Circulating microRNAs signature correlates with positive [18F]fluorodeoxyglucose-positron emission tomography in patients with abdominal aortic aneurysm.

BACKGROUND: Prediction of abdominal aortic aneurysm (AAA) rupture is a challenging issue. Small noncoding microRNAs (miRNAs) are potent regulators of gene expression and are considered as valuable circulating biomarkers. Recently, [18F]fluorodeoxyglucose (FDG) uptake detected by positron emission tomography (PET) in AAA was correlated with cellular and molecular alterations involved in wall instability and its potential rupture. Our study aimed at identifying circulating miRNAs correlated with a positive PET that could help discriminate patients at high risk of rupture. METHODS: The level of 372 miRNAs was evaluated by polymerase chain reaction array in plasma from 35 AAA patients displaying no FDG uptake (A0) and 22 patients with a positive PET uptake (A+). The modulated miRNAs were validated by quantitative polymerase chain reaction and measured in aneurysmal tissues from both groups of patients. RESULTS: Six circulating miRNAs were found significantly modulated in A+ vs A0 patients. They were significantly correlated not only between them but also with the intensity of FDG uptake. Two of them correlated also with the AAA diameter. These miRNAs displayed significant discriminating power between the A+ and A0 groups as determined by receiver operating characteristic curves. Three downregulated circulating miRNAs (miR-99b-5p, miR-125b-5p, and miR-204-5p) were also significantly reduced in the aneurysmal tissue, specifically in the FDG-uptake site, compared with a negative zone in the same aneurysm and with A0 aneurysms. They were further significantly inversely correlated with the expression, at the positive uptake site, of some of their potential gene targets, most notably matrix metalloproteinase 13. CONCLUSIONS: Six miRNAs were identified as potential new circulating biomarkers of PET+ AAA. Three of these were similarly modulated in the metabolically active aneurysmal wall and might be directly involved in AAA instability.

Gene expression study in positron emission tomography-positive abdominal aortic aneurysms identifies CCL18 as a potential biomarker for rupture risk.

Rupture of abdominal aortic aneurysm (AAA) is a cause of significant mortality and morbidity in aging populations. Uptake of 18-fluorodeoxyglucose (FDG) detected by positron emission tomography (PET) is observed in the wall of 12% of AAA (A+), with most of them being symptomatic. We previously showed that the metabolically active areas displayed adventitial inflammation, medial degeneration and molecular alterations prefacing wall rupture. The aim of this study was to identify new factors predictive of rupture. Transcriptomic analyses were performed in the media and adventitia layers from three types of samples: AAA with-out FDG uptake (A0) and with FDG uptake (A+), both at the positive spot (A+(Pos)) and at a paired distant negative site (A+(Neg)) of the same aneurysm. Follow-up studies included reverse-transcriptase-polymerase chain reaction (RT-PCR), immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). A large number of genes, including matrix metalloproteinases, collagens and cytokines as well as genes involved in osteochondral development, were differentially expressed in the A+(Pos) compared with A+(Neg). Moreover, a series of genes (notably CCL18) was differentially expressed both in the A+(Neg) and A+(Pos) compared with the A0. A significant increase of CCL18 was also found at the protein level in the aortic wall and in peripheral blood of A+ patients compared with A0. In conclusion, new factors, including CCL18, involved in the progression of AAA and, potentially, in their rupture were identified by a genome-wide analysis of PET-positive and -negative human aortic tissue samples. Further work is needed to study their role in AAA destabilization and weakening.

Quantifying excess mortality during the COVID-19 pandemic in 2020 in The Gambia: a time-series analysis of three health and demographic surveillance systems.

OBJECTIVES: Estimates for COVID-19-related excess mortality for African populations using local data are needed to design and implement effective control policies. METHODS: We applied time-series analysis using data from three health and demographic surveillance systems in The Gambia (Basse, Farafenni, and Keneba) to examine pandemic-related excess mortality during 2020, when the first SARS-CoV-2 wave was observed, compared to the pre-pandemic period (2016-2019). RESULTS: Across the three sites, average mortality during the pre-pandemic period and the total deaths during 2020 were 1512 and 1634, respectively (Basse: 1099 vs 1179, Farafenni: 316 vs 351, Keneba: 98 vs 104). The overall annual crude mortality rates per 100,000 (95% CI) were 589 (559, 619) and 599 (571, 629) for the pre-pandemic and 2020 periods, respectively. The adjusted excess mortality rate was 8.8 (-34.3, 67.6) per 100,000 person-month with the adjusted rate ratio (aRR) = 1.01 (0.94,1.11). The age-stratified analysis showed excess mortality in Basse for infants (aRR = 1.22 [1.04, 1.46]) and in Farafenni for the 65+ years age group (aRR = 1.19 [1, 1.44]). CONCLUSION: We did not find significant excess overall mortality in 2020 in The Gambia. However, some age groups may have been at risk of excess death. Public health response in countries with weak health systems needs to consider vulnerable age groups and the potential for collateral damage.

Risk factors of infant mortality in rural The Gambia: a retrospective cohort study.

Objective: The main objective was to assess the risk factors for infant mortality among children living in the Health and Demographic Surveillance System (HDSS) in Farafenni, The Gambia. Our secondary objective was to assess these risks separately in the neonatal and postneonatal (>28 days) period. Design: Retrospective cohort study. Setting: HDSS in an urban centre and surrounding area in The Gambia. Patients: 7365 infants (47% female) born between 2014 and 2018, of which 126 (1.71%) died in the first year. Main outcome measures: Infant mortality. Results: Risk factors for mortality were death of any sibling (HR 2.78, 95% CI 1.54 to 5.00), having a twin (HR 1.96, 95% CI 1.01 to 3.80), being born in the harvest season (HR 1.55, 95% CI 1.07 to 2.24), living in a rural village (HR 4.34, 95% CI 2.03 to 9.29) and longer distance to the nearest village with a public health centre (HR 1.33, 95% CI 1.11 to 1.59). In addition, no breast feeding (HR 10.73, 95% CI 6.83 to 16.86) and no BCG vaccination in the first week of life (HR 3.47, 95% CI 1.07 to 11.24) were associated with infant mortality. Similar risk factors were found in the neonatal and postneonatal periods. Conclusion: Most risk factors associated with infant mortality (neonatal and postneonatal) are not easily modifiable at the individual level and would require programmatic approaches to target vulnerable infants and facilitate access to health services.

Effect of maternal death on child survival in rural West Africa: 25 years of prospective surveillance data in The Gambia.

BACKGROUND: The death of a mother is a tragedy in itself but it can also have devastating effects for the survival of her children. We aim to explore the impact of a mother's death on child survival in rural Gambia, West Africa. METHODS: We used 25 years of prospective surveillance data from the Farafenni Health and Demographic surveillance system (FHDSS). Mortality rates per 1,000 child-years up to ten years of age were estimated and Kaplan-Meier survival curves plotted by maternal vital status. Cox proportional hazard models were used to examine factors associated with child survival. FINDINGS: Between 1st April 1989 and 31st December 2014, a total of 2, 221 (7.8%) deaths occurred during 152,906 child-years of follow up. Overall mortality rate was 14.53 per 1,000 child-years (95% CI: 13.93-15.14). Amongst those whose mother died, the rate was 25.89 (95% CI: 17.99-37.25) compared to 14.44 (95% CI: 13.84-15.06) per 1,000 child-years for those whose mother did not die. Children were 4.66 (95% CI: 3.15-6.89) times more likely to die if their mother died compared to those with a surviving mother. Infants whose mothers died during delivery or shortly after were up to 7 times more likely to die within the first month of life compared to those whose mothers survived. Maternal vital status was significantly associated with the risk of dying within the first 2 years of life (p-value <0.05), while this was no longer observed for children over 2 years of age (P = 0.872). Other factors associated with an increased risk of dying were living in more rural areas, and birth spacing and year of birth. CONCLUSIONS: Mother's survival is strongly associated with child survival. Our findings highlight the importance of the continuum of care for both the mother and child not only throughout pregnancy, and childbirth but beyond 6 weeks post-partum.

Barriers to timely administration of birth dose vaccines in The Gambia, West Africa.

OBJECTIVE: Although vaccine coverage in infants in sub-Saharan Africa is high, this is estimated at the age of 6-12 months. There is little information on the timely administration of birth dose vaccines. The objective of this study was to assess the timing of birth dose vaccines (hepatitis B, BCG and oral polio) and reasons for delayed administration in The Gambia. METHODS: We used vaccination data from the Farafenni Health and Demographic Surveillance System (FHDSS) between 2004 and 2014. Coverage was calculated at birth (0-1 day), day 7, day 28, 6 months and 1 year of age. Logistic regression models were used to identify demographic and socio-economic variables associated with vaccination by day 7 in children born between 2011 and 2014. RESULTS: Most of the 10,851 children had received the first dose of hepatitis B virus (HBV) vaccine by the age of 6 months (93.1%). Nevertheless, only 1.1% of them were vaccinated at birth, 5.4% by day 7, and 58.4% by day 28. Vaccination by day 7 was associated with living in urban areas (West rural: adjusted OR (AOR)=6.13, 95%CI: 3.20-11.75, east rural: AOR=6.72, 95%CI: 3.66-12.33) and maternal education (senior-educations: AOR=2.43, 95%CI: 1.17-5.06); and inversely associated with distance to vaccination delivery points (≧2km: AOR=0.41, 95%CI: 0.24-0.70), and Fula ethnicity (AOR=0.60, 95%CI: 0.40-0.91). CONCLUSION: Vaccine coverage in The Gambia is high but infants are usually vaccinated after the neonatal period. Interventions to ensure the implementation of national vaccination policies are urgently needed.

Health & Demographic Surveillance System Profile: Farafenni Health and Demographic Surveillance System in The Gambia.

The Farafenni Health and Demographic Surveillance System (Farafenni HDSS) is located 170 km from the coast in a rural area of The Gambia, north of the River Gambia. It was set up in 1981 by the UK Medical Research Council Laboratories to generate demographic and health information required for the evaluation of a village-based, primary health care programme in 40 villages. Regular updates of demographic events and residency status have subsequently been conducted every 4 months. The surveillance area was extended in 2002 to include Farafenni Town and surrounding villages to support randomized, controlled trials. With over three decades of prospective surveillance, and through specific scientific investigations, the platform (population ≈ 50,000) has generated data on: morbidity and mortality due to malaria in children and during pregnancy; non-communicable disease among adults; reproductive health; and levels and trends in childhood and maternal mortality. Other information routinely collected includes causes of death through verbal autopsy, and household socioeconomic indicators. The current portfolio of the platform includes tracking Millennium Development Goal 4 (MDG4) attainments in rural Gambia and cause-of-death determination.

Multifactorial relationship between 18F-fluoro-deoxy-glucose positron emission tomography signaling and biomechanical properties in unruptured aortic aneurysms.

BACKGROUND: The relationship between biomechanical properties and biological activities in aortic aneurysms was investigated with finite element simulations and 18F-fluoro-deoxy-glucose (18F-FDG) positron emission tomography. METHODS AND RESULTS: The study included 53 patients (45 men) with aortic aneurysms, 47 infrarenal (abdominal aortic) and 6 thoracic (thoracic aortic), who had ≥1 18F-FDG positron emission tomography/computed tomography. During a 30-month period, more clinical events occurred in patients with increased 18F-FDG uptake on their last examination than in those without (5 of 18 [28%] versus 2 of 35 [6%]; P=0.03). Wall stress and stress/strength index computed by finite element simulations and 18F-FDG uptake were evaluated in a total of 68 examinations. Twenty-five (38%) examinations demonstrated ≥1 aneurysm wall area of increased 18F-FDG uptake. The mean number of these areas per examination was 1.6 (18 of 11) in thoracic aortic aneurysms versus 0.25 (14 of 57) in abdominal aortic aneurysms, whereas the mean number of increased uptake areas colocalizing with highest wall stress and stress/strength index areas was 0.55 (6 of 11) and 0.02 (1 of 57), respectively. Quantitatively, 18F-FDG positron emission tomographic uptake correlated positively with both wall stress and stress/strength index (P<0.05). 18F-FDG uptake was particularly high in subjects with personal history of angina pectoris and familial aneurysm. CONCLUSIONS: Increased 18F-FDG positron emission tomographic uptake in aortic aneurysms is strongly related to aneurysm location, wall stress as derived by finite element simulations, and patient risk factors such as acquired and inherited susceptibilities.

Disease-specific mortality burdens in a rural Gambian population using verbal autopsy, 1998-2007.

OBJECTIVE: To estimate and evaluate the cause-of-death structure and disease-specific mortality rates in a rural area of The Gambia as determined using the InterVA-4 model. DESIGN: Deaths and person-years of observation were determined by age group for the population of the Farafenni Health and Demographic Surveillance area from January 1998 to December 2007. Causes of death were determined by verbal autopsy (VA) using the InterVA-4 model and ICD-10 disease classification. Assigned causes of death were classified into six broad groups: infectious and parasitic diseases; cancers; other non-communicable diseases; neonatal; maternal; and external causes. Poisson regression was used to estimate age and disease-specific mortality rates, and likelihood ratio tests were used to determine statistical significance. RESULTS: A total of 3,203 deaths were recorded and VA administered for 2,275 (71%). All-age mortality declined from 15 per 1,000 person-years in 1998-2001 to 8 per 1,000 person-years in 2005-2007. Children aged 1-4 years registered the most marked (74%) decline from 27 to 7 per 1,000 person-years. Communicable diseases accounted for half (49.9%) of the deaths in all age groups, dominated by acute respiratory infections (ARI) (13.7%), malaria (12.9%) and pulmonary tuberculosis (10.2%). The leading causes of death among infants were ARI (5.59 per 1,000 person-years [95% CI: 4.38-7.15]) and malaria (4.11 per 1,000 person-years [95% CI: 3.09-5.47]). Mortality rates in children aged 1-4 years were 3.06 per 1,000 person-years (95% CI: 2.58-3.63) for malaria, and 1.05 per 1,000 person-years (95% CI: 0.79-1.41) for ARI. The HIV-related mortality rate in this age group was 1.17 per 1,000 person-years (95% CI: 0.89-1.54). Pulmonary tuberculosis and communicable diseases other than malaria, HIV/AIDS and ARI were the main killers of adults aged 15 years and over. Stroke-related mortality increased to become the leading cause of death among the elderly aged 60 years or more in 2005-2007. CONCLUSIONS: Mortality in the Farafenni HDSS area was dominated by communicable diseases. Malaria and ARI were the leading causes of death in the general population. In addition to these, diarrhoeal disease was a particularly important cause of death among children under 5 years of age, as was pulmonary tuberculosis among adults aged 15 years and above.

Pregnancy-related mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Women continue to die in unacceptably large numbers around the world as a result of pregnancy, particularly in sub-Saharan Africa and Asia. Part of the problem is a lack of accurate, population-based information characterising the issues and informing solutions. Population surveillance sites, such as those operated within the INDEPTH Network, have the potential to contribute to bridging the information gaps. OBJECTIVE: To describe patterns of pregnancy-related mortality at INDEPTH Network Health and Demographic Surveillance System sites in sub-Saharan Africa and southeast Asia in terms of maternal mortality ratio (MMR) and cause-specific mortality rates. DESIGN: Data on individual deaths among women of reproductive age (WRA) (15-49) resident in INDEPTH sites were collated into a standardised database using the INDEPTH 2013 population standard, the WHO 2012 verbal autopsy (VA) standard, and the InterVA model for assigning cause of death. RESULTS: These analyses are based on reports from 14 INDEPTH sites, covering 14,198 deaths among WRA over 2,595,605 person-years observed. MMRs varied between 128 and 461 per 100,000 live births, while maternal mortality rates ranged from 0.11 to 0.74 per 1,000 person-years. Detailed rates per cause are tabulated, including analyses of direct maternal, indirect maternal, and incidental pregnancy-related deaths across the 14 sites. CONCLUSIONS: As expected, these findings confirmed unacceptably high continuing levels of maternal mortality. However, they also demonstrate the effectiveness of INDEPTH sites and of the VA methods applied to arrive at measurements of maternal mortality that are essential for planning effective solutions and monitoring programmatic impacts.

Adult non-communicable disease mortality in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System sites.

BACKGROUND: Mortality from non-communicable diseases (NCDs) is a major global issue, as other categories of mortality have diminished and life expectancy has increased. The World Health Organization's Member States have called for a 25% reduction in premature NCD mortality by 2025, which can only be achieved by substantial reductions in risk factors and improvements in the management of chronic conditions. A high burden of NCD mortality among much older people, who have survived other hazards, is inevitable. The INDEPTH Network collects detailed individual data within defined Health and Demographic Surveillance sites. By registering deaths and carrying out verbal autopsies to determine cause of death across many such sites, using standardised methods, the Network seeks to generate population-based mortality statistics that are not otherwise available. OBJECTIVE: To describe patterns of adult NCD mortality from INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories, with separate consideration of premature (15-64 years) and older (65+ years) NCD mortality. DESIGN: All adult deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 80,726 adult (over 15 years) deaths were documented over 7,423,497 person-years of observation. NCDs were attributed as the cause for 35.6% of these deaths. Slightly less than half of adult NCD deaths occurred in the 15-64 age group. Detailed results are presented by age and sex for leading causes of NCD mortality. Per-site rates of NCD mortality were significantly correlated with rates of HIV/AIDS-related mortality. CONCLUSIONS: These findings present important evidence on the distribution of NCD mortality across a wide range of African and Asian settings. This comes against a background of global concern about the burden of NCD mortality, especially among adults aged under 70, and provides an important baseline for future work.

Mortality from external causes in Africa and Asia: evidence from INDEPTH Health and Demographic Surveillance System Sites.

BACKGROUND: Mortality from external causes, of all kinds, is an important component of overall mortality on a global basis. However, these deaths, like others in Africa and Asia, are often not counted or documented on an individual basis. Overviews of the state of external cause mortality in Africa and Asia are therefore based on uncertain information. The INDEPTH Network maintains longitudinal surveillance, including cause of death, at population sites across Africa and Asia, which offers important opportunities to document external cause mortality at the population level across a range of settings. OBJECTIVE: To describe patterns of mortality from external causes at INDEPTH Network sites across Africa and Asia, according to the WHO 2012 verbal autopsy (VA) cause categories. DESIGN: All deaths at INDEPTH sites are routinely registered and followed up with VA interviews. For this study, VA archives were transformed into the WHO 2012 VA standard format and processed using the InterVA-4 model to assign cause of death. Routine surveillance data also provide person-time denominators for mortality rates. RESULTS: A total of 5,884 deaths due to external causes were documented over 11,828,253 person-years. Approximately one-quarter of those deaths were to children younger than 15 years. Causes of death were dominated by childhood drowning in Bangladesh, and by transport-related deaths and intentional injuries elsewhere. Detailed mortality rates are presented by cause of death, age group, and sex. CONCLUSIONS: The patterns of external cause mortality found here generally corresponded with expectations and other sources of information, but they fill some important gaps in population-based mortality data. They provide an important source of information to inform potentially preventive intervention designs.

Malaria mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: Malaria continues to be a major cause of infectious disease mortality in tropical regions. However, deaths from malaria are most often not individually documented, and as a result overall understanding of malaria epidemiology is inadequate. INDEPTH Network members maintain population surveillance in Health and Demographic Surveillance System sites across Africa and Asia, in which individual deaths are followed up with verbal autopsies. OBJECTIVE: To present patterns of malaria mortality determined by verbal autopsy from INDEPTH sites across Africa and Asia, comparing these findings with other relevant information on malaria in the same regions. DESIGN: From a database covering 111,910 deaths over 12,204,043 person-years in 22 sites, in which verbal autopsy data were handled according to the WHO 2012 standard and processed using the InterVA-4 model, over 6,000 deaths were attributed to malaria. The overall period covered was 1992-2012, but two-thirds of the observations related to 2006-2012. These deaths were analysed by site, time period, age group and sex to investigate epidemiological differences in malaria mortality. RESULTS: Rates of malaria mortality varied by 1:10,000 across the sites, with generally low rates in Asia (one site recording no malaria deaths over 0.5 million person-years) and some of the highest rates in West Africa (Nouna, Burkina Faso: 2.47 per 1,000 person-years). Childhood malaria mortality rates were strongly correlated with Malaria Atlas Project estimates of Plasmodium falciparum parasite rates for the same locations. Adult malaria mortality rates, while lower than corresponding childhood rates, were strongly correlated with childhood rates at the site level. CONCLUSIONS: The wide variations observed in malaria mortality, which were nevertheless consistent with various other estimates, suggest that population-based registration of deaths using verbal autopsy is a useful approach to understanding the details of malaria epidemiology.

HIV/AIDS-related mortality in Africa and Asia: evidence from INDEPTH health and demographic surveillance system sites.

BACKGROUND: As the HIV/AIDS pandemic has evolved over recent decades, Africa has been the most affected region, even though a large proportion of HIV/AIDS deaths have not been documented at the individual level. Systematic application of verbal autopsy (VA) methods in defined populations provides an opportunity to assess the mortality burden of the pandemic from individual data. OBJECTIVE: To present standardised comparisons of HIV/AIDS-related mortality at sites across Africa and Asia, including closely related causes of death such as pulmonary tuberculosis (PTB) and pneumonia. DESIGN: Deaths related to HIV/AIDS were extracted from individual demographic and VA data from 22 INDEPTH sites across Africa and Asia. VA data were standardised to WHO 2012 standard causes of death assigned using the InterVA-4 model. Between-site comparisons of mortality rates were standardised using the INDEPTH 2013 standard population. RESULTS: The dataset covered a total of 10,773 deaths attributed to HIV/AIDS, observed over 12,204,043 person-years. HIV/AIDS-related mortality fractions and mortality rates varied widely across Africa and Asia, with highest burdens in eastern and southern Africa, and lowest burdens in Asia. There was evidence of rapidly declining rates at the sites with the heaviest burdens. HIV/AIDS mortality was also strongly related to PTB mortality. On a country basis, there were strong similarities between HIV/AIDS mortality rates at INDEPTH sites and those derived from modelled estimates. CONCLUSIONS: Measuring HIV/AIDS-related mortality continues to be a challenging issue, all the more so as anti-retroviral treatment programmes alleviate mortality risks. The congruence between these results and other estimates adds plausibility to both approaches. These data, covering some of the highest mortality observed during the pandemic, will be an important baseline for understanding the future decline of HIV/AIDS.

18F-FDG uptake assessed by PET/CT in abdominal aortic aneurysms is associated with cellular and molecular alterations prefacing wall deterioration and rupture.

UNLABELLED: Rupture of abdominal aortic aneurysms (AAAs) leads to a significant morbidity and mortality in aging populations, and its prediction would be most beneficial to public health. Spots positive for uptake of (18)F-FDG detected by PET are found in 12% of AAA patients (PET+), who are most often symptomatic and at high rupture risk. Comparing the (18)F-FDG-positive site with a negative site from the same aneurysm and with samples collected from AAA patients with no (18)F-FDG uptake should allow the discrimination of biologic alterations that would help in identifying markers predictive of rupture. METHODS: Biopsies of the AAA wall were obtained from patients with no (18)F-FDG uptake (PET0, n = 10) and from PET+ patients (n = 8), both at the site positive for uptake and at a distant negative site of the aneurysmal wall. Samples were analyzed by immunohistochemistry, quantitative real-time polymerase chain reaction, and zymography. RESULTS: The sites of the aneurysmal wall with a positive (18)F-FDG uptake were characterized by a strikingly increased number of adventitial inflammatory cells, highly proliferative, and by a drastic reduction of smooth muscle cells (SMCs) in the media as compared with their negative counterpart and with the PET0 wall. The expression of a series of genes involved in the maintenance and remodeling of the wall was significantly modified in the negative sites of PET+, compared with the PET0 wall, suggesting a systemic alteration of the aneurysmal wall. Furthermore, a striking increase of several matrix metalloproteinases (MMPs), notably the MMP1 and MMP13 collagenases, was observed in the positive sites, mainly in the adventitia. Moreover, PET+ patients were characterized by a higher circulating C-reactive protein. CONCLUSION: Positive (18)F-FDG uptake in the aneurysmal wall is associated with an active inflammatory process characterized by a dense infiltrate of proliferating leukocytes in the adventitia and an increased circulating C-reactive protein. Moreover, a loss of SMC in the media and alterations of the expression of genes involved in the remodeling of adventitia and collagen degradation potentially participate in the weakening of the aneurysmal wall preceding rupture.