scholarly journals Association of 4 epigenetic clocks with measures of functional health, cognition, and all-cause mortality in The Irish Longitudinal Study on Ageing (TILDA)

2020 ◽  
Author(s):  
Cathal McCrory ◽  
Giovanni Fiorito ◽  
Belinda Hernandez ◽  
Silvia Polidoro ◽  
Aisling M. O’Halloran ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Functional Health ◽  
Interindividual Variation ◽  
Predictive Utility ◽  
Clinical Phenotypes ◽  
Age Related ◽  
Wide Range ◽  
All Cause Mortality ◽  
Health Cognition

ABSTRACTThe aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. The present study examines the associations of four epigenetic clocks - Horvath, Hannum, PhenoAge, GrimAge - with a wide range of clinical phenotypes, and with all-cause mortality at up to 10-year follow-up in a sample of 490 participants in the Irish Longitudinal Study on Ageing. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes.

scholarly journals GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality

2020 ◽  
Author(s):  
Cathal McCrory ◽  
Giovanni Fiorito ◽  
Belinda Hernandez ◽  
Silvia Polidoro ◽  
Aisling M O’Halloran ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Reaction Time ◽  
Grip Strength ◽  
Walking Speed ◽  
Interindividual Variation ◽  
Biological Aging ◽  
Clinical Phenotypes ◽  
Age Related ◽  
Wide Range ◽  
All Cause Mortality

Abstract The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.

scholarly journals P238 RA and multimorbidity in UK Biobank: association with all-cause mortality and major adverse cardiac events

Rheumatology ◽  
2020 ◽  
Vol 59 (Supplement_2) ◽  
Author(s):  
Barbara Nicholl ◽  
Ross McQueenie ◽  
Bhautesh Jani ◽  
Sara Macdonald ◽  
Colin McCowan ◽  
...  
Keyword(s):  
Health Outcomes ◽  
Major Adverse Cardiac Events ◽  
Uk Biobank ◽  
Cardiac Events ◽  
Long Term Conditions ◽  
Increased Risk ◽  
Adverse Cardiac Events ◽  
Wide Range ◽  
All Cause Mortality

Abstract Background Multimorbidity, the presence of ≥ 2 long-term conditions (LTCs) is common in people with rheumatoid arthritis (RA). However, most research in RA has focused on cardiovascular disease and depression as co-occurring morbidities, rather than multiple LTCs or a wide range of conditions. This study hypothesised that risk of all-cause mortality and major adverse cardiac events (MACE) would be greater in those with RA and ≥2 LTCs than those with RA only. Further, we explored which individual LTCs were associated with increased risk of mortality and MACE. Methods Data from UK Biobank, a cohort of over 500,000 adults aged 37-73 years across England, Scotland and Wales was analysed. RA and 42 other LTCs of interest were self-reported by participants in a questionnaire and nurse-led interview. Information on sociodemographic (age, gender, socioeconomic status) and lifestyle factors (smoking status, BMI, alcohol frequency, physical activity) were also gathered. Rheumatoid factor levels were also determined. MACE and mortality were classified using linked hospitalisations and mortality register data (median follow up time 9 years). Data were analysed using age-adjusted Cox’s proportional hazard modelling to calculate risk of all-cause mortality or MACE, adjusted for variables listed above. Predictor variable: no RA no LTCs (reference group), only RA, RA + 1-3LTCs, RA + ≥4LTCs. Finally, the relationship between comorbidity with individual LTCs (of the 42 studied) and both health outcomes was considered. Results 5,658 (1.1%) of participants in UK Biobank self-reported RA (69.8% female, mean age 59 years). 74.7% of participants reported at least one LTC in addition to RA (1-3 LTCs 64.3%, ≥4 LTCs 10.4%), compared to 63.8% of participants without RA. 7.7% (N = 437) of participants with RA died and 5.9% (n = 331) had MACE events during the follow-up period. There was a dose response relationship in RA between LTC category and all-cause mortality and MACE risk. Only RA: mortality HR 1.42, 95% CI 1.08, 1.87, MACE HR 1.61 95% CI 1.20, 2.18; RA + 1-3LTCs: mortality HR 1.99 95% CI 1.74, 2.27, MACE HR 1.89, 95% CI 1.61, 2.20; RA + ≥4LTCs: mortality HR 3.34, 95% CI 2.64, 4.22; MACE HR 3.45, 95% CI 2.66, 4.49) compared to those with no RA no LTCs (results presented from fully adjusted models). Of the 42 individual LTCs considered, comorbid osteoporosis was the most concerning; participants with both RA and osteoporosis had a two-fold increased risk of all-cause mortality (HR 2.20, 95% CI 1.55, 3.12) and three-fold increased risk of MACE outcomes (HR 3.17, 95% CI 2.17, 4.64) compared to those with neither condition. Conclusion Participants with RA and multimorbidity or comorbidity, particularly osteoporosis, are at increased risk of adverse health outcomes. These results have important clinical relevance for the monitoring and optimal management of RA across the healthcare system. Disclosures B. Nicholl None. R. McQueenie None. B. Jani None. S. Macdonald None. C. McCowan None. J. Canning None. F. Mair None. S. Siebert None.

scholarly journals Association of BMI, comorbidities and all-cause mortality by using a baseline mortality risk model

PLoS ONE ◽  
2021 ◽  
Vol 16 (7) ◽  
pp. e0253696
Author(s):  
Jia Li ◽  
Gyorgy Simon ◽  
M. Regina Castro ◽  
Vipin Kumar ◽  
Michael S. Steinbach ◽  
...  
Keyword(s):  
Body Mass ◽  
Mortality Risk ◽  
Risk Model ◽  
Risk Groups ◽  
Baseline Risk ◽  
Increased Risk ◽  
Wide Range ◽  
Baseline Mortality ◽  
All Cause Mortality

Objective The association of body mass index (BMI) and all-cause mortality is controversial, frequently referred to as a paradox. Whether the cause is metabolic factors or statistical biases is still controversial. We assessed the association of BMI and all-cause mortality considering a wide range of comorbidities and baseline mortality risk. Methods Retrospective cohort study of Olmsted County residents with at least one BMI measurement between 2000–2005, clinical data in the electronic health record and minimum 8 year follow-up or death within this time. The cohort was categorized based on baseline mortality risk: Low, Medium, Medium-high, High and Very-high. All-cause mortality was assessed for BMI intervals of 5 and 0.5 Kg/m2. Results Of 39,739 subjects (average age 52.6, range 18–89; 38.1% male) 11.86% died during 8-year follow-up. The 8-year all-cause mortality risk had a “U” shape with a flat nadir in all the risk groups. Extreme BMI showed higher risk (BMI <15 = 36.4%, 15 to <20 = 15.4% and ≥45 = 13.7%), while intermediate BMI categories showed a plateau between 10.6 and 12.5%. The increased risk attributed to baseline risk and comorbidities was more obvious than the risk based on BMI increase within the same risk groups. Conclusions There is a complex association between BMI and all-cause mortality when evaluated including comorbidities and baseline mortality risk. In general, comorbidities are better predictors of mortality risk except at extreme BMIs. In patients with no or few comorbidities, BMI seems to better define mortality risk. Aggressive management of comorbidities may provide better survival outcome for patients with body mass between normal and moderate obesity.

scholarly journals Creating and Keeping Exercise Gains Into Your 70s, 80s and 90s

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 771-772
Author(s):  
Kenneth Manning ◽  
Teresa Kopp ◽  
Kris ann Oursler ◽  
Michelle McDonald ◽  
Miriam Morey ◽  
...  
Keyword(s):  
Gait Speed ◽  
Functional Outcomes ◽  
Exercise Program ◽  
Functional Health ◽  
First Year ◽  
Mean Values ◽  
Age Related ◽  
Functional Assessments ◽  
Minute Walk

Abstract Background: Gerofit, an exercise program for older Veterans, is undergoing national dissemination (17 sites in 6 years). Four sites have accrued 4-year functional outcomes (gait speed, 8-foot-up-and-go, 30-second chair stand, and six-minute walk). Methods: Functional assessments were administered quarterly in first year and annually thereafter. Individuals with baseline and at least two follow up measures were included for analysis (n=587). Means were gathered across each timepoint. Results: Mean values for functional assessments from baseline to 4 year were as follows: gait speed m/s- 1.04, 1.12, 1.13, 1.13, 1.09, 1.07, 1.13; 8 ft-up-and-go seconds- 7.6, 6.82, 6.69, 6.69, 7.29, 7.29, 7.51; 30 second chair stands 11.88, 14.06, 14.72, 14.89, 14.69, 14.71, 14.96; and six-minute-walk yards- 499, 532, 541, 544, 531, 530, 556. All follow up measures were significantly improved over baseline (P&lt;.01) and superior to normative age-related decline. Implications: Results indicate that exercise promotes compression of morbidity and improved functional health.

P5982Transcatheter aortic valve replacement in elderly patients with severe symptomatic aortic stenosis

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
P J Antunez Muinos ◽  
L Alvarez Rodrigez ◽  
J Lopez Pais ◽  
D Lopez Otero ◽  
X Sanmartin Pena ◽  
...  
Keyword(s):  
Elderly Patients ◽  
Descriptive Analysis ◽  
Cardiac Conduction ◽  
First Year ◽  
Safe Procedure ◽  
Age Related ◽  
Wide Range ◽  
Risk Patients ◽  
Valve Implantation

Abstract Introduction TAVR has proven to be a safe technique for high-risk patients. The objective of our work is to know the results of TAVR in patients older than 90 years; which are the riskiest and had more complications during the admission. Methods Observational retrospective analysis based on all a single-center registry of all consecutive TAVR (N=518) during the last 10 years (2008–2018). Patients older than 90 years old represent 5.8 of the procedures (N=30). We performed a descriptive analysis of the baseline characteristics of our patient cohort, and the development of events during follow-up. Results Our population, as reflected in TABLE 1, had a median age of 91,32 years old, and the majority were women (57.58%). The procedures were mostly elective, unless in 4 patients (12.12%) that were urgent. None valvuloplasty was done before TAVR in this cohort, neither Valve-in-valve. Stratification scores had a wide range, from 1.45 to 28.8% for EurSCORE II and from 4.19 to 17.19% for STS, with a median of 5.53 and 8.49% respectively. Mortality in the first 30 days and in the first year was 0.00%. Mortality after the first year was 71.40% due to non-cardiovascular events (median time of follow-up of 34.34 months). Finally, we would also like to remark that the incidence of heart failure during the first year was 14.29%, taking into account all the follow-up, the incidence was 37.04%. Despite these data, in our registry, the need for pacemaker after the valve implantation was higher than in younger populations (40.62%), probably due to the age-related fibrosis of the cardiac conduction system. Conclusions TAVR is a very safe procedure with very successful results in elderly patients, nevertheless, due to the frailty of this population, individualization is mandatory in order to optimize the resources. Acknowledgement/Funding None

scholarly journals Low-density lipoprotein cholesterol and all-cause mortality: findings from the China health and retirement longitudinal study

BMJ Open ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. e036976
Author(s):  
Liang Zhou ◽  
Ying Wu ◽  
Shaobo Yu ◽  
Yueping Shen ◽  
Chaofu Ke
Keyword(s):  
Longitudinal Study ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Total Mortality ◽  
Low Density ◽  
Low Density Lipoprotein Cholesterol ◽  
Middle Aged ◽  
Elderly Chinese ◽  
All Cause Mortality

ObjectivesTo investigate the relationship between low-density lipoprotein cholesterol (LDL-C) and all-cause mortality among middle-aged and elderly Chinese population.DesignProspective cohort study.SettingThis study used data from the China Health and Retirement Longitudinal Study.ParticipantsMiddle-aged and elderly participants with complete data were enrolled for a 4-year follow-up of total mortality and plasma levels of LDL-C, including 4981 male respondents and 5529 female respondents.ResultsDuring a 4-year follow-up, there were 305 and 219 deaths in men and women, respectively. Compared with the first quintile (Q1) of LDL-C, the adjusted HRs (95% CIs) were 0.818 (0.531 to 1.260) for Q2, 0.782 (0.507 to 1.208) for Q3, 0.605 (0.381 to 0.962) for Q4 and 0.803 (0.506 to 1.274) for Q5 in men. The results from restricted cubic spine (RCS) showed that when the 20th percentile of LDL-C levels (84 mg/dL) was used as the reference, a lower LDL-C concentration (<84 mg/dL) was associated with a higher 4-year all-cause mortality risk. By contrast, both quintile analysis and RCS analysis did not show a statistically significant association in women.ConclusionsCompared with moderately elevated LDL-C (eg, 117–137 mg/dL), a lower plasma level of LDL-C (eg, ≤84 mg/dL) was associated with an increased risk of 4-year all-cause mortality in middle-aged and elderly Chinese men. The results suggest the potential harmful effect of a quite low level of LDL-C on total mortality.

scholarly journals Individual testosterone decline and future mortality risk in men

2018 ◽  
Vol 178 (1) ◽  
pp. 121-128 ◽  
Author(s):  
Stine A Holmboe ◽  
Niels E Skakkebæk ◽  
Anders Juul ◽  
Thomas Scheike ◽  
Tina K Jensen ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Serum Levels ◽  
Proportional Hazard ◽  
Cox Proportional Hazard ◽  
Age Related ◽  
National Mortality ◽  
All Cause Mortality ◽  
Specific Mortality ◽  
Cox Proportional Hazard Models

Objective Male aging is characterized by a decline in testosterone (TS) levels with a substantial variability between subjects. However, it is unclear whether differences in age-related changes in TS are associated with general health. We investigated associations between mortality and intra-individual changes in serum levels of total TS, SHBG, free TS and LH during a ten-year period with up to 18 years of registry follow-up. Design 1167 men aged 30–60 years participating in the Danish Monitoring Trends and Determinants of Cardiovascular Disease (MONICA1) study and who had a follow-up examination ten years later (MONICA10) were included. From MONICA10, the men were followed up to 18 years (mean: 15.2 years) based on the information from national mortality registries via their unique personal ID numbers. Methods Cox proportional hazard models were used to investigate the association between intra-individual hormone changes and all-cause, CVD and cancer mortalities. Results A total of 421 men (36.1%) died during the follow-up period. Men with most pronounced decline in total TS (<10th percentile) had a higher all-cause mortality risk compared to men within the 10th to 90th percentile (hazard ratio (HR): 1.60; 95% confidence interval (CI): 1.08–2.36). No consistent associations were seen in cause-specific mortality analyses. Conclusion Our study showed that higher mortality rates were seen among the men who had the most pronounced age-related decline in TS, independent of their baseline TS levels.

scholarly journals Cataract surgery and age-related cognitive decline: A 13-year follow-up of the English Longitudinal Study of Ageing

PLoS ONE ◽  
2018 ◽  
Vol 13 (10) ◽  
pp. e0204833 ◽  
Author(s):  
Asri Maharani ◽  
Piers Dawes ◽  
James Nazroo ◽  
Gindo Tampubolon ◽  
Neil Pendleton ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cognitive Decline ◽  
Cataract Surgery ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
English Longitudinal Study

scholarly journals Correction: Cataract surgery and age-related cognitive decline: A 13-year follow-up of the English Longitudinal Study of Ageing

PLoS ONE ◽  
2018 ◽  
Vol 13 (11) ◽  
pp. e0208045 ◽  
Author(s):  
Asri Maharani ◽  
Piers Dawes ◽  
James Nazroo ◽  
Gindo Tampubolon ◽  
Neil Pendleton ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cognitive Decline ◽  
Cataract Surgery ◽  
Age Related ◽  
Age Related Cognitive Decline ◽  
English Longitudinal Study

scholarly journals Impact of sex and APOE ε4 on age-related cerebral perfusion trajectories in cognitively asymptomatic middle-aged and older adults: A longitudinal study

2021 ◽  
pp. 0271678X2110213
Author(s):  
Rui Wang ◽  
Jennifer M Oh ◽  
Alice Motovylyak ◽  
Yue Ma ◽  
Mark A Sager ◽  
...  
Keyword(s):  
Longitudinal Study ◽  
Cerebral Perfusion ◽  
Apoe Genotype ◽  
Cerebral Hypoperfusion ◽  
Time Varying ◽  
Period Range ◽  
Biological Sex ◽  
Age Related ◽  
Cardiometabolic Profile

Cerebral hypoperfusion is thought to contribute to cognitive decline in Alzheimer’s disease, but the natural trajectory of cerebral perfusion in cognitively healthy adults has not been well-studied. This longitudinal study is consisted of 950 participants (40—89 years), who were cognitively unimpaired at their first visit. We investigated the age-related changes in cerebral perfusion, and their associations with APOE-genotype, biological sex, and cardiometabolic measurements. During the follow-up period (range 0.13—8.24 years), increasing age was significantly associated with decreasing cerebral perfusion, in total gray-matter (β=−1.43), hippocampus (−1.25), superior frontal gyrus (−1.70), middle frontal gyrus (−1.99), posterior cingulate (−2.46), and precuneus (−2.14), with all P-values < 0.01. Compared with male-ɛ4 carriers, female-ɛ4 carriers showed a faster decline in global and regional cerebral perfusion with increasing age, whereas the age-related decline in cerebral perfusion was similar between male- and female-ɛ4 non-carriers. Worse cardiometabolic profile (i.e., increased blood pressure, body mass index, total cholesterol, and blood glucose) was associated with lower cerebral perfusion at all the visits. When time-varying cardiometabolic measurements were adjusted in the model, the synergistic effect of sex and APOE-ɛ4 on age-related cerebral perfusion-trajectories became largely attenuated. Our findings demonstrate that APOE-genotype and sex interactively impact cerebral perfusion-trajectories in mid- to late-life. This effect may be partially explained by cardiometabolic alterations.

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