abdominal aortic aneurysms

Molecular Imaging Flags Risk of AAA Rupture

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Uptake of 18F-sodium fluoride (18F-NaF) can point to active vascular calcification associated with high-risk atherosclerotic plaque and may be a marker of high-risk abdominal aortic aneurysms (AAAs), according to a molecular imaging study.

Uptake of the biomarker on positron emission tomography (PET) and CT was significantly higher in the AAA (aortic diameter exceeding 40 mm) than in nonaneurysmal regions of the same aorta in the 20 patients studied. It was also significantly higher than in aortas of 20 controls in the prospective SoFIA3 study from researchers led by Rachael Forsythe, MD, of University of Edinburgh.

In a 72-person longitudinal cohort, the highest tertile of 18F-NaF uptake had aneurysms expand 3.10 mm per year versus 1.24 mm annually for the lowest tertile (P=0.008). The highest tertile also had triple the risk of AAA repair or rupture (15.3% versus 5.6%, log-rank P=0.043).

In this group with a baseline aneurysm diameter of 48.8 mm, 26.4% had their aneurysm repaired and 4.2% had a rupture and died without repair over 1.5 years of follow-up, Forsythe’s group reported in the Feb. 6 issue of the Journal of the American College of Cardiology.

“Fluorine-18-NaF PET-CT is a novel and promising approach to the identification of disease activity in patients with AAA and is an additive predictor of aneurysm growth and future clinical events,” the SoFIA3study authors concluded from their single-center, proof-of-concept study.

“This is the first study to demonstrate that an imaging biomarker of disease activity can add to the risk prediction of AAA and to suggest that this approach might refine clinical decisions regarding the need for surgery and improve patient outcomes,” they said. “We suggest that 18F-NaF uptake again relates to microcalcification and is particular to the most diseased areas associated with tissue disruption and loss of integrity.”

“Importantly, areas of fluoride uptake did not correspond to regions of macrocalcification on CT, suggesting the importance of dynamic calcification process,” noted an accompanying editorial.

In that commentary, Parmanand Singh, MD, of Weill Cornell Medical College, and Jagat Narula, MD, PhD, of Icahn School of Medicine at Mount Sinai, both in New York City, emphasized that “earlier detection of high-risk aneurysms is important to render appropriate care to the highest risk patients.”

“Despite significant advances in aortic imaging, pharmacotherapy and surgical interventions over the past decade, patients with AAA complications continue to have high rates of mortality,” they wrote. “The identification of aortic features linked to aortic vulnerability is crucial, both in guiding selection of patients for preemptive surgical repair and for optimizing timing of intervention to prevent complications. Noninvasive molecular imaging holds promise to identify markers of aortic instability earlier in the course of disease progression, and could offer a major advance in the diagnosis, surveillance and management of AAA.”

Psoriasis Linked to AAA

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Patients with psoriasis — whether mild or severe — are at increased risk of abdominal aortic aneurysms (AAA), a Danish nationwide cohort study found.

In an analysis adjusted for multiple factors including age, sex, comorbidities, smoking, and medications, the incidence rate ratios for AAA were 1.20 (95% CI 1.03-1.39, P=0.017) for mild psoriasis and 1.67 (95% CI 1.21-2.32, P=0.002) for severe psoriasis compared with the general population, according to Usman Khalid, MD, PhD, of Copenhagen University Gentofte Hospital in Hellerup, and colleagues.

“These findings add importantly to current evidence of psoriasis as a clinically relevant risk factor for cardiovascular disease and may require increased focus on heightened risk of AAA in patients with psoriasis,” the researchers wrote in Atherosclerosis, Thrombosis, and Vascular Biology.

AAA is relatively common and can be asymptomatic, with progressive dilation of the abdominal aorta that can rupture — often with fatal results.

“Emerging evidence suggests that AAA is a focal representation of a systemic disease with a distinct inflammatory component, rather than a mere consequence of atherosclerosis,” Khalid explained.

Earlier case series have linked AAA with other autoimmune diseases such as rheumatoid arthritis, but a possible association with psoriasis has not previously been explored.

Accordingly, Khalid and colleagues conducted a retrospective study of the Danish national registries for the years 1997 to 2011. The team identified 70,989 patients with psoriasis (59,423 mild and 11,566 severe) and a reference population of 5,404,544 individuals.

Mean ages at baseline ranged from 41 to 44, and slightly less than half were men. More patients with severe psoriasis were ever-smokers, but in general, the psoriasis groups and the reference population were similar in their comorbidities and the medications used.

During the study period, AAA was diagnosed in 23,986 patients.

During a mean follow-up of 14.4 years in the reference population, the incidence rate of AAA was 3.72 per 10,000 person-years. In contrast, with a mean follow-up of 5.7 years, the incidence rates were 7.30 per 10,000 for mild psoriasis and 9.87 per 10,000 for severe psoriasis.

In an analysis adjusted only for age, sex, and calendar year, the incidence rate ratios were 1.36 (95% CI 1.19-1.54, P<0.001) for mild psoriasis and 2 (95% CI 1.51-2.64, P<0.001) for severe psoriasis.

A supplementary analysis found that the incidence rate ratios of AAA rupture were 1.60 (95% CI 1.21-2.12) for mild and 1.94 (95% CI 1.01-3.36) for severe psoriasis, and the incidence rates for surgical repair were 3.03, 7.73, and 8.09 per 10,000 person-years for the reference population, mild psoriasis, and severe psoriasis groups, respectively.

 And in an additional analysis that excluded patients who developed atherosclerosis, the incidence rate ratios were 1.36 (95% CI 1.20-1.54, P<0.001) for mild psoriasis and 1.92 (95% CI 1.46-2.52, P<0.001) for severe psoriasis.

Patients with atherosclerotic disease at baseline also had been excluded, so these findings suggest that unlike “the traditional view that atherosclerotic disease is the primary driving factor for the development of AAA,” the disease today is considered “a multifactorial process that comprises, for example, inflammation, matrix degradation, thrombosis, increased biomechanical aortic wall stress, and a host of associated mediator molecules,” the researchers wrote.

Systemic inflammatory markers such as C-reactive protein and tumor necrosis factor (TNF)-α also are elevated in patients with AAA and in those with psoriasis.

In a murine model of AAA, TNF-α was shown to be involved in matrix remodeling and aortic wall inflammation, while administration of the TNF blocker infliximab inhibited the development of aneurysms. In addition, a systematic review found that TNF inhibition improved endothelial function in patients with psoriasis and psoriatic arthritis.

“Taken together, these data support the notion that shared inflammatory mechanisms contribute to the psoriasis severity-dependent increased risk of AAA observed in the current study,” the researchers observed.

However, the implications for treatment are as yet uncertain, Khalid told MedPage Today. “At present, it is unclear whether treatment with anti-inflammatory agents would reduce the observed risk.

“Further studies are clearly required to investigate the mechanisms and consequences of these novel findings.”

A limitation of the study was the possibility of surveillance bias if patients were followed more closely after being diagnosed with psoriasis.

Longer Surveillance Intervals Might Be Safe in Men with Small Abdominal Aortic Aneurysms.

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Results are not as clear for women, but risk of rupture appears to be higher with smaller diameters.

Professional organizations recommend a wide range of surveillance intervals when an abdominal aortic aneurysm (AAA) is found, but most are in the range of 12 to 24 months for AAA diameters of 3.0 to 4.5 cm. To evaluate optimal surveillance intervals, researchers conducted a meta-analysis of 18 studies in which 15,500 patients (90% men) with known AAAs were assessed with serial ultrasounds or computed tomography until their AAAs reached diameters of 5.5 cm or ruptured.

Growth rate increased with AAA diameter: In men, the mean annual growth rate of a 3.0-cm AAA was 1.3 mm, compared with 3.6 mm for a 5.0-cm AAA. Estimated times for AAAs to reach 5.5 cm or to rupture generally were longer than recommended screening intervals. For example, it would take about 8 years for 10% of 3-cm AAAs to expand beyond 5.5 cm or for 1% of them to rupture. In contrast, it would take only about 1 year for 10% of 5-cm AAAs to expand beyond 5.5 cm or for 1% of them to rupture.

Comment: Because of the heterogeneity and lack of a firm scientific foundation for the current expert recommendations, these data probably are appropriate to guide longer surveillance intervals in men — perhaps 3 years for AAA diameters of 3.0 to 3.9 cm and 2 years for diameters of 4.0 to 4.4 cm, as recommended by the authors. In women and men with similar AAA diameters, growth and rupture rates were faster in women, but the numbers were too small to provide data for a recommendation.

Source: Journal Watch General Medicine

Repeat Screening for AAA Might Be Cost-Effective.

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In a hypothetical cohort, screening men twice for abdominal aortic aneurysms, at ages 65 and 70, cost US$15,500 per quality-adjusted life-year.

The U.S. Preventive Services Task Force recommends one-time screening by ultrasonography for abdominal aortic aneurysm (AAA) in older men (age range, 65–75) who have ever smoked (JW Gen Med Feb 18 2005). But, is screening in the general population (both smokers and nonsmokers) or repeat screening justified? Using a hypothetical cohort of 100,000 65-year-old men, Danish investigators assessed the cost-effectiveness of no screening, screening once, screening twice (5-year interval), and repeat lifetime screening (every 5 years).

The researchers assumed that large AAAs would be detected without screening (i.e., by physical examination) in 934 per 100,000 men. In contrast, screening once would detect 3115 AAAs per 100,000 men, screening twice would detect 3539 per 100,000, and lifetime screening would detect 3832 per 100,000. The corresponding outcomes for the no-screening strategy and the three screening strategies would be as follows:

  • Elective AAA surgery: 861, 1390, 1496, and 1530 per 100,000 men
  • Acute AAA surgery (due to symptoms and rupture): 610, 382, 363, and 360 per 100,000 men
  • AAA-related mortality: 788, 538, 520, and 511 per 100,000 men

Screening once at age 65 was cost-effective (£555 [US$860] per quality-adjusted life-year [QALY]). Cost of screening twice and lifetime screening were £10,000 ($15,500) and £30,000 ($47,000) per QALY, respectively.

Comment: This analysis confirms that, compared with no screening, screening once with ultrasonography for AAA in older men is cost-effective. Screening results in more elective AAA surgeries, fewer acute surgeries, and fewer AAA-related deaths. The results also suggest that repeat screening is cost-effective, especially screening twice in men with aortic diameters of 25 to 29 mm at initial screening. These finding should be investigated prospectively.

Source: Journal Watch General Medicine