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1.
Eur J Vasc Endovasc Surg ; 53(3): 371-379, 2017 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-27919605

RESUMEN

OBJECTIVES: International guidelines recommend revascularisation as the preferred treatment for patients with critical limb ischaemia (CLI). Most contemporary research focuses on the outcome of invasive procedures for CLI, but little is known about the outcome of conservative management. Amputation free survival (AFS) and overall survival (OS) was investigated in patients with CLI who did or did not receive revascularisation, and characteristics associated with clinical outcomes were explored. METHODS: This was a retrospective cohort study of consecutive patients with chronic CLI between 2010 and 2014 in a Dutch university hospital. CLI was defined as the presence of ischaemic rest pain or tissue loss in conjunction with an absolute systolic ankle pressure < 50 mmHg or a toe pressure < 30 mmHg. Patients were divided into invasive (revascularisation within 6 weeks), deferred invasive (revascularisation after 6 weeks), or permanently conservative treatment groups. Univariable and multivariable survival analyses were used to identify factors associated with AFS and OS. RESULTS: The majority (66.7%; N = 96) of the identified 144 patients with CLI (mean age 71.2 years; median follow-up 99 weeks) underwent revascularisation within 6 weeks of diagnosis. Deferred invasive treatment was provided in 18.1% (N = 26) patients and 22 patients (15.3%) were treated permanently conservatively. AFS and OS did not differ significantly between the three groups (Breslow-Wilcoxon p = .16 for AFS and p = .09 for OS). Age, chronic obstructive pulmonary disease (COPD), and heart disease were significant independent predictors of AFS. Age, COPD, and hypertension were significant independent predictors of OS. Treatment was not a significant predictor of either AFS or OS. CONCLUSIONS: Not all patients with CLI require revascularisation to achieve an AFS that is similar to patients undergoing revascularisation, although the efficacy of conservative versus invasive treatment in CLI patients is still unclear. Further prospective studies should determine subgroups of patients in whom revascularisation may be omitted.


Asunto(s)
Isquemia/terapia , Anciano , Anciano de 80 o más Años , Amputación Quirúrgica , Distribución de Chi-Cuadrado , Enfermedad Crítica , Supervivencia sin Enfermedad , Femenino , Hospitales Universitarios , Humanos , Isquemia/diagnóstico por imagen , Isquemia/mortalidad , Isquemia/fisiopatología , Estimación de Kaplan-Meier , Recuperación del Miembro , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos , Selección de Paciente , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento , Procedimientos Innecesarios
2.
Atherosclerosis ; 240(2): 318-23, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25864162

RESUMEN

AIMS: Intensive glucose control, often involving insulin treatment, failed to improve cardiovascular outcomes in several clinical trials. Observational studies reported an association between insulin use and cardiovascular disease (CVD) risk. It has therefore been suggested that insulin adversely affects CVD risk. To investigate the feasibility of this hypothesis, we studied the association between insulin dose and CVD risk in type 2 diabetes. METHODS: A case-control study was conducted of new users of oral antidiabetics who were prescribed insulin, using the Dutch Pharmo database. Cases were hospitalized for a cardiovascular event (CVE) and matched 1:2 to patients who were not hospitalized for a CVE, by sex, age, duration of diabetes and type of oral antidiabetic. Patients were divided into tertiles according to mean daily insulin dose. Conditional logistic regression analyses were used to explore the association between insulin exposure and CVE risk. RESULTS: We included 836 patients (517 (62%) male, mean age 66 years). After adjusting for available potential confounders, including HbA1c and triglycerides, insulin exposure was positively related to CVE risk (odds ratios for high (≥53.0 U/day) and intermediate (24.3-52.9 U/day) vs. low exposure (≤24.2 U/day): 3.00 [95% confidence interval (CI) 1.70 to 5.28] and 2.03 [95% CI 1.17 to 3.52]. CONCLUSION: Our findings are in line with the suggestion that high-dose insulin therapy adversely affects CVD risk, but need to be interpreted with caution due to the observational nature of the study. The role of particularly high-dose insulin in the progression of CVD warrants further investigation.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/efectos adversos , Insulina/efectos adversos , Anciano , Biomarcadores/sangre , Glucemia/efectos de los fármacos , Glucemia/metabolismo , Enfermedades Cardiovasculares/diagnóstico , Bases de Datos Factuales , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiología , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Hemoglobina Glucada/metabolismo , Humanos , Hipoglucemiantes/administración & dosificación , Insulina/administración & dosificación , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Países Bajos/epidemiología , Oportunidad Relativa , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
3.
Handb Exp Pharmacol ; 224: 631-48, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-25523005

RESUMEN

A wealth of evidence indicates that plasma levels of high-density lipoprotein cholesterol (HDL-C) are inversely related to the risk of cardiovascular disease (CVD). Consequently, HDL-C has been considered a target for therapy in order to reduce the residual CVD burden that remains significant, even after application of current state-of-the-art medical interventions. In recent years, however, a number of clinical trials of therapeutic strategies that increase HDL-C levels failed to show the anticipated beneficial effect on CVD outcomes. As a result, attention has begun to shift toward strategies to improve HDL functionality, rather than levels of HDL-C per se. ApoA-I, the major protein component of HDL, is considered to play an important role in many of the antiatherogenic functions of HDL, most notably reverse cholesterol transport (RCT), and several therapies have been developed to mimic apoA-I function, including administration of apoA-I, mutated variants of apoA-I, and apoA-I mimetic peptides. Based on the potential anti-inflammatory effects, apoA-I mimetics hold promise not only as anti-atherosclerotic therapy but also in other therapeutic areas.


Asunto(s)
Apolipoproteína A-I/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , Diseño de Fármacos , Dislipidemias/tratamiento farmacológico , Hipolipemiantes/uso terapéutico , Imitación Molecular , Fragmentos de Péptidos/uso terapéutico , Animales , Apolipoproteína A-I/administración & dosificación , Apolipoproteína A-I/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/metabolismo , Dislipidemias/complicaciones , Dislipidemias/metabolismo , Humanos , Hipolipemiantes/administración & dosificación , Infusiones Parenterales
4.
Eur J Vasc Endovasc Surg ; 49(2): 192-8, 2015 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-25516530

RESUMEN

OBJECTIVE/BACKGROUND: Arterial calcification may render the ankle-brachial index (ABI) unreliable in diabetic patients. Although guidelines recommend the toe-brachial index (TBI) for patients with falsely elevated ABI arbitrarily defined as an ABI > 1.4, arterial calcification is also common among diabetic patients with an ABI ≤ 1.4. This could result in a "falsely normalized" ABI and under-diagnosis of peripheral arterial disease (PAD). We investigated whether diabetes invalidates the ABI as opposed to the TBI, and if the TBI may therefore be more suitable for detecting PAD in diabetic patients. METHODS: The difference between ABI and TBI was compared between diabetic and non-diabetic patients with an ABI ≤ 1.4 referred to the vascular laboratory. A Bland-Altman plot was constructed to assess whether ABI-TBI differences were dependent on the magnitude of the measurements. Subgroup analyses were performed for patients with a normal ABI, and for patients with critical ischemia. RESULTS: The population comprised 161 diabetic (252 limbs) and 160 non-diabetic (253 limbs) patients (mean age 67). Median ABIs (0.79 vs. 0.80) were similar, while median TBI was 0.07 higher in diabetics (p = 0.024). The ABI-TBI difference in diabetics and non-diabetics was similar (0.32 vs. 0.35; p = .084), and was also similar for patients with a normal ABI. Moreover, ABI-TBI differences in diabetic- and non-diabetic patients overlapped, irrespective of the magnitude of the measurements. Diabetes was not associated with larger differences between ankle and toe pressures (mean difference -0.9 mmHg, 95% confidence interval -15 to 13 mmHg) among patients with critical ischemia. CONCLUSION: No evidence was found that the TBI may overcome the potentially invalidated ABI in diabetic patients with an ABI ≤ 1.4. ABI and TBI are strongly associated, and this relationship is not influenced by diabetes. Therefore, the TBI does not allow for earlier detection of ischemia in diabetes.


Asunto(s)
Índice Tobillo Braquial , Angiopatías Diabéticas/diagnóstico , Enfermedad Arterial Periférica/diagnóstico , Calcificación Vascular/diagnóstico , Anciano , Anciano de 80 o más Años , Presión Arterial , Estudios Transversales , Angiopatías Diabéticas/fisiopatología , Diagnóstico Precoz , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad Arterial Periférica/fisiopatología , Valor Predictivo de las Pruebas , Flujo Sanguíneo Regional , Reproducibilidad de los Resultados , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Calcificación Vascular/fisiopatología , Rigidez Vascular
5.
Eur J Vasc Endovasc Surg ; 47(6): 647-55, 2014 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-24726143

RESUMEN

OBJECTIVE: A systematic review of randomized clinical trials (RCTs) to assess the additional value of hyperbaric oxygen therapy (HBOT) in promoting the healing of diabetic foot ulcers and preventing amputations was performed. METHODS: MEDLINE, Embase, and the Cochrane Library were searched to identify RCTs in patients with diabetic foot ulcers published up to August 2013. Eligible studies reported the effectiveness of adjunctive HBOT with regard to wound healing, amputations, and additional interventions. RESULTS: Seven of the 669 identified articles met the inclusion criteria, comprising 376 patients. Three trials included 182 patients with ischaemic ulcers, two trials studied 64 patients with non-ischaemic ulcers, and two trials comprising 130 patients did not specify ulcer type. Two trials were of good methodological quality. Pooling of data was deemed inappropriate because of heterogeneity. Two RCTs in patients with ischaemic ulcers found increased rates of complete healing at 1-year follow-up (number needed to treat (NNT) 1.8 (95% CI: 1.1 to 4.6) and 4.1 (95% CI: 2.3 to 19)), but found no difference in amputation rates. A third trial in ischaemic ulcers found significantly lower major amputation rates in patients with HBOT (NNT 4.2, 95% CI: 2.4 to 17), but did not report on wound healing. None of the RCTs in non-ischaemic ulcers reported differences in wound healing or amputation rates. Two trials with unknown ulcer types reported beneficial effects on amputation rates, although the largest trial used a different definition for both outcomes. HBOT did not influence the need for additional interventions. CONCLUSION: Current evidence shows some evidence of the effectiveness of HBOT in improving the healing of diabetic leg ulcers in patients with concomitant ischaemia. Larger trials of higher quality are needed before implementation of HBOT in routine clinical practice in patients with diabetic foot ulcers can be justified.


Asunto(s)
Pie Diabético/terapia , Oxigenoterapia Hiperbárica , Isquemia/terapia , Cicatrización de Heridas , Amputación Quirúrgica , Terapia Combinada , Pie Diabético/diagnóstico , Pie Diabético/fisiopatología , Humanos , Isquemia/diagnóstico , Isquemia/fisiopatología , Recuperación del Miembro , Flujo Sanguíneo Regional , Resultado del Tratamiento
6.
Neth J Med ; 71(1): 29-31, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23412821

RESUMEN

Familial LCAT deficiency (FLD) is a recessive lipid disorder ultimately leading to end-stage renal disease (ESRD). We present two brothers with considerable variation in the age at which they developed ESRD. Kidney biopsies revealed both tubular and glomerular pathology. To date, no causal therapy is available, yet enzyme replacement therapy is in development.


Asunto(s)
Fallo Renal Crónico/etiología , Deficiencia de la Lecitina Colesterol Aciltransferasa/genética , Adulto , Progresión de la Enfermedad , Terapia de Reemplazo Enzimático/tendencias , Humanos , Fallo Renal Crónico/terapia , Deficiencia de la Lecitina Colesterol Aciltransferasa/complicaciones , Masculino , Persona de Mediana Edad , Linaje , Terapia de Reemplazo Renal
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