo/efectos de los fármacos , Femenino , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/uso terapéutico , Claudicación Intermitente/genética , Claudicación Intermitente/fisiopatología , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/terapia , Calidad de Vida , Insuficiencia del Tratamiento
17.
Clin Sci (Lond) ; 123(5): 307-12, 2012 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-22439818

RESUMEN

BNP (B-type natriuretic peptide) has been reported to be elevated in preclinical states of vascular damage. To elucidate the relationship between plasma BNP and endothelial function, we have investigated the relationship between BNP and endothelial function in a cohort of subjects comprising healthy subjects as well as at-risk subjects with cardiovascular risk factors. To also clarify the relative contribution of different biological pathways to the individual variation in endothelial function, we have examined the relationship between a panel of multiple biomarkers and endothelial function. A total of 70 subjects were studied (mean age, 58.1±4.6 years; 27% had a history of hypertension and 18% had a history of hypercholesterolaemia). Endothelium-dependent vasodilatation was evaluated by the invasive ACH (acetylcholine)-induced forearm vasodilatation technique. A panel of biomarkers of biological pathways was measured: BNP, haemostatic factors PAI-1 (plasminogen-activator inhibitor 1) and tPA (tissue plasminogen activator), inflammatory markers, including cytokines [hs-CRP (high sensitive C-reactive protein), IL (interleukin)-6, IL-8, IL-18, TNFα (tumour necrosis factor α) and MPO (myeloperoxidase] and soluble adhesion molecules [E-selectin and sCD40 (soluble CD40)]. The median BNP level in the study population was 26.9 pg/ml. Multivariate regression analyses show that age, the total cholesterol/HDL (high-density lipoprotein) ratio, glucose and BNP were independent predictors of endothelial function, and BNP remained an independent predictor (P=0.009) in a binary logistic regression analysis using FBF (forearm blood flow) as a dichotomous variable based on the median value. None of the other plasma biomarkers was independently related to ACH-mediated vasodilatation. In a strategy using several biomarkers to relate to endothelial function, plasma BNP was found to be an independent predictor of endothelial function as assessed by endothelium-dependent vasodilatation in response to ACH.


Asunto(s)
Arteria Braquial/fisiología , Endotelio Vascular/fisiología , Péptido Natriurético Encefálico/sangre , Vasodilatación , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Estudios de Cohortes , Femenino , Humanos , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Factores de Riesgo
18.
Ann Vasc Surg ; 26(8): 1093-9, 2012 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-22682930

RESUMEN

BACKGROUND: A number of surgical strategies and graft enhancements have been trialled to improve the performance of prosthetic grafts. Neointimal hyperplasia may, in part, be a normal cellular response to an abnormal (turbulent) flow environment. This first-in-many study assesses the safety and medium-term patency performance of a new graft designed to induce stable laminar flow through the distal anastomosis. METHOD: Forty patients who required an infrainguinal bypass graft were recruited/registered from a number of centers in Belgium and The Netherlands. Thirty-nine received a Spiral Laminar Flow graft as part of a standard treatment protocol (23 above-the-knee and 16 below-the-knee bypasses). Kaplan-Meier analyses were used to calculate primary and secondary patency rates. RESULTS: The 12-, 24-, and 30-month primary patency rates were 86%, 81%, and 81% for above-the-knee bypasses and 73%, 57%, and 57% for below-the-knee bypasses, respectively. In the case of secondary patency rates, numbers were unchanged for above-the-knee bypasses and were 86%, 64%, and 64%, respectively, for below-the-knee bypasses. There were no amputations in the study population. CONCLUSION: This first-in-man series shows potential for the idea of spiral flow-enhanced prosthetic grafts. As always, randomized studies are required to explore the role of different enhanced prosthetic grafts.


Asunto(s)
Implantación de Prótesis Vascular/instrumentación , Prótesis Vascular , Extremidad Inferior/irrigación sanguínea , Enfermedad Arterial Periférica/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Bélgica , Velocidad del Flujo Sanguíneo , Implantación de Prótesis Vascular/efectos adversos , Femenino , Oclusión de Injerto Vascular/etiología , Oclusión de Injerto Vascular/fisiopatología , Humanos , Estimación de Kaplan-Meier , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Países Bajos , Enfermedad Arterial Periférica/diagnóstico por imagen , Enfermedad Arterial Periférica/fisiopatología , Estudios Prospectivos , Diseño de Prótesis , Flujo Sanguíneo Regional , Sistema de Registros , Estrés Mecánico , Factores de Tiempo , Resultado del Tratamiento , Ultrasonografía Doppler en Color , Grado de Desobstrucción Vascular
19.
BMJ Open ; 12(10): e063594, 2022 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-36270757

RESUMEN

PURPOSE: Risk factor-based models struggle to accurately predict the development of cardiovascular disease (CVD) at the level of the individual. Ways of identifying people with low predicted risk who will develop CVD would allow stratified advice and support informed treatment decisions about the initiation or adjustment of preventive medication, and this is the aim of this prospective cohort study. PARTICIPANTS: The Tayside Screening for Cardiac Events (TASCFORCE) study recruited men and women aged≥40 years, free from known CVD, with a predicted 10-year risk of coronary heart disease<20%. If B-type natriuretic peptide (BNP) was greater than their gender median, participants were offered a whole-body contrast-enhanced MRI (WBCE-MRI) scan (cardiac imaging, whole-body angiography to determine left ventricular parameters, delayed gadolinium enhancement, atheroma burden). Blood, including DNA, was stored for future biomarker assays. Participants are being followed up using electronic record-linkage cardiovascular outcomes. FINDINGS TO DATE: 4423 (1740, 39.3% men) were recruited. Mean age was 52.3 years with a median BNP of 7.50 ng/L and 15.30 ng/L for men and women, respectively. 602 had a predicted 10-year risk of 10%-19.9%, with the remainder<10%. Age, female sex, ex-smoking status, lower heart rate, higher high-density lipoprotein and lower total cholesterol were independently associated with higher log10 BNP levels. Mean left ventricular mass was 129.2 g and 87.0 g in men and women, respectively. FUTURE PLANS: The TASCFORCE study is investigating the ability of a screening programme, using BNP and WBCE-MRI, at the time of enrolment, to evaluate prediction of CVD in a population at low/intermediate risk. Blood stored for future biomarker analyses will allow testing/development of novel biomarkers. We believe this could be a new UK Framingham study allowing study for many years to come. CLINICAL TRIAL REGISTRATION: ISRCTN38976321.


Asunto(s)
Enfermedades Cardiovasculares , Masculino , Humanos , Femenino , Persona de Mediana Edad , Estudios Prospectivos , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Péptido Natriurético Encefálico , Gadolinio , Medios de Contraste , Factores de Riesgo , Factores de Riesgo de Enfermedad Cardiaca , Biomarcadores , Colesterol , Lipoproteínas HDL
20.
Prev Med ; 52(5): 387-9, 2011 May.
Artículo en Inglés | MEDLINE | ID: mdl-21419792

RESUMEN

OBJECTIVE: To assess the feasibility of a lifestyle intervention, focusing on diet and activity, in adults participating in cardiovascular screening. METHODS: The 12-week lifestyle intervention comprised three personalised counselling sessions plus telephone contact. Outcome data were collected by anthropometry, activity monitoring and lifestyle questionnaires. Acceptability of study measures was assessed by questionnaire and the intervention delivery by in-depth interviews. RESULTS: Between June 2008 and March 2009, 75 (62%) of 121 eligible individuals were recruited from Tayside, Scotland. Randomisation was to intervention (IV) (n=55) or comparison group (CG) (n=20). Retention was 99% across both groups. In the IV group, 63% increased moderate-vigorous activity by ≥ 30 minutes/week, 82% successfully maintained or lost weight (mean loss 1.1 kg, and 2.6 cm waist circumference) and 85% reported eating five portions of fruit and vegetables compared with 56% at baseline. No behaviour changes were detected in the CG. Feedback highlighted the value of lifestyle "checks," realising that current habits were sub-optimal, receiving personalised advice on specific behaviours, and feeling "healthier" through participation. CONCLUSIONS: HealthForce was feasible to deliver and implement, acceptable to participants, and associated with reported changes in health behaviours over a 12-week period.


Asunto(s)
Enfermedades Cardiovasculares , Promoción de la Salud , Estilo de Vida , Tamizaje Masivo , Estudios de Factibilidad , Femenino , Humanos , Entrevistas como Asunto , Masculino , Persona de Mediana Edad , Medición de Riesgo , Conducta de Reducción del Riesgo
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