Estudio de biomarcadores y modelos predictivos de crecimiento en el aneurisma de aorta abdominal / Biomarkers and predictive models for abdominal aortic aneurysm growth

OBJETIVO: El diagnóstico y seguimiento de los pacientes con aneurisma de aorta abdominal (AAA) se realizan mediante medición seriada del diámetro aórtico máximo con ultrasonografía o tomografía computerizada, pero la expansión aórtica es mayoritariamente discontinua, e impredecible en un paciente concreto. Un modelo predictivo fiable de crecimiento y/o rotura aórticos podría ayudar a individualizar el manejo. Nuestro objetivo ha sido definir un modelo predictivo de crecimiento aneurismático a corto plazo a partir de variables clínicas, serológicas y anatómicas. MÉTODOS: Se reclutaron 148 pacientes con AAA aterosclerótico infrarrenal asintomático consecutivos. Se recogieron: datos clínicos (edad, sexo, factores de riesgo cardiovascular, comorbilidad, medicación), diámetro basal de los AAA, crecimiento aórtico prospectivo a un año, y concentraciones basales circulantes de MMP-2, MMP-9, cistatina C, alfa1-antitripsina, mieloperoxidasa, MCP-1, homocisteína, dímero D, PAP y proteína C reactiva. Se elaboraron modelos predictivos del crecimiento prospectivo a un año de los AAA, crecimiento valorado como variable continua (mm/año) y dicotómica (estabilidad, si la tasa de crecimiento era ≤ 2 mm/año; expansión, si era > 2 mm/año), utilizando regresión lineal y logística, simple y múltiple. RESULTADOS: Cada incremento en las concentraciones de dímero D en 1 ng/mL se asoció al aumento medio de 0,0062 mm/año en el crecimiento prospectivo de los AAA. La insuficiencia renal crónica aumentó el crecimiento medio en 2,95 mm/año. Mayores concentraciones de PAP y la coexistencia de IRC aumentaban el riesgo de expansión aórtica (OR 1,01 y 14523,62; IC 95% 1,00-1,02 y 0-7,39E + 40, respectivamente). CONCLUSIONES: Las concentraciones plasmáticas de dímero D y PAP constituyen prometedores biomarcadores predictivos de la expansión prospectiva de los AAA a corto plazo. La insuficiencia renal crónica es un importante factor clínico pronóstico de expansion aórtica. La clasificación del crecimiento de los AAA de forma dicotómica, estabilidad versus expansión, puede ser útil para la elaboración de modelos de decisión y su aplicación clínica

OBJECTIVE: Abdominal aortic aneurysms (AAA) are currently followed-up by measuring their diameter with serial ultrasound or computed tomography scanning, but evidence shows that AAA growth is mostly discontinuous and unpredictable in a given patient. A reliable predictive model of AAA growth and/or rupture risk could help individualize management. The aim of this study was to define a predictive model of short-term AAA growth with clinical, serological and anatomical data. METHODS: A total of 148 consecutive asymptomatic infrarenal atherosclerotic AAA patients were included. The following details were recorded: clinical data (age, gender, cardiovascular risk factors, comorbidity, medication), baseline aortic diameter, prospective 1-year AAA growth, and the concentration of MMP-2, MMP-9, cystatin C, alpha1-antitrypsin, myeloperoxidase, MCP-1, homocysteine, D-dimer, PAP and C-reactive protein in peripheral blood at the time of baseline assessment. Predictive models were constructed for 1-year AAA growth assessed as a continuous variable (mm/year) as well as a dichotomic variable (defined as stability, if AAA growth rate was ≤ 2 mm/year, versus expansion, if AAA growth rate was > 2 mm/year), using simple and multiple linear and logistic regression. RESULTS: Every increase by 1 ng/mL in the plasma concentration of D-dimer was related to a mean 1-year increase of 0.0062 mm in the AAA growth. Likewise, CRF increased the 1-year prospective AAA growth by a mean of 2.95 mm. When AAA growth was assessed as a dichotomic variable, both the increase in the peripheral concentrations of PAP and the presence of chronic renal failure (CRF) increased the risk of AAA expansion (odds ratio [OR]: 1.01 and 14,523.62; 95% confidence interval [CI]: 1.00-1.02 and 0-7.39E + 40 respectively). CONCLUSIONS: D-dimer and PAP seem to be promising biomarkers of short-term AAA activity. CRF is an important independent prognostic factor of AAA expansion. The dichotomic classification of AAA growth can be useful in the development of management models and their clinical application

Anaemia, iron and vitamin deficits in patients with peripheral arterial disease.

INTRODUCTION: Anaemia can compromise muscle and organ function. Related iron and vitamin body stores have seldom been assessed in patients with peripheral arterial disease. REPORT: We retrospectively analysed basal prevalence of anaemia, iron, B(12)-vitamin and folic acid deficits in 420 patients with claudication and 204 patients with critical limb ischaemia (CLI). The prevalence of the evaluated parameters was 9.8%, 6.7%, 6.7% and 2.9% among patients with claudication but 49.5%, 31.9%, 15.7% and 6.4% among CLI patients, respectively (p < 0.05 for all). DISCUSSION: Anaemia, iron and vitamin deficits are uncommon among patients with ischemic claudication but very prevalent among patients with CLI.

Prevalencia de aneurismas de aorta abdominal en varones de 65 años de la Comarca Interior de Bizkaia (Estudio PAV65) / Prevalence of abdominal aortic aneurysms in 65 year-old men (PAV65 Study)

Objetivo. Conocer la prevalencia de los aneurismas de aorta abdominal infrarrenal (AAA), factoresde riesgo y posibles alteraciones analíticas en los varones de 65 años, nacidos en 1943,censados en la Comarca Interior de Bizkaia, y compararla con la obtenida en estudiosepidemiológicos realizados en varones con edades entre 65-74 años.Diseño. Transversal.Material y métodos. Entre octubre y diciembre de 2007 invitamos a participar en este estudio alos 1.413 varones nacidos en 1943. Se realizó exploración física, índice de masa corporal (IMC) yeco-doppler de aorta abdominal. Analítica general y específi ca.Resultados. De los 1.413 hombres censados, 19 habían fallecido (1,3 %), 41 no quisieron participaren el estudio, en 250 casos (17,7 %) se desconocía la dirección actual, por lo que el númeroreal fue de 1.103, participando 781 (70,8 %). Se diagnosticaron 37 AAA (4,7 %). Los varones conhermanos portadores de AAA, los fumadores, hipertensos y/o con una arteriopatía periféricatienen una probabilidad mayor de tener un AAA, mientras que los diabéticos están protegidoscontra esta patología. Los portadores de AAA presentaron niveles más elevados de metaloproteinasas(MMP-9) y proteína C reactiva (PCR) que los individuos normales: 5,9 ± 3,9 ng/dl y4,1 ± 3,4 mg/l frente a 4,2 ± 3,4 ng/dl y 2,6 ± 2,5 mg/l, con una p de 0,0042 y 0,002, respectivamente.Conclusión. La prevalencia de los AAA en varones de 65 años es similar a la encontrada en losvarones entre 65 y 74 años. Los niveles de MMP-9 y PCR son signifi cativamente mayores en pacientescon AAA en relación al grupo control(AU)

Objective. To analyse the prevalence of abdominal aortic aneurysms (AAA), risk factors andpossible changes in serological parameters in 65-year-old men, born in 1943, registered in theInner Region of Bizkaia, and to compare this prevalence with that obtained in other previousepidemiological studies performed in 65 to 74-year-old men.Design. Cross-sectional epidemiological study.Material and methods. In October-December 2007 the 1,413 men born in 1943 were invited toparticipate in this study. A physical examination, body mass index (BMI), abdominal ultrasoundand general and specifi c blood tests were performed.Results. Nineteen (1.3 %) of the 1,413 registered men were deceased, 41 openly refused toparticipate in the study and we could not fi nd the current address of 250 men (17.7 %), so thefi nal number of available candidates was 1,103, of whom 781 (70.8 %) fi nally attended theirappointments. We diagnosed 37 AAA (4.7 %). Men with brothers diagnosed with an AAA, smokers,hypertensive and/or suffering from peripheral arterial disease had a greater probability ofdeveloping an AAA, in contrast with diabetic patients, who showed lower risk. The AAA patientshad higher levels of metalloproteinase-9 (MMP-9) and C-reactive protein (CRP) than the controls(mean ± standard deviation): 5.9 ± 3.9 ng/dl and 4.1 ± 3.4 mg/l versus 4.2 ± 3.4 ng/dl and2.6 ± 2.5 mg/l; p = 0.0042 and 0.002, respectively.Conclusion. The prevalence of AAA in 65-year-old men in our area is similar to that described in65 to 74-year-old men in other previous international studies. Peripheral MMP-9 and CRP levelsare increased in AAA patients compared to controls(AU)

Long-term cardiovascular outcome after elective abdominal aortic aneurysm open repair.

BACKGROUND: We analyzed the incidence of late cardiovascular events and mortality after elective infra-/juxtarenal abdominal aortic aneurysm open repair (AAA-OR). METHODS: We included patients who survived AAA-OR in our center in 1988-2006. We registered late cardiac, cerebrovascular, and peripheral vascular events, as well as all-cause and cardiovascular mortality. We calculated patient survival and freedom from cardiovascular events (Kaplan-Meier) and evaluated risk factors (multivariate analysis). RESULTS: We studied 297 patients: 292 (98.3%) men, aged 67 +/- 7 (44-83) years, 143 (48.1%) bifurcated grafts. In a mean follow-up of 78.7 +/- 52.9 months, we registered 203 cardiovascular events in 123 (41.4%) patients, at a rate of 0.16 cardiovascular events/patient-year. Eleven (3.7%) patients suffered graft-related complications. Freedom from cardiovascular events was 94.2%, 67.2%, 45.7%, and 27.6% at 1, 5, 10, and 15 years, respectively. Survival was 96.6%, 74.7%, 50.7%, and 31.5%, respectively. The main cause of death was cardiovascular disease (n = 54, 18.2%), followed by cancer (n = 43, 14.5%). Only four (1.3%) deaths were graft-related. Coronary artery disease and chronic renal failure were predictive of cardiovascular mortality (p = 0.033 and 0.006). CONCLUSION: Although long-term survival is similar to that in the general population, successful AAA-OR patients remain at increased risk of cardiovascular events throughout their lifetime. Graft-related complications are rare, confirming the durability of the procedure.

Search for serum biomarkers associated with abdominal aortic aneurysm growth--a pilot study.

INTRODUCTION: Serological biomarkers could reflect asymptomatic infrarenal aortic aneurysm (AAA) activity and guide patient management. REPORT: Serum concentrations of C-reactive protein (CRP), alpha 1-antitrypsin and lipoprotein(a) were measured in blood samples from 35 AAA patients and 35 controls and correlated with the aortic diameter and AAA growth in the previous 12 months. We found a positive correlation between CRP and AAA diameter (r=0.46; p=0.007) and alpha 1-antitrypsin and AAA growth (r=0.55; p=0.004). CONCLUSIONS: Alpha 1-antitrypsin may be a promising biomarker of AAA growth.

Analysis of expansion patterns in 4-4.9 cm abdominal aortic aneurysms.

Our objective was to analyze the growth pattern of 4-4.9 cm infrarenal abdominal aortic aneurysms (AAAs). We used an observational, longitudinal, prospective study design. We followed 4-4.9 cm AAAs with 6-monthly abdominal computed tomographic (CT) scans (January 1988-August 2004). AAA growth was defined as an increase in aortic diameter > or =2 mm in each surveillance period. We established the aortic expansion pattern in AAA with three or more CT scans as continuous, discontinuous. The latter includes at least one period of nongrowth (<2 mm/6 months). We studied the influence of cardiovascular risk factors (CVRFs), comorbidity, and AAA anatomical characteristics using the chi-squared test, t-test, life tables, and Kaplan-Meier for statistical analysis. We included 195 patients: 183 (93.8%) men, age 71 +/- 8.3 years (50-90). The follow-up period was 50 +/- 36.4 months (6.5-193.7). The growth pattern (n =131) was continuous in 15 (11.5%) and discontinuous in 116 (88.5%) AAA. The mean expansion rate was higher in AAAs with continuous expansion (7.92 +/- 3.74 vs. 2.74 +/- 2.94 mm/year, p < 0.0001). No CVRFs or comorbidity influenced the expansion pattern (p > 0.05). The eccentric thrombus was associated with a greater incidence of continuous growth (p = 0.05), with no influence of aortic calcification (p > 0.1). The expansion of 4-4.9 cm AAA is mostly irregular and unpredictable. We have not found any modifiable risk factors which influence their growth pattern. The eccentric distribution of the thrombus is associated with continuous expansion.

Growth rate and associated factors in small abdominal aortic aneurysms.

OBJECTIVE: To study the growth rate and factors influencing progression of small infrarenal abdominal aortic aneurysms (AAA). DESIGN: Observational, longitudinal, prospective study. PATIENTS AND METHODS: We followed patients with AAA <5 cm in diameter in two groups. Group I (AAA 3-3.9 cm, n = 246) underwent annual ultrasound scans. Group II (AAA 4-4.9 cm, n = 106) underwent 6-monthly CT scans. RESULTS: We included 352 patients (333 men and 19 women) followed for a mean of 55.2+/-37.4 months (6.3-199.8). The mean growth rate was significantly greater in group II (4.72+/-5.93 vs. 2.07+/-3.23 mm/year; p<0.0001). Group II had a greater percentage of patients with rapid aneurysm expansion (>4 mm/year) (36.8 vs. 13.8%; p<0.0001). The classical cardiovascular risk factors did not influence the AAA growth rate in group I. Chronic limb ischemia was associated with slower expansion (< or = 4 mm/year) (OR 0.47; CI 95% 0.22-0.99; p = 0.045). Diabetic patients in group II had a significantly smaller mean AAA growth rate than non-diabetics (1.69+/-3.51 vs. 5.22+/-6.11 mm/year; p = 0.032). CONCLUSIONS: The expansion rate of small AAA increases with the AAA size. AAA with a diameter of 3-3.9 cm expand slowly, and they are very unlikely to require surgical repair in 5 years. Many 4-4.9 cm AAA can be expected to reach a surgical size in the first 2 years of follow-up. Chronic limb ischemia and diabetes are associated with reduced aneurysm growth rates.

Detection of abdominal aortic aneurysm in patients with peripheral artery disease.

OBJECTIVE: To describe the prevalence of abdominal aortic aneurysms (AAA) in patients with peripheral artery disease (PAD). DESIGN: Observational, descriptive, transverse study. PATIENTS AND METHODS: We performed an abdominal ultrasound in 1190 consecutive patients with lower limb chronic ischemia (1/99-12/04). We registered cardiovascular risk factors and clinical data for analysis. RESULTS: The ultrasound was inconclusive in 24 (2%) patients; 1166 patients completed the study. They were mostly male (93.7%), with an age mean of 67+/-9.9 years (37.7-93.4). The main cardiovascular risk factors were: smoking (80.9%), hypertension (41.7%) and hypercholesterolemia (31.4%). The prevalence of AAA was 13% (n = 151). Only 1.5% (n = 17) of the patients had a large AAA (>5 cm). The AAA was clearly more prevalent in men (n = 148; 13.6%) than in women (n = 3; 4.1%) (RR 3.47; 95% CI 1.11-10.89; p = 0.02). The prevalence significantly increased with age, with a maximum of 17.1% in over 75-year-old men (p = 0.006). Patients with tibial disease had a significantly higher prevalence of AAA than aortoiliac or femoro-popliteal disease (p = 0.02). CONCLUSIONS: The prevalence of AAA in patients with PAD is much higher than that reported in the general population. We recommend that an abdominal ultrasound be routinely included in the study of these patients. Over 75-year-old men are at particularly high-risk.