Associations of IGF1 and its binding proteins with abdominal aortic aneurysm and aortic diameter in older men

ObjectiveAbdominal aortic aneurysm (AAA) is most prevalent in older men. GH secretion declines with age resulting in reduced IGF1 levels. IGF1 and its binding proteins (IGFBPs) are expressed in vasculature, and lower IGF1 levels have been associated with cardiovascular risk factors and disease. However, the relationship of the IGF1 system with aortic dilation and AAA is unclear. We tested the hypothesis that circulating IGF1 and IGFBPs are associated with AAA and aortic diameter in older men.DesignA cross-sectional analysis involving 3981 community-dwelling men aged 70–89 years was performed.MethodsAbdominal aortic diameter was measured by ultrasound. Plasma total IGF1, IGFBP1 and IGFBP3 were measured by immunoassays.ResultsAfter adjustment for age, body mass index, waist:hip ratio, smoking, hypertension, dyslipidemia, diabetes, coronary heart disease and serum creatinine, a higher IGF1 level was associated with AAA (odds ratio (OR)/1 s.d. increase 1.18, 95% confidence interval (CI) 1.05–1.33, P=0.006), as was the ratio of IGF1/IGFBP3 (OR=1.22, 95% CI 1.10–1.35, P<0.001). Highest IGF1 concentrations compared with lowest quintile were significantly associated with AAA (quintile (Q) 5 vs Q1: OR=1.80, 95% CI 1.20–2.70, P=0.004) as were IGF1/IGFBP3 ratios (Q5 vs Q1: OR=2.52, 95% CI 1.59–4.02, P<0.001). IGF1 and IGFBP1 were independently associated with aortic diameter (β=0.200, 95% CI 0.043–0.357, P=0.012 and β=0.274, 95% CI 0.098–0.449, P=0.002 respectively).ConclusionsIn older men, higher IGF1 and an increased ratio of IGF1/IGFBP3 are associated with AAA, while IGFBP1 is independently associated with increased aortic diameter. Components of the IGF1 system may contribute to, or be a marker for, aortic dilation in ageing men.

Download Full-text

Plasma total homocysteine is associated with abdominal aortic aneurysm and aortic diameter in older men

Journal of Vascular Surgery ◽

10.1016/j.jvs.2013.01.046 ◽

2013 ◽

Vol 58 (2) ◽

pp. 364-370 ◽

Cited By ~ 22

Author(s):

Yuen Y.E. Wong ◽

Jonathan Golledge ◽

Leon Flicker ◽

Kieran A. McCaul ◽

Graeme J. Hankey ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Older Men ◽

Aortic Diameter ◽

Abdominal Aortic ◽

Total Homocysteine ◽

Plasma Total Homocysteine

Download Full-text

An association between rs7635818 polymorphism located on chromosome 3p12.3 and the presence of abdominal aortic aneurysm

Physiological Research ◽

10.33549/physiolres.934624 ◽

2021 ◽

pp. 193-201

Author(s):

M Rašiová ◽

V Habalová ◽

J Židzik ◽

M Koščo ◽

L Farkašová ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Association Studies ◽

Univariate Analysis ◽

Aortic Diameter ◽

Control Group ◽

Genome Wide Association Studies ◽

Cross Sectional ◽

Slovak Population ◽

Abdominal Aortic

The association between gene variant rs7635818 located on chromosome 3p12.3 and abdominal aortic aneurysm (AAA) was not unambiguously determined by the results of genome-wide association studies. The aim of our study was to examine this possible association in the Slovak population, with respect to the presence and severity of AAA. A cross-sectional study was conducted between August 2016 and March 2020. The study included 329 participans, 166 AAA patients and a control group of 163 subjects without confirmed AAA with comparable distribution of genders. The anteroposterior diameter of the abdominal aorta was determined by duplex ultrasonography. AAA was defined as subrenal aortic diameter ≥ 30 mm. DNA samples were genotyped using real-time polymerase chain reaction and subsequent high-resolution melting analysis in presence of unlabelled probe. Genetic models studying the possible association were adjusted to age, sex, smoking, arterial hypertension, diabetes mellitus, creatinine and body mass index (BMI) in multivariate analysis. In the additive model, presence of each C-allele of rs7635818 polymorphism was associated with an almost 50 % increase in probability of developing AAA (OR 1.49; 95 % CI 1.06‒2.08; p=0.020). Compared to GG homozygotes, CC homozygotes had more than two times higher risk of developing AAA (OR 2.23; 95 % CI 1.14‒4.39; p=0.020). The risk of AAA was also in the recessive model higher for CC homozygotes compared to G-allele carriers (GC/GG) (OR 1.79; 95 %CI 1.01‒3.19; p=0.047). The abdominal aortic diameter in CC homozygotes of the rs7635818 polymorphism was 7.66 mm greater compared to GG homozygotes (42.5±22.0 mm vs 34.8±21.3 mm; p=0.022) and 5.88 mm greater compared to G-allele carriers (GC/GG) (42.5±22.0 mm vs 36.6±21.0 mm; p=0.04) in univariate analysis. C-allele variant in rs7635818 G>C polymorphism is associated with a higher probability of developing AAA in the Slovak population.

Download Full-text

Reported High Salt Intake Is Associated with Increased Prevalence of Abdominal Aortic Aneurysm and Larger Aortic Diameter in Older Men

PLoS ONE ◽

10.1371/journal.pone.0102578 ◽

2014 ◽

Vol 9 (7) ◽

pp. e102578 ◽

Cited By ~ 7

Author(s):

Jonathan Golledge ◽

Graeme J. Hankey ◽

Bu B. Yeap ◽

Osvaldo P. Almeida ◽

Leon Flicker ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Salt Intake ◽

Older Men ◽

High Salt ◽

Aortic Diameter ◽

Abdominal Aortic ◽

High Salt Intake

Download Full-text

Abstract 032: Associations between Middle-age Risk Factors and Future Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽

10.1161/circ.127.suppl_12.a032 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Weihong Tang ◽

Alvaro Alonso ◽

Pamela L Lutsey ◽

Frank A Lederle ◽

Lu Yao ◽

...

Keyword(s):

Risk Factors ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Middle Age ◽

Disease Risk ◽

Atherosclerotic Disease ◽

Cross Sectional ◽

Abdominal Aortic ◽

Aric Study

Introduction: Abdominal aortic aneurysm (AAA) is an important manifestation of vascular disease in older age and rupture of an AAA is a life threatening condition. Traditional atherosclerotic disease risk factors, particularly male sex, smoking and hypertension, are known to contribute to the etiology of AAA. However, epidemiologic studies of AAA have often been cross-sectional, and few have employed a prospective cohort design, especially with long follow-up. The objective of this study was to prospectively assess the association between atherosclerotic disease risk factors and hospitalized AAA in 15,722 participants (68% whites) of the ARIC study, a large, community-based cohort. Methods: Risk factors were measured at baseline at 45-64 year of age. Clinical AAAs were ascertained through hospital discharge diagnoses or death certificates. Over 15 years of follow-up, a total of 265 AAAs (85.3% whites) were identified, including repair procedures, AAA rupture or dissection, and incidental detection. Multivariable Cox proportional hazard models were used to estimate the association of risk factors with the risk of future AAA. Results: Consistent with the literature from prospective studies, we identified age, male gender, white race, smoking, height, total and HDL cholesterols, triglycerides, white blood cell count, and hypertension as risk factors for AAA (Table). In addition, LDL-C, fibrinogen, and peripheral artery disease that were previously reported only in cross-sectional case-control studies were also strongly associated with AAA (Table). Body mass index, diabetes, and alcohol consumption were not associated with AAA occurrence. Conclusions: Several lifestyle and clinical variables measured in middle-age were strong risk factors for future AAA during a long follow-up.

Download Full-text

Abstract P440: Diabetes and the Long-term Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study

Circulation ◽

10.1161/circ.141.suppl_1.p440 ◽

2020 ◽

Vol 141 (Suppl_1) ◽

Author(s):

Kunihiro Matsushita

Keyword(s):

Blood Pressure ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Lower Risk ◽

Aortic Diameter ◽

Time Varying ◽

Glycemic Status ◽

Duration Of Diabetes ◽

Abdominal Aortic ◽

Cumulative Duration

Introduction: Diabetes mellitus is known to be related to lower risk of abdominal aortic aneurysm (AAA). However, the full spectrum of glycemic status including prediabetes and the duration of diabetes have not been extensively investigated in the context of AAA risk. Methods: We prospectively studied incident AAA (defined using outpatient records, hospitalization discharge, or death certificate) according to the baseline glycemic status defined using physician diagnosed diabetes, self-reported anti-diabetic medication use and glucose or hemoglobin A1c (diabetes, pre-diabetes, vs. normal glycemia) in 13,116 participants (1990-1992) and the time-varying exposure of duration of incident diabetes in 11,675 participants (1987-1989) using Cox models. We cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4,710 participants (2011-2013) using linear regression models. Results: There were 489 incident AAA cases during a median follow-up of ~20 years. Diabetes but not pre-diabetes (vs. normal glycemia) at baseline was independently associated with lower risk of AAA (HR: 0.71 [95%CI 0.51 - 0.99]). The association was largely driven by long-standing diabetes (≥10 years duration: HR: 0.58 [95%CI 0.38 - 0.87]). Longer duration of diabetes was associated with lower risk of AAA (Figure 1A), with 30-50% lower risk in 8 years after incident diabetes diagnosis, as well as smaller aortic diameter measured cross-sectionally (Figure 1B) compared to non-diabetes. Pre-diabetes consistently showed relatively greater diameter (e.g., +0.26 mm [-0.03, +0.54]). Conclusions: Diabetes (but not prediabetes) and its longer duration were independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that the cumulative effects of hyperglycemia may play a role in the counterintuitively lower AAA risk. Reduced aortic diameter might be a structural mechanism of decreased AAA risk in diabetes. Figure 1A. Adjusted hazard ratio of incident AAA according to the duration of diabetes among incident cases as a time-varying exposure; Figure 1B. Adjusted difference in maximum diameter (mm) for diabetes vs. non-diabetes by cumulative duration of diabetes. Both models adjusted for age, sex, race, education, BMI, height, total cholesterol, HDL cholesterol, systolic blood pressure, diastolic blood pressure, anti-hypertensive medication, cholesterol-lowering medication, cigarette smoking pack-years, alcohol drinking, eGFR, prevalent peripheral artery disease, prevalent coronary heart disease, and prevalent stroke (time-varying covariates for Figure 1A and baseline covariates for Figure 1B).

Download Full-text

Retrospective review of abdominal aortic aneurysm deaths in New Zealand: what proportion of deaths is potentially preventable by a screening programme in the contemporary setting?

BMJ Open ◽

10.1136/bmjopen-2018-027291 ◽

2019 ◽

Vol 9 (7) ◽

pp. e027291

Author(s):

Wing Cheuk Chan ◽

Dean Papaconstantinou ◽

Doone Winnard ◽

Gary Jackson

Keyword(s):

Abdominal Aortic Aneurysm ◽

New Zealand ◽

Aortic Aneurysm ◽

Screening Programme ◽

Population Based ◽

Cross Sectional ◽

The People ◽

Abdominal Aortic ◽

High Prevalence ◽

History Of

ObjectivesTo describe the proportions of people dying from abdominal aortic aneurysm (AAA) who might have benefited from a formal screening programme for AAA.DesignRetrospective cross-sectional review of deaths.Setting and study populationsAll AAA deaths registered in New Zealand from 2010 to 2014 in the absence of a national AAA screening programme.Main outcome measuresKnown history of AAA prior to the acute event leading to AAA death, prognosis limiting comorbidities, history of prior abdominal imaging and a validated multimorbidity measure (M3-index scores).Results1094 AAA deaths were registered in the 5 years between 2010 and 2014 in New Zealand. Prior to the acute AAA event resulting in death, 31.3% of the cohort had a known AAA diagnosis, and 10.9% had a previous AAA procedure. On average, the AAA diagnosis was known 3.7 years prior to death. At least 77% of the people dying from AAA also had one or more other prognosis limiting diagnosis. The hazard of 1-year mortality associated with the non-AAA related comorbidities for the AAA cohort aged 65 or above were 1.5–2.6 times higher than to the age matched general population based on M3-index scores. In 2014, overall AAA deaths accounted for only 0.7% of total deaths, and 1.0% of deaths among men aged 65 or above in New Zealand. At most, 20% of people dying from AAA in New Zealand between 2010 and 2014 might have had the potential to derive full benefit from a screening programme. About 51% of cases would have derived no or very limited benefit from a screening programme.ConclusionFalling AAA mortality, and high prevalence of competing comorbidities and/or prior AAA diagnosis and procedure raises the question about the likely value of a national AAA screening programme in a country such as New Zealand.

Download Full-text

Further evidence on the relationship between abdominal aortic aneurysm and periodontitis: A cross‐sectional study

Journal of Periodontology ◽

10.1002/jper.19-0671 ◽

2020 ◽

Vol 91 (11) ◽

pp. 1453-1464

Author(s):

Leila Salhi ◽

Natzi Sakalihasan ◽

Ambre Gau Okroglic ◽

Nicos Labropoulos ◽

Laurence Seidel ◽

...

Keyword(s):

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Abdominal Aortic ◽

The Relationship

Download Full-text

Proteomic analysis of aortic smooth muscle cell secretions reveals an association of myosin heavy chain 11 with abdominal aortic aneurysm

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00329.2018 ◽

2018 ◽

Vol 315 (4) ◽

pp. H1012-H1018 ◽

Cited By ~ 3

Author(s):

Utako Yokoyama ◽

Noriaki Arakawa ◽

Ryo Ishiwata ◽

Shota Yasuda ◽

Tomoyuki Minami ◽

...

Keyword(s):

Smooth Muscle ◽

Abdominal Aortic Aneurysm ◽

Aortic Aneurysm ◽

Myosin Heavy Chain ◽

Heavy Chain ◽

Endovascular Aneurysm Repair ◽

Aortic Diameter ◽

Tunica Media ◽

Abdominal Aortic ◽

Aneurysm Repair

Abdominal aortic aneurysm (AAA) is a life-threatening disease, and no disease-specific circulating biomarkers for AAA screening are currently available. We have identified a smooth muscle cell (SMC)-specific biomarker for AAA. We cultured aneurysmal tunica media that were collected from eight patients undergoing elective open-repair surgeries. Secreted proteins in culture medium were subjected to liquid chromatography/tandem mass spectrometry. Myosin heavy chain 11 (myosin-11) was identified as a SMC-specific protein in the tunica media-derived secretions of all patients. We then examined myosin-11 protein concentrations by ELISA in plasma samples from patients with AAA ( n = 35) and age-matched healthy control subjects ( n = 34). Circulating myosin-11 levels were significantly higher in patients with AAA than control subjects. The area under the receiver-operating characteristic curve (AUC) of myosin-11 was 0.77, with a specificity of 65% at a sensitivity of 91%. Multivariate logistic regression analysis showed a significant association between the myosin-11 level and presence of AAA. When the myosin-11 level was combined with hypertension, it improved the prediction of AAA (AUC 0.88) more than hypertension per se. We then investigated the correlation between aortic diameter and circulating myosin-11 levels using AAA serum samples from patients undergoing endovascular aneurysm repair ( n = 20). Circulating myosin-11 levels were significantly correlated with maximum aortic diameter. Furthermore, changes in myosin-11 concentrations from the baseline 12 mo after endovascular aneurysm repair were associated with those in aortic diameter. These data suggest that circulating levels of myosin-11, which is a SMC-specific myosin isoform, may be useful as a biomarker for AAA. NEW & NOTEWORTHY Extensive studies have revealed that inflammation- or proteolysis-related proteins are proposed as biomarkers for abdominal aortic aneurysm (AAA). Changes in these protein concentrations are not specific for smooth muscle, which is a major part of AAA pathologies. Hence, no disease-specific circulating markers for AAA are currently available. We found, using secretome-based proteomic analysis on human AAA tunica media, that myosin heavy chain 11 was associated with AAA. Circulating myosin heavy chain 11 may be a new tissue-specific AAA marker.

Download Full-text