scholarly journals The Association of Biomarkers of Inflammation and Extracellular Matrix Degradation With the Risk of Abdominal Aortic Aneurysm: The ARIC Study

Angiology ◽  
2018 ◽  
Vol 70 (2) ◽  
pp. 130-140 ◽  
Author(s):  
Weihong Tang ◽  
Lu Yao ◽  
Ron C. Hoogeveen ◽  
Alvaro Alonso ◽  
David J. Couper ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinase ◽  
Abdominal Ultrasound ◽  
Aortic Aneurysms ◽  
Blood Concentrations ◽  
Atherosclerosis Risk In Communities ◽  
Hazard Ratios ◽  
Abdominal Aortic ◽  
Aric Study

Animal and human laboratory studies suggest that the pathogenesis of abdominal aortic aneurysms (AAAs) involves inflammation and degradation and remodeling of the extracellular matrix. This study prospectively assessed the association between biomarkers for these mechanisms and the presence of AAA during 24 years of follow-up in the Atherosclerosis Risk in Communities (ARIC) study. The ARIC prospectively identified clinically diagnosed AAAs in 15 792 men and women from baseline in 1987 to 1989 to 2011 using hospital discharge codes and death records. Additional asymptomatic AAAs were detected by an abdominal ultrasound scan in 2011 to 2013. Matrix metalloproteinase (MMP)-3, MMP-9, interleukin 6 (IL-6), N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin were measured in blood samples collected between 1987 and 1992 in participants with AAA (544 clinically diagnosed AAAs and 72 ultrasound-detected AAAs) and a random sample of 723 participants selected from baseline and matched with AAAs by age, race and sex. Higher concentrations of MMP-9 and IL-6 were associated with future risk of clinically diagnosed AAA (hazard ratios [95% confidence intervals]: 1.55 [1.22-1.97] and 1.87 [1.48-2.35], respectively, comparing highest versus lowest tertiles) after multivariable adjustment ( P for trend < .001). Matrix metalloproteinase-9 was also associated with ultrasound-detected AAA. In conclusion, blood concentrations of MMP-9 and IL-6 measured in middle age predicted the risk of AAA during 24 years of follow-up.

Abstract MP47: Associations Between Novel Biomarkers and Risk of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Weihong Tang ◽  
Lu Yao ◽  
Ron C Hoogeveen ◽  
Alvaro Alonso ◽  
David J Couper ◽  
...  
Keyword(s):  
Risk Factors ◽  
Disease Risk ◽  
Aortic Aneurysms ◽  
Matrix Remodeling ◽  
Cross Sectional ◽  
Blood Concentrations ◽  
Abdominal Aortic ◽  
Novel Biomarkers ◽  
Aric Study

Introduction: Abdominal aortic aneurysms (AAA) are an important manifestation of vascular disease in older age and rupture of an AAA is associated with high mortality. Traditional atherosclerotic disease risk factors contribute to the etiology of AAA. Biomarkers for novel etiopathogenic mechanisms, including extracellular matrix remodeling and inflammation, have been assessed primarily in cross-sectional studies of AAA. The objective of this study was to prospectively assess the association between biomarkers for these novel mechanisms and clinical AAA during 24 years of follow-up in the ARIC study, a large, community-based cohort. Methods: Clinical AAAs were ascertained from baseline in 1987-1989 (45-64 years of age) to 2011 through hospital discharge codes, death codes, and Medicare outpatient claims. Over a maximum 24 years of follow-up, a total of 554 AAAs (85.3% whites) were identified. Using a nested case-cohort design, novel biomarkers, including MMP3, MMP9, IL6, IL1-beta, N-terminal propeptide of Type III procollagen (PIIINP), and osteopontin, were measured at baseline (90% of sample) or Visit 2 (1990-1992, 10% of sample) in all AAAs and a random sample of 747 participants who were selected from baseline and matched with AAAs by age (≤55 and >55), race, and gender. The association of the biomarkers with the risk of future AAA was estimated using multivariable Cox proportional hazard models with weighting to adjust for the varying sampling fractions of cases and controls across strata. Results: MMP9, IL6, PIIINP, and osteopontin were significantly associated with future risk of AAA after adjusting for age, gender, race and field center (Table). The associations for PIIINP and osteopontin were no longer significant after further adjusting for other traditional risk factors for AAA. Conclusions: Blood concentrations of MMP9, IL6, and osteopontin measured in middle-age were risk markers for incident AAA. These results highlight the role of inflammation and extracellular remodeling in the development of AAA.

Abstract P038: Serum Calcium, 25-hydroxyvitamin D and Incidence of Abdominal Aortic Aneurysm: The Atherosclerosis Risk in Communities Study

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Mary R Rooney ◽  
Weihong Tang ◽  
Aaron R Folsom ◽  
Erin D Michos ◽  
Alvaro Alonso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Serum Calcium ◽  
Aortic Aneurysms ◽  
Serum Concentrations ◽  
Atherosclerosis Risk In Communities ◽  
Hydroxyvitamin D ◽  
Abdominal Aortic ◽  
Atherosclerosis Risk ◽  
25 Hydroxyvitamin D

Introduction: Serum concentrations of calcium and 25-hydroxyvitamin D [25(OH)D] may potentially contribute to the development of abdominal aortic aneurysms (AAA), likely predominately through established AAA risk factors such as hypertension and inflammation. To date, no prospective epidemiologic studies have examined the association between calcium and 25(OH)D and AAA risk. Hypothesis: We hypothesized that 20-year risk of AAA is higher among individuals with elevated serum calcium and among those with low serum of 25(OH)D. Methods: Serum calcium and 25(OH)D were measured in Atherosclerosis Risk in Communities (ARIC) study participants without prior AAA and who attended visit 2 (1990-92) (N=13,452). Serum calcium was corrected for serum albumin. AAA events were identified through 2011 via annual follow-up phone calls for hospitalized AAAs, and through Medicare for both hospitalized and outpatient AAAs. Multi-variable Cox proportional hazards models were used. Calcium was modeled as quartiles and 25(OH)D as <10, 10-<20, 20-<30, ≥30 ng/ml. Additionally, sex-stratified analysis was conducted. Results: The participants were mean±SD age 57±6y, 44% men and 75% white. Mean serum concentrations were 9.2±0.4 mg/dl for calcium and 24.3±8.5 ng/ml for 25(OH)D. Over a median 19.7 years of follow-up, 484 AAA cases were identified. High serum calcium was associated with an increased incidence of AAA [HR Q4 v Q1=1.60 (95% CI: 1.24-2.08)] after adjustment for demographics and with additional adjustment for height, weight and smoking [1.39 (1.05-1.82)], but not after other CVD risk factors were controlled for [1.20 (0.91-1.58)]. In the fully adjusted model, a sex-interaction was present [p-value sex*calcium interaction=0.03], whereby the association was present in women [2.28 (1.20-4.34)] not men [1.05 (0.75-1.47)]. Those with 25(OH)D ≥30 ng/ml vs. <10 ng/ml had a HR for AAA of 1.54 (1.03-2.29) after demographic adjustment, but the association was attenuated with further adjustment for height, weight and smoking [1.24 (0.82-1.88)]. No sex-25(OH)D interaction was detected. As such, stratified results are not presented. Conclusions: In this large prospective cohort, there was little evidence that markers of vitamin D metabolism are associated with risk of incident AAA. The positive association of calcium with AAA among women may warrant further investigation and replication in other populations.

Matrix Metalloproteinase 9 Activity in Patients before and after Endovascular or Surgical Repair of Abdominal Aortic Aneurysms

Vascular ◽  
2004 ◽  
Vol 12 (5) ◽  
pp. 312-317
Author(s):  
Maurizio Taurino ◽  
Vincenzo Visco ◽  
Salvatore Raffa ◽  
Benedetto Ricci ◽  
Massimo Ruggiero ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Endovascular Repair ◽  
Open Surgery ◽  
Endovascular Aneurysm Repair ◽  
Abdominal Aortic Aneurysms ◽  
Matrix Metalloproteinase 9 ◽  
Aortic Aneurysms ◽  
Abdominal Aortic ◽  
Metalloproteinase 9

The objective of this prospective study was to assess matrix metalloproteinase 9 (MMP-9) activity in patients undergoing open surgery or endovascular repair of abdominal aortic aneurysms (AAAs), comparing changes in plasma levels in the two groups. We studied 12 patients after conventional open surgery and 9 patients after endovascular aneurysm repair. MMP-9 was assayed in plasma at baseline and 1 week and 1 month thereafter. Preoperative MMP-9 levels were similar in the two groups (41.7 ± 19.1 vs 44.4 ± 24.6 ng/mL; p = not significant). Assessment 1 week later showed that MMP levels in both repair groups had increased. In the open surgery group, they increased significantly (59.7 ± 16.8 ng/mL; p < .05) but not in the endovascular group (49.3 ± 32.4 ng/mL). One month later, MMP-9 levels decreased in both groups but not significantly (to 32.6 ± 24.6 ng/mL for open surgery repair and to 34.7 ± 23.5 ng/mL for endovascular repair). At 1 month after repair, MMP-9 levels decreased significantly only in smokers, whereas in nonsmokers, they did not (from 46.9 ± 22.1 to 31.7 ± 21.5 ng/mL in smokers [ p < .05] vs from 34.7 ± 17.4 to 37.1 ± 28.9 ng/mL in nonsmokers). This study confirms that enzyme secretion changes during the postoperative course. The differing patterns of MMP-9 expression prevent us from reaching definitive conclusions about the use of MMP-9 as a marker during early postprocedural follow-up. An important matter to clarify is the role of MMP-9 in long-term follow-up, especially after endovascular AAA repairs.

scholarly journals Targeting the Extracellular Matrix in Abdominal Aortic Aneurysms Using Molecular Imaging Insights

2021 ◽  
Vol 22 (5) ◽  
pp. 2685
Author(s):  
Lisa Adams ◽  
Julia Brangsch ◽  
Bernd Hamm ◽  
Marcus R. Makowski ◽  
Sarah Keller
Keyword(s):  
Extracellular Matrix ◽  
Molecular Imaging ◽  
Molecular Targets ◽  
Abdominal Aortic Aneurysms ◽  
Aortic Aneurysms ◽  
Type I ◽  
Target Tissue ◽  
Pharmacologic Treatment ◽  
Abdominal Aortic

This review outlines recent preclinical and clinical advances in molecular imaging of abdominal aortic aneurysms (AAA) with a focus on molecular magnetic resonance imaging (MRI) of the extracellular matrix (ECM). In addition, developments in pharmacologic treatment of AAA targeting the ECM will be discussed and results from animal studies will be contrasted with clinical trials. Abdominal aortic aneurysm (AAA) is an often fatal disease without non-invasive pharmacologic treatment options. The ECM, with collagen type I and elastin as major components, is the key structural component of the aortic wall and is recognized as a target tissue for both initiation and the progression of AAA. Molecular imaging allows in vivo measurement and characterization of biological processes at the cellular and molecular level and sets forth to visualize molecular abnormalities at an early stage of disease, facilitating novel diagnostic and therapeutic pathways. By providing surrogate criteria for the in vivo evaluation of the effects of pharmacological therapies, molecular imaging techniques targeting the ECM can facilitate pharmacological drug development. In addition, molecular targets can also be used in theranostic approaches that have the potential for timely diagnosis and concurrent medical therapy. Recent successes in preclinical studies suggest future opportunities for clinical translation. However, further clinical studies are needed to validate the most promising molecular targets for human application.

scholarly journals Changes in hypertension control in a community-based population of older adults, 2011-2013 to 2016-2017

2020 ◽  
Author(s):  
Kathryn Foti ◽  
Kunihiro Matsushita ◽  
Silvia Koton ◽  
Keenan A Walker ◽  
Josef Coresh ◽  
...  
Keyword(s):  
Older Adults ◽  
Baseline Risk ◽  
Treatment Goals ◽  
Hypertension Control ◽  
Community Based ◽  
Study Objective ◽  
Atherosclerosis Risk In Communities ◽  
Black And White ◽  
Aric Study

Abstract Background The 2014 hypertension guideline raised treatment goals in older adults. The study objective was to examine changes in blood pressure (BP) control (&lt;140/90 mmHg) from 2011-2013 to 2016-2017 among Black and white older adults with treated hypertension. Methods Participants were 1600 white and 650 Black adults aged 71-90 years in the Atherosclerosis Risk in Communities (ARIC) Study with treated hypertension in 2011-2013 (baseline) who had BP measured in 2016-2017 (follow up). Factors associated with changes in BP control were examined by race. Results BP was controlled among 75.3% of white and 65.7% of Black participants at baseline and 59.0% of white and 56.5% of Black participants at follow up. Among those with controlled BP at baseline, risk factors for incident uncontrolled BP included age (RR 1.15 per 5 years, 95% CI 1.07-1.25), female sex (RR 1.36, 95% CI 1.16-1.60), and chronic kidney disease (CKD) (RR 1.19, 95% CI 1.01-1.40) among white participants, and hypertension duration (RR 1.14 per 5 years, 95% CI 1.03-1.27) and diabetes (RR 1.48, 95% CI 1.15-1.91) among Black participants. Among those with uncontrolled BP at baseline, white females vs males (RR 0.60, 95% CI 0.46-0.78) and Black participants with CKD vs without (RR 0.58, 95% CI 0.36-0.93) were less likely to have incident controlled BP. Conclusions BP control decreased among white and Black older adults. Black individuals with diabetes or CKD were less likely to have controlled BP at follow up. Higher treatment goals may have contributed to these findings and unintended differences by race.

Abstract P116: Trait Anger Increases Short-term and Long-term Risk for Recurrent CHD: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Janice E Williams ◽  
Sharon B Wyatt ◽  
Kathryn M Rose ◽  
David J Couper ◽  
Anna Kucharska-Newton
Keyword(s):  
Cigarette Smoking ◽  
Trait Anger ◽  
Middle Aged ◽  
Short Term ◽  
Men And Women ◽  
Atherosclerosis Risk In Communities ◽  
Atherosclerosis Risk ◽  
Aric Study

Though several large epidemiologic studies have demonstrated the positive association of anger with coronary heart disease (CHD) onset, a dearth of population-based evidence exists regarding the relationship of anger to the clinical course of CHD among people with established disease. Trait anger is conceptualized as a stable personality trait and defined as the tendency to experience frequent and intense anger. Therefore, it is plausible that the effects of trait anger on CHD are long standing. We assessed the hypothesis that trait anger predicts short-term and long-term risk for recurrent CHD among middle-aged men and women. Participants were 611 black or white men and women, ages 48 - 67, who had a history of CHD at the second clinical examination (1990-1992) of the Atherosclerosis Risk in Communities (ARIC) Study. They were followed for the recurrence of CHD (myocardial infarction or fatal CHD) from 1990 through three different time intervals: 1995, 2003, and 2009 (maximum follow-up = 19.0 years). Trait anger (measured at Visit 2) was assessed using the Spielberger Trait Anger Scale, with scores categorized as high, moderate, and low. Cox proportional hazards regression analyses were adjusted for age, sex, race-center, educational level, waist-to-hip ratio, plasma LDL-and HDL-cholesterol levels, hypertension, diabetes, cigarette smoking status, and pack-years of cigarette smoking. After 3 - 5 years of follow-up, the risk for recurrent CHD among participants with high trait anger was more than twice that of their counterparts with low trait anger (2.24 [95% C.I: 1.14 to 4.40]). After 11 - 13 years, the risk was 80% greater (1.80 [95% C.I: 1.17 to 2.78]) and after 17 - 19 years, it was 70% greater (1.70 [95% C.I: 1.15 to 2.52]). The risk for recurrent CHD was strongest in the first time interval but remained strong and statistically significant through 19 years of follow-up. In conclusion, the experience of frequent and intense anger increases short-term and long-term risk for recurrent CHD in middle-aged men and women.

Abstract 15380: Association of Change in Body Mass Index With Premature Atrial Contractions Frequency and Atrial Fibrillation in Older Age: The Atherosclerosis Risk in Communities (ARIC) Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Joseph Decker ◽  
Wendy Wang ◽  
Faye L Norby ◽  
Romil Parikh ◽  
Jorge L Reyes ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Body Mass Index ◽  
Body Mass ◽  
The Elderly ◽  
Atherosclerosis Risk In Communities ◽  
Aging Adults ◽  
Aric Study ◽  
Multivariable Adjustment ◽  
Adjustment Table

Introduction: The proportions of obese and aging adults are rapidly growing. While obesity and advancing age are associated with atrial fibrillation (AF), data are limited on weight change in the elderly as a risk factor for premature atrial contractions (PACs)—which are known to precede AF—or AF. Hypothesis: Compared to a stable body mass index (BMI) over time, increasing BMI will be associated with a higher PAC frequency and AF in elderly participants in ARIC. Methods: We included N=2,070 ARIC participants [age mean ± SD 79 ± 4.5 years, 59% female] without known AF who attended visit 6 and wore an ambulatory ECG-monitoring device (Zio XT® Patch, iRhythm Technologies Inc.) for ≥48 hours. BMI change was defined as change between V5 (2011-13) and V6 (2016-17) and was categorized into 4 groups: >10% decrease, 2 to 10% decrease, -2 to 2% change (stable BMI) and > 2% increase. PAC frequency was defined as percent of beats that are PACs. Linear regression was used to evaluate the association between BMI change and % PAC. Incident AF was ascertained after V6 through 2018 from hospital discharge codes and death certificates. Logistic regression was used to evaluate the association between BMI change and incident AF. Results: Median PACs per hour were 8.84. Participants with >2% BMI increase had 0.35% (95% CI: 0.06%-0.64%) higher frequency of PACs compared to those with stable BMI after multivariable adjustment (Table). After a mean (SD) follow-up of 19 (7) months, there were 82 incident AF cases. Compared to stable BMI, both >2% BMI increase and 2 to 10% decrease were nonsignificantly associated with higher odds of AF compared with stable BMI after multivariable adjustment (Table). Conclusion: Increasing BMI in the elderly is associated with higher PAC frequency and is nonsignificantly associated with higher odds of AF compared to stable BMI. This finding suggests that weight management, which is currently emphasized in middle age, may also apply in late-life to prevent atrial arrhythmias.

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