Three-year Change Research Articles

Effect of Hearing Intervention Versus Health Education Control on Fatigue: A Secondary Analysis of the ACHIEVE Study.

Fatigue is a common complaint among older adults with hearing loss. The impact of addressing hearing loss on fatigue symptoms has not been studied in a randomized controlled trial. In a secondary analysis of the Aging and Cognitive Health Evaluation in Elders (ACHIEVE) study, we investigated the effect of hearing intervention versus health education control on 3-year change in fatigue in community-dwelling older adults with hearing loss. Participants aged 70-84 years old with untreated hearing loss recruited across 4 study sites in the United States (Forsyth County, North Carolina; Jackson, Mississippi; Minneapolis, Minnesota; Washington County, Maryland) were randomized (1:1) to hearing intervention or health education control and followed for 3 years. Three-year change in fatigue symptoms was measured by 2 instruments (RAND-36 and PROMIS). We estimated the intervention effect as the difference in the 3-year change in fatigue between intervention and control groups using a linear mixed-effects model under the intention-to-treat principle. Participants (n = 977) had a mean age (SD) of 76.8 (4.0) years, were 53.5% female and 87.8% White. Over 3 years, a beneficial effect of the hearing intervention versus health education control on fatigue was observed using the RAND-fatigue score (β = -0.12 [95% CI: -0.22, -0.02]). Estimates also suggested beneficial effect of hearing intervention on fatigue when measured by the PROMIS-fatigue score (β = -0.32 [95% CI: -1.15, 0.51]). Our findings suggest that hearing intervention may reduce fatigue over 3 years among older adults with hearing loss.

Effect of artificial natural light on the development of myopia among primary school-age children in China: a three-year longitudinal study.

To assess the efficacy of artificial natural light in preventing incident myopia in primary school-age children. This is a prospective, randomized control, intervention study. A total of 1840 students from 39 classes in 4 primary schools in Foshan participated in this study. The whole randomization method was adopted to include classes as a group according to 1:1 randomized control. Classrooms in the control group were illuminated by usual light, and classrooms in the intervention group were illuminated by artificial natural light. All students received uncorrected visual acuity and best-corrected visual acuity measurement, non-cycloplegic autorefraction, ocular biometric examination, slit lamp and strabismus examination. Three-year follow-up, the students underwent same procedures. Myopia was defined as spherical equivalent refraction ≤ -0.50 D and uncorrected visual acuity <20/20. There were 894 students in the control group and 946 students in the intervention group with a mean±SD age of 7.50±0.53y. The three-year cumulative incidence rate of myopia was 26.4% (207 incident cases among 784 eligible participants at baseline) in the control group and 21.2% (164 incident cases among 774 eligible participants at baseline) in the intervention group [difference of 5.2% (95%CI, 3.7% to 10.1%); P=0.035]. There was also a significant difference in the three-year change in spherical equivalent refraction for the control group (-0.81 D) compared with the intervention group [-0.63 D; difference of 0.18 D (95%CI, 0.08 to 0.28 D); P<0.001]. Elongation of axial length was significantly different between in the control group (0.77 mm) and the intervention group [0.72 mm; difference of 0.05 mm (95%CI, 0.01 to 0.09 mm); P=0.003]. Artificial natural light in the classroom of primary schools can result in reducing incidence rate of myopia during a period of three years.

Longitudinal changes in crystalline lens thickness and power in children aged 6-12 years old.

To determine the three-year changes in crystalline lens power (LP) and thickness (LT) in children and their associated factors. Schoolchildren aged 6-12 years living in Shahroud, northeast Iran were examined in 2015 and 2018. The Bennett formula was used to calculate LP. Multiple generalized estimating equations (GEE) analysis was used for data analysis. Among the 8089 examined eyes, the mean LP in Phase 1 and 2, and the three-year change were 21.61 ± 1.47D, 21.00 ± 1.42D, and -0.61 ± 0.52D, respectively. The GEE model showed that negative shifts in LP were less pronounced with increasing age (β = 0.176; p < 0.001), and were also less noticeable in hyperopes compared to emmetropes (β = 0.120; p < 0.001). The changes in LP decreased when outdoor activity increased among urban residents (β = 0.013; p = 0.039), while it increased in rural area (β = -0.020; p = 0.047). Mean three-year change in LT was 0.002 ± 0.13 mm. Female sex and aging by one year increased the LT by 0.022 mm (P < 0.001). However, LT decreased in 6-8-year-olds, while it increased in 10-12-year-old children, both in a linear fashion. The change in LT was less in myopes than in emmetropes (β = -0.018, P-value = 0.010). LP decreases after three years in 6 to 12-year-old children. LT increases slightly after three years in 6 to 12-year-old children. The changes in LP and LT were associated with the refractive errors, place of residence, age and gender and outdoor activity time.

Dietary amino acids and anthropometric indices: Tehran Lipid and Glucose Study.

Recent studies investigated the role of amino acids (AAs) in weight management. We aimed to determine the association between AAs and three-year change of anthropometric indices and incident obesity. Height, weight, hip, and waist circumference (WC) were collected at baseline and follow up. Three-year changes in anthropometric indices and obesity incident according to body mass index (BMI) (overweight & obesity) and WC cutoffs (obesity-WC) were ascertained. Dietary intakes of AAs were collected at baseline, using a food frequency questionnaire. Data analyses were conducted on 4976 adult participants and two subsamples, including 1,570 and 2,918 subjects, for assessing the AAs relationship with 3-year changes on anthropometric indices and obesity incident. Lysine and aspartic acid were positively associated with higher weight change, whereas acidic AAs, cysteine, and glutamic acid showed a negative correlation with weight change. Furthermore, a weak positive correlation was shown for alkaline AAs, lysine, and valine with WC; however, acidic AAs, tryptophan, cysteine, and glutamic acid were negatively associated with WC. Aromatic and acidic AAs also demonstrated a weak negative relation with changes in BAI. Phenylalanine and Aromatic AAs showed a negative association with overweight &obesity incidence adjusting for potential confounders. Each quartile increases the dietary lysine, arginine, alanine, methionine, aspartic acid, and alkaline AAs related to a greater risk of obesity-WC, while tryptophan, glutamic acid, proline, and acidic AAs associated with lower obesity-WC risk. Our results suggested that certain dietary AAs may potentially change anthropometric indices and risk of obesity incident.

Myostatin and follistatin as monitoring and prognostic biomarkers in dysferlinopathy

Myostatin is a myokine which acts upon skeletal muscle to inhibit growth and regeneration. Myostatin is endogenously antagonised by follistatin. This study assessed serum myostatin and follistatin concentrations as monitoring or prognostic biomarkers in dysferlinopathy, an autosomal recessively inherited muscular dystrophy. Myostatin was quantified twice with a three-year interval in 76 patients with dysferlinopathy and 38 controls. Follistatin was quantified in 62 of these patients at the same timepoints, and in 31 controls. Correlations with motor function, muscle fat fraction and contractile cross-sectional area were performed. A regression model was used to account for confounding variables. Baseline myostatin, but not follistatin, correlated with baseline function and MRI measures. However, in individual patients, three-year change in myostatin did not correlate with functional or MRI changes. Linear modelling demonstrated that function, serum creatine kinase and C-reactive protein, but not age, were independently related to myostatin concentration. Baseline myostatin concentration predicted loss of ambulation but not rate of change of functional or MRI measures, even when relative inhibition with follistatin was considered. With adjustment for extra-muscular causes of variation, myostatin could form a surrogate measure of functional ability or muscle mass, however myostatin inhibition does not form a promising treatment target in dysferlinopathy.

Changes in Stress-Strain Index in School-Aged Children: A 3-Year Longitudinal Study.

To determine three-year change of the corneal biomechanical parameter stress-strain index (SSI) in schoolchildren aged 7- 9 years and their correlation with refractive error and axial length (AL). This is a prospective cohort study. Data of the AL, refractive error, and corneal biomechanical parameter SSI were collected at baseline and a 3-year follow-up for 217 schoolchildren. SSI, AL, and refractive error were measured via corneal visualization Scheimpflug technology (Corvis ST), IOLMaster biometry, and cycloplegic refraction. Three years of changes in SSI and its association with refractive error and AL were analyzed. Participants were divided into persistent nonmyopia (PNM), newly developed myopia (NDM), and persistent myopia (PM). The three-year difference in SSI among the three groups was analyzed. After three years of follow-up, the corneal biomechanical parameter SSI decreased in all participants (P < 0.01). There was a negative correlation between the change in SSI and the change in AL (r = -0.205, P=0.002) and a positive correlation between the change in refractive error (r = 0.183, P=0.007). After three years of follow-up, there was a decrease in the SSI for the NDM, PM, and PNM participants, with a median change of -0.05 for PNM and -0.13 and -0.09 for the NDM and PM, respectively. There was a significant decrease in corneal biomechanical properties for NDM patients compared with PNM patients (P < 0.01). In 7- to 9-year-old schoolchildren, SSI decreased after three years of the longitudinal study, and the change in SSI was correlated with the change in AL and refractive error. There was a rapid decrease in corneal biomechanical properties among newly developed myopic patients.

Three-year change in glycemic state and the future risk of incident hypertension among Iranian adults: Tehran Lipid and Glucose Study.

The impact of 3-year change in glycemic state on the risk of hypertension among Tehranian adults aged ≥20 years was assessed. The study population included 1679 men and 2348 women who were non-diabetic normotensive at enrollment. The following categories were defined both at baseline visit and three years later (second visit): normoglycemia [normal fasting glucose (NFG) and normal glucose tolerance (NGT)] and prediabetes [impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)]. Changes in the categories, i.e., regression to normoglycemia, remaining in previous status, and progression to diabetes were assessed. Changes in fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) categories were also considered separately. We used theCox models adjusted for traditional hypertension risk factors to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). During a median follow-up of 9.4 years, 485 men and 589 women developed hypertension. Among men, considering both FPG and 2hPG, compared to individuals remaining normoglycemic, changing from prediabetes to normoglycemia had a HR of 1.30 (95% CI: 0.98-1.71; P-value: 0.064). Defining changes by 2hPG showed that compared to remaining NGT, incident IGT (progression from NGT to IGT) had a significant association with increased risk of hypertension development by a HR of 1.61 (1.13-2.30). Among women, on the other hand, change in glycemic state generally didn't show a significant association with incident hypertension. To sum up, change in glycemic state hadn't a significant association with hypertension development among women; however, compared to remaining NGT,menwith incident IGT had a significant higher risk.

Three-year change in corneal asphericity in children at the age of emmetropisation.

To determine the 3-year changes in anterior and posterior values of corneal asphericity (Q) in 6- to 12-year-old children. The first and second phases of the study were conducted in 2015 and 2018, respectively. The target population in the first phase was 6- to 12-year-old students in Shahroud, Iran. Multistage cluster sampling was performed on urban students. Additionally, all rural students in Shahroud county were invited to participate. Corneal imaging and ocular biometry were performed using the Pentacam-HR and Allegro Biograph, respectively. A total of 4961 right eyes were analysed in this report. The mean (95% confidence interval) anterior and posterior Q values for an 8-mm chord diameter were -0.38 ± 0.11 (-0.39 to -0.38) and -0.32 ± 0.12 (-0.33 to -0.32) in the first phase of the study, respectively. The mean 3-year changes in anterior and posterior Q values were 0.00 ± 0.08 (95% CI: 0.00-0.00) and -0.01 ± 0.06 (95% CI: -0.01 to -0.01), respectively. Based on a multiple regression model, advancing age (β=-0.002; [-0.003 to -0.001]), 3-year increase in mean keratometry (β=-0.04; [-0.06 to -0.02]), central corneal thickness (β=-0.001; [-0.001 to -0.000]), lens thickness (-0.05; [-0.11 to -0.003]) and anterior chamber depth (-0.09; [-0.15 to -0.03]) showed a statistically significant association with increased anterior Q prolation. Increased axial length was associated with a decrease in Q (β=0.02; [0.004 to 0.03]). In addition, female gender (β=-0.004; [-0.007 to -0.001]) was significantly associated with a more prolate posterior Q value, while rural residence (β=0.005; [0.002 to 0.009]) was significantly associated with a more oblate posterior Q value. Three-year changes in anterior and posterior Q values were very small. The cornea tends to become more prolate with increasing age.

Three-year change in refractive error and its risk factors: results from the Shahroud School Children Eye Cohort Study.

To determine spherical equivalent (SE) progression among children in the Shahroud School Children Eye Cohort Study. A prospective cohort study recruited children aged 6 to 12 years in 2015 (baseline) with a follow-up in 2018. Cycloplegic autorefraction and axial length (AL) measurements were included. SE progression over 3 years was analysed in non-myopic (SE ≥ + 0.76 D), pre-myopic (PM; SE between +0.75 D and -0.49 D), low myopic (LM; SE between -0.5 D and -5.99 D), and high myopic (HM; SE ≤ - 6 D) eyes. Age, sex, near work, outdoor time, living place, parental myopia, mother's education, and baseline SE were evaluated as risk factors for SE progression (≤ -0.50 D). Data were available for 3989 children (7945 eyes). At baseline, 40.3% (n = 3205), 3.4% (n = 274) and 0.1% (n = 7) eyes had PM, LM and HM, respectively. At the 3-year follow-up, 40.5% (n = 3216), 7.5% (n = 599) and 0.2% (n = 15) eyes had PM, LM, and HM, respectively. SE progression in eyes with LM and HM was -1.08 ± 0.76 D and -1.60 ± 1.19 D, respectively. SE progression was associated with age at baseline (Odds Ratio [OR] = 1.14; 95% confidence interval [CI], 1.08-1.21), female sex (OR = 1.80; 95% CI: 1.48-2.18), near work (OR = 1.08; 95% CI: 1.02-1.14), parental myopia (OR = 1.20; 95% CI: 1.01-1.42) and baseline SE (OR = 2.28; 95% CI: 1.88-2.78). A myopic shift was associated with older age, female sex, near work, parental myopia and greater myopic baseline SE. These results help identifying children at risk of progression that may benefit from treatment and lifestyle counselling.

Do changes in frailty, physical functioning, and cognitive functioning predict mortality in old age? Results from the Longitudinal Aging Study Amsterdam

BackgroundThe ability to accurately predict survival in older adults is crucial as it guides clinical decision making. The added value of using various health indicators as well as changes in these indicators for predicting mortality remains unclear. The aim of this study was to investigate whether changes in health indicators such as frailty and physical performance improve mortality predictions in old age.MethodsThis is a population based prospective cohort study on 995 community-dwelling people aged 68–92 years from the Longitudinal Aging Study Amsterdam. Two measurements at a three-year interval (1995/1996 and 1998/1999) were available for the frailty index, frailty phenotype, grip strength, walking speed, and Mini-Mental State Examination (MMSE). Cox regression was used to analyze mortality risks associated with the current health status and changes in health, with mortality data up to 2017. The extent to which these health indicators improved mortality predictions compared to models with age and sex only was assessed by the area under the receiver operating characteristic curve (AUC).ResultsThe AUC of age and sex for five-year mortality was 72.8% (95% CI 69.0 – 76.5) and was the lowest in the oldest old (age > 80.5 years). The added AUC of the current status of health indicators ranged from 0.7 to 3.3%. The added AUC of the three-year change was lower, ranging from -0.0 to 1.1%, whereas the added AUC of three-year change and current status combined was similar to current status alone, ranging from 0.6 to 3.2%. Across age, the added AUC of current status was highest in the oldest old, however there was no such pattern using three-year change. Overall, the frailty index appeared to improve mortality predictions the most, followed by the frailty phenotype, MMSE, grip strength, and walking speed.ConclusionsCurrent health status improved mortality predictions better than changes in health. Its contribution was highest in the oldest old, but the added value to models with age and sex only was limited.

The Association of Heart/Vascular Aging with Mild Cognitive Impairment in a Rural Multiethnic Cohort: The Project FRONTIER Study.

Cardiovascular disease (CVD) and Alzheimer's disease and related dementias (ADRD) disproportionately affect rural communities. Identifying strategies to effectively communicate CVD risk to prevent these conditions remains a high priority. We assessed the relation between predicted heart/vascular age (PHA), an easily communicated metric of CVD risk, and mild cognitive impairment (MCI), an early manifestation of ADRD. Data were from 967 rural West Texas residents aged ≥40 years without CVD at baseline (2009-2012) enrolled in Project FRONTIER, an ongoing, multi-ethnic cohort study on cognitive aging. MCI was diagnosed using the standardized consensus review criteria. PHA was calculated using the Framingham CVD risk equation. High excess PHA (HEPHA) was defined as the difference between PHA and chronological age >5 years. Logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI). At baseline, the mean age of participants (70% women and 64% Hispanics) was 55 years. Almost 13% had MCI and 65% had HEPHA. After adjusting for socio-demographic and health factors, HEPHA was positively associated with MCI (OR=2.98; 95%CI: 1.72-5.15). Among participants without MCI at baseline who returned for follow-up exam after three years (n=238), a three-year negative change in PHA was seemingly associated with reduced odds for MCI (OR=0.98; 95%CI: 0.96-1.01). In this study, PHA was positively associated with MCI, with improvement in CVD risk profile seemingly related to reduced odds for MCI. PHA may provide a low-cost means of communicating CVD risk in rural settings to prevent both CVD and ADRD.

Adherence to Mediterranean diet and its associations with circulating cytokines, musculoskeletal health and incident falls in community-dwelling older men: The Concord Health and Ageing in Men Project

Mediterranean dietary patterns may exert favourable effects on various health conditions. This study aimed to determine associations of adherence to Mediterranean diet as well as its components, with circulating cytokine levels, musculoskeletal health and incident falls in community-dwelling older men. Seven hundred ninety-four (794) community-dwelling men with mean age 81.1±4.5 years, who participated in the five-year follow-up of the Concord Health and Ageing in Men Project (CHAMP) were included in the cross-sectional analysis, and 616 attended follow-up three years later. Adherence to Mediterranean diet was assessed using MEDI-LITE (literature-derived Mediterranean diet) score which was obtained using a validated diet history questionnaire. Twenty-four evaluable circulating cytokines were analyzed using Bio-Plex Pro Human Cytokine 27-plex Assay kit. Appendicular lean mass (ALM) and bone mineral density (BMD) were measured using dual-energy x-ray absorptiometry (DXA). Three-year changes in gait speed and hand grip strength were assessed by walking a 6-m course and using a dynamometer respectively and analyzed using linear mixed-effects models. Incident falls over three years were determined through telephone interviews every four months. Multivariable linear regression was utilized to determine the cross-sectional associations between MEDI-LITE scores and circulating cytokines, bone mineral density, ALM, and ALMBMI. Linear mixed-effects models were performed to estimate associations between MEDI-LITE scores and three-year change in hand grip strength and gait speed while negative binomial regression was applied to estimate associations between MEDI-LITE scores and three-year incident falls as well as associations between each MEDI-LITE component and three-year incident falls. Adjustments for multiple comparisons were performed using Benjamini-Hochberg adjustment for multiple testing. A higher MEDI-LITE score, indicating greater adherence to Mediterranean diet, was associated with higher appendicular lean mass adjusted for body mass index (ALMBMI) (β: 0.004kg; 95% CI: 0.000, 0.008), and lower incident falls rates (IRR: 0.94; 95% CI: 0.89, 0.99). Higher consumption of monounsaturated fatty acids (IRR: 0.76; 95% CI: 0.59, 0.98) and monounsaturated fatty acids to saturated fatty acids ratio (IRR: 0.72; 95% CI: 0.57, 0.90) were associated with 24%, and 28% lower falls risk in older men respectively. MEDI-LITE scores were not associated with BMD or physical function parameters. Adherence to a Mediterranean diet is associated with higher ALMBMI, and fewer falls in community-dwelling older men. Monounsaturated and saturated fatty acids were the most important contributors to the association between Mediterranean diet and falls risk.

1195Brain-predicted age difference is associated with cognitive processing and delayed recall in later life

Abstract Background Brain age is a novel neuroimaging-based marker of ageing that uses machine learning to predict a person’s biological brain age. A higher brain age relative to chronological age (i.e., brain-predicted age difference [brain-PAD]) is considered a sign of accelerated ageing. We examined whether brain-PAD is associated with cognition and the change in cognitive function over time. Methods This study involved 531 cognitively healthy community-dwelling older adults (70+ years). Using a previously trained algorithm, brain age was estimated using T1-weighted structural magnetic resonance images acquired at baseline. Psychomotor speed, delayed recall, verbal fluency and global cognition were assessed at baseline, years 1 and 3. Results At baseline, a significant negative association was observed between brain-PAD and psychomotor speed (r=-0.14, p = 0.001), delayed recall (r=-0.09, p = 0.04), and the three-year change in delayed recall (r=-0.15, p = 0.02), which persisted after adjusting for covariates. Conclusions These findings indicate that accelerated brain ageing in cognitively unimpaired older people is associated with worse psychomotor speed, and delayed recall. This study also provides new evidence that accelerated brain ageing is a risk factor for progressive memory decline. Future research would benefit from further prospective analyses of associations between brain-PAD and cognitive function in community dwelling older adults. Key messages Brain age is a neuroimaging-based marker of biological ageing. A higher estimate of brain age relative to chronological age (i.e., accelerated ageing) is associated with worse psychomotor speed and memory, and memory decline.

Calling out the laggards: shareholder activism and board gender diversity

PurposeWhile the presence of women in the boardroom has been steadily increasing, shareholders have taken action to push firms which lag in this area to add women to their boards. The purpose of this study is to examine whether firms with more gender homogenous (i.e. male-dominated) boards are disproportionately targeted with shareholder proposals calling for increased board gender diversity, how gender diversity among other firm leadership moderates this relationship, and whether firms respond.Design/methodology/approachFirth logistic regression is used to analyze the rare occurrence of a shareholder proposal within a sample of 7,226 firm year observations from S&P 1,500 firms in the USA between 2010 and 2017. Ordinary least squares regression is used to examine the subsequent three-year change in board gender diversity using a sample of 3,917 firm year observations.FindingsThe empirical findings indicate that firms with gender homogenous boards are more likely to incur shareholder proposals aimed at increasing board gender diversity. Having women in leadership positions (e.g. as the Chief Executive Officer) weakens this relationship. Finally, despite most proposals failing to pass, board gender diversity dramatically increases following the rendering of a proposal.Originality/valueThis study adds to the understanding of the principal-agent relationship, offering novel insights into shareholder responses to the lack of gender diversity among the board and firm responses to such activism. Furthermore, the authors add to the understanding of expectation violations with regard to gender diversity within firm boards. Finally, the authors find that women in other leadership positions insulate the firm from such shareholder activism – an important boundary condition of the findings.

Composition of time in movement behaviors and weight change in Latinx, Black and white participants.

The relationship between time-use behaviors and prospective weight change is poorly understood. A subset of Cancer Prevention Study-3 participants (n = 549, 58% women, 66% non-Latinx white) self-reported weight in 2015 and 2018 and completed an accelerometer protocol for seven days. Sedentary time, sleep, light, moderate, and vigorous intensity physical activity (PA) were treated as a compositional variable and multiple linear regression was used to examine associations between activity composition and weight change stratified by sex and race/ethnicity. Compositional isotemporal substitution analysis was used to quantify change in weight associated with reallocating 30 min./day. Activity composition was associated with weight change among women (p = 0.007), but not men (p = 0.356), and among Latinx (p = 0.032) and white participants (p = 0.001), but not Black participants (p = 0.903). Replacement of 30 min./day sedentary time with moderate-vigorous PA was associated with 3.49 lbs. loss (-6.76, -0.22) in Latinx participants and replacement with sleep was associated with 1.52 (0.25, 2.79) and 1.31 (0.40, 2.21) lbs. gain in white women and men. The distribution of time spent in daily behaviors was associated with three-year weight change in women, Latinx, and white participants. This was the first longitudinal compositional study of weight change; thus, more studies are needed.

Corporate debt booms, financial constraints and the investment nexus

Does corporate debt overhang affect investment over the medium term? To uncover this association, I measure debt overhang with a concept of debt accumulation or debt boom, and combine leverage with liquid assets to capture financial constraints. Using a large US firm-level panel over 1985 Q1–2019 Q1, I find that debt overhang leads financially vulnerable firms to cut permanently back on investment: a 10 percentage point increase in the three-year change in the leverage ratio is associated with lower investment growth of 5 percentage points after five years compared to the most resilient firms. I also find that vulnerable firms experience weaker intangible capital growth in the aftermath of debt booms. Finally, I find that general equilibrium effects dominate, stressing the risk that firm-specific debt booms in a subset of firms may spill over to the rest of the economy.

Corporate credit booms, financial constraints, and the investment nexus

Does corporate debt overhang affect investment over the medium term? To better uncover this association, I argue that we need to measure debt overhang with a concept of debt accumulation or debt boom, and to combine leverage with liquid assets to capture financial constraints. Using firm-level data for a large panel of US non-financial firms over 1985Q1-2019Q1, I find that debt overhang leads financially vulnerable firms – high debt and low liquid asset holdings – to cut back on investment: a 10 p.p. increase in the three-year change in the leverage ratio is associated with 5% lower capex investment after five years compared to the most resilient firms. I also find that vulnerable firms experience weaker intangible capital growth in the aftermath of debt booms. Finally, I find that general equilibrium effects dominate, stressing the risk that firm-specific debt booms in a subset of firms may spill over to the rest of the economy.

P6246Three-year change in high-sensitivity cardiac troponin T and total mortality in older adults - The ActiFE Study

Abstract Background High sensitivity cardiac troponin-T (hs-cTnT) levels in asymptomatic older adults have been associated with adverse outcomes such as total mortality. In this context little is known about the implications of changes over time in this population. Purpose We aimed to investigate the three-year change of hs-cTnT and its association with subsequent total mortality in a cohort of community dwelling older adults. Methods We measured hs-cTnT at baseline (BL) and at three-year follow-up (FU) in participants at the Activity and Function in the Elderly (ActiFE) Study. Having those with BL und FU hs-cTnT &lt;5 ng/L (undetectable) as the reference group (Group 1, n=156) five categories were built among those with an increment of hs-cTnT overtime: For those with undetectable BL: FU 5 to &lt;14 ng/L (Group 2, n=295), FU ≥14 ng/L (Group 3, n=24). Among those with BL levels between 5 to &lt;14 ng/L: FU 5 to &lt;14 ng/L (Group 4, n=101), FU ≥14 ng/L (Group 5, n=96). Group 6 included those with BL and FU &gt;14 ng/L (n=74). Using Cox proportional hazards models we evaluated the association between the identified groups and total mortality adjusting for age, sex, education, history of cardiovascular disease (CVD), chronic kidney disease (CKD), number of medications, CRP, and NT-proBNP measured at FU. Results Among 746 participants (median age at FU 75.9 years, 58.9% male) we observed a total of 98 deaths (median FU 4.8 years) with a mortality rate of 28.6 [95% CI 23.5, 34.9] per 1000 person-years. Those with undetectable hs-cTnT levels at both time point (Group 1, reference group) had the lowest mortality rate (5.2 [95% CI 2.0, 13.9] per 1000 person-years) and were noted to be most likely younger, women, with BMI ≥18.5 but &lt;30 kg/m2, and had less comorbidities. The highest mortality rates were observed in i) those who went from undetectable levels at BL to FU levels ≥14 ng/L (Group 3: 95.4 [95% CI 49.6, 183.4] per 1000 person-years), and in ii) those with hs-cTnT levels &gt;14 ng/L at both time points (Group 6: 100.4 [95% CI 69.8, 144.5] per 1000 person-years). These both groups showed the highest median hs-cTnT at FU (16.7 and 30.1 ng/L respectively), and the highest incidence proportion from BL to FU of CVD and CKD. Highest FU median levels of CRP were measured in Group 3, of NT-proBNP in Group 6. In the multivariable analysis we observed a significant increased hazard for total mortality with a hazard ratio of 5.62 [95% CI 1.57, 20.14] for those in Group 3 and 3.87 [95% CI 1.17, 12.80] for those in Group 6, when compared to the reference group. Conclusion Evaluating trajectories of hs-cTnT even in asymptomatic older adults could help to identify those subjects with a high risk to die even after adjustment for other covariates including NT-proBNP. Further research is needed in order to identify pathophysiological mechanisms behind these changes in older adults, and the possible effect of preventive measures in the identified risk groups. Acknowledgement/Funding This work was supported by a grant from the Ministry of Science, Research and Arts, state of Baden-Wuerttemberg, Germany.

Three-year change in oxidative stress markers is linked to target organ damage in black and white men: the SABPA study.

Oxidative stress is implicated in hypertension, carotid wall thickening, and renal dysfunction. Oxidative stress is linked to cardiovascular pathology in the black South African individuals who have a high prevalence of hypertension and early vascular aging. However, there are limited data relating changes in oxidative stress with vascular and renal deterioration over time. We aimed to investigate whether changes in oxidative stress over 3 years are associated with target organ damage in black (N = 89) and white (N = 91) men. Carotid intima-media thickness was measured using the SonoSite Micromaxx ultrasound system, and cross-sectional wall area (CSWA) was calculated. The estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease formula. The percentage change (%∆) in oxidative stress markers was calculated and included reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR). Over 3 years, black men exhibited decreased ROS, SOD, and GR, while white men revealed decreased SOD and GPx. Black men displayed positive associations of CSWA with %∆ ROS (β = 0.28; p = 0.017) and %∆ SOD (β = 0.24; p = 0.047). White men displayed a negative association of CSWA with %∆ SOD (β = -0.22; p = 0.042) and positive associations of eGFR with %∆ GPx (β = 0.33; p = 0.001) and %∆ GR (β = 0.39; p < 0.001). In white men, the association of CSWA with decreased SOD activity suggests oxidative-stress-related carotid remodeling, while associations of eGFR with the glutathione system suggests a postponement of microvascular deterioration. In black men, associations of oxidative stress markers with CSWA suggest that a sufficiently functioning antioxidant system may delay target organ damage.

Transforming growth factor beta 1 levels predict echocardiographic changes at three years after adjuvant radiotherapy for breast cancer

BackgroundTransforming growth factor beta 1 (TGF-β1) and platelet-derived growth factor (PDGF) are cytokines involved in fibrotic processes causing radiotherapy (RT)-induced cardiovascular changes. We aimed to investigate the associations between TGF-β1 and PDGF and the echocardiographic changes that occur during RT and during three-year follow-up.MethodsThe study included 63 women receiving adjuvant RT for early-stage breast cancer or ductal carcinoma in situ. Serum TGF-β1 (ng/ml) and PDGF (ng/ml) levels were measured by enzyme-linked immunoassay and echocardiographic examination was performed before RT, after RT and at 3 years. Patients were grouped by biomarker behavior by a trajectory analysis.ResultsTGF-β1 decreased from 19.2 (IQR 17.1–22.3) before RT to 18.8 (14.5–22.0) after RT (p = 0.003) and the decrease persisted at 17.2 (13.7–21.2) 3 years after RT (p = 0.101). PDGF decreased from 15.4 (12.6–19.1) before RT to 13.8 (11.7–16.2) after RT, p = 0.001, and persisted at 15.6 (10.4–18.4) at 3 years, p = 0.661. The TGF-β1 level before RT (Spearman’s rho 0.441, p < 0.001) and the three-year change in TGF-β1 (rho = − 0.302, p = 0.018) correlated with global longitudinal strain (GLS) in echocardiography at 3 years.In trajectory analysis, two TGF-β1 behavior groups were found. Group 1 had significantly higher TGF-β1 levels before RT, 25.6 (22.3–28.6), than group 2, 17.8 (15.9–19.9), p < 0.001. In multivariable analysis, TGF-β1 trajectory group 1 (β = 0.27, p = 0.013), left-sided breast cancer (β = 0.39, p = 0.001) and the use of aromatase inhibitors (β = 0.29, p = 0.011) were significantly associated with a worsening in GLS from before RT to 3 years.ConclusionAn elevated pretreatment TGF-β1 may predict RT-associated changes in echocardiography.