Asociación de PCR plasmática y evolución del aneurisma de aorta infrarrenal / Association between C-reactive protein and the progression of the abdominal aortic aneurysm

OBJETIVO: Valorar la asociación entre las concentraciones plasmáticas de la proteína C reactiva (PCR) y la evolución de los aneurismas de aorta abdominal (AAA) infrarrenal, para verificar su validez como biomarcador de crecimiento aneurismático. MATERIAL Y MÉTODOS: Cohorte prospectiva de AAA asintomáticos seguidos en consultas externas desde 2008. Registramos: datos clínicos, mediciones seriadas del diámetro máximo de los AAA (mediante ecografía y angio-TAC) y determinaciones seriadas de PCR ultrasensible. El seguimiento fue anual para los AAA de 30-39 mm y semestral para aquellos ≥ 40 mm. Excluimos las determinaciones de PCR > 15 mg/L para evitar que posibles procesos agudos pudieran actuar como factor de confusión. Calculamos las tasas del crecimiento aórtico en cada periodo de seguimiento mediante la diferencia entre los diámetros aórticos en mediciones consecutivas y los clasificamos de forma dicotómica (progresión si el crecimiento fue > 2 mm, estabilidad si el crecimiento fue ≤ 2 mm). Empleamos para el análisis de datos la correlación de Pearson y los modelos mixtos lineales. RESULTADOS: Incluimos 218 AAA con un diámetro basal medio de 41,2 mm (desviación estándar [DE] 10,3 mm, intervalo 30-90 mm). El seguimiento medio fue 28,8 meses (DE 13,7; intervalo 4,8-62), y la concentración basal de PCR media fue 4,1 mg/L (DE 3,3; intervalo 0,5-15). Observamos una relación significativa entre los niveles basales de PCR y el diámetro basal (r = 0,23; p = 0,001), asociación que se mantuvo en las determinaciones seriadas a lo largo del seguimiento (p < 0,0001). No detectamos asociación significativa entre las concentraciones de PCR y las tasas de crecimiento aórtico medidas como variable continua (p = 0,10), pero concentraciones crecientes de PCR se asociaron a la progresión de los AAA, tomada la variable de forma dicotómica (OR = 1,008; IC 95%: 1,000-1,016; p = 0,04). CONCLUSIONES: Las concentraciones plasmáticas de PCR mantienen una asociación con el diámetro aneurismático a lo largo del seguimiento y se relacionan con la progresión de los AAA

OBJECTIVE: To assess the association between high sensitivity C-reactive protein (hs-CRP) plasma levels and the prospective progression of aortic abdominal aneurysm (AAA) in order to test its value as a biomarker. MATERIAL AND METHODS: Prospective cohort of asymptomatic AAA patients followed up in an outpatient clinic since 2008. Clinical data, serial maximum aneurysm diameter (ultrasound and CT) and hs-CRP plasma levels were recorded. Small AAA (30-39 mm) were followed up annually, and large AAA (≥ 40 mm) every 6 months. Hs-CRP levels > 15 mg/L were excluded from the study to avoid acute events acting as potential confounders. Aortic expansion rates were calculated in each follow up period, as well as the difference between aortic diameters in consecutive measurements. Aortic growth was also classified as a dichotomic variable (progression if the growth was > 2 mm, and stability if the growth was ≤ 2 mm). The Pearson correlation and mixed linear models were used for statistical analysis. RESULTS: The study included 218 AAA with a mean baseline diameter of 41.2 mm (SD 10.3 mm, range 30-90). The average follow up time was 28.8 months (SD 13.7, range 4.8-62) and the mean baseline hs-CRP level was 4.1 mg/dL (SD 3.3, range 0.5-15). A significant association was observed between hs-CRP levels and baseline AAA diameter (r = 0.23, P = .001), and this association was maintained over serial determinations throughout the follow-up (P < .0001). No statistically significant association was observed between hs-CRP concentrations and aortic growth rates, measured as a continuous variable (P = .10). However, increasing hs-CRP levels were associated with AAA progression [(OR = 1.008; 95% (1.000-1.016) P = .04)]. CONCLUSIONS: hs-CRP plasma levels are consistently associated with AAA diameter throughout the follow-up of the patients, and increased levels are associated with AAA progression

From tissue iron retention to low systemic haemoglobin levels, new pathophysiological biomarkers of human abdominal aortic aneurysm.

Iron deposits are observed in tissue of abdominal aortic aneurysm (AAA) patients, although the underlying mechanisms are not completely elucidated. Therefore we explored circulating markers of iron metabolism in AAA patients, and tested if they could serve as biomarkers of AAA. Increased red blood cell (RBC)-borne iron retention and transferrin, transferrin receptor and ferritin expression was observed in AAA tissue compared to control aorta (immunohistochemistry and western blot). In contrast, decreased circulating iron, transferrin, mean corpuscular haemoglobin concentration (MCHC) and haemoglobin concentration, along with circulating RBC count, were observed in AAA patients (aortic diameter >3 cm, n=114) compared to controls (aortic diameter <3 cm, n=88) (ELISA), whereas hepcidin concentrations were increased in AAA subjects (MS/MS assay). Moreover, iron, transferrin and haemoglobin levels were negatively, and hepcidin positively, correlated with aortic diameter in AAA patients. The association of low haemoglobin with AAA presence or aortic diameter was independent of specific risk factors. Moreover, MCHC negatively correlated with thrombus area in another cohort of AAA patients (aortic diameter 3-5 cm, n=357). We found that anaemia was significantly more prevalent in AAA patients (aortic diameter >5 cm, n=8,912) compared to those in patients with atherosclerotic aorto-iliac occlusive disease (n=17,737) [adjusted odds ratio=1.77 (95% confidence interval: 1.61;1.93)]. Finally, the mortality risk among AAA patients with anaemia was increased by almost 30% [adjusted hazard ratio: 1.29 (95% confidence interval: 1.16;1.44)] as compared to AAA subjects without anaemia. In conclusion, local iron retention and altered iron recycling associated to high hepcidin and low transferrin systemic concentrations could lead to reduced circulating haemoglobin levels in AAA patients. Low haemoglobin levels are independently associated to AAA presence and clinical outcome.

Evaluación de la proteína C reactiva, alfa1-antitripsina y lipoproteína(a) como potenciales marcadores biológicos asociados al crecimiento del aneurisma de aorta abdominal / Evaluation of C-Reactive protein, Alpha1-Antitrypsin and lipoprotein (a) as potential biomarkers associated with abdominal aortic aneuriysm growth

Introducción. Actualmente, la valoración del aneurisma de aorta abdominal (AAA) infrarrenal asintomáticose realiza únicamente con pruebas de imagen seriadas. Buscamos un marcador plasmático útil como indicador de la actividaddel AAA y potencial valor pronóstico. Pacientes y métodos. Obtuvimos muestras de sangre periférica de 35 pacientescon AAA (13 AAA 30-39 mm; 11 40-49 mm; 11 >= 50 mm) y 35 controles. Determinamos la concentración plasmáticade proteína C reactiva (PCR), alfa1-antitripsina y lipoproteína(a). Registramos: datos clínicos, diámetro aórtico(ecografía/TC) en el momento de la extracción y crecimiento del AAA en el año previo. Analizamos la correlación entrecada proteína y el diámetro y crecimiento aórticos con los tests de Mann-Whitney, Kruskal-Wallis, Spearman y regresiónlineal. Resultados. Los pacientes eran mayoritariamente varones (n =33; 94,3%), con edad 71 ± 6,8 (54-83) años. El diámetrodel AAA (n = 35) era 45 ± 12 (30-71) mm, con crecimiento (n = 25) 3,1 ± 3,1 (0-10) mm/año previo. Las tres proteínaspresentaban concentraciones mayores en los pacientes que los controles: PCR 4,1 (1,9-7,3) frente a 1,9 (0,5-4,9)mg/L (p = 0,026); alfa1-antitripsina 147 (131-168) frente a 125,5 (113,8-135,5) mg/dL (p < 0,0001); lipoproteína(a) 47(20-117,5) frente a 27 (9-47) mg/dL (p = 0,022). Encontramos correlaciones positivas PCR-diámetro AAA (r = 0,46; p =0,007) y alfa1-antitripsina-crecimiento AAA (r = 0,55; p = 0,004), sin correlación entre lipoproteína(a)-diámetro/crecimientoAAA (p > 0,52). Las concentraciones de PCR estaban influidas por la toma de estatinas (p = 0,036). No existíancorrelaciones en los controles para ninguno de los marcadores (p > 0,22). Conclusiones. La alfa1-antitripsina pareceprometedora como marcador biológico de la actividad del AAA. La PCR muestra correlación con el tamaño del AAA, perose ve influida por las estatinas. Se descarta la utilidad de la lipoproteína(a)(AU)

Introduction. Current assessment of asymptomatic infrarenal abdominal aortic aneurysms (AAA) is donesolely with serial image techniques. We try to find a useful serological biomarker of AAA activity with potentialprognostic value. Patients and methods.We obtained peripheral blood samples from 35 AAA patients (13 3-3.9 cm AAA;11 4-4.9 cm AAA; 11 >= 5 cm AAA) and 35 controls. We quantified the serum concentration of C-reactive protein(CRP), alpha1-antitrypsin and lipoprotein(a). We registered: clinical data, aortic diameter (ultrasound/CT) at the timeof blood sample harvest, and AAA growth in the previous 12 months. We analysed the correlation between each proteinand the aortic diameter and growth, using Mann-Whitney, Kruskal-Wallis and Spearman’s tests and linear regression.Results. The AAA patients were mostly male (n = 33; 94.3%) and aged 71 ± 6.8 (54-83) years. The AAA diameter (n =35) was 45 ± 12 (30-71) mm, with expansion (n = 25) 3,1 ± 3,1 (0-10) mm/previous year. The levels of the three proteinswere significantly higher in the AAA patients compared to the controls: CRP 4.1 (1.9-7.3) v. 1.9 (0.5-5) mg/L (p = 0.026);alpha1-antitrypsin 147 (131-168) v. 125.5 (114-135.5) mg/dL (p < 0.0001); lipoprotein(a) 47 (20-117.5) v. 27 (9-47)mg/dL (p = 0.022). We found positive correlations CRP-AAA diameter (r = 0.46; p = 0.007) and alpha1-antitrypsin-AAAgrowth (r = 0,55; p = 0,004), but no association between lipoprotein(a) and AAA diameter or expansion (p > 0.52). CRPconcentrations were influenced by statin intake (p = 0.036). There were no correlations for any of the proteins in thecontrol group (p > 0.22). Conclusions. Alpha1-antitrypsin seems promising as a biomarker of AAA activity. CRP showscorrelation with AAA size, but is influenced by statin intake. Lipoprotein(a) has not proved useful(AU)

Regional reference values for some quantities measured with the ADVIA Centaur analyser. A model of co-operation between the in vitro diagnostic industry and clinical laboratories.

This work is a model of co-operation between the in vitro diagnostic industry and clinical laboratories for the production of reference values. Thirteen clinical laboratories having an ADVIA Centaur analyser and representing the majority of the geographical regions of Spain have shared the search for reference individuals and the production of reference values for thyrotropin, free thyroxine, free triiodothyronine, cobalamine and folate concentrations in serum. All the logistic work has been done in co-operation with the Spanish supplier of the ADVIA Centaur analyser. The reference limits produced in the virtual laboratory are derived from the blend of reference values obtained by each laboratory. The multicentre reference limits were estimated according to the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC).

Analytical and clinical evaluation of two homogeneous assays for LDL-cholesterol in hyperlipidemic patients.

BACKGROUND: LDL-cholesterol (LDL-C) concentrations are the primary basis for treatment guidelines established for hyperlipidemic patients. LDL-C concentrations are commonly monitored by means of the Friedewald formula, which provides a relative estimation of LDL-C concentration when the triglyceride concentration is <2000 mg/L and there are no abnormal lipids. The Friedewald formula has several limitations and may not meet the current total error requirement of <12% in LDL-C measurements. METHODS: We evaluated the analytical and clinical performance of two direct methods (Roche and Wako) by analyzing 313 fresh serum samples obtained from dyslipidemic patients in a lipid clinic and comparing them with modified beta-quantification. RESULTS: Both homogeneous assays displayed excellent precision (CV <2%). The Roche method showed a mean total error of 7.72%, and the Wako method showed a mean total error of 4.46% over a wide range of LDL-C concentrations. The Roche method correlated highly with the modified beta-quantification assay (r = 0.929; y = 1.052x - 168 mg/L; n = 166) and showed a bias of -4. 5% as a result of the assigned standard value. The Wako method also correlated highly with beta-quantification (r = 0.966; y = 0.9125x + 104.8 mg/L; n = 145) without significant bias. The Roche method correctly classified 97% of patients with triglycerides <2000 mg/L, 75% of patients with type IIb hyperlipemia (HPL), and 84% of patients with type IV HPL based on the cutpoints of 1300 and 1600 mg/L, compared with 98%, 78.4%, and 89%, respectively, for the Wako method. In dysbetalipoproteinemic patients, both methods have a 30% mean positive bias compared with beta-quantification. CONCLUSIONS: Both direct methods can be a useful alternative when ultracentrifugation is not available for the diagnosis and control of lipid-lowering medication for patients with mixed HPL, but not for patients with type III hyperlipidemia.