Moncef Zarrouk

The importance of socioeconomic factors for compliance and outcome at screening for abdominal aortic aneurysm in 65-year-old men

OBJECTIVE To evaluate compliance with screening and prevalence of abdominal aortic aneurysm (AAA) in relation to background data regarding area-based socioeconomic status. METHODS Our department annually invites 4300 65-year-old men from the city of Malmö and 15 neighboring municipalities to ultrasound AAA screening. In a cross-sectional cohort study, compliance and AAA prevalence among 8269 men were related to background socioeconomic data such as mean income, proportion of immigrants, percentage of subjects on welfare, smoking habits, and unemployment rate in the different municipalities. The 10 different administrative areas in Malmö were evaluated separately. RESULTS Compliance with screening in the entire area was 6630/8269 (80.2%) but varied between 64.4% and 89.3% in different municipalities (P < .001). In univariate analysis, compliance increased with increasing mean income (r = 0.873; P < .001) but decreased with increasing proportion of immigrants (r = -0.685; P =.005) and subjects on welfare (r = -0.698; P = .004). Compliance in 10 different administrative parts of Malmö (P = .002) also increased with increasing mean income (r = 0.948; P < .001), and decreased with increasing proportion of immigrants (r = -0.650; P = .042) and increasing unemployment rate (r = -0.796; P = .006). Altogether, 117 (1.8%) AAAs were found, the prevalence differing between both different municipalities (P =.003) and the 10 different administrative parts of Malmö (P =.02). The prevalence of AAA in the 10 administrative parts of Malmö increased with increasing percentage of smokers (r = 0.784; P = .007), percentage of immigrants (r = 0.644; P = .044), and unemployment rate (r = 0.783; P =.007) but decreased with increasing mean income (r = -0.754; P = .012). CONCLUSIONS Compliance with ultrasound screening for AAA differed between different geographical areas. In areas with low socioeconomic status, compliance rates were lower, whereas AAA prevalence was higher. The identification of contextual factors associated with low compliance is important to be able to allow targeted actions to increase efficacy of ultrasound screening for AAA. Targeted actions to increase compliance in those areas are being scientifically investigated and implemented.

Cost-effectiveness of Screening for Abdominal Aortic Aneurysm in Combination with Medical Intervention in Patients with Small Aneurysms.

OBJECTIVES Screening for abdominal aortic aneurysm (AAA) among 65 year old men has been proven cost-effective, but nowadays is conducted partly under new conditions. The prevalence of AAA has decreased, and endovascular aneurysm repair (EVAR) has become the predominant surgical method for AAA repair in many centers. At the Malmö Vascular Center pharmacological secondary prevention with statins, antiplatelet therapy, and blood pressure reduction is initiated and given to all patients with AAA. This study evaluates the cost-effectiveness of AAA screening under the above mentioned conditions. METHODS This was a Markov cohort simulation. A total of 4,300 65 year old men were invited to annual AAA screening; the attendance rate was 78.3% and AAA prevalence was 1.8%. A Markov model with 11 health states was used to evaluate cost-effectiveness of AAA screening. Background data on rupture risks, costs, and effectiveness of surgical interventions were obtained from the participating unit, the national Swedvasc Registry, and from the scientific literature. RESULTS The additional costs of the screening strategy compared with no screening were €169 per person and year. The incremental health gain per subject in the screened cohort was 0.011 additional quality adjusted life years (QALYs), corresponding to an incremental cost-effectiveness ratio (ICER) of €15710 per QALY. Assuming a 10% reduction of all cause mortality, the incremental cost of screening was €175 per person and year. The gain per subject in the screened cohort was 0.013 additional QALYs, corresponding to an ICER of €13922 per QALY CONCLUSIONS: AAA screening remains cost-effective according to both the Swedish recommendations and the UK National Institute for Health and Care Excellence recommendations in the new era of lower AAA prevalence, EVAR as the predominant surgical method, and secondary prevention for all AAA patients.

Inflammatory markers associated with abdominal aortic aneurysm

PurposeInflammation with leukocytic infiltration, degradation of extracellular matrix (ECM), and depletion of vascular smooth muscle cells (VSMC) are pathological hallmarks of abdominal aortic aneurysm (AAA). The aim of this study was to further evaluate relationships betweenAAAand inflammatory biomarkers, interleukin- 6 (IL-6), tumour necrosis factor-α (TNF-α), endothelin-1 (ET-1) and soluble urokinase-type plasminogen activator receptor (suPAR), by comparing levels in 65-year-old men with and without AAA at ultrasound screening.We also evaluated whether any biomarker can independently predict AAA at screening, and clarified potential correlations between aortic diameter and blood levels of these biomarkers.ResultsThere were significant (p ɤ 0.05) differences between subjects with and without AAA for the following variables: p-leukocyte count (TLC) (p<0.001), p-homocysteine (p<0.001), p-TNF-α (p = 0.023), p-IL-6 (p<0.001), p-ET-1 (p = 0.002), p-suPAR (p<0.001), ankle brachial index (ABI) (p<0.001), plasma (p)-creatinine (p = 0.049), p-total cholesterol (p<0.001), p-high density lipoprotein (HDL) (p<0.001) and low density lipoprotein (LDL) cholesterol (p = 0.001), smoking habits (p<0.001), and use of antihypertensive (p<0.001) and lipid-lowering (p = 0.001) drugs. When the above variables were stepwise excluded in a logistic regression model, only p-IL-6 (p = 0.002), p-homocysteine (p = 0.015), p-HDL (p = 0.004), ABI in the right (p = 0.005) and left (p = 0.094) leg, smoking habits (p = 0.003), and antihypertensive drug use (p = 0.045), differed between groups. Significant correlations with aortic diameter existed for p-TNF-α (p = 0.028), p-IL-6 (p<0.001), p-ET-1 (p = 0.002) and p-suPAR (p<0.001) in the entire study population, and for p-TNF-α (p = 0.023), p-ET-1 (p = 0.009) and p-suPAR (p = 0.001) among men with AAA.ConclusionsSeveral inflammatory biomarkers were significantly elevated and correlated with aortic diameter among 65-year old men with AAA at ultrasound screening. IL-6, homocysteine and use of antihypertensive medication remained elevated in the logistic regression model, together with known risk markers for AAA such as smoking and signs of atherosclerosis.

Aortic diameter at age 65 in men with newly diagnosed type 2 diabetes

Abstract Objectives. Type 2 diabetes mellitus has been linked to a decreased risk for abdominal aortic aneurysm (aortic diameter ≥30 mm, AAA) development in men. The aim of this study was to evaluate if such an effect is detectable already around the time of diabetes diagnosis. Design. We cross-sectionally compared aortic diameter at ultrasound screening for AAA in 691 men aged 65 years with incipient or newly diagnosed type 2 diabetes (group A) with 18,262 65-year old control men without diabetes (group B). Results. Aortic diameter did not differ between groups (18.8[17.4–20.8] vs. 19.0[17.5–28.7] mm; p = 0.43). AAA prevalence was 2.5% in group A and 1.5% in group B (p = .010). In logistic regression taking group differences in body mass index (BMI), smoking, presence of atherosclerotic disease and hypertension into account, the difference in AAA prevalence was no longer significant (p = .15). Among men in group A, C-peptide (r = .093; p = .034), but not HbA1c (r = .060; p = .24) correlated with aortic diameter. Conclusion. Among 65 year old men aortic diameter and AAA prevalence do not differ between those with newly diagnosed type 2 diabetes and those without diabetes. Putative protective effects of type 2 diabetes mellitus against aortic dilatation and AAA development therefore probably occur later after diagnosis of diabetes.

No association between glucose at age 30 and aortic diameter at age 65 in men: a population-based study

Abstract Objectives Impaired glucose metabolism and diabetes mellitus has been linked to a decreased risk for abdominal aortic aneurysm development in men. We evaluated potential relationships between blood glucose levels in 1722 men with mean age 34 years and their aortic diameter measured by ultrasound at age 65 years. Design Prospective cohort study. Results Mean follow-up between baseline glucose investigation and aortic ultrasound was 32.8 ± 1.8 years. There was no correlation between baseline blood glucose and later aortic diameter (r = 0.035, p = 0.146), whereas a weak correlation between body mass index (BMI) and aortic diameter was observed (r = 0.097 p < 0.001). In a partial correlation between aortic diameter and glucose levels adjusted for BMI, the correlation did not change (r = 0.011, p = 0.66). Neither were there any significant differences in mean aortic diameter between men belonging to different quartiles of baseline blood glucose levels (19.5, 19.1, 19.6 and 19.7 mm, p = 0.18). Conclusion Fasting blood glucose in 33-year-old men was not associated with their aortic diameter at age 65 years. Potential pathophysiological processes linking disturbed glucose metabolism to a decreased risk for development of abdominal aortic aneurysm in men are therefore probably not relevant until later in life.

Reduced Long-Term Risk of Aortic Aneurysm and Aortic Dissection Among Individuals With Type 2 Diabetes Mellitus : A Nationwide Observational Study

Background No studies have examined long‐term risks for aortic aneurysm (AA) and aortic dissection (AD) or mortality after AA or AD hospitalization among patients with type 2 diabetes mellitus (T2DM). Methods and Results In this observational cohort study, we linked data for patients with T2DM in the Swedish National Diabetes Register, and 5 individually matched population‐based control subjects (CSs) without diabetes mellitus (on the basis of sex, age, and county), to other national databases to capture hospitalizations and death. We examined the risk of hospitalization for AA and AD, as well as mortality risk after AA and AD using Kaplan‐Meier curves and Cox regression hazards models. Data on 448 319 patients with T2DM and 2 251 015 CSs were obtained between 1998 and 2015. Mean follow‐up time was 7.0 years for the T2DM group and 7.2 years for the CS group. Patients with T2DM had a relative risk reduction of 28% (hazard ratio, 0.72; 95% confidence interval, 0.68–0.76; P<0.0001) for AA and a 47% relative risk reduction (hazard ratio, 0.53; 95% confidence interval, 0.42–0.65; P<0.0001) for AD compared with CSs. Patients with T2DM had a relative risk reduction of 12% (hazard ratio, 0.88; 95% confidence interval, 0.82–0.94; P<0.0001) for mortality after hospitalization for AA, and unaltered risk (hazard ratio, 1.07; 95% confidence interval, 0.85–1.34; P=0.5859) for mortality after AD, up to 2 years compared with CSs. Conclusions Patients with T2DM had significantly reduced risks of AA and AD as well as reduced risk of mortality after hospitalization for AA, compared to CS. Data suggest that glycated cross‐links in aortic tissue may play a protective role in the progression of aortic diseases among patients with T2DM.

Circulating Midregional Proadrenomedullin and Risk of Incident Abdominal Aortic Aneurysm : A Prospective Longitudinal Cohort Study

Prospective clinical plasma biomarker studies in abdominal aortic aneurysm (AAA) pathogenesis have been hampered by the need for very large cohorts and long follow-up time. The main aim of the present study was to evaluate the association of adrenomedullin, a cardiovascular (CV) stress marker, and incident AAA risk. Prospective longitudinal cohort of middle-aged individuals from the CV cohort of the Malmö Diet and Cancer Study (n = 5551; 1991-1994) was assessed. Plasma concentrations of midregional proadrenomedullin (MR-proADM), C-reactive protein (CRP), and conventional risk factors were measured at baseline. Incidence of AAA was studied up to December 31, 2013. Cumulative incidence of AAA was 1.5% (men 2.9%, women 0.5%). Mean age of individuals with incident AAA was 59.7 years at study entry, and AAA was diagnosed on average 14 years later. Adjusting for age, gender, smoking, body mass index, hypertension, diabetes mellitus, and CRP, MR-proADM (hazard ratio: 1.28; 95% confidence interval: 1.01-1.62) was independently associated with incident AAA. The plasma biomarker MR-proADM seems to be a marker of AAA risk, implying that AAA development may be driven by long-standing CV stress on the aortic wall.

No relation between biomarkers at age 47–49 and aortic diameter after 14–19 years of follow-up – a population-based study

BACKGROUND Biomarkers reflecting diverse pathophysiological pathways may play an important role in the pathogenesis of abdominal aortic aneurysm (aortic diameter ≥30 mm, AAA), levels of many biomarkers are elevated and correlated to aortic diameter among 65-year-old men undergoing ultrasound (US) screening for AAA. PROBANDS AND METHODS To evaluate potential relationships between biomarkers and aortic dilatation after long-term follow-up, levels of C-reactive protein (CRP), proneurotensin (PNT), copeptin (CPT), lipoprotein-associated phospholipase 2 (Lp-PLA2), cystatin C (Cyst C), midregional proatrial natriuretic peptide (MR-proANP), and midregional proadrenomedullin (MR-proADM) were measured in 117 subjects (114 [97 %] men) aged 47-49 in a prospective population-based cohort study, and related to aortic diameter at US examination of the aorta after 14-19 years of follow-up. RESULTS Biomarker levels at baseline did not correlate with aortic diameter after 14-19 years of follow up (CRP [r = 0.153], PNT [r = 0.070], CPT [r = -.156], Lp-PLA2 [r = .024], Cyst C [r = -.015], MR-proANP [r = 0.014], MR-proADM [r = -.117]). Adjusting for age and smoking at baseline in a linear regression model did not reveal any significant correlations. CONCLUSIONS Tested biomarker levels at age 47-49 were not associated with aortic diameter at ultrasound examination after 14-19 years of follow-up. If there are relationships between these biomarkers and aortic dilatation, they are not relevant until closer to AAA diagnosis.

Psychosocial consequences in men taking part in a national screening program for abdominal aortic aneurysm

Screening for abdominal aortic aneurysm (AAA) has proven to reduce AAA-related mortality, but how the knowledge of having an untreated AAA affects health and daily life requires further clarification. The aim was to investigate the psychosocial consequences and sense of coherence (SOC) in 65-year-old men diagnosed with AAA and participating in a national screening program during a 6-month follow-up compared with men with no AAA. The single-center cohort study included 52 men with AAA and 118 men without AAA. A questionnaire including the Short Form 36 Health Survey, Hospital Anxiety and Depression Scale, SOC, questions concerning stress, and questions related to AAA were answered at baseline and after 6 months. Men with AAA reported more problems with physical functioning, pain, and general health than men with a normal aorta at baseline. After 6 months, men with AAA still reported more problems with physical functioning and stress in relation to disease than men with normal aortic diameter. No differences were observed between groups in SOC, anxiety, and depression. A significantly higher satisfaction with information from the physician and desire to learn about the AAA diagnosis was reported at baseline compared with that at follow-up. Having knowledge about the AAA diagnosis may moderately impact physical health and perceived stress, and in combination with the increased prevalence of other cardiovascular diseases, may lead to impaired perceived health for men diagnosed with AAA.

Academic vascular unit collaboration with advertising agency yields higher compliance in screening for abdominal aortic aneurysm.

To improve compliance with abdominal aortic aneurysm (AAA) screening in low compliance areas, individually tailored invitations were developed in collaboration with a professional advertising agency. Compliance increased in two intervention municipalities from 71.4% in 2010–2012 to 78.1% in 2013 (p = 0.025), and was then higher [odds ratio 1.7; 95% confidence interval 1.1–2.6; p = 0.013] than in two control municipalities in which compliance was unchanged (417/552 [75.5%] in 2010–12 and 122/180 [67.8%] in 2013). Compliance with AAA-screening can be increased by collaboration with a professional advertising agency, albeit at a comparably high cost.