Increased diameter and stiffness of elastic but not muscular arteries in men with abdominal aortic aneurysm.

It has been proposed that formation of abdominal aortic aneurysm (AAA) is part of a systemic arterial dilatative disease. However, arteries in the upper extremities are scarcely studied and it remains unclear whether both muscular and elastic arteries are affected by the proposed systemic arterial dilatation. The aim of this study was to investigate the diameter and stiffness of muscular and elastic arteries in arterial branches originating from the aortic arch. Twenty-six men with AAA (69 ± 4 yr) and 57 men without AAA (70 ± 5 yr) were included in the study. Ultrasound was used to examine the distal and proximal brachial artery, axillary artery, and common carotid artery (CCA), and measurement of diameter and diameter change was performed with wall-tracking software. Blood pressure measurements were used to calculate local arterial wall stiffness indices. The AAA cohort presented larger arterial diameters in the CCA and axillary artery after adjustment for body surface area (P = 0.002, respectively), whereas the brachial artery diameters were unchanged. Indices of increased stiffness in CCA (e.g., lower distensibility, P = 0.003) were seen in subjects with AAA after adjustments for body mass index and mean arterial blood pressure. This study supports the theory of a systemic arterial dilating diathesis in peripheral elastic, but not in muscular, arteries. Peripheral elastic arteries also exhibited increased stiffness, in analogy with findings in the aorta in AAA.NEW & NOTEWORTHY We present data partially supporting the notion of abdominal aortic aneurysm being a systemic vascular disease with focal manifestation in the abdominal aorta, from two well-defined groups recruited from a regional screening program. We show that elastic arteries distal from the aorta exhibit vascular alterations without aneurysmal formation in subjects with AAA compared with controls while muscular arteries seem unaffected.

No differences in FBN1 genotype between men with and without abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA) is an aortic enlargement in which the transverse diameter reaches at least 30 mm. Certain risk factors, such as age, male gender, and smoking, are well known; however, less is known about the genetic factors involved. Fibrillin-1 (FBN1) is a protein that coordinates the deposition of elastin fibres in the extracellular matrix and is therefore likely to affect the elastic properties in the aortic wall. Previously studies have found associations between the FBN1-2/3 genotype and arterial stiffness, but how different FBN1 genotypes, AAA, and arterial stiffness are related has been less frequently investigated. AIM: This study aimed to investigate whether there is a difference in FBN1 genotype between men with and without AAA. A further aim was to study whether the FBN1 genotype affects arterial wall stiffness differently in men with and without AAA. METHODS: Pulse wave velocity and FBN1 genotyping were performed in 229 men (159 with AAA, 70 without AAA). Participants were recruited from ultrasound AAA surveillance programs or ongoing ultrasound screening programs from 2011 to 2016. RESULTS: The distribution of the FBN1 genotype in the AAA and control groups were as follows: FBN1-2/2: 62% vs. 64%; FBN1-2/3: 8% vs. 14%; and FBN1-2/4: 30% vs. 21%, respectively. Men with AAA and FBN1-2/2 had increased central pulse wave velocity (p < 0.005) compared to the control group (those without AAA) with the FBN1-2/2 genotype. CONCLUSION: No differences were found with respect to FBN1 genotypes between men with and without AAA. The development of AAA in men does not appear to be linked to a specific FBN1 genotype. Nevertheless, men with FBN1-2/2 and AAA have increased central arterial stiffness compared to men with the same FBN1 genotype but without AAA.

Association of IL-10 and CRP with Pulse Wave Velocity in Patients with Abdominal Aortic Aneurysm.

BACKGROUND: Markers of inflammation and arterial stiffness are predictors of cardiovascular morbidity and events, but their roles in the mechanisms and progression of abdominal aortic aneurysm (AAA) in males have not been fully investigated. This study explored possible associations between inflammatory marker levels and arterial stiffness in males with AAA. METHODS: A total of 270 males (191 AAA and 79 controls) were included in the study. Arterial stiffness was assessed using non-invasive applanation tonometry to measure the regional pulse wave velocity between the carotid and femoral arteries and the carotid and radial arteries. Blood samples were obtained, and interleukin-10 (IL-10) and CRP levels were analysed. RESULTS: Subjects with an AAA had higher levels of IL-10 (21.5 ± 14.0 ng/mL versus 16.6 ± 9.3 ng/mL) compared to controls (p = 0.007). In the AAA cohort, subjects with T2DM showed higher levels of IL-10 (26.4 ± 17.3 versus 20.4 ± 13.0, p = 0.036). We observed a positive correlation between PWVcf and CRP in the control group (r = 0.332) but not the AAA group. PWVcf and CRP were negatively correlated (r = 0.571) in the T2DM subjects treated with metformin in the AAA group. CONCLUSION: Arterial stiffness is related to the degree of inflammation reflected by CRP and IL-10 levels in males with an AAA. IL-10 is negatively correlated with arterial stiffness in these subjects. This finding suggests that IL-10 may decrease arterial stiffness in males with AAA. The negative correlation between CRP and PWVcf in males with T2DM treated with metformin may indicate that metformin influences the arterial wall to decrease stiffness in subjects with AAA.

Males with abdominal aortic aneurysm have reduced left ventricular systolic and diastolic function.

BACKGROUND: Abdominal aortic aneurysm (AAA) increases the risk of chronic heart failure and other major cardiovascular events. Knowledge about left ventricular function in patients with AAA is lacking. This echocardiographic study aimed to investigate whether AAA is associated with left ventricular systolic and diastolic dysfunction. METHODS: Echocardiography was performed in 307 males (199 AAA and 108 controls) recruited from a regional ultrasound surveillance programme of known AAA, or from an ongoing ultrasound screening programme, during 2011-2016. RESULTS: Subjects with AAA had thicker septal and posterior walls and a reduced left ventricular function compared to controls. Left ventricular ejection fraction (AAA 55 ± 8%, controls 57 ± 7%) and global longitudinal strain (AAA 19 ± 3%, controls 20 ± 3%) were lower in the group with AAA (both p < 0·05). Moreover, decreased mitral annular plane systolic excursion (12 ± 2 mm versus 13 ± 2 mm) and higher E/e' (13 ± 5 versus 11 ± 4) were observed in subjects with AAA (both p < 0·05). The aortic sinus (38 ± 4 mm versus 35 ± 2 mm) and ascending aorta (36 ± 4 mm versus 34 ± 5 mm) were also wider in the AAA group compared to controls (both p < 0·01). CONCLUSION: AAAs are associated with reduced left ventricular systolic and diastolic function in males. The larger diameter of the aortic sinus and ascending aorta among AAA patients suggests that AAA is a general aortic disease.

Increased arterial stiffness in males with abdominal aortic aneurysm.

BACKGROUND: Abdominal aortic aneurysm (AAA), a localized dilatation of the abdominal aorta, has a prevalence of about 1.5%-3% among 65- to 70-year-old males in Europe. AAA confers an increased risk of developing major cardiovascular events in addition to the risk of aneurysm rupture. The aim of this study was to evaluate whether the arterial wall distensibility is altered in subjects with AAA. METHODS: Two hundred and eighty-four male subjects (182 with AAA and 102 controls) were enrolled in the study. Arterial wall distensibility was evaluated using non-invasive applanation tonometry to measure regional pulse wave velocity between the carotid and femoral arteries and the carotid and radial arteries. In addition, blood pressure was measured, and the pulse pressure waveform was analysed. RESULTS: Higher aortic augmentation index (25.1% versus 20.6%; p < .001) and higher aortic pulse wave velocity (12.3 m/s versus 10.9 m/s; p < .001) were demonstrated in the AAA cohort. The slightly higher arm pulse wave velocity in the AAA group (9.4 m/s versus 9.1 m/s; p < .05) was abolished after adjusting for mean arterial blood pressure. CONCLUSIONS: Males with AAA have decreased aortic wall distensibility and enhanced reflection waves in central aorta during systole. These results imply that increased arterial wall stiffness may be a contributing factor to the overall higher cardiovascular risk seen in patients with AAA.

Metformin Prescription Associated with Reduced Abdominal Aortic Aneurysm Growth Rate and Reduced Chemokine Expression in a Swedish Cohort.

BACKGROUND: Recent reports suggest that the negative association between diabetes mellitus and abdominal aortic aneurysm (AAA) may be driven by metformin, the world's most common antidiabetic drug rather than diabetes per se. We sought to investigate the association among AAA growth rate, chemokine profile, and metformin prescription in a contemporary Swedish cohort. METHODS: Patients under surveillance for small AAA were identified at 4 Swedish vascular centers with active AAA screening programs. Annual AAA growth rate, medical history, and prescribed medications were recorded for linear regression analysis. In a subset of patients with AAA and control subjects without AAA or diabetes, plasma samples were available and analyzed for 40 inflammatory chemokines. RESULTS: A total of 526 patients were included for AAA growth analysis: 428 without type 2 diabetes mellitus (T2DM), 65 with T2DM and metformin prescription, and 33 with T2DM but without metformin prescription. Patients were included from 2005 to 2017 with mean follow-up of 3.2 (1.7) years and median annual AAA growth rate 1.6 mm, range -4.8 to 15.4 mm. Mean (standard deviation) annual AAA growth rates were 2.3 (2.2) mm in non-T2DM patients versus 1.1 (1.1) mm in patients with T2DM with metformin prescription and 1.6 (1.4) mm among those with T2DM without metformin prescription. With non-T2DM patients as reference in an unadjusted and 2 adjusted models, metformin prescription was significantly associated with reduced AAA growth rate (P < 0.001, P = 0.005, and P = 0.024, respectively), but not T2DM without metformin prescription (P = 0.137, P = 0.331, and P = 0.479, respectively). Among 240 patients with AAA (152 without T2DM, 51 with T2DM and metformin, and 37 with T2DM without metformin) and 59 without AAA or T2DM, metformin prescription was associated with reduced expression of chemokines representing all classes of leukocytes. CONCLUSIONS: Metformin prescription is associated with reduced AAA growth rate, possibly mediated by broad anti-inflammatory effects. A randomized controlled trial is needed to determine what role metformin may play in AAA disease, particularly in the absence of T2DM.

Higher blood pressure in elderly hypertensive females, with increased arterial stiffness and blood pressure in females with the Fibrillin-1 2/3 genotype.

BACKGROUND: Elderly patients have a relatively high cardiovascular risk due to increased arterial stiffness, elevated blood pressure and decreased amounts of elastin in the arteries. The composition of the media layer in the arterial wall, comprising elastin, collagen, smooth muscle cells, proteoglycans, fibronectin and fibrillin-1, influences its mechanical properties. Mutations in the fibrillin-1 gene leads to increased aortic stiffness, elevated pulse pressure and aortic root dilatation. This study investigates whether there is a sex difference among hypertensive elderly patients regarding blood pressure, arterial stiffness and fibrillin-1 genotypes. METHODS: A total of 315 hypertensive subjects (systolic blood pressure > 140 mmHg) were included in this study (155 men and 160 women aged 71-88 years). Aortic pulse wave velocity and augmentation index were determined using SphygmoCor, and brachial blood pressure was measured using an oscillometric technique. Fibrillin-1 was genotyped by polymerase chain reaction and with a capillary electrophoresis system. RESULTS: Females showed a significantly higher peripheral mean arterial pressure (females; 107.20 mmHg, males 101.6 mmHg, p = 0.008), central mean arterial pressure (females; 107.2 mmHg, males 101.6 mmHg p = 0.008), central systolic blood pressure (females; 148.1 mmHg, males 139.2 mmHg, p <  0.001) and central pulse pressure (females; 68.9 mmHg, males 61.6 mmHg, p = 0.035) than males. Females with the Fibrillin-1 2/3 genotype showed a significantly higher augmentation index (FBN1 2/3; 39.9%, FBN1 2/2 35.0%, FBN1 2/4 35.8, p = 0.029) and systolic blood pressure (FBN1 2/3; 174.6 mmHg, FBN1 2/2168.9 mmHg, FBN1 2/4169.9 mmHg, p = 0.025) than females with the 2/2 and 2/4 genotypes. CONCLUSION: The findings of this study may indicate that hypertensive elderly females, especially elderly females with Fibrillin-1 2/3, have increased systolic blood pressure and arterial stiffness.

Screening of circulating microRNA biomarkers for prevalence of abdominal aortic aneurysm and aneurysm growth.

BACKGROUND AND AIMS: MicroRNA (miR) are important regulators of gene expression and biological processes and have recently been suggested as possible biomarkers for abdominal aortic aneurysm (AAA) disease. The aim of the present study was to assess the role of miR as biomarkers for initiation and progression of AAA disease, through evaluation of a wide range of miRs in a large population-based cohort, with AAA patients with linked clinical data regarding risk factors, AAA size and growth, as well as controls. METHODS: The expression of the 172 most commonly expressed miRs in plasma was analyzed by real-time PCR in samples from 169 screening-detected AAA patients and 48 age-matched controls. RESULTS: For 103 miRs, there was a significant difference in expression between AAA and controls. Of these, 20 miRs were differently expressed between fast and slow growing aneurysms. These miRs target genes known to be involved in AAA disease as well as novel genes and pathways. By combining the top altered miRs together with clinical variables, strong predictive values, determining growth of AAA, were obtained (area under curve = 0.86, p < 0.001). CONCLUSIONS: This large cohort study identified several novel miRs with altered expression in AAA patients when compared to controls. Assessment of miR expression may offer an opportunity to predict disease progression and aneurysm growth.

Increased cardiovascular risk without generalized arterial dilating diathesis in persons who do not have abdominal aortic aneurysm but who are first-degree relatives of abdominal aortic aneurysm patients.

There is a strong genetic predisposition towards abdominal aortic aneurysm (AAA), but it is unknown whether persons without AAA but with first-degree relatives who are AAA patients have a generalized dilating diathesis, defect arterial wall mechanics, or increased cardiovascular risk. The aim of the study was to investigate arterial diameters and wall mechanics at multiple arterial sites in these subjects and compare them with controls without a family history of AAA. This study included 118 first-degree relatives of patients with AAA and 66 controls (age: 40-80 years). The abdominal aorta, common carotid artery, common femoral artery, and popliteal artery were investigated by echo-tracking ultrasound. The relatives had no arterial dilatation, but they did tend to have smaller diameters than controls. Relatives had a higher heart rate, diastolic blood pressure, and mean arterial pressure than controls. The distensibility coefficient and the compliance coefficient were decreased in all arteries in male relatives, adjusted for age and smoking; these coefficients were normalized after adjustment for mean arterial pressure and heart rate. Female relatives had a lower compliance coefficient in the abdominal aorta, adjusted for age and smoking. After adjustment for mean arterial pressure and heart rate, the difference disappeared. No general arterial dilatation in relatives without AAA was found, supporting the hypothesis that the dilating diathesis is linked to the aneurysmal manifestation in the abdominal aorta. Although the threat of aneurysmal dilatation and rupture seems to be lacking in these subjects, heart rate, blood pressure, and arterial wall stiffness were all increased, which may indicate a higher risk of developing cardiovascular morbidity and mortality.

Increased carotid plaque burden in men with the fibrillin-1 2/3 genotype.

Fibrillin-1 (FBN1) is an important constituent of the vascular wall and earlier studies have indicated an effect of the FBN1 2/3 genotype on blood pressure as well as aortic stiffness in men. The aim of the present study was to determine whether the FBN1 2/3 genotype was associated with the presence of carotid plaque and incident cardiovascular morbidity and mortality in middle-aged subjects. The FBN1 genotype was characterized in 5765 subjects (2424 men, 3341 women; age 45-69 years) recruited from the Malmö Diet and Cancer Study Cardiovascular Cohort, Sweden. Plaque occurrence and intima-media thickness (IMT) of the carotid artery were assessed by ultrasound. The incidence of first cardiovascular events (myocardial infarction and stroke) and cause-specific mortality were monitored over a mean follow-up period of 13.2 years. The most common FBN1 genotypes were 2/2, 2/3 and 2/4, which accounted for 92.2% (n = 5317) of subjects. There were no differences between the three genotypes regarding age, blood pressure, glucose, lipids, smoking habits, common carotid artery diameter and intima-media thickness in men and women. The presence of plaque in the carotid artery was higher in men with the 2/3 genotype compared with the 2/2 and 2/4 genotypes (55% vs 46% and 50%, respectively; P = 0.007). No similar differences were observed in women. No significant relationship was observed between FBN1 genotypes and the incidence of cardiovascular disease or all-cause mortality. The increased prevalence of plaque in the carotid artery of middle-aged men with the FBN1 2/3 genotype indicates pathological arterial wall remodelling with a more pronounced atherosclerotic burden.

Low wall stress in the popliteal artery: Other mechanisms responsible for the predilection of aneurysmal dilatation?

The popliteal artery (PA) is, after aorta, the most common site for aneurysm formation. Why the PA is more susceptible than other peripheral muscular arteries is unknown. We hypothesized that the wall composition, which in turn affects wall properties, as well as the circumferential wall stress (WS) imposed on the arterial wall, might differ compared to other muscular arteries. The aim was to study the WS of the PA in healthy subjects with the adjacent, muscular, common femoral artery (CFA) as a comparison. Ninety-four healthy subjects were included in this study (45 males, aged 10-78 years and 49 females, aged 10-83 years). The diameter and intima-media thickness (IMT) in the PA and CFA were investigated with ultrasound. Together with blood pressure the WS was defined according to the law of Laplace adjusted for IMT. The diameter increased with age in both PA and CFA (p<0.001), with males having a larger diameter than females (p<0.001). IMT increased with age in both PA and CFA (p<0.001), with higher IMT values in males only in PA (p<0.001). The calculated WS was unchanged with age in both arteries, but lower in PA than in CFA in both sexes (p<0.001). In conclusion, this study shows that the PA and CFA WS is maintained during aging, probably due to a compensatory remodelling response with an increase in arterial wall thickness. However, the stress imposed on the PA wall is quite low, indicating that mechanisms other than WS contribute to the process of pathological arterial dilatation in the PA.

Gender-specific association of the plasminogen activator inhibitor-1 4G/5G polymorphism with central arterial blood pressure.

BACKGROUND: The functional plasminogen activator inhibitor-1 (PAI-1) 4G/5G polymorphism has previously been associated with hypertension. In recent years, central blood pressure, rather than brachial has been argued a better measure of cardiovascular damage and clinical outcome. The aim of this study was to investigate the possible influence of the 4G/5G polymorphism on central arterial blood pressure in a cohort of elderly individuals. METHODS: We studied 410 individuals, 216 men and 194 women, aged 70-88. Central pressures and pulse waveforms were calculated from the radial artery pressure waveform by the use of the SphygmoCor system and a generalized transfer function. Brachial pressure was recorded using oscillometric technique (Dinamap, Critikon, Tampa, FL). PAI-1 antigen was determined in plasma. RESULTS: The results showed that central pressures were higher in women carrying the PAI-1 4G/4G genotype compared to female carriers of the 5G/5G genotype, (P = 0.025, P = 0.002, and P = 0.002 for central systolic-, diastolic-, and mean arterial pressure, respectively). The association remained after adjustment for potentially confounding factors related to hypertension. No association of the PAI-1 genotype with blood pressure was found in men. Multiple regression analysis revealed an association between PAI-1 genotype and plasma PAI-1 levels (P = 0.048). CONCLUSIONS: Our findings show a gender-specific association of the PAI-1 4G/5G polymorphism with central arterial blood pressure. The genotype effect was independent of other risk factors related to hypertension, suggesting that impaired fibrinolytic potential may play an important role in the development of central hypertension in women.

The association between circulating angiotensin-converting enzyme and cardiovascular risk in the elderly: a cross-sectional study.

INTRODUCTION: A polymorphism in the angiotensin-converting enzyme gene (ACE I/D polymorphism) has been associated with increased risk for cardiovascular disease (CVD). This polymorphism affects the level of circulating ACE, but there is great individual variation, even between those with the same genotype. Few previous studies have investigated the link between circulating ACE and cardiovascular risk. The aim of this study was to investigate this association, and to examine the relationship between ACE level, ACE genotype and CVD. MATERIALS AND METHODS: The study population consisted of 322 men and 350 women aged 69-87. Plasma ACE level was determined using enzyme-linked immunosorbent assay (ELISA), and ACE genotype was analysed using PCR followed by gel electrophoresis. RESULTS: In men, ACE levels increased with increasing number of cardiovascular risk factors (p = 0.003). There was a significant association in men between increased ACE level and both diabetes (p = 0.007) and smoking (p = 0.037). CONCLUSIONS: This study shows that cardiovascular risk factors (such as smoking and diabetes) are associated with higher levels of circulating ACE in men. High ACE levels may represent one of the cellular mechanisms involved in producing the vascular damage associated with cardiovascular risk factors.