Polygenic and socioeconomic risk for high body mass index: 69 years of follow-up across life

Genetic influences on body mass index (BMI) appear to markedly differ across life, yet existing research is equivocal and limited by a paucity of life course data. We thus used a birth cohort study to investigate differences in association and explained variance in polygenic risk for high BMI across infancy to old age (2–69 years). A secondary aim was to investigate how the association between BMI and a key purported environmental determinant (childhood socioeconomic position) differed across life, and whether this operated independently and/or multiplicatively of genetic influences. Data were from up to 2677 participants in the MRC National Survey of Health and Development, with measured BMI at 12 timepoints from 2–69 years. We used multiple polygenic indices from GWAS of adult and childhood BMI, and investigated their associations with BMI at each age. For polygenic liability to higher adult BMI, the trajectories of effect size (β) and explained variance (R²) diverged: explained variance peaked in early adulthood and plateaued thereafter, while absolute effect sizes increased throughout adulthood. For polygenic liability to higher childhood BMI, explained variance was largest in adolescence and early adulthood; effect sizes were marginally smaller in absolute terms from adolescence to adulthood. All polygenic indices were related to higher variation in BMI; quantile regression analyses showed that effect sizes were sizably larger at the upper end of the BMI distribution. Socioeconomic and polygenic risk for higher BMI across life appear to operate additively; we found little evidence of interaction. Our findings highlight the likely independent influences of polygenic and socioeconomic factors on BMI across life. Despite sizable associations, the BMI variance explained by each plateaued or declined across adulthood while BMI variance itself increased. This is suggestive of the increasing importance of chance (‘non-shared’) environmental influences on BMI across life.     

A Novel Integrated Score Index of Echocardiographic Indices for the Evaluation of Left Ventricular Diastolic Function

Background

We propose a novel integrated score index, which could be used to quantify and grade left ventricular (LV) diastolic function.

Methods

We enrolled 629 participants [393 healthy subjects, 145 with hypertension (HTN), 24 with hypertrophic cardiomyopathy (HCM), and 67 with coronary artery disease (CAD)]. This score index was with a score of 1 for an E/A ratio < 1, a score of 1 for a septal e’/a’ ratio ≤ 0.8, a score of 2 for a lateral e’/a’ ratio ≤ 1, a score of 2 for a septal E/e’ ratio ≥10–15, a score of 3 for a lateral E/e’ ratio ≥8–15, and a score of 1 for a deceleration time >240 ms. The sum of each score was considered as the final value in this scoring method (either a septal or a lateral E/e’ ratio > 15 was given a total score of 10, regardless of the other measurements).

Results

After analysis, the AUROC of this integrated score index for predicting any diastolic dysfunction (discriminated by the American Society of Echocardiography guidelines) was 0.962, and the AUROC of the method from the logistic regression was 0.970. The mean values of the score index for the groups were 3.81 ± 0.12 in healthy, 6.48 ± 0.19 in HTN, 7.35 ± 0.46 in HCM, and 6.62 ± 0.29 in CAD. Using the score index, the healthy subjects obtained lower scores compared with those of HTN (p = 0.00), HCM (p = 0.00), and CAD (p = 0.00). Therefore, this score index could discriminate patients with diseases with impaired diastolic function from the healthy subjects when the total sum of the score was equal to or greater than 4.

Conclusions

If the presently used methods cannot allow the clear diagnosis of LV diastolic dysfunction, this integrated score index might be helpful for discriminating diseases with impaired diastolic function.     

Childhood Environment and Mental Wellbeing at Age 60-64 Years: Prospective Evidence from the MRC National Survey of Health and Development

Background

Mental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention.

Methods

Using data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64.

Results

Whilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered.

Conclusions

Childhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age.     

Influence of Intraaortic Balloon Pump Counterpulsation on Transesophageal Echocardiography Derived Determinants of Diastolic Function

Introduction

Intraaortic balloon pump counterpulsation (IABP) is often used in patients with acute coronary syndrome for its favourable effects on left ventricular (LV) systolic function and coronary perfusion. However, the effects of IABP on LV diastolic function have not been comprehensively investigated. Acute diastolic dysfunction has been linked to increased morbidity and mortality. The aim of this study was to examine the influence of IABP on LV diastolic dysfunction using standard TEE derived parameters.

Methods

Intraoperative TEE was performed in 10 patients (mean age 65 ± 11 yrs) undergoing urgent coronary artery bypass graft surgery (CABG), who had received an IABP preoperatively. TEE derived measures of diastolic dysfunction included early to late transmitral Doppler inflow velocity ratio (E/A), deceleration time (Dt), pulmonary venous systolic to diastolic Doppler velocity ratio (S/D), transmitral propagation velocity (Vp), and the ratio of early to late mitral annular tissue Doppler velocities (e’/a’). Statistical analyses included the Wilcoxon Sign-Rank test, and a p<0.05 was considered significant.

Results

Transmitral inflow E/A ratios increased significantly from 0.86 to 1.07 (p < 0.05), while Dt decreased significantly from 218 to 180 ms (p < 0.05) with the use of IABP. Significant increases in Vp (34 cm/s to 43 cm/s; p < 0.05), and e’/a’ (0.58 to 0.71; p < 0.05) suggested a favourable influence of intraaortic counterpulsation on diastolic function.

Conclusion

The use of perioperative IABP significantly improves TEE derived parameters of diastolic function consistent with a favourable impact on LV relaxation in cardiac surgery patients undergoing CABG.     

Parental death in childhood and pathways to increased mortality across the life course in Stockholm,Sweden: A cohort study

BackgroundPrevious studies have shown that the experience of parental death during childhood is associated with increased mortality risk. However, few studies have examined potential pathways that may explain these findings. The aim of this study is to examine whether familial and behavioural factors during adolescence and socioeconomic disadvantages in early adulthood mediate the association between loss of a parent at age 0 to 12 and all-cause mortality by the age of 63.Methods and findingsA cohort study was conducted using data from the Stockholm Birth Cohort Multigenerational Study for 12,615 children born in 1953, with information covering 1953 to 2016. Familial and behavioural factors at age 13 to 19 included psychiatric and alcohol problems in the surviving parent, receipt of social assistance, and delinquent behaviour in the offspring. Socioeconomic disadvantage in early adulthood included educational attainment, occupational social class, and income at age 27 to 37. We used Cox proportional hazard regression models, combined with a multimediator analysis, to separate direct and indirect effects of parental death on all-cause mortality.Among the 12,582 offspring in the study (men 51%; women 49%), about 3% experienced the death of a parent in childhood. During follow-up from the age of 38 to 63, there were 935 deaths among offspring. Parental death was associated with an elevated risk of mortality after adjusting for demographic and household socioeconomic characteristics at birth (hazard ratio [HR]: 1.52 [95% confidence interval: 1.10 to 2.08, p-value = 0.010]). Delinquent behaviour in adolescence and income during early adulthood were the most influential mediators, and the indirect associations through these variables were HR 1.03 (1.00 to 1.06, 0.029) and HR 1.04 (1.01 to 1.07, 0.029), respectively. After accounting for these indirect paths, the direct path was attenuated to HR 1.35 (0.98 to 1.85, 0.066). The limitations of the study include that the associations may be partly due to genetic, social, and behavioural residual confounding, that statistical power was low in some of the subgroup analyses, and that there might be other relevant paths that were not investigated in the present study.ConclusionsOur findings from this cohort study suggest that childhood parental death is associated with increased mortality and that the association was mediated through a chain of disadvantages over the life course including delinquency in adolescence and lower income during early adulthood. Professionals working with bereaved children should take the higher mortality risk in bereaved offspring into account and consider its lifelong consequences. When planning and providing support to bereaved children, it may be particularly important to be aware of their increased susceptibility to delinquency and socioeconomic vulnerability that eventually lead to higher mortality.

In this cohort study, Ayako Hiyoshi and colleagues show associations between parental death in a child’s life and mortality risk later in that child’s life.     

Which Circulating Antioxidant Vitamins Are Confounded by Socioeconomic Deprivation? The MIDSPAN Family Study

Background

Antioxidant vitamins are often described as having “independent” associations with risk of cancer, cardiovascular disease (CVD) and mortality. We aimed to compare to what extent a range of antioxidant vitamins and carotenoids are associated with adulthood and childhood markers of socioeconomic deprivation and to adverse lifestyle factors.

Methods and Findings

Socioeconomic and lifestyle measures were available in 1040 men and 1298 women from the MIDSPAN Family Study (30–59 years at baseline) together with circulating levels of vitamins A, C, E, and carotenoids (α-carotene, β-carotene, lutein and lycopene). Markers of socioeconomic deprivation in adulthood were consistently as strongly associated with lower vitamin C and carotenoid levels as markers of adverse lifestyle; the inverse association with overcrowding was particularly consistent (vitamin C and carotenoids range from 19.1% [95% CI 30.3–6.0] to 38.8% [49.9–25.3] lower among those in overcrowded residencies). These associations were consistent after adjusting for month, classical CVD risk factors, body mass index, physical activity, vitamin supplements, dietary fat and fibre intake. Similar, but weaker, associations were seen for childhood markers of deprivation. The association of vitamin A or E were strikingly different; several adult adverse lifestyle factors associated with higher levels of vitamin A and E, including high alcohol intake for vitamin A (9.5% [5.7–13.5]) and waist hip ratio for vitamin E (9.5% [4.8–14.4]), with the latter associations partially explained by classical risk factors, particularly cholesterol levels.

Conclusions

Plasma vitamin C and carotenoids have strong inverse associations with adulthood markers of social deprivation, whereas vitamin A and E appear positively related to specific adverse lifestyle factors. These findings should help researchers better contextualize blood antioxidant vitamin levels by illustrating the potential limitations associated with making causal inferences without consideration of social deprivation.     

Where We Used to Live: Validating Retrospective Measures of Childhood Neighborhood Context for Life Course Epidemiologic Studies

Early life exposures influence numerous social determinants of health, as distal causes or confounders of later health outcomes. Although a growing literature is documenting how early life socioeconomic position affects later life health, few epidemiologic studies have tested measures for operationalizing early life neighborhood context, or examined their effects on later life health. In the Life-course Influences on Fetal Environments (LIFE) Study, a retrospective cohort study among Black women in Southfield, Michigan (71% response rate), we tested the validity and reliability of retrospectively-reported survey-based subjective measures of early life neighborhood context(N=693). We compared 3 subjective childhood neighborhood measures (disorder, informal social control, victimization), with 3 objective childhood neighborhood measures derived from 4 decades of historical census tract data 1970-2000, linked through geocoded residential histories (tract % poverty, tract % black, tract deprivation score derived from principal components analysis), as well as with 2 subjective neighborhood measures in adulthood. Our results documented that internal consistency reliability was high for the subjective childhood neighborhood scales (Cronbach’s α =0.89, 0.93). Comparison of subjective with objective childhood neighborhood measures found moderate associations in hypothesized directions. Associations with objective variables were strongest for neighborhood disorder (rhos=.40), as opposed to with social control or victimization. Associations between subjective neighborhood context in childhood versus adulthood were moderate and stronger for residentially-stable populations. We lastly formally tested for, but found little evidence of, recall bias of the retrospective subjective reports of childhood context. These results provide evidence that retrospective reports of subjective neighborhood context may be a cost-effective, valid, and reliable method to operationalize early life context for health studies.     

Effect of ultra-endurance exercise on left ventricular performance and plasma cytokines in healthy trained men

The purpose of this study was to investigate the effect of ultra-endurance exercise on left ventricular (LV) performance and plasma concentration of interleukin (IL)-6, IL-10, IL-18 and tumour necrosis factor alpha (TNF-α) as well as to examine the relationships between exercise-induced changes in plasma cytokines and those in echocardiographic indices of LV function in ultra-marathon runners. Nine healthy trained men (mean age 30±1.0 years) participated in a 100-km ultra-marathon. Heart rate, blood pressure, ejection fraction (EF), fractional shortening (FS), ratio of early (E) to late (A) mitral inflow peak velocities (E/A), ratio of early (E’) to late (A’) diastolic mitral annulus peak velocities (E’/A’) and E-wave deceleration time (DT) were obtained by echocardiography before, immediately after and in the 90th minute of the recovery period. Blood samples were taken before each echocardiographic evaluation. The ultra-endurance exercise caused significant increases in plasma IL-6, IL-10, IL-18 and TNF-α. Echocardiography revealed significant decreases in both E and the E/A ratio immediately after exercise, without any significant changes in EF, FS, DT or the E/E’ ratio. At the 90th minute of the recovery period, plasma TNF-α and the E/A ratio did not differ significantly from the pre-exercise values, whereas FS was significantly lower than before and immediately after exercise. The increases in plasma TNF-α correlated with changes in FS (r=0.73) and DT (r=-0.73). It is concluded that ultra-endurance exercise causes alterations in LV diastolic function. The present data suggest that TNF-α might be involved in this effect.     

On Cross-Sectional Associations of Leukocyte Telomere Length with Cardiac Systolic,Diastolic and Vascular Function: The Asklepios Study

Background

Systemic telomere length has been associated with measures of diastolic function, vascular stiffness and left ventricular mass mainly in smaller, patient-specific settings and not in a general population. In this study we describe the applicability of these findings in a large, representative population.

Methods and Results

Peripheral blood leukocyte telomere length (PBL TL) was measured using telomere restriction fragment analysis in the young to middle-aged (>2500 volunteers, ∼35 to 55 years old) Asklepios study population, free from overt cardiovascular disease. Subjects underwent extensive echocardiographic, hemodynamic and biochemical phenotyping. After adjusting for relevant confounders (age, sex, systolic blood pressure, heart rate, body mass index and use of antihypertensive drugs) we found no associations between PBL TL and left ventricular mass index (P = 0.943), ejection fraction (P = 0.933), peak systolic septal annular motion (P = 0.238), pulse wave velocity (P = 0.971) or pulse pressure (P = 0.999). In contrast, our data showed positive associations between PBL TL and parameters of LV filling: the transmitral flow early (E) to late (A) velocity ratio (E/A-ratio; P<0.001), the ratio of early (e′) to late (a′) mitral annular velocities (e′/a′-ratio; P = 0.012) and isovolumic relaxation time (P = 0.015). Interestingly, these associations were stronger in women than in men and were driven by associations between PBL TL and the late diastolic components (A and a′).

Conclusions

In a generally healthy, young to middle-aged population, PBL TL is not related to LV mass or systolic function, but might be associated with an altered LV filling pattern, especially in women.     

Diastolic Dysfunction Is an Independent Predictor of Cardiovascular Events in Incident Dialysis Patients with Preserved Systolic Function

Background

Diastolic heart failure (HF), the prevalence of which is gradually increasing, is associated with cardiovascular (CV) morbidity and mortality in the general population and, more specifically, in patients with end-stage renal disease (ESRD). However, the impact of diastolic dysfunction on CV outcomes has not been studied in incident dialysis patients with preserved systolic function.

Methods

This prospective observational cohort study investigates the clinical consequence of diastolic dysfunction and the predictive power of diastolic echocardiographic parameters for CV events in 194 incident ESRD patients with normal or near normal systolic function, who started dialysis between July 2008 and August 2012.

Results

During a mean follow-up duration of 27.2 months, 57 patients (29.4%) experienced CV events. Compared to the CV event-free group, patients with CV events had a significantly higher left ventricular (LV) mass index, ratio of early mitral flow velocity (E) to early mitral annulus velocity (E’) (E/E’), LA volume index (LAVI), deceleration time, and right ventricular systolic pressure, and a significantly lower LV ejection fraction and E’. In multivariate Cox proportional hazard analysis, E/E’>15 and LAVI>32 mL/m² significantly predicted CV events (E/E’>15: hazard ratio [HR] = 5.40, 95% confidence interval [CI] = 2.73–10.70, P< .001; LAVI>32 mL/m²: HR = 5.56, 95% CI = 2.28–13.59, P< .001]. Kaplan-Meier analysis revealed that patients with both E/E’>15 and LAVI>32mL/m² had the worst CV outcomes.

Conclusion

An increase in E/E’ or LAVI is a significant risk factor for CV events in incident dialysis patients with preserved LV systolic function.     

Association of cardiovascular disease risk factors with socioeconomic position during childhood and during adulthood.

OBJECTIVE: To investigate strength of associations between risk factors for cardiovascular disease and socioeconomic position during childhood and adulthood. DESIGN: Cross sectional analysis of status of cardiovascular risk factors and past and present social circumstances. SUBJECTS: 5645 male participants in the west of Scotland collaborative study, a workplace screening study. MAIN OUTCOME MEASURES: Strength of association between each risk factor for cardiovascular disease (diastolic blood pressure, serum cholesterol concentration, level of recreational physical exercise, cigarette smoking, body mass index, and FEV1 score (forced expiratory volume in one second as percentage of expected value) and social class during childhood (based on father''s main occupation) and adulthood (based on own occupation at time of screening). RESULTS: All the measured risk factors were significantly associated with both father''s and own social class (P < 0.05), apart from exercise and smoking (not significantly associated with father''s social class) and body mass index (not significantly associated with own social class). For all risk factors except body mass index, the regression coefficient of own social class was larger than the regression coefficient of father''s social class. The difference between the coefficients was significant for serum cholesterol concentration, cigarette smoking, body mass index, and FEV1 score (all P < 0.001). CONCLUSIONS: Subjects'' status for behavioural risk factors (exercise and smoking) was associated primarily with current socioeconomic circumstances, while status for physiological risk factors (serum cholesterol, blood pressure, body mass index, and FEV1) was associated to varying extents with both past and present socioeconomic circumstances.     

Socioeconomic position at different stages of the life course and its influence on body weight and weight gain in adulthood: a longitudinal study with 13-year follow-up

Socioeconomic inequalities in body weight have been demonstrated in numerous cross-sectional studies; however, little research has investigated these inequalities from a life course and longitudinal perspective. We examined the association between child- and adulthood socioeconomic position (SEP) and BMI and overweight/obesity in 1991 (baseline) and changes in BMI and the prevalence of overweight and obesity between 1991 and 2004. Data from the 1991 and 2004 waves of the longitudinal Dutch GLOBE study were used. Participants (n = 1,465) were aged 40-60 years at baseline. BMI was calculated from self-reported height and weight collected by postal questionnaire. Retrospective recall of father's occupation was used as childhood socioeconomic indicator, and adulthood SEP was measured by the occupation of the main income earner of the household. The findings showed that among women, childhood SEP exerted a greater influence on body weight than SEP in adulthood: at baseline, women from disadvantaged backgrounds in childhood had a higher BMI and were more likely to be overweight or obese, and they gained significantly more weight between baseline and follow-up. In contrast, adult SEP had a greater impact than childhood circumstances on men's body weight: those from disadvantaged households had a higher mean BMI and were more likely to be overweight or obese at baseline, and they gained significantly more weight between 1991 and 2004. The findings suggest that exposure to disadvantaged circumstances at critically important periods of the life course is associated with body weight and weight gain in adulthood. Importantly, these etiologically relevant periods differ for men and women, suggesting gender-specific pathways to socioeconomic inequalities in body weight in adulthood.     

Left Atrial Structure and Function in Heart Failure with Preserved Ejection Fraction: A RELAX Substudy

Given the emerging recognition of left atrial structure and function as an important marker of disease in heart failure with preserved ejection fraction (HF-pEF), we investigated the association between left atrial volume and function with markers of disease severity and cardiac structure in HF-pEF. We studied 100 patients enrolled in the PhosphdiesteRasE-5 Inhibition to Improve CLinical Status and EXercise Capacity in Diastolic Heart Failure (RELAX) trial who underwent cardiac magnetic resonance (CMR), cardiopulmonary exercise testing, and blood collection before randomization. Maximal left atrial volume index (LAVi; N = 100), left atrial emptying fraction (LAEF; N = 99; including passive and active components (LAEF_P, LAEF_A; N = 80, 79, respectively) were quantified by CMR. After adjustment for multiple testing, maximal LAVi was only associated with age (ρ = 0.39), transmitral filling patterns (medial E/e’ ρ = 0.43), and N-terminal pro-BNP (NT-proBNP; ρ = 0.65; all p<0.05). Lower LAEF was associated with older age, higher transmitral E/A ratio and higher NT-proBNP. Peak VO₂ and V_E/VCO₂ slope were not associated with left atrial structure or function. After adjustment for age, sex, transmitral E/A ratio, CMR LV mass, LV ejection fraction, and creatinine clearance, NT-proBNP remained associated with maximal LAVi (β = 0.028, p = 0.0007) and total LAEF (β = -0.033, p = 0.001). Passive and active LAEF were most strongly associated with age and NT-proBNP, but not gas exchange or other markers of ventricular structure or filling properties. Left atrial volume and emptying function are associated most strongly with NT-proBNP and diastolic filling properties, but not significantly with gas exchange, in HFpEF. Further research to explore the relevance of left atrial structure and function in HF-pEF is warranted.     

Family and Neighbourhood Socioeconomic Inequalities in Childhood Trajectories of BMI and Overweight: Longitudinal Study of Australian Children

Background

Socioeconomic inequalities in longitudinal patterning of childhood overweight could cause marked differentials in total burden by adulthood. This study aims to determine timing and strength of the association between socioeconomic status (SES) and children’s body mass index (BMI) in the pre- and primary school years, and to examine socioeconomic differences in overweight trajectories across childhood.

Methods

Participants were 4949 children from the Longitudinal Study of Australian Children. BMI was measured at four biennial waves starting at age 4–5 years in 2004. Developmental trajectories of childhood overweight were identified with latent class analyses. Composite variables of family and neighbourhood SES were used.

Results

Socioeconomic differences in mean BMI z-scores already present at age 4–5 more than doubled by age 10–11 years, reflecting decreasing mean BMI among advantaged rather than increasing means among disadvantaged children. Latent class analysis identified children with ‘stable normal weight’ (68%), and with ‘persistent’ (15%), ‘late-onset’ (14%), and ‘resolving’ overweight (3%). Risks of persistent and late-onset childhood overweight were highest among low SES families (e.g. most disadvantaged quintile: OR_persistent = 2.51, 95%CI: 1.83–3.43), and only partly explained by birth weight and parental overweight. Relationships with neighbourhood SES were weaker and attenuated fully on adjustment for family SES. No socioeconomic gradient was observed for resolving overweight.

Conclusions

Childhood has become the critical period when socioeconomic inequalities in overweight emerge and strengthen. Although targeting disadvantaged children with early overweight must be a top priority, the presence of childhood overweight even among less-disadvantaged families suggests only whole-society approaches will eliminate overweight-associated morbidity.     

What the future held: childhood psychosocial adversity is associated with health deterioration through adulthood in a cohort of British women

Childhood psychosocial adversity is associated with accelerated onset of reproductive effort in women. Adaptive explanations for this phenomenon are built on the assumption that greater childhood psychosocial adversity is statistically associated with having a shorter period of healthy adult life during which reproduction will be possible. However, this critical assumption is never actually tested using individual-level longitudinal data. In this study, I revisit a large, longitudinally-studied cohort of British women. In an earlier paper, we showed that a simple index of psychosocial adversity in the first seven years of life predicted age at first pregnancy in a dose-dependent manner. Here, I show that the same index of adversity also predicts accelerated deterioration of health across the potentially reproductive period, and increased levels of the inflammatory biomarker c-reactive protein at age 44–46. These associations are robust to controlling for adult socioeconomic position, and do not appear to be solely a consequence of accelerated reproductive schedule. I argue that childhood psychosocial adversity may cause latent somatic damage that will, in adulthood, accelerate age-related physical decline. This provides a compelling adaptive rationale for the accelerated reproductive schedules observed in women who experience childhood psychosocial adversity.     

Childhood Household Dysfunction,Social Inequality and Alcohol Related Illness in Young Adulthood. A Swedish National Cohort Study

The aim of this paper is to estimate the cumulative effect of childhood household dysfunction (CHD) on alcohol related illness and death later in life and to test the interaction between CHD and socioeconomic background. The study utilised Swedish national registers including data of a Swedish national cohort born 1973–82 (n = 872 912), which was followed from age 18 to 29–40 years. Cox regression analyses were used to calculate hazard ratios (HR) for alcohol related illness or death in young adulthood. The CHD measure consisted of seven indicators: parental alcohol/drug misuse, mental health problems, criminality, death, divorce, social assistance, and child welfare interventions. Childhood socioeconomic position (SEP) was indicated by parental occupational status. Outcomes were alcohol related inpatient hospital care, specialised outpatient care or deaths. Using the highest socioeconomic group without CHD experience as a reference, those in the same socioeconomic group with one indicator of CHD had HRs of 2.1 [95% CI: 1.7–2.5], two CHD indicators 5.6 [4.4–7.1], three or more indicators 9.4 [7.1–12.4] for retrieving inpatient care. Socioeconomic disadvantage further increased the risks–those with low socioeconomic background and three CHD indicators or more had a HR of 12.5 [10.9–14.3]. Testing for interaction suggests that the combined HRs deviates from additivity [Synergy index: 1.6, 95% CI: 1.4–1.9]. The results for outpatient care were similar, but not as pronounced. In conclusion, this Swedish national cohort study shows that childhood household dysfunction is strongly and cumulatively associated to alcohol related illness later in life and that it interacts with socioeconomic disadvantage.     

Socioeconomic inequalities in prevalence and development of multimorbidity across adulthood: A longitudinal analysis of the MRC 1946 National Survey of Health and Development in the UK

BackgroundWe aimed to estimate multimorbidity trajectories and quantify socioeconomic inequalities based on childhood and adulthood socioeconomic position (SEP) in the risks and rates of multimorbidity accumulation across adulthood.Methods and findingsParticipants from the UK 1946 National Survey of Health and Development (NSHD) birth cohort study who attended the age 36 years assessment in 1982 and any one of the follow-up assessments at ages 43, 53, 63, and 69 years (N = 3,723, 51% males). Information on 18 health conditions was based on a combination of self-report, biomarkers, health records, and prescribed medications. We estimated multimorbidity trajectories and delineated socioeconomic inequalities (based on childhood and adulthood social class and highest education) in multimorbidity at each age and in longitudinal trajectories.Multimorbidity increased with age (0.7 conditions at 36 years to 3.7 at 69 years). Multimorbidity accumulation was nonlinear, accelerating with age at the rate of 0.08 conditions/year (95% CI 0.07 to 0.09, p < 0.001) at 36 to 43 years to 0.19 conditions/year (95% CI 0.18 to 0.20, p < 0.001) at 63 to 69 years. At all ages, the most socioeconomically disadvantaged had 1.2 to 1.4 times greater number of conditions on average compared to the most advantaged. The most disadvantaged by each socioeconomic indicator experienced an additional 0.39 conditions (childhood social class), 0.83 (adult social class), and 1.08 conditions (adult education) at age 69 years, independent of all other socioeconomic indicators. Adverse adulthood SEP was associated with more rapid accumulation of multimorbidity, resulting in 0.49 excess conditions in partly/unskilled compared to professional/intermediate individuals between 63 and 69 years. Disadvantaged childhood social class, independently of adulthood SEP, was associated with accelerated multimorbidity trajectories from age 53 years onwards.Study limitations include that the NSHD cohort is composed of individuals of white European heritage only, and findings may not be generalizable to the non-white British population of the same generation and did not account for other important dimensions of SEP such as income and wealth.ConclusionsIn this study, we found that socioeconomically disadvantaged individuals have earlier onset and more rapid accumulation of multimorbidity resulting in widening inequalities into old age, with independent contributions from both childhood and adulthood SEP.

Amal Khanolkar and co-workers study associations between multimorbidity and socioeconomic position in the UK.     

Analysis of postextrasystolic relaxation response in the human heart

Postextrasystolic potentiation is the phenomenon in which ventricular contractile force is strengthened by a preceding premature beat. However, the response of diastolic function after an extrasystole is unknown. We studied 58 patients with chronic heart failure (CHF) and two control subjects to evaluate the response of relaxation following extrasystole. At cardiac catheterization, from the derivative of the left ventricular (LV) pressure, the ratio of LV peak negative dP/dt (–dP/dt) of a postextrasystole to a basal beat was calculated and defined as the postextrasystolic relaxation response (PRR). PRR was compared with parameters of left ventriculography: LV end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI), and LV ejection fraction (EF). The PRRs of the two control subjects were 0.80 and 0.84. The mean PRR of the CHF patients was 0.99 ± 0.15. In all subjects, including patients and controls, correlation analysis between (EDVI, ESVI, and EF) and PRR yielded the following: (a) EDVI vs. PRR: R = 0.273, p = 0.036; (b) ESVI vs. PRR: R = 0.446, p < 0.001; and (c) EF vs. PRR: R = –0.520, p < 0.001. Thus, normal or non-failing human hearts showed a decline of –dP/dt in postextrasystole compared with the basal beats, but failing hearts had potentiated relaxation following an extrasystole.     

Life Course Socioeconomic Position and C-Reactive Protein: Mediating Role of Health-Risk Behaviors and Metabolic Alterations. The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Background

Chronic inflammation has been postulated to be one mediating mechanism explaining the association between low socioeconomic position (SEP) and cardiovascular disease (CVD). We sought to examine the association between life course SEP and C-reactive protein (CRP) levels in adulthood, and to evaluate the extent to which health-risk behaviors and metabolic alterations mediate this association. Additionally, we explored the possible modifying influence of gender.

Methods and Findings

Our analytical sample comprised 13,371 participants from ELSA-Brasil baseline, a multicenter prospective cohort study of civil servants. SEP during childhood, young adulthood, and adulthood were considered. The potential mediators between life course SEP and CRP included clusters of health-risk behaviors (smoking, low leisure time physical activity, excessive alcohol consumption), and metabolic alterations (obesity, hypertension, low HDL, hypertriglyceridemia, and diabetes). Linear regression models were performed and structural equation modeling was used to evaluate mediation. Although lower childhood SEP was associated with higher levels of CRP in adult life, this association was not independent of adulthood SEP. However, CRP increased linearly with increasing number of unfavorable social circumstances during the life course (p trend <0.001). The metabolic alterations were the most important mediator between cumulative SEP and CRP. This mediation path accounted for 49.5% of the total effect of cumulative SEP on CRP among women, but only 20.2% among men. In consequence, the portion of the total effect of cumulative SEP on CRP that was mediated by risk behaviors and metabolic alterations was higher among women (55.4%) than among men (36.8%).

Conclusions

Cumulative SEP across life span was associated with elevated systemic inflammation in adulthood. Although health-risk behaviors and metabolic alterations were important mediators of this association, a sizable fraction of this association was not mediated by these factors, suggesting that other pathways might play a role, especially among men.