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The article presents information on a genome-wide study which investigated the association of novel genetic loci with circulating fibrinogen levels. A brief overview is given on fibrinogen as central to blood coagulation and an acute-phase reactant. It also reveals the findings which highlight biological pathways that may be essential in inflammation regulation underlying cardiovascular disease.

Background: Biological age may be estimated by proteomic aging clocks (PACs). Previous published PACs were constructed either in smaller studies or mainly in white individuals, and they used proteomic measures from only one-time point. In this study, we created de novo PACs and compared their performance to published PACs at 2 different time points in the Atherosclerosis Risk in Communities (ARIC) study of white and black participants (around 75% white and 25% black). Medthods and findings: A total of 4,712 plasma proteins were measured using SomaScan in blood samples collected in 1990 to 1992 from 11,761 midlife participants (aged 46 to 70 years) and in 2011 to 2013 from 5,183 late-life participants (aged 66 to 90 years). The de novo ARIC PACs were constructed by training them against chronological age using elastic net regression in two-thirds of healthy participants in midlife and late life and validated in the remaining one-third of healthy participants at the corresponding time point. We also computed 3 published PACs. We estimated age acceleration for each PAC as residuals after regressing each PAC on chronological age. We also calculated the change in age acceleration from midlife to late life. We examined the associations of age acceleration and change in age acceleration with mortality through 2019 from all-cause, cardiovascular disease (CVD), cancer, and lower respiratory disease (LRD) using Cox proportional hazards regression in participants (irrespective of health) after excluding the training set. The model was adjusted for chronological age, smoking, body mass index (BMI), and other confounders. We externally validated the midlife PAC using the Multi-Ethnic Study of Atherosclerosis (MESA) Exam 1 data. The ARIC PACs had a slightly stronger correlation with chronological age than published PACs in healthy participants at each time point. Associations with mortality were similar for the ARIC PACs and published PACs. For late-life and midlife age acceleration for the ARIC PACs, respectively, hazard ratios (HRs) per 1 standard deviation were 1.65 and 1.38 (both p < 0.001) for all-cause mortality, 1.37 and 1.20 (both p < 0.001) for CVD mortality, 1.21 (p = 0.028) and 1.04 (p = 0.280) for cancer mortality, and 1.46 and 1.68 (both p < 0.001) for LRD mortality. For the change in age acceleration, HRs for all-cause, CVD, and LRD mortality were comparable to the HRs for late-life age acceleration. The association between the change in age acceleration and cancer mortality was not significant. The external validation of the midlife PAC in MESA showed significant associations with mortality, as observed for midlife participants in ARIC. The main limitation is that our PACs were constructed in midlife and late-life participants. It is unknown whether these PACs could be applied to young individuals. Conclusions: In this longitudinal study, we found that the ARIC PACs and published PACs were similarly associated with an increased risk of mortality. These findings suggested that PACs show promise as biomarkers of biological age. PACs may be serve as tools to predict mortality and evaluate the effect of anti-aging lifestyle and therapeutic interventions. Shuo Wang and colleagues, apply machine learning to develop proteomic aging clocks from 5000 proteins sampled from participants at mid- and late-life and explore the impact of lifestyle factors and medical conditions on biological aging and the association with mortality. Author summary: Why was this study done?: Proteomic aging clocks (PACs), which are protein-based aging measures, may be used to estimate an individual's biological age and have been shown to be associated with mortality and other health conditions. However, previous published PACs were developed in relatively small studies that mainly included white individuals. The aim of this study was to develop new PACs in a large population-based prospective cohort of white and black participants that have approximately 5,000 proteins measured in blood samples collected at midlife and late life and to compare the performance of new and published PACs in midlife and late-life participants. What did the researchers do and find?: We applied machine learning to develop new PACs among a group of healthy participants at midlife (aged 46 to 70 years) and late life (aged 66 to 90 years) in a prospective population-based cohort study and validated these clocks in the remaining participants. We examined the association between the new PACs and mortality among 8,768 midlife participants and 4,553 late-life participants irrespective of their health status. We also examined the association between the change in PACs from midlife to late life and mortality. We found that the midlife PAC and the late-life PAC and the change in PACs from midlife to late life were associated with increased mortality by 20 to 68 percent. We examined whether midlife lifestyle factors and medical conditions were associated with higher biological age in late life. We found that smoking, and having high BMI, diabetes, hypertension, cardiovascular disease (CVD), and lower eGFR in midlife were associated with a higher biological age in late life. What do these findings mean?: These findings suggest that PACs show promise as a biomarker of biological age. PACs could be applied in clinical trials that evaluate the effect of anti-aging lifestyle and therapeutic interventions. The notable contribution of modifiable risk factors, such as smoking and BMI, and cardiometabolic disorders to biological aging as identified by this study, may help to further inform public policies targeted at prevention. The limitation of this study is that our PACs were created in midlife and late-life participants. It is unknown whether these PACs could be applied to young individuals. [ABSTRACT FROM AUTHOR]

Aging adults experience increased health vulnerability and compromised abilities to cope with stressors, which are the clinical manifestations of frailty. Frailty is complex, and efforts to identify biomarkers to detect frailty and pre‐frailty in the clinical setting are rarely reproduced across cohorts. We developed a predictive model incorporating biological and clinical frailty measures to identify robust biomarkers across data sets. Data were from two large cohorts of older adults: "Invecchiare in Chianti (Aging in Chianti, InCHIANTI Study") (n = 1453) from two small towns in Tuscany, Italy, and replicated in the Atherosclerosis Risk in Communities Study (ARIC) (n = 6508) from four U.S. communities. A complex systems approach to biomarker selection with a tree‐boosting machine learning (ML) technique for supervised learning analysis was used to examine biomarker population differences across both datasets. Our approach compared predictors with robust, pre‐frail, and frail participants and examined the ability to detect frailty status by race. Unique biomarker features identified in the InCHIANTI study allowed us to predict frailty with a model accuracy of 0.72 (95% confidence interval (CI) 0.66–0.80). Replication models in ARIC maintained a model accuracy of 0.64 (95% CI 0.66–0.72). Frail and pre‐frail Black participant models maintained a lower model accuracy. The predictive panel of biomarkers identified in this study may improve the ability to detect frailty as a complex aging syndrome in the clinical setting. We propose several concrete next steps to keep research moving toward detecting frailty with biomarker‐based detection methods. [ABSTRACT FROM AUTHOR]

Habitual physical activity (PA) impacts the plasma proteome and reduces the risk of developing type 2 diabetes (T2D). Using a large-scale proteome-wide approach in Atherosclerosis Risk in Communities study participants, we aimed to identify plasma proteins associated with PA and determine which of these may be causally related to lower T2D risk. PA was associated with 92 plasma proteins in discovery (P < 1.01 × 10−5), and 40 remained significant in replication (P < 5.43 × 10−4). Eighteen of these proteins were independently associated with incident T2D (P < 1.25 × 10−3), including neuronal growth regulator 1 (NeGR1; hazard ratio per SD 0.85; P = 7.5 × 10−11). Two-sample Mendelian randomization (MR) inverse variance weighted analysis indicated that higher NeGR1 reduces T2D risk (odds ratio [OR] per SD 0.92; P = 0.03) and was consistent with MR-Egger, weighted median, and weighted mode sensitivity analyses. A stronger association was observed for the single cis-acting NeGR1 genetic variant (OR per SD 0.80; P = 6.3 × 10−5). Coupled with previous evidence that low circulating NeGR1 levels promote adiposity, its association with PA and potential causal role in T2D shown here suggest that NeGR1 may link PA exposure with metabolic outcomes. Further research is warranted to confirm our findings and examine the interplay of PA, NeGR1, adiposity, and metabolic health. Article Highlights: Physical activity alters tissue and plasma proteomes, which have been shown to have roles in type 2 diabetes development. We aimed to identify protein signatures through which physical activity may influence type 2 diabetes pathogenesis. Of 40 proteins associated with physical activity, 18 of these were further related to incident type 2 diabetes over an ∼24-year follow-up. Two-sample Mendelian randomization analysis indicated that circulating neuronal growth regulator 1 reduces risk of type 2 diabetes. These findings suggest that plasma neuronal growth regulator 1 may link physical activity to reduced risk of type 2 diabetes. [ABSTRACT FROM AUTHOR]

Background: Pulmonary rehabilitation (PR) has been recognized to be an effective therapy for chronic obstructive pulmonary disease (COPD). However, in China, the application of PR interventions is still less promoted. Therefore, this cross-sectional study aimed to understand COPD patients' intention to receive PR, capture the potential personal, social and environmental barriers preventing their willingness of receiving PR, and eventually identify demanding PR services with the highest priority from patients' point of view. Methods: In total 237 COPD patients were recruited from 8 health care facilities in Zhejiang, China. A self-designed questionnaire was applied to investigate patients' intention to participate in PR and potentially associated factors, including personal dimension such as personal awareness, demographic factors, COPD status and health-related literacy/behaviors, as well as social policies and perceived environmental barriers. The demand questionnaire of PR interventions based on the Kano model was further adopted. Results: Among the 237 COPD patients, 75.1% of COPD patients were willing to participate in PR interventions, while only 62.9% of the investigated patients had heard of PR interventions. Over 90% of patients believed that the cost of PR services and the ratio of medical insurance reimbursement were potential obstacles hindering them from accepting PR services. The multiple linear regression analysis indicated that the PR skills of medical staff, knowledge promotion and public education levels of PR in the community, patients' transportation concerns and degree of support from family and friends were significantly associated with willingness of participation in PR interventions. By using the Kano model, the top 9 most-requisite PR services (i.e., one-dimensional qualities) were identified from patients' point of view, which are mainly diet guidance, education interventions, psychological interventions and lower limb exercise interventions. Subgroup analysis also revealed that patients' demographics, such as breathlessness level, age, education and income levels, could influence their choice of priorities for PR services, especially services related to exercise interventions, respiratory muscle training, oxygen therapy and expectoration. Conclusions: This study suggested that PR-related knowledge education among patients and their family, as well as providing basic package of PR services with the most-requisite PR items to COPD patients, were considerable approaches to promote PR attendance in the future. [ABSTRACT FROM AUTHOR]

Aims: Neutrophil activity contributes to adverse cardiac remodelling in experimental acute cardiac injury and is modifiable with pharmacologic agents like colchicine. Methods and results: Neutrophil activity‐related plasma proteins known to be affected by colchicine treatment were measured at Visit 3 (1993–1995) and Visit 5 (2011–2013) of the ARIC cohort study. A protein‐based neutrophil activity score was derived from 10 candidate proteins using LASSO Cox regression. Associations with incident heart failure (HF) and with cardiac function using Cox proportional hazards regression and linear regression models, respectively. The mean ages at Visits 3 and 5 were 60 ± 6 and 75 ± 5 years, respectively, and 54% and 57% were women, respectively. Each 1‐standard deviation increase in the neutrophil activity score was associated with a higher risk of incident HF in mid‐life (hazard ratio [HR] 1.31, 95% confidence interval [CI] 1.25–1.37) and late‐life (HR 1.23, 95% CI 1.14–1.34), with a higher HR for HF with preserved than reduced ejection fraction (HR 1.30, 95% CI 1.16–1.47 vs. HR 1.13, 95% CI 0.98–1.30). Higher neutrophil activity was associated with greater left ventricular end‐diastolic volume index, mass index and diastolic and systolic dysfunction. Conclusions: Plasma proteins related to neutrophil function associate with incident HF in mid‐ and late‐life and with adverse cardiac remodelling. Therapies that modify these proteins, such as colchicine, may represent promising targets for the prevention or treatment of HF. [ABSTRACT FROM AUTHOR]

We previously identified a QTL on 15q13 for basal insulin sensitivity and pancreatic beta-cell function among 661 family members from 89 obese families ascertained through the NHLBI Family Heart Study [Peak LOD = 2.8 (empirical p-values ranging from 0.03 to 0.05) around GAAA1C11 (31.46 cM), GX50C03 (34.83 cM) and GX63A03 (43.47 cM) for both phenotypes]. These scans were limited to white families to reduce heterogeneity and because too few non-white families were available for consideration. To further localize the QTLs influencing adjusted levels of insulin sensitivity and beta-cell function we assessed the association between these 3 polymorphisms and insulin sensitivity and beta-cell function phenotypes in obese white families of the FHS study. Participants with diabetes and lipid-lowering medications were excluded. Basal measures of insulin sensitivity and beta-cell function were derived from overnight fasting glucose and insulin concentrations using the non-linear HOMA, and were appropriately transformed to approximate normality. Both phenotypes were adjusted for age, BMI, and field center location within gender. Non-independence among family members was addressed using an empirical 'sandwich estimator' in the SAS MIXED procedure. We found that allele 287 in GAAA1C11 was associated with reduced insulin sensitivity (p = 0.0093 after Bonferroni correction for multiplicity). No additional significant associations (p > 0.01) were found in examining the remaining 2 markers and the beta-cell function phenotype. This method maximizes phenotype and genotype information and thus detection power assuming same degree of dependence among family members, whereas classical TDT tests take into account family structure information and avoid many sources of biases. We used FBAT with assumption of linkage and no association to examine our finding at this marker site, but this effort was hampered largely because of a significant reduction in informative families with complete genotype and phenotype data among parents and offspring. Other promising approaches will be attempted to validate this finding. Integrating our linkage and association results, we identified a QTL on 15q13 at GAAA1C11 which may harbor gene(s) predisposing individuals to reduced insulin sensitivity, insulin resistance, and pre-diabetes in obese families. [ABSTRACT FROM AUTHOR]

Ovarian aging affects the reproductive health of elderly women due to decline in oocyte quality, which is closely related to mitochondrial dysfunction. Nicotinamide mononucleotide (NMN), as a precursor of NAD+, effectively regulate mitochondria metabolism in mice. However, roles of NMN in improving age-related diminished ovary reserve remain to be determined. In present study, 4, 8, 12, 24, 40-week old female ICR mice were collected and a 20-week-long administration of NMN was conducted to 40-week-old mice (60WN), meanwhile the control group is given water (60WC). First, we found that 20-week-long administration of NMN to 40-week-old mice exhibited anti-aging and anti-inflammatory effects on organ structures, along with the improvement of estrus cycle condition and endocrine function. The number of primordial, primary, secondary, antral follicles and corpora luteum of ovaries in 60WN group was significantly increased compared with those in 60WC group. Additionally, the protein and gene expressions of P16 of ovaries were significantly reduced in 60WN group than in 60WC group. the mitochondria biogenesis, autophagy level, and proteases activity enhanced in granulosa cells after 20-week-administration of NMN. Present results indicate that NMN has the potential to save diminished ovary reserve by long-term treatment, providing a basis for exploring the role of NMN in anti-ovarian aging by enhancing the mitophagy level of granulosa cells. [ABSTRACT FROM AUTHOR]

Symptomatic peripheral artery disease (PAD) is a risk factor for abdominal aortic aneurysm (AAA). However, data on the association of asymptomatic PAD with AAA are limited. We explored the association of symptomatic and asymptomatic PAD with AAA. We primarily assessed a prospective association of symptomatic (based on clinical history) and asymptomatic (ankle-brachial index ≤0.9) PAD at baseline (1987–89 [ages 45–64 years]) with incident AAA in a biracial community-based cohort, the Atherosclerosis Risk in Communities Study. We secondarily investigated a cross-sectional association of PAD with ultrasound-based AAA (diameter≥3.0 cm) (2011–13 [ages 67–91 years]). Of 14,148 participants (55.1% female, 25.5% black, 0.9% with symptomatic PAD) in our prospective analysis (median follow-up 22.5 years), 530 (3.7%) developed incident AAA. Symptomatic PAD had a higher hazard ratio (HR) of incident AAA [4.91 (95%CI 2.88–8.37)], as did asymptomatic PAD with ABI≤0.9 [2.33 (1.55–3.51)], compared to the reference ABI>1.1–1.2 in demographically-adjusted models. Crude 15-year cumulative incidence of AAA in these three groups were 12.3%, 3.9%, and 1.5%, respectively. The associations remained significant after accounting for other potential confounders [corresponding HR 2.96 (95%CI 1.73–5.07) and 1.52 (95%CI 1.00–2.30), respectively]. The cross-sectional analysis demonstrated similar patterns with ultrasound-based AAA [odds ratio 2.46 (95%CI 1.26–4.81) for symptomatic PAD and 3.98 (1.96–8.08) for asymptomatic PAD in a demographically-adjusted model]. Our prospective and cross-sectional data show elevated risk of AAA in both symptomatic and asymptomatic PAD. Our data support the current recommendation of AAA screening in symptomatic PAD patients and suggest the potential extension to asymptomatic PAD patients as well. [Display omitted] • Symptomatic and asymptomatic peripheral artery disease (PAD) patients are independently associated with a higher risk of incident clinical abdominal aortic aneurysm (AAA) based on a 22.5-year follow-up. • Symptomatic and asymptomatic PAD patients are associated with ultrasound-based AAA based on cross-sectional analysis. • Our data support the current recommendation of AAA screening in symptomatic PAD patients. • AAA screening may be appropriate for asymptomatic PAD patients as well. [ABSTRACT FROM AUTHOR]

We aimed at comprehensively evaluate the independent association of diabetes and its duration with incident abdominal aortic aneurysm (AAA) and aortic diameter. We prospectively studied incident AAA according to baseline glycemic status (diabetes, prediabetes, normal glycemia) in 13,116 ARIC participants (1990–1992) and the time-varying exposure of duration post incident diabetes in 11,675 participants (1987–1989) using Cox models. Additionally, we cross-sectionally explored ultrasound-based abdominal aortic diameter by glycemic status and cumulative duration of diabetes in 4710 participants (2011–2013) using linear regression models. Over ~20 years of follow-up, diabetes (vs. normal glycemia) at baseline was independently associated with lower AAA risk (489 cases) (hazard ratio: 0.71 [95%CI 0.51–0.99]), especially after 10 years (hazard ratio: 0.58 [0.38–0.87]). Prediabetes did not demonstrate an independent association. The inverse association was more evident with longer duration of diabetes (p for trend = 0.045), with 30–50% lower risk in eight years after diabetes diagnosis. The cross-sectional analysis demonstrated smaller aortic diameters with longer duration of diabetes (e.g., −0.76 mm [−1.24, −0.28] in diabetes with 8–12 years) compared to non-diabetes, whereas prediabetes consistently showed nominally greater diameter. Diabetes, especially with longer duration, but not prediabetes, was independently associated with lower risk of AAA and smaller aortic diameter. Our findings suggest that long lasting clinical hyperglycemia plays an important role in the reduced AAA risk, and the reduced aortic diameter may be a structural mechanism behind this paradoxical association. Image 1 • Diabetes, especially with longer duration, is negatively associated with the risk of abdominal aortic aneurysm (AAA). • Pre-diabetes was not associated with incident AAA and showed relatively greater aortic diameter compared to non-diabetes. • Reduced aortic diameter is likely to be a structural mechanism of decreased AAA risk in diabetes. [ABSTRACT FROM AUTHOR]

Background: Quantitative red blood cell (RBC) traits are highly polygenic clinically relevant traits, with approximately 500 reported GWAS loci. The majority of RBC trait GWAS have been performed in European- or East Asian-ancestry populations, despite evidence that rare or ancestry-specific variation contributes substantially to RBC trait heritability. Recently developed combined-phenotype methods which leverage genetic trait correlation to improve statistical power have not yet been applied to these traits. Here we leveraged correlation of seven quantitative RBC traits in performing a combined-phenotype analysis in a multi-ethnic study population. Results: We used the adaptive sum of powered scores (aSPU) test to assess combined-phenotype associations between ~ 21 million SNPs and seven RBC traits in a multi-ethnic population (maximum n = 67,885 participants; 24% African American, 30% Hispanic/Latino, and 43% European American; 76% female). Thirty-nine loci in our multi-ethnic population contained at least one significant association signal (p < 5E-9), with lead SNPs at nine loci significantly associated with three or more RBC traits. A majority of the lead SNPs were common (MAF > 5%) across all ancestral populations. Nineteen additional independent association signals were identified at seven known loci (HFE, KIT, HBS1L/MYB, CITED2/FILNC1, ABO, HBA1/2, and PLIN4/5). For example, the HBA1/2 locus contained 14 conditionally independent association signals, 11 of which were previously unreported and are specific to African and Amerindian ancestries. One variant in this region was common in all ancestries, but exhibited a narrower LD block in African Americans than European Americans or Hispanics/Latinos. GTEx eQTL analysis of all independent lead SNPs yielded 31 significant associations in relevant tissues, over half of which were not at the gene immediately proximal to the lead SNP. Conclusion: This work identified seven loci containing multiple independent association signals for RBC traits using a combined-phenotype approach, which may improve discovery in genetically correlated traits. Highly complex genetic architecture at the HBA1/2 locus was only revealed by the inclusion of African Americans and Hispanics/Latinos, underscoring the continued importance of expanding large GWAS to include ancestrally diverse populations. [ABSTRACT FROM AUTHOR]

Abstract Background and aims Despite its strong link to cardiovascular outcomes, the association of chronic kidney disease (CKD) with abdominal aortic aneurysm (AAA) has not been explicitly and comprehensively investigated. Methods In 10,724 participants in the Atherosclerosis Risk in Communities Study (aged 53–75 years during 1996–1998), we evaluated the associations of two key CKD measures - estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR) - with incident AAA (AAA diagnosis in outpatient, hospitalization discharge, or death records). Additionally, we performed a cross-sectional analysis for the CKD measures and ultrasound-based abdominal aortic diameter in 4258 participants during 2011–2013. Results During a median follow-up of 13.9 years, 347 participants developed AAA. The demographically-adjusted hazard ratio (HR) was 4.44 (95% CI 1.58–12.49) for eGFR <30, 3.29 (1.89–5.72) for 30–44, 2.03 (1.29–3.19) for 45–59, and 1.62 (1.11–2.35) for 60–74 compared to eGFR ≥90 mL/min/1.73 m2 and was 2.49 (1.28–4.87) for ACR ≥300, 1.99 (1.40–2.83) for 30–299, and 1.46 (1.08–1.97) for 10–29 compared to ACR <10 mg/g. The associations were generally similar after accounting for additional confounders, such as smoking (although attenuated), or after stratifying by subgroups, including diabetes. The cross-sectional analysis also showed continuous positive associations of these CKD measures with aortic diameter, particularly at the distal aortic segment assessed. Conclusions Reduced eGFR and elevated albuminuria were independently associated with greater incidence of AAA and greater abdominal aortic diameter. Our results suggest the potential usefulness of CKD measures to identify persons at high risk of AAA and the need to investigate pathophysiological pathways linking CKD to AAA. Highlights • Chronic kidney disease was positively related to incident clinical abdominal aortic aneurysm. • Both kidney function and damage showed independent associations. • We also confirmed greater ultrasound-based aortic diameter related to chronic kidney disease. [ABSTRACT FROM AUTHOR]

Sillenite bismuth ferrite (S-BFO) Bi 25 FeO 40 was synthesized by a hydrothermal process and firstly adopted for the activation of peroxymonosulfate (PMS). Multiple characterization was conducted for the morphology and physicochemical features of S-BFO. Degradation of aquatic levofloxacin (LVF) was thoroughly evaluated by using a coupled process for the decontamination of the typical emerging organics. Some crucial parameters for the activation kinetics as well as economic recyclability were examined with the detailed mechanism proposed. For the first time, singlet oxygen ( 1 O 2 ) was identified as the main reactive oxygen species through radical scavenging experiments, electron paramagnetic resonance spectroscopy (EPR) and HPLC-MS determination. Based on the XPS and EPR results, a catalytic mechanism is proposed concerning the parallel generations of 1 O 2 : (i) Bi 5+ is replaced by Bi 3+ , resulting in the formation of an oxygen vacancy in the lattice and an active oxygen (O ∗ ), which could produce 1 O 2 through the reactions with PMS; (ii) direct formation of 1 O 2 from radSO-5 generated by the interaction between Bi 5+ and PMS. This study demonstrates a novel catalyst for heterogeneous activation of PMS via a non-radical mechanism, which could be alternatively adopted in the decontamination in surface/ground water. [ABSTRACT FROM AUTHOR]

Background and aims Individuals with atherosclerosis and stiffness often have increased abdominal aortic diameters, but prospective evidence linking them to the risk of abdominal aortic aneurysm (AAA) is limited. Methods We prospectively examined the relationship of carotid atherosclerosis and stiffness with future risk of AAA in ARIC. At Visits 1 (1987–89) or 2 (1990–1992), we assessed carotid atherosclerosis (represented by greater carotid intima-media thickness [cIMT] or presence of atherosclerotic plaque) and lower carotid distensibility (reflected by a higher carotid Beta Index). We identified incident, clinical AAAs during follow-up through 2011 using hospital discharge codes, Medicare outpatient diagnoses, or death certificates. Results Participants' mean age at baseline was 54.2 years (SD 5.8), 45% were male and 73% white. During a median of 22.5 years of follow-up, 542 clinical AAAs were ascertained. After multivariable adjustment, the presence of carotid atherosclerotic plaque at baseline was associated with 1.31 (95% CI: 1.10–1.57; p  = 0.003) times higher risk of clinical AAA. Greater cIMT and Beta Index were also associated with clinical AAA with a dose-response across quartiles ( p trend for both: 0.006; hazard ratios [95% CI] for the highest vs. lowest quartiles: 1.55 [1.13–2.11] and 1.68 [1.16–2.43], respectively). The associations of cIMT and Beta Index with AAA were independent of each other. Conclusions This prospective population-based study found that indices of greater carotid atherosclerosis and lower carotid distensibility are markers of increased AAA risk. [ABSTRACT FROM AUTHOR]

Background and aims No prospective study has investigated whether individuals with respiratory impairments, including chronic obstructive pulmonary disease (COPD) and restrictive lung disease (RLD), are at increased risk of abdominal aortic aneurysm (AAA). We aimed to prospectively investigate whether those respiratory impairments are associated with increased AAA risk. Methods In 1987–1989, the Atherosclerosis Risk in Communities (ARIC) study followed 14,269 participants aged 45–64 years, without a history of AAA surgery, through 2011. Participants were classified into four groups, “COPD” [forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC)

Background and aims No prospective study has investigated whether elevated lipoprotein(a) concentrations are associated with an increased risk of abdominal aortic aneurysm (AAA). We aimed to prospectively investigate this association. Methods In 1987–1989, the Atherosclerosis Risk in Communities study measured plasma lipoprotein(a) in 13,683 participants aged 45–64 years, without a history of AAA surgery. We followed them for incident, clinical AAA events through 2011. Results During the 272,914 person-years of follow-up, over a median of 22.6 years, we documented 505 incident AAA events. The age-, sex-, and race-adjusted model showed that individuals in the highest quintile of plasma lipoprotein(a) had an increased risk of AAA. Further adjustment for the other potential confounding factors, including other plasma lipids (high- and low-density lipoprotein cholesterol and triglyceride concentrations), attenuated the association, but individuals in the highest versus lowest quintile of plasma lipoprotein(a) still had a significantly increased risk of AAA [hazard ratio (95% confidence interval): 1.57 (1.19–2.08)]. Interaction testing suggested no difference in the associations for whites and African Americans ( p for interaction = 0.96). A restricted cubic spline analysis demonstrated a positive dose-response relation of plasma lipoprotein(a) with AAA, with a steep increase in AAA risk above the 75th percentile ( p for overall association = 0.0086, p for non-linear association = 0.097). Conclusions In this population-based cohort study, elevated lipoprotein(a) concentrations were independently associated with an increased risk of AAA. The association reflected a threshold of increased AAA risk at high lipoprotein(a) concentrations, rather than a steady monotonic association. [ABSTRACT FROM AUTHOR]