scholarly journals A Direct Comparison of the Relationship of Epigenetic Aging and Epigenetic Substance Consumption Markers to Mortality in the Framingham Heart Study

Genes ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 51 ◽  
Author(s):  
James Mills ◽  
Steven Beach ◽  
Meeshanthini Dogan ◽  
Ron Simons ◽  
Frederick Gibbons ◽  
...  
Keyword(s):  
Substance Use ◽  
Framingham Heart Study ◽  
Healthy Aging ◽  
Methylation Status ◽  
Cox Proportional Hazards ◽  
Independent Effect ◽  
Epigenetic Aging ◽  
Heart Study ◽  
Relationship Of ◽  
The Relationship

A number of studies have examined the relationship of indices of epigenetic aging (EA) to key health outcomes. Unfortunately, our understanding of the relationship of EA to mortality and substance use-related health variables is unclear. In order to clarify these interpretations, we analyzed the relationship of the Levine EA index (LEA), as well as established epigenetic indices of cigarette (cg05575921) and alcohol consumption (cg04987734), to all-cause mortality in the Framingham Heart Study Offspring Cohort (n = 2256) Cox proportional hazards regression. We found that cg05575921 and cg04987734 had an independent effect relative to LEA and vice versa, with the model including all the predictors having better performance than models with either LEA or cg05575921 and cg04987734 alone. After correction for multiple comparisons, 195 and 327, respectively, of the 513 markers in the LEA index, as well as the overall index itself, were significantly associated with cg05575921 and cg04987734 methylation status. We conclude that the epigenetic indices of substance use have an independent effect over and above LEA, and are slightly stronger predictors of mortality in head-to-head comparisons. We also conclude that the majority of the strength of association conveyed by the LEA is secondary to smoking and drinking behaviors, and that efforts to promote healthy aging should continue to focus on addressing substance use.

AHRR Methylation is a Significant Predictor of Mortality Risk in Framingham Heart Study

2019 ◽  
Vol 48 (1) ◽  
pp. 79-89 ◽  
Author(s):  
Robert A Philibert ◽  
Meeshanthini V Dogan ◽  
James A Mills ◽  
Jeffrey D Long
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
Mortality Risk ◽  
Framingham Heart Study ◽  
Methylation Status ◽  
Current Time ◽  
Predictors Of Mortality ◽  
Heart Study ◽  
Relationship Of ◽  
The Relationship

Background.—The ability to predict mortality is useful to clinicians, policy makers and insurers. At the current time, prediction of future mortality is still an inexact process with some proposing that epigenetic assessments could play a role in improving prognostics. In past work, we and others have shown that DNA methylation status at cg05575921, a well-studied measure of smoking intensity, is also a predictor of mortality. However, the exact extent of that predictive capacity and its independence of other commonly measured mortality risk factors are unknown. Objective.—To determine the capacity of methylation to predict mortality. Method.—We analyzed the relationship of methylation at cg05575921 and cg04987734, a recently described quantitative marker of heavy alcohol consumption, to mortality in the Offspring Cohort of the Framingham Heart Study using proportional hazards survival analysis. Results.—In this group of participants (n = 2278) whose average age was 66 ± 9 years, we found that the inclusion of both cg05575921 and cg04987734 methylation to a base model consisting of age and sex only, or to a model containing 11 commonly used mortality risk factors, improved risk prediction. What is more, prediction accuracy for the base model plus methylation data was increased compared to the base model plus known predictors of mortality (CHD, COPD, or stroke). Conclusion.—Cg05575921, and to a smaller extent cg04987734, are strong predictors of mortality risk in older Americans and that incorporation of DNA methylation assessments to these and other loci may be useful to population scientists, actuaries and policymakers to better understand the relationship of environmental risk factors, such as smoking and drinking, to mortality.

scholarly journals Array-Based Epigenetic Aging Indices May Be Racially Biased

Genes ◽  
2020 ◽  
Vol 11 (6) ◽  
pp. 685 ◽  
Author(s):  
Robert Philibert ◽  
Steven R.H. Beach ◽  
Man-Kit Lei ◽  
Frederick X. Gibbons ◽  
Meg Gerrard ◽  
...  
Keyword(s):  
Methylation Status ◽  
Area Under The Curve ◽  
European Ancestry ◽  
Bonferroni Correction ◽  
Aging Index ◽  
Epigenetic Aging ◽  
Important Health ◽  
Characteristic Area ◽  
Relationship Of ◽  
The Relationship

Epigenetic aging (EA) indices are frequently used as predictors of mortality and other important health outcomes. However, each of the commonly used array-based indices has significant heritable components which could tag ethnicity and potentially confound comparisons across racial and ethnic groups. To determine if this was possible, we examined the relationship of DNA methylation in cord blood from 203 newborns (112 African American (AA) and 91 White) at the 513 probes from the Levine PhenoAge Epigenetic Aging index to ethnicity. Then, we examined all sites significantly associated with race in the newborn sample to determine if they were also associated with an index of ethnic genetic heritage in a cohort of 505 AA adults. After Bonferroni correction, methylation at 50 CpG sites was significantly associated with ethnicity in the newborn cohort. The five most significant sites predicted ancestry with a receiver operator characteristic area under the curve of 0.97. Examination of the top 50 sites in the AA adult cohort showed that methylation status at 11 of those sites was also associated with percentage European ancestry. We conclude that the Levine PhenoAge Index is influenced by cryptic ethnic-specific genetic influences. This influence may extend to similarly constructed EA indices and bias cross-race comparisons.

scholarly journals The Relationship of Manic Episodes and Drug Abuse to Sexual Risk Behavior in Patients with Co-Occurring Bipolar and Substance Use Disorders: a 15-Month Prospective Analysis

2010 ◽  
Vol 15 (8) ◽  
pp. 1829-1833 ◽  
Author(s):  
Christina S. Meade ◽  
Garrett M. Fitzmaurice ◽  
Amy K. Sanchez ◽  
Margaret L. Griffin ◽  
Leah J. McDonald ◽  
...  
Keyword(s):  
Substance Use ◽  
Drug Abuse ◽  
Risk Behavior ◽  
Sexual Risk ◽  
Substance Use Disorders ◽  
Sexual Risk Behavior ◽  
Prospective Analysis ◽  
Relationship Of ◽  
The Relationship

Abstract MP35: Association Of Orthostatic Blood Pressure Response With Incident Heart Failure: The Framingham Heart Study

Circulation ◽  
2021 ◽  
Vol 143 (Suppl_1) ◽  
Author(s):  
Tara A Shrout ◽  
Vasan S Ramachandran ◽  
Vanessa Xanthakis
Keyword(s):  
Heart Failure ◽  
Blood Pressure ◽  
Ejection Fraction ◽  
Framingham Heart Study ◽  
Proportional Hazards ◽  
Blood Pressure Response ◽  
The Elderly ◽  
Cox Proportional Hazards ◽  
Heart Study ◽  
Orthostatic Blood Pressure

Introduction: Orthostatic hypotension (OH) and hypertension (OHT) are associated with cardiovascular disease and mortality. The relation of OH and OHT with heart failure (HF) in the community is not well explored, particularly among the elderly and those with hypertension. Moreover, there remains a paucity of longitudinal data on the development of HF subtypes (HF with reduced ejection fraction [HFrEF] and HF with preserved ejection fraction [HFpEF]) in those with OH and OHT. Hypothesis: We hypothesized that OH and OHT are associated with a higher risk of HF. Methods: We evaluated 1914 Framingham Heart Study participants (mean age 72 years, 1159 women [61%]), with available orthostatic blood pressure (BP) measurements. OH was defined as a decrease and OHT as an increase of 20/10 mmHg in systolic/diastolic BP from supine to standing position, respectively. We used a categorical variable (OH, OHT, absence of OH and OHT [referent]). Using Cox proportional hazards regression, we related OH and OHT to risk of HF and its subtypes (HFrEF, HFpEF), compared to the referent group, adjusting for age, sex, body mass index, systolic BP, diastolic BP, hypertension treatment, smoking, and diabetes. Results: There were 275 participants with OH (181 women, 66%) and 411 with OHT (236 women, 57%). On median follow-up of 13 years, 492 developed HF (292 women, 59%). In multivariable-adjusted analyses, OH was associated with higher risk of HF (Hazards Ratio [HR] 1.47; 95% CI, 1.13-1.92; Figure ) compared to referent. Further, OH was associated with higher risk of HFrEF (HR 2.56; 95% CI, 1.46-4.48), but not HFpEF. OHT was not associated with incident HF. Conclusions: Assessment of orthostatic BP response in the elderly may identify future HF risk. Further studies are warranted to investigate mechanisms underlying the observed associations.

The Relationship of Substance use and the Onset of Spinal Cord Injuries

2019 ◽  
Vol 100 (10) ◽  
pp. e133-e134
Author(s):  
Lori Eldridge ◽  
Jennifer Piatt ◽  
Jon Agley ◽  
Steven Gerke
Keyword(s):  
Spinal Cord ◽  
Substance Use ◽  
Spinal Cord Injuries ◽  
Relationship Of ◽  
The Relationship

scholarly journals Eosinophil count and mortality risk in incident hemodialysis patients

2020 ◽  
Vol 35 (6) ◽  
pp. 1032-1042
Author(s):  
Duk-Hee Kang ◽  
Yuji Lee ◽  
Carola Ellen Kleine ◽  
Yong Kyu Lee ◽  
Christina Park ◽  
...  
Keyword(s):  
Mortality Risk ◽  
Eosinophil Count ◽  
Proportional Hazards ◽  
Cox Proportional Hazards ◽  
Time Varying ◽  
Cox Proportional Hazards Models ◽  
Lower Baseline ◽  
All Cause Mortality ◽  
Relationship Of ◽  
The Relationship

Abstract Background Eosinophils are traditionally known as moderators of allergic reactions; however, they have now emerged as one of the principal immune-regulating cells as well as predictors of vascular disease and mortality in the general population. Although eosinophilia has been demonstrated in hemodialysis (HD) patients, associations of eosinophil count (EOC) and its changes with mortality in HD patients are still unknown. Methods In 107 506 incident HD patients treated by a large dialysis organization during 2007–11, we examined the relationships of baseline and time-varying EOC and its changes (ΔEOC) over the first 3 months with all-cause mortality using Cox proportional hazards models with three levels of hierarchical adjustment. Results Baseline median EOC was 231 (interquartile range 155–339) cells/μL and eosinophilia (>350 cells/μL) was observed in 23.4% of patients. There was a gradual increase in EOC over time after HD initiation with a median ΔEOC of 5.1 (IQR −53–199) cells/μL, which did not parallel the changes in white blood cell count. In fully adjusted models, mortality risk was highest in subjects with lower baseline and time-varying EOC (<100 cells/μL) and was also slightly higher in patients with higher levels (≥550 cells/μL), resulting in a reverse J-shaped relationship. The relationship of ΔEOC with all-cause mortality risk was also a reverse J-shape where both an increase and decrease exhibited a higher mortality risk. Conclusions Both lower and higher EOCs and changes in EOC over the first 3 months after HD initiation were associated with higher all-cause mortality in incident HD patients.

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