Abstract P146: Telomere Length, DNA Methylation, and Risk of Cardiovascular Diseases: Meta-EWAS of Four Multi-ethnic Prospective Cohorts

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Pooja Subedi ◽  
Huaizhen Qin ◽  
Shelley A Cole ◽  
Maria T Plaza ◽  
Arce Domingo-Relloso ◽  
...  
Keyword(s):  
Risk Factors ◽  
Dna Methylation ◽  
African Americans ◽  
Telomere Length ◽  
Cox Regression ◽  
Heart Study ◽  
Methylation Score ◽  
Prospective Cohorts ◽  
Reduced Risk

Background: Biological aging assessed by both leukocyte telomere length (LTL) and DNA methylation (DNAm) has been associated with CVD and its risk factors. Moreover, LTL is epigenetically regulated. We hypothesized that LTL-associated epigenetic changes are associated with risk of CVD in the community. Objective: To test whether LTL-associated loci are associated with incident CVD, independent of standard risk factors in multi-ethnic cohorts. Method: We evaluated 3,628 participants with complete LTL and DNAm data in four prospective cohorts, including 1,531 American Indians from the Strong Heart Study (SHS, mean age 56, 60% women), 821 non-Hispanic Whites (NHW) from the Framingham Heart Study (FHS, mean age 60, 51% women), 471 NHW, 150 Hispanics, and 162 African Americans from the Multi-ethnic Study of Atherosclerosis (MESA, mean age 70 , 55% women), and 471 NHW and 342 African Americans from the Women’s Health Initiative (WHI, mean age 65 , all women). LTL was quantified by qPCR (SHS, MESA) or Southern blot (FHS, WHI). DNAm was assayed by Illumina EPIC (SHS) or 450K (FHS, MESA and WHI) arrays. We imputed 450K to 850K using random forest algorithms. CVD events included fatal and nonfatal MI, CHD, heart failure, stroke, peripheral artery diseases, and cardiovascular deaths. Cohort-specific EWAS was conducted to identify CpGs associated with LTL, adjusting for age, sex, race/ethnicity, smoking, alcohol, BMI, site, cell proportion, and batch. Multiple testing was Bonferroni-corrected (genome-wide P < 2.4 x10 -7 ). Results across studies were combined by random-effects meta-analysis. To examine whether LTL-associated epigenetic loci are associated with CVD risk, we used a weighted methylation score to predict incident CVD by Cox regression, adjusting for age, sex, site, smoking, alcohol, BMI, glucose, SBP, LDL-C, and total cholesterol. Results: We ascertained 2,001 CVD events, including 986 in the SHS (average follow-up 15.2 years), 208 in FHS (average follow-up 7.7 years), 74 in MESA (average follow-up 4.9 years), and 733 in WHI (average follow-up 12.2 years). Meta-EWAS identified 22 CpGs (mapped to 17 unique genes) associated with LTL. Of these, 19 loci (15 negatively and 4 positively associated with LTL) had consistent directionality of association across four cohorts. The most significant genes harboring altered CpG sites included TLL2 (cg10549018, P= 2.42 x 10 -12 ) and TPST1 ( cg10691866, P =8.6 x 10 -10 ). A higher composite methylation score, which reflects longer LTL ( P <0.0001), was significantly associated with a reduced risk of CVD in the SHS (HR=0.16, 95% CI: 0.07–0.37), FHS (HR=0.08, 95% CI: 0.01–0.40), and WHI (HR=0.32, 95%CI: 0.13–0.82), but not MESA (HR=0.47, 95% CI: 0.04–5.09). Conclusion: Altered DNA methylation at 19 CpG loci was significantly associated with LTL. Their combined effects may predict a reduced risk of CVD. The observed associations warrant further investigation.

Abstract P488: Discrimination and Hypertension Risk Among African Americans in The Jackson Heart Study

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Allana T Forde ◽  
Mario Sims ◽  
Paul Muntner ◽  
Tené Lewis ◽  
Amanda Onwuka ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
African Americans ◽  
The United States ◽  
Jackson Heart Study ◽  
Incident Hypertension ◽  
Hypertension Risk ◽  
Heart Study ◽  
Low Levels

Background: African Americans have a higher risk for hypertension compared to other racial or ethnic groups in the United States. One possible explanation for this health disparity is perceived discrimination. Few studies have prospectively examined the association between discrimination and the incidence of hypertension. Methods: We examined the associations of everyday, lifetime, and stress from lifetime discrimination with incident hypertension and whether these associations differed by sex, discrimination attribution (i.e. the main reason for the discrimination event), and coping responses to discrimination among African Americans enrolled in the Jackson Heart Study. Discrimination was self-reported by 1845 African Americans aged 21 to 85 years without hypertension at baseline (2000-2004). Participants completed two follow-up study visits from 2005-2008 and 2009-2013. We used interval-censored Cox regression to estimate associations of discrimination with incident hypertension (antihypertensive medication use; and/or systolic blood pressure ≥ 140 mm Hg and diastolic blood pressure ≥ 90 mm Hg at follow-up visits 2 or 3) after adjustment for confounding variables. Results: Overall, 52% (954 of 1845) of participants developed hypertension over the follow-up period. After adjustment for age, sex, education and hypertension risk factors (body mass index, alcohol use, smoking, diet and physical activity), medium versus low levels of lifetime discrimination (hazard ratio-HR: 1.45, 95% confidence interval-CI: 1.15-1.82) and high versus low levels of lifetime discrimination (HR: 1.35, CI: 1.08-1.68) were associated with a higher incidence of hypertension. High versus low stress from lifetime discrimination was associated with hypertension risk after adjustment for demographics (HR: 1.20, CI: 1.02-1.41), but the association was attenuated after adjustment for hypertension risk factors (HR: 1.14, CI: 0.97-1.35). Lifetime discrimination and stress from discrimination were associated with an increased hypertension risk among females, but not males. No interactions with age, attribution or coping were present for any type of discrimination. Conclusions: Findings from this study support an association between lifetime discrimination and incident hypertension in African Americans.

Abstract 005: Cumulative Stress Exposure is Associated With Incident Hypertension in African Americans: Findings From the Jackson Heart Study

Circulation ◽  
2018 ◽  
Vol 137 (suppl_1) ◽  
Author(s):  
Tanya M Spruill ◽  
Mark J Butler ◽  
S J Thomas ◽  
Gabriel S Tajeu ◽  
Sheila F Castaneda ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Chronic Stress ◽  
Cumulative Exposure ◽  
Stress Exposure ◽  
Jackson Heart Study ◽  
Incident Hypertension ◽  
Heart Study ◽  
Increased Risk

Introduction and Hypothesis: Chronic stress has been associated with incident hypertension but evidence is mixed, particularly in African Americans. We tested the hypothesis that higher cumulative exposure to stress would be associated with increased risk of developing hypertension in the Jackson Heart Study (JHS), a prospective study of cardiovascular disease in African Americans. Methods: Analyses included 1,442 JHS participants free of hypertension at baseline (2000-2004) who completed at least 3 annual follow-up telephone interviews. Incident hypertension was defined as systolic blood pressure (SBP) ≥140 mm Hg or diastolic BP (DBP) ≥90 mm Hg or use of antihypertensive medications at Exam 2 (2005-2008) or Exam 3 (2009-2013). A single-item measure of stress (“How much stress have you experienced over the past year?”) was completed during annual interviews, and the percentage of assessments in each measurement interval (i.e., between Exams 1 and 2, between Exams 2 and 3) in which high stress was reported was categorized as No Chronic Stress (0%), Low Chronic Stress (1-33.3%) or High Chronic Stress (>33.3%). Chronic stress exposure in each interval was used to predict incident hypertension at the following exam among participants free of hypertension at the start of the interval using repeated measures Poisson regression models with progressive adjustment for age, sex, years between exams and other relevant risk factors (education, marital status, parental history of hypertension, baseline SBP and DBP, body mass index, diabetes, chronic kidney disease). Results: The 1,442 participants in this analysis contributed data to 1,987 measurement intervals. The mean age was 49±0.26 years and 41% were male. During follow-up (median, 8 years), 44.0% of participants developed hypertension. The percentage of intervals with No, Low and High chronic stress was 62.3%, 9.2% and 28.6%, respectively. Multivariable-adjusted risk ratios (95% confidence interval) for incident hypertension associated with Low (vs. No) and High (vs. No) chronic stress were 1.11 (0.90-1.37) and 1.21 (1.06-1.38), respectively ( P trend=0.005). This association remained statistically significant after further adjustment for baseline stress ( P trend=0.014) and potential behavioral mediators (smoking, alcohol use, physical activity, diet; P trend=0.03). In stratified analyses, the association was present in women ( P trend=0.002), younger participants (<50 years old; P trend=0.007) and those with normal BP at baseline ( P trend=0.001). Conclusion: We found that African Americans reporting higher chronic stress over time are at increased risk of developing hypertension, independent of baseline stress levels and cardiovascular and behavioral risk factors. Future studies should evaluate the use of stress management interventions to support primary prevention of hypertension in this high risk population.

scholarly journals Discrimination and Hypertension Risk Among African Americans in the Jackson Heart Study

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 715-723 ◽  
Author(s):  
Allana T. Forde ◽  
Mario Sims ◽  
Paul Muntner ◽  
Tené Lewis ◽  
Amanda Onwuka ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
The United States ◽  
Hazard Ratio ◽  
Jackson Heart Study ◽  
Incident Hypertension ◽  
Hypertension Risk ◽  
Heart Study ◽  
Low Levels

African Americans have a higher risk of hypertension compared with other racial or ethnic groups in the United States. One possible explanation for this disparity is discrimination. Few studies have examined the association between discrimination and incidence of hypertension. We examined whether everyday discrimination, lifetime discrimination, and stress from discrimination were associated with incident hypertension and whether these associations differed by gender, age, discrimination attribution, and coping responses to discrimination among African Americans in the Jackson Heart Study. Discrimination was self-reported by 1845 African Americans aged 21 to 85 years without hypertension at baseline (2000–2004). Participants completed 2 follow-up study visits from 2005 to 2008 and 2009 to 2013. We used Cox proportional hazards regression to estimate associations of discrimination with incident hypertension. Overall, 52% (n=954) of the participants developed hypertension over the follow-up period. After adjustment for age, gender, socioeconomic status and hypertension risk factors, medium versus low levels of lifetime discrimination (hazard ratio, 1.49 [95% CI, 1.18–1.89]), and high versus low levels of lifetime discrimination (hazard ratio, 1.34 [95% CI, 1.07–1.68]) were associated with a higher incidence of hypertension. No statistically significant interactions with gender, age, attribution, or coping were present. Higher stress from lifetime discrimination was associated with higher hypertension risk after adjustment for demographics (hazard ratio for high versus low, 1.19 [95% CI, 1.01–1.40]), but the association was attenuated after adjustment for hypertension risk factors (hazard ratio, 1.14 [95% CI, 0.97–1.35]). Lifetime discrimination may increase the risk of hypertension in African Americans.

scholarly journals Long-term follow-up results of medial opening wedge high tibia osteotomy with a pre-countered non-locking steel plate

2021 ◽  
Author(s):  
Simo S. A. Miettinen ◽  
Hannu J. A. Miettinen ◽  
Jussi Jalkanen ◽  
Antti Joukainen ◽  
Heikki Kröger
Keyword(s):  
Risk Factors ◽  
Adverse Events ◽  
Mechanical Axis ◽  
Steel Plate ◽  
Cox Regression ◽  
Opening Wedge ◽  
Cumulative Survival ◽  
Long Term Follow Up

Abstract Introduction This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. Materials and methods Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2–16.1) years. The Kaplan–Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. Results The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1–13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. Conclusions The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.

scholarly journals A multicenter, prospective, observational study to determine association of mesangial C1q deposition with renal outcomes in IgA nephropathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Li Tan ◽  
Yi Tang ◽  
Gaiqin Pei ◽  
Zhengxia Zhong ◽  
Jiaxing Tan ◽  
...  
Keyword(s):  
Risk Factors ◽  
Iga Nephropathy ◽  
Cox Regression ◽  
Renal Outcome ◽  
Matched Cohort ◽  
Negative Group ◽  
Renal Survival ◽  
Cox Regression Analysis ◽  
Renal Outcomes

AbstractIt was reported that histopathologic lesions are risk factors for the progression of IgA Nephropathy (IgAN). The aim of this study was to investigate the relationships between mesangial deposition of C1q and renal outcomes in IgAN. 1071 patients with primary IgAN diagnosed by renal biopsy were enrolled in multiple study centers form January 2013 to January 2017. Patients were divided into two groups: C1q-positive and C1q-negative. Using a 1: 4 propensity score matching (PSM) method identifying age, gender, and treatment modality to minimize confounding factors, 580 matched (out of 926) C1q-negative patients were compared with 145 C1q-positive patients to evaluate severity of baseline clinicopathological features and renal outcome. Kaplan–Meier and Cox proportional hazards analyses were performed to determine whether mesangial C1q deposition is associated with renal outcomes in IgAN. During the follow-up period (41.89 ± 22.85 months), 54 (9.31%) patients in the C1q negative group and 23 (15.86%) patients in C1q positive group reached the endpoint (50% decline of eGFR and/or ESRD or death) respectively (p = 0.01) in the matched cohort. Significantly more patients in C1q negative group achieved complete or partial remission during the follow up period (P = 0.003) both before and after PSM. Three, 5 and 7-year renal survival rates in C1q-positive patients were significantly lower than C1q-negative patients in either unmatched cohort or matched cohort (all p < 0.05). Furthermore, multivariate Cox regression analysis showed that independent risk factors influencing renal survival included Scr, urinary protein, T1-T2 lesion and C1q deposition. Mesangial C1q deposition is a predictor of poor renal survival in IgA nephropathy.Trial registration TCTR, TCTR20140515001. Registered May 15, 2014, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=1074.

scholarly journals Neighborhood social environment as risk factors to health behavior among African Americans: The Jackson Heart Study

2017 ◽  
Vol 45 ◽  
pp. 199-207 ◽  
Author(s):  
Xu Wang ◽  
Amy H. Auchincloss ◽  
Sharrelle Barber ◽  
Stephanie L. Mayne ◽  
Michael E. Griswold ◽  
...  
Keyword(s):  
Risk Factors ◽  
African Americans ◽  
Health Behavior ◽  
Social Environment ◽  
Jackson Heart Study ◽  
Heart Study

Abstract 88: Social Inequalities in Stroke Mortality, Incidence and Case-fatality in Europe.

Stroke ◽  
2016 ◽  
Vol 47 (suppl_1) ◽  
Author(s):  
Marco M Ferrario ◽  
Giovanni Veronesi ◽  
Kari Kuulasmaa ◽  
Martin Bobak ◽  
Lloyd E Chambless ◽  
...  
Keyword(s):  
Risk Factors ◽  
Social Inequalities ◽  
Cox Regression ◽  
Case Fatality ◽  
Stroke Mortality ◽  
Stroke Incidence ◽  
Low Education ◽  
Mortality Incidence ◽  
European Populations

Introduction and aim: There are limited comparative data on social inequalities in stroke morbidity across Europe. We aimed to assess the magnitude of educational class inequalities in stroke mortality, incidence and 1-year case-fatality in European populations. Methods: The MORGAM study comprised 45 cohorts from Finland, Denmark, Sweden, Northern Ireland, Scotland, France, Germany, Italy, Lithuania, Poland and Russia, mostly recruited in mid 1980s-early 90s. Baseline data collection and follow-up (median 12 years) for fatal and non-fatal strokes adhered to MONICA-like procedures. Stroke mortality was defined according to the underlying cause of death (ICD-IX codes 430-438 or ICD-X I60-I69). We derived 3 educational classes from population-, sex- and birth year-specific tertiles of years of schooling. We estimated the age-adjusted difference in event rates, and the age- and risk factor-adjusted hazard ratios (HRs), between the bottom and the top of the educational class distribution from sex- and population-specific Poisson and Cox regression models, respectively. The association between 1-year case-fatality and education was estimated through logistic models adjusted for risk factors. Results: Among the 91,563 CVD-free participants aged 35-74 at baseline, 1037 stroke deaths and 3902 incident strokes occurred during follow-up. Low education accounted for 26 additional stroke deaths per 100,000 person-years in men (95%CI: 9 to 42), and 19 (7 to 32) in women. In both genders, inequalities in fatal stroke rates were larger in the East EU and in the Nordic Countries populations. The age-adjusted pooled HRs of first stroke, fatal or non-fatal, for the least educated men and women were 1.52 (95%CI: 1.29-1.78) and 1.51 (1.25-1.81), respectively, consistently across populations. Adjustment for smoking, blood pressure, HDL-cholesterol and diabetes attenuated the pooled HRs to 1.34 (95%CI: 1.14-1.57) in men and 1.29 (1.07-1.55) in women. A significant association between low education and increased 1-year case-fatality was observed in Northern Sweden only. Conclusions: Social inequalities in stroke incidence are widespread in most European populations, and less than half of the gap is explained by major risk factors.

scholarly journals Facets of Conscientiousness and risk of dementia

2017 ◽  
Vol 48 (6) ◽  
pp. 974-982 ◽  
Author(s):  
A. R. Sutin ◽  
Y. Stephan ◽  
A. Terracciano
Keyword(s):  
Risk Factors ◽  
Cognitive Impairment ◽  
Personality Assessment ◽  
Genetic Risk ◽  
Cox Regression ◽  
Genetic Risk Factors ◽  
Self Control ◽  
Standard Deviation Increase ◽  
Study Participants

BackgroundMultiple studies have found Conscientiousness to be protective against dementia. The purpose of this study is to identify which specific aspects, or facets, of Conscientiousness are most protective against cognitive impairment and whether these associations are moderated by demographic factors and/or genetic risk.MethodsHealth and Retirement Study participants were selected for analysis if they completed the facets of Conscientiousness measure, scored in the range of normal cognitive functioning at the baseline personality assessment, and had at least one follow-up assessment of cognition over the up to 6-year follow-up (N = 11 181). Cox regression was used to test for risk of incident dementia and risk of incident cognitive impairment not dementia (CIND).ResultsOver the follow-up, 278 participants developed dementia and 2186 participants developed CIND. The facet of responsibility had the strongest and most consistent association with dementia risk: every standard deviation increase in this facet was associated with a nearly 35% decreased risk of dementia; self-control and industriousness were also protective. Associations were generally similar when controlling for clinical, behavioral, and genetic risk factors. These three facets were also independent predictors of decreased risk of CIND.ConclusionsThe present research indicates that individuals who see themselves as responsible, able to control their behavior, and hard workers are less likely to develop CIND or dementia and that these associations persist after accounting for some common clinical, behavioral, and genetic risk factors.

Impact of the Bag Exchange Procedure on Risk of Peritonitis

2010 ◽  
Vol 30 (4) ◽  
pp. 440-447 ◽  
Author(s):  
Jie Dong ◽  
Yuan Chen
Keyword(s):  
Risk Factors ◽  
Peritoneal Dialysis ◽  
Cox Regression ◽  
Face Mask ◽  
First Episode ◽  
Independent Risk Factors ◽  
Randomized Control ◽  
The Relationship ◽  
Control Study

ObjectiveWe studied whether improper bag exchange predicts the first peritonitis episode in continuous ambulatory peritoneal dialysis (CAPD) patients.Patients and MethodsOur single-center prospective observational study of 130 incident urban CAPD patients who started peritoneal dialysis (PD) between March 2005 and August 2008 aimed to determine the relationship between bag exchange procedures examined at the 6th month of PD and risk for a first peritonitis episode. All patients were followed until a first peritonitis episode, censoring, or the end of the study.ResultsThese 130 patients experienced 22 first peritonitis episodes during the 14-month follow-up. During bag exchange evaluation, 51.5% of patients washed their hands improperly, 46.2% failed to check expiration date or bag leakage, and 11.5% forgot to wear a face mask and cap. Patients experiencing peritonitis were more likely to forget to wear a face mask and cap. In multivariate Cox regression model, not wearing a face mask and cap [hazard ratio (HR): 7.26; 95% confidence interval (CI): 2.6 to 20.1; p < 0.001] and having anemia (HR: 0.96; 95% CI: 0.94 to 0.99; p = 0.005) were independent risk factors for a first episode of peritonitis.ConclusionsNot wearing a face mask and cap and having anemia were independent risk factors for peritonitis. A further randomized control study needs to verify the correlation between improper bag exchange technique and peritonitis in PD patients.

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