Personality Pathways to Mortality: Interleukin-6 Links Conscientiousness to Mortality Risk

Personality is associated consistently with mortality hazards, but the physiological pathways are not yet clear. Immune system dysregulation may be one such pathway due to its role in age-related morbidity and mortality. In this preregistered study, we tested whether interleukin-6 (IL-6) and C-reactive protein (CRP) mediated the associations between personality traits and mortality hazards. The sample included 957 participants (M ± SD = 58.65 ± 11.51 years; range = 35 – 86 years) from the Midlife in the United States Survey that had 14 years of follow-up. Higher conscientiousness was associated with lower mortality hazards, with each one standard deviation higher conscientiousness associated with a 35% lower mortality risk. IL-6, but not CRP, partially mediated this association, with IL-6 accounting for 18% of this association in the fully adjusted model. While there was initial evidence that the biomarkers mediated both neuroticism and agreeableness and mortality risk, the indirect effects were not significant when controlling for the sociodemographic variables. Taken together, higher conscientiousness may lead to a longer life partially as a result of lower IL-6. This work highlights the importance of biological pathways that link personality to future mortality risk.

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Abstract P075: Influence of Systemic Interleukin-6 on the Inverse Association between Your-Choice American Heart Diet and a 41-Year Mortality Risk from Coronary Heart Disease among Men

Circulation ◽

10.1161/circ.129.suppl_1.p075 ◽

2014 ◽

Vol 129 (suppl_1) ◽

Author(s):

Jun Dai ◽

Anthony J Acton ◽

Robert V Considine ◽

Ruth E Krasnow ◽

Terry Reed

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Systemic Inflammation ◽

Mortality Risk ◽

Interleukin 6 ◽

Reactive Protein ◽

Chd Risk ◽

Long Term Mortality

Introduction: Whole diet evaluated using dietary pattern is associated with systemic inflammation and coronary heart disease (CHD). Systemic inflammation also contributes to CHD risk. Genetic factors explain variations in whole diet, systemic inflammation, and CHD. However, it is unknown whether systemic inflammation is a mechanism linking whole diet to the long-term mortality risk from coronary heart disease independent of genes. Hypothesis: Systemic inflammation measured as plasma interleukin-6 levels medicates the association between whole diet and long-term mortality risk from coronary heart disease independent of genes. Methods: From the National Heart, Lung, and Blood Institute Twin Study, we included 554 white, middle-aged, veteran male twins (105 monozygotic and 109 dizygotic twin pairs; 65 monozygotic and 61 dizygotic unpaired twins). The twins were not on antihypertensive medication and had diastolic blood pressure below 105 mmHg at baseline (1969-1973) and did not have suspected acute inflammation [plasma levels of interleukin-6 (IL-6) above 10 pg/mL or C-reactive protein above 30 mg/L)]. Usual dietary data at baseline were collected through nutritionist-administered dietary history interview. Your-Choice American Heart Diet (YCARD) score was devised to quantitatively evaluate whole diet. Plasma interleukin-6 and C-reactive protein levels were measured with ELISA. Data on vital status and death causes were collected through death certificates until Dec 31, 2010. A frailty survival model was used to estimate various associations: overall (equivalent to the association in the general population), within-pair (independent of genes and environment common to co-twins), and between-pair (indicating influence of the common factors). We controlled for total caloric intake and known CHD risk factors including body mass index and modified Framingham Risk Score. Results: There were 75 CHD deaths during a 41-year follow-up (median follow-up of 34 years). The adjusted overall association between YCARD score and the CHD mortality risk was negative [partial coefficient for a 10-unit increment in the YCARD score: βo (95% confidence interval (CI)): -0.13 (-0.24, -0.02); hazard ratio (95% CI): 0.88 (0.78, 0.98)]. The partial regression coefficient was -0.02 [95% CI (-0.23, 0.19)] for the within-pair effect of YCARD (βw) and -0.12 [95% CI (-0.26, 0)] for the between-pair effect of YCARD (βb) in relation to CHD mortality risk. Additional adjustment for IL-6 led to a 15.4% reduction in the βo, a 100% increment in the βw, and a 16.7% reduction in the βb. Conclusions: Systemic inflammation measured as interleukin-6 mediates the association between whole diet and long-term coronary heart mortality risk, which is largely through genetic and environmental factors shared between co-twins.

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The Association Between Psychological Distress and Cancer Mortality in the United States: Results from the 1997–2014 NHIS-NDI Record Linkage Study

Annals of Behavioral Medicine ◽

10.1093/abm/kaaa111 ◽

2021 ◽

Author(s):

Hyunjung Lee ◽

Gopal K Singh

Keyword(s):

Psychological Distress ◽

Mortality Risk ◽

Cancer Mortality ◽

Well Being ◽

The United States ◽

Poverty Level ◽

Adjusted Model ◽

Distress Scale ◽

Cancer Mortality Risk

Abstract Background/Purpose Psychological distress can influence cancer mortality through socioeconomic disadvantage, health-risk behaviors, or reduced access to care. These disadvantages can result in higher risks of cancer occurrence, a delayed cancer diagnosis, hamper adherence to treatment, and provoke inflammatory responses leading to cancer. Previous studies have linked psychological distress to cancer mortality. However, studies are lacking for the U.S. population. Methods This study examines the Kessler six-item psychological distress scale as a risk factor for U.S. cancer mortality using the pooled 1997–2014 data from the National Health Interview Survey (NHIS) linked to National Death Index (NDI) (N = 513,012). Cox proportional hazards regression was used to model survival time as a function of psychological distress and sociodemographic and behavioral covariates. Results In Cox models with 18 years of mortality follow-up, the cancer mortality risk was 80% higher (hazard ratio [HR] = 1.80; 95% CI = 1.64, 1.97) controlling for age; 61% higher (HR = 1.61; 95% CI = 1.46, 1.76) in the SES-adjusted model, and 33% higher (HR = 1.33; 95% CI = 1.21, 1.46) in the fully-adjusted model among adults with serious psychological distress (SPD), compared with adults without psychological distress. Males, non-Hispanic Whites, and adults with incomes at or above 400% of the federal poverty level had greater cancer mortality risk associated with SPD. Using an 8 years of mortality follow-up, those with SPD had 108% increased adjusted risks of mortality from breast cancer. Conclusion Our study findings underscore the significance of addressing psychological well-being in the population as a strategy for reducing cancer mortality.

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Joint associations of fruit and vegetable consumption and physical activity with mortality risk

European Journal of Public Health ◽

10.1093/eurpub/ckz187.028 ◽

2019 ◽

Vol 29 (Supplement_4) ◽

Author(s):

E Mauramo ◽

J Salmela ◽

N Kanerva ◽

E Lahelma ◽

T Lallukka ◽

...

Keyword(s):

Physical Activity ◽

Mortality Risk ◽

Vegetable Consumption ◽

Premature Mortality ◽

Fruit And Vegetable Consumption ◽

Lower Mortality ◽

Fruit And Vegetable ◽

Lower Mortality Risk ◽

Joint Associations

Abstract Background Fruit and vegetable consumption (FVC) and leisure-time physical activity (LTPA) are associated with better health outcomes but less is known about their joint associations with the risk of mortality. We examined the joint associations of FVC and LTPA with premature mortality among midlife and ageing municipal employees, adjusting for key covariates. Methods Survey data collected in 2000–2002 among 40–60-year-old employees of the City of Helsinki, Finland, were linked with complete register data on mortality from Statistics Finland (4961 women, 1373 men; response rate 67%; written consent for register linkages 74%). FVC was dichotomised into daily or non-daily, and LTPA into high (>14 MET-hours/week including vigorous exercise) or low. Covariates included age, sex, marital status, socioeconomic position, binge drinking, smoking and self-rated health. Cox regression models were fitted. The follow-up continued until the event of death or the end of 2015. Results A total of 281 deaths occurred during the follow-up. The mortality rate was 7.1% in men and 3.7% in women. A gender interaction was found, showing differing associations for women and men. Men with both daily FVC and high LTPA had the lowest mortality risk (HR 0.19, 95% CI 0.06-0.63) after adjusting for covariates. Men with high LTPA and non-daily FVC also had a lower mortality risk (HR 0.51, 95% CI 0.29-0.90) compared to those with non-daily FVC and low LTPA. Women with daily FVC and high LTPA had a lower mortality risk initially, but after adjusting for covariates no statistically significant associations were observed. Conclusions The joint associations of FVC and LTPA with premature mortality differed between women and men. This could be related to gender differences in e.g. the causes of death, and further studies are needed to clarify this. Increasing FVC and LTPA might prevent premature mortality among men. Key messages Fruit and vegetable consumption jointly with physical activity decreased the risk of premature mortality among men only. Further studies are needed to clarify the gender difference which could be related to for example death causes.

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Association of Lower Plasma Homoarginine Concentrations with Greater Risk of All-Cause Mortality in the Community: The Framingham Offspring Study

Journal of Clinical Medicine ◽

10.3390/jcm9062016 ◽

2020 ◽

Vol 9 (6) ◽

pp. 2016

Author(s):

Edzard Schwedhelm ◽

Rebecca J. Song ◽

Ramachandran S. Vasan ◽

Edwin R. van den Heuvel ◽

Juliane Hannemann ◽

...

Keyword(s):

Mortality Risk ◽

Lower Mortality ◽

Cvd Risk ◽

Multivariable Regression ◽

Cross Classification ◽

Male Sex ◽

Low Levels ◽

Study Participants ◽

Lower Mortality Risk

Lower circulating homoarginine concentrations have been associated with morbidity and mortality in patients with established cardiovascular disease (CVD). We assayed plasma homoarginine concentrations in 3331 Framingham Offspring Study participants attending examination cycle six (mean age 58.6 years, 53% women). We evaluated correlates of plasma homoarginine and related homoarginine to incident CVD and death. We also classified participants as having higher (upper quartile) versus lower (lower three quartiles) homoarginine and previously assayed asymmetric dimethylarginine (ADMA) concentrations, and created cross-classification groups. We observed 630 incident CVD events and 940 deaths during a median follow-up of 18 years. In multivariable regression analysis, homoarginine was associated positively with male sex, body mass index, anti-hypertensive medication use and systolic blood pressure, but inversely with age and smoking. Higher homoarginine levels were associated with a lower mortality risk (hazard ratio (HR) per SD increment, 0.83, 95% CI: 0.74–0.93) adjusting for standard CVD risk factors, and ADMA. Among the cross-classification groups, participants with higher homoarginine and lower ADMA had a lower mortality risk (HR, 0.81, 95% CI: 0.67–0.98) compared to those with low levels of both. Further studies are needed to dissect the mechanisms of the association of homoarginine and mortality over decades in the community.

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Residing in urban areas with higher green space is associated with lower mortality risk: A census-based cohort study with ten years of follow-up

Environment International ◽

10.1016/j.envint.2020.106365 ◽

2021 ◽

Vol 148 ◽

pp. 106365

Author(s):

Mariska Bauwelinck ◽

Lidia Casas ◽

Tim S. Nawrot ◽

Benoit Nemery ◽

Sonia Trabelsi ◽

...

Keyword(s):

Cohort Study ◽

Mortality Risk ◽

Urban Areas ◽

Green Space ◽

Lower Mortality ◽

Lower Mortality Risk

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Association of physical activity intensity and bout length with mortality: An observational study of 79,503 UK Biobank participants

PLoS Medicine ◽

10.1371/journal.pmed.1003757 ◽

2021 ◽

Vol 18 (9) ◽

pp. e1003757

Author(s):

Lousise A. C. Millard ◽

Kate Tilling ◽

Tom R. Gaunt ◽

David Carslake ◽

Deborah A. Lawlor

Keyword(s):

Physical Activity ◽

Mortality Risk ◽

Sedentary Time ◽

The United States ◽

Lower Mortality ◽

Uk Biobank ◽

Bout Length ◽

All Cause Mortality ◽

Light Activity

Background Spending more time active (and less sedentary) is associated with health benefits such as improved cardiovascular health and lower risk of all-cause mortality. It is unclear whether these associations differ depending on whether time spent sedentary or in moderate-vigorous physical activity (MVPA) is accumulated in long or short bouts. In this study, we used a novel method that accounts for substitution (i.e., more time in MVPA means less time sleeping, in light activity or sedentary) to examine whether length of sedentary and MVPA bouts associates with all-cause mortality. Methods and findings We used data on 79,503 adult participants from the population-based UK Biobank cohort, which recruited participants between 2006 and 2010 (mean age at accelerometer wear 62.1 years [SD = 7.9], 54.5% women; mean length of follow-up 5.1 years [SD = 0.73]). We derived (1) the total time participants spent in activity categories—sleep, sedentary, light activity, and MVPA—on average per day; (2) time spent in sedentary bouts of short (1 to 15 minutes), medium (16 to 40 minutes), and long (41+ minutes) duration; and (3) MVPA bouts of very short (1 to 9 minutes), short (10 to 15 minutes), medium (16 to 40 minutes), and long (41+ minutes) duration. We used Cox proportion hazards regression to estimate the association of spending 10 minutes more average daily time in one activity or bout length category, coupled with 10 minutes less time in another, with all-cause mortality. Those spending more time in MVPA had lower mortality risk, irrespective of whether this replaced time spent sleeping, sedentary, or in light activity, and these associations were of similar magnitude (e.g., hazard ratio [HR] 0.96 [95% CI: 0.94, 0.97; P < 0.001] per 10 minutes more MVPA, coupled with 10 minutes less light activity per day). Those spending more time sedentary had higher mortality risk if this replaced light activity (HR 1.02 [95% CI: 1.01, 1.02; P < 0.001] per 10 minutes more sedentary time, with 10 minutes less light activity per day) and an even higher risk if this replaced MVPA (HR 1.06 [95% CI: 1.05, 1.08; P < 0.001] per 10 minutes more sedentary time, with 10 minutes less MVPA per day). We found little evidence that mortality risk differed depending on the length of sedentary or MVPA bouts. Key limitations of our study are potential residual confounding, the limited length of follow-up, and use of a select sample of the United Kingdom population. Conclusions We have shown that time spent in MVPA was associated with lower mortality, irrespective of whether it replaced time spent sleeping, sedentary, or in light activity. Time spent sedentary was associated with higher mortality risk, particularly if it replaced MVPA. This emphasises the specific importance of MVPA. Our findings suggest that the impact of MVPA does not differ depending on whether it is obtained from several short bouts or fewer longer bouts, supporting the recent removal of the requirement that MVPA should be accumulated in bouts of 10 minutes or more from the UK and the United States policy. Further studies are needed to investigate causality and explore health outcomes beyond mortality.

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Plasma Lutein, a Nutritional Biomarker for Development of Advanced Age-Related Macular Degeneration: The Alienor Study

Nutrients ◽

10.3390/nu13062047 ◽

2021 ◽

Vol 13 (6) ◽

pp. 2047

Author(s):

Bénédicte M. J. Merle ◽

Audrey Cougnard-Grégoire ◽

Jean-François Korobelnik ◽

Wolfgang Schalch ◽

Stéphane Etheve ◽

...

Keyword(s):

Macular Degeneration ◽

High Performance ◽

Population Based ◽

Age Related Macular Degeneration ◽

Cox Proportional Hazard ◽

Age Related ◽

Cox Proportional Hazard Models ◽

Adjusted Model ◽

Reduced Risk

Lutein and zeaxanthin may lower the risk of age-related macular degeneration (AMD). We evaluated the associations of plasma lutein and zeaxanthin with the incidence of advanced AMD in the Alienor study (Antioxydants Lipides Essentiels Nutrition et Maladies Oculaires). Alienor study is a prospective population-based cohort of 963 residents of Bordeaux, France, who were 73 years or older at baseline (2006–2008). The present study included 609 participants with complete ophthalmologic and plasma carotenoids data. Examinations were performed every two years over an eight-year period (2006 to 2017). Plasma lutein and zeaxanthin were determined at baseline from fasting blood samples using high-performance liquid chromatography. Cox proportional hazard models were used to assess associations between plasma lutein, zeaxanthin, and their (total cholesterol (TC) + triglycerides (TG)) ratios with AMD. Among the 609 included participants, 54 developed advanced incident AMD during a median follow-up time of 7.6 years (range 0.7 to 10.4). Participants with higher plasma lutein had a reduced risk for incident advanced AMD in the fully adjusted model (HR = 0.63 per 1-SD increase (95% CI, 0.41–0.97), p = 0.03). A similar association was observed using the lutein/(TC + TG) ratio (HR = 0.59 (95% CI, 0.39–0.90), p = 0.01). No associations were evidenced for other carotenoids. Higher plasma lutein was associated with a 37% reduced risk of incident advanced AMD.

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Effects of Caloric Restriction and Exercise on Age-Related, Chronic Inflammation Assessed by C-Reactive Protein and Interleukin-6

The Journals of Gerontology Series A ◽

10.1093/gerona/61.3.211 ◽

2006 ◽

Vol 61 (3) ◽

pp. 211-217 ◽

Cited By ~ 57

Author(s):

R. Kalani ◽

S. Judge ◽

C. Carter ◽

M. Pahor ◽

C. Leeuwenburgh

Keyword(s):

Chronic Inflammation ◽

Caloric Restriction ◽

Interleukin 6 ◽

C Reactive Protein ◽

Reactive Protein ◽

Age Related

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P4679Changes in systemic inflammation and endothelial dysfunction after balloon pulmonary angioplasty

European Heart Journal ◽

10.1093/eurheartj/ehz745.1061 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Cited By ~ 1

Author(s):

W Magon ◽

J Stepniewski ◽

K Jonas ◽

M Waligora ◽

P Podolec ◽

...

Keyword(s):

Endothelial Dysfunction ◽

Serum Concentration ◽

Systemic Inflammation ◽

Interleukin 6 ◽

C Reactive Protein ◽

Pulmonary Hemodynamics ◽

Endothelin 1 ◽

Reactive Protein ◽

Balloon Pulmonary Angioplasty

Abstract Introduction Pulmonary endarterectomy leads to a decrease in systemic inflammation and improvement in endothelial function in patients with chronic thromboembolic pulmonary hypertension (CTEPH). Balloon pulmonary angioplasty (BPA) improves pulmonary hemodynamics in patients with inoperable CTEPH. Aim To assess changes in systemic inflammation and endothelial dysfunction after a single BPA session and after completion of the treatment. Methods We enrolled consecutive, inoperable CTEPH patients who underwent BPA. Interleukin 6, 10 (IL-6, IL-10), and C-reactive protein (hsCRP) constituted markers of systemic inflammation. Endothelin-1 (ET-1) served as a marker of endothelial dysfunction. Serum concentration of selected markers was assessed in every patient before, 24 hours after the first BPA session and 6 months after completion of the BPA treatment. Age- and sex-matched healthy subjects served as a control group. Results We recruited 20 patients with inoperable CTEPH (6 males [30%]), aged 67 [61–74] years in New York Heart Association class III (n=19 [95%]) and II (n=1 [5%]). BPA treatment was completed with a median of 5 [2–8] BPA sessions per patient. Before starting the treatment CTEPH patients, as compared to controls (n=10), had raised serum level of IL-6 (3.82 [2.75 - 6.03] vs. 2.64 [0.88 - 4.75] pg/ml; p=0.04), hsCRP (2.47 [0.93 - 4.27] vs. 1.23 [0.48–3.21] ng/ml; p=0.02) and ET-1 (2.68 [2.24 - 3.64] vs. 1.47 [1.4 - 1.82] pg/ml; p=0.004). There was no difference in IL-10 level. 24 hours after a BPA session we observed an increased level of IL-6, IL-10 and hsCRP. (Tab.) 6 months after completion of the BPA treatment there was a reduced level of IL-6, hsCRP and ET-1 (Tab.) Table 1. Changes (Δ) in serum concentration of analyzed markers 24 hours after a single BPA session and at 6-months assessment after completion of the BPA treatment (n=20) Initial Δ at 24 hours after single BPA p Δ at 6-months follow-up p ET-1 [pg/ml] 2.68 [2.24; 3.64] −0.2 [−0.5; 0.23] 0.21 −0.47 [−0.96; 0.05] 0.004 IL-6 [pg/ml] 3.82 [2.75; 6.03] 3.67 [1.41; 7.16] 0.008 −0.82 [−3.11; 0.54] 0.04 IL-10 [pg/ml] 0.53 [0.44; 0.58] 0.32 [0.21; 0.87] 0.006 −0.11 [−0.33; 0.14] 0.94 hsCRP [ng/ml] 2.47 [0.93; 4.27] 5.4 [3.96; 10.59] 0.008 −0.36 [−0.94; 0.16] 0.02 ET-1, endothelin 1; hsCRP, C-reactive protein; IL-6, interleukin 6; IL-10, interleukin 10. Conclusions Patients with inoperable CTEPH, as compared to healthy controls, exhibit an increased systemic inflammation and endothelial dysfunction, which both improve after completion of the BPA treatment. At short-term follow-up after single BPA session there is an increase in systemic inflammatory response.

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