Effects Of Common Risk Factors Research Articles

418 CXCL-10 Influences Local Regulation of Neuroinflammation After Intracranial Hemorrhage

INTRODUCTION: Mitigating secondary injury from neuroinflammation is a critical investigation to identify therapeutic targets and improve ICH outcomes. Plasma CXCL10, a chemokine of chemo-attraction for monocytes/macrophages, T cells, and NK cells, is significantly elevated in hypertensive patients; therefore, we investigated the role of CXCL10 in local neuro-inflammation after hypertensive ICH. Furthermore, it is also vital to understand the local effects of common risk factors of ICH such as hypertension and cardiometabolic disease on pro-inflammatory chemokines. METHODS: A pilot study of autologous-injection ICH was induced in hypertensive (mREN2)7 (n = 5) and normotensive Hanover Sprague-Dawley male rats (n = 5). Tail-cuff blood pressure measurements and pre- and post-ICH neurobehavioral testing was performed. Rat sacrifice was performed at 5 days post-ICH with subsequent homogenization of hematoma area and contralateral area (2 mm brain slice around injection site). Hemoglobin was measured using whole hemispheres, but small slices were used for assessing immune inflammation. Lastly, qPCR testing was performed to determine CXCL-10 level of expression. RESULTS: CXCL-10 was significantly different in the local ipsilateral hemisphere of both the cardiometabolic mREN model (P = 0.012) and control SD (P = 0.025) rats compared to the contralateral hemisphere at 5 days post-ICH. There was no significant difference in CXCL-10 expression between SD and mREN rat models in contralateral or ipsilateral hemispheres. CONCLUSIONS: Cerebral CXCL-10 levels ipsilateral to ICH are significantly elevated compared to the contralateral hemisphere indicating the locally injured brain tissue expressed CXCL-10 to recruit immunocyte infiltration. CXCL-10 elevation does not appear to be influenced by comorbidities of cardiometabolic disease or hypertension. These results implicate CXCL-10 mediated processes such as activation and recruitment of leukocytes in post-ICH secondary injury, which may prove to be an important therapeutic target.

Risk trajectories of complications in over one thousand newly diagnosed individuals with type 2 diabetes

Although the increased risk of complications of type 2 diabetes (T2D) is well known, there is still little information about the long-term development of comorbidities in relation to risk factors. The purpose of the present study was to describe the risk trajectories of T2D complications over time in an observational cohort of newly diagnosed T2D patients, as well as to evaluate the effect of common risk factors on the development of comorbidities. This national cohort study investigated individuals with T2D in the Swedish National Diabetes Register regarding prevalence of comorbidities at the time of diagnosis, and the incidence of cardiovascular disease (CVD), chronic kidney disease (CKD) and heart failure in the entire patient cohort and stratified by HbA1c levels and age at baseline. Multivariable Cox regressions were used to evaluate risk factors predicting outcomes. We included 100,878 individuals newly diagnosed with T2D between 1998 and 2012 in the study, with mean 5.5 years follow-up (max 17 years). The mean age at diagnosis was 62.6 ± SD12.5 years and 42.7% of the patients were women. Prevalent CVD was reported for 17.5% at baseline. Although the prevalence of comorbidities was generally low for individuals 50 years or younger at diagnosis, the cumulative incidence of the investigated comorbidities increased over time. Newly diagnosed CVD was the most common comorbidity. Women were shown to have a lower risk of developing comorbid conditions than men. When following the risk trajectory of comorbidities over a period of up to 15 years in individuals with type 2 diabetes, we found that all comorbidities gradually increased over time. There was no distinct time point when onset suddenly increased.

Comparison of Risk Factors for Cholangiocarcinoma and Hepatocellular Carcinoma: A Prospective Cohort Study in Korean Adults.

Simple SummaryCholangiocarcinoma (CCA), especially intrahepatic cholangiocarcinoma, shares many of the commonly cited risk factors for hepatocellular carcinoma (HCC). Therefore, a common pathogenesis has been suggested for HCC and CCA; liver cirrhosis (LC) is considered a key factor in this “common pathway” hypothesis. In this large-scale prospective cohort study in Koreans, choledocholithiasis, cholelithiasis, HBV infection, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors for CCA. In the current study, LC (the most important risk factor of HCC) did not increase the risk for CCA and there were also differences between CCA and HCC in the magnitude of common risk factors. Our study suggests that there is weak epidemiologic evidence for the hypothesis that LC is a key common factor involved in the pathogenesis of both CCA and HCC.Cholangiocarcinoma (CCA), especially intrahepatic CCA, is known to share several risk factors with hepatocellular carcinoma (HCC) and liver cirrhosis has been proposed as a common pathogenic factor. We aimed to identify the risk factors of CCA and to examine differences in risk factors between CCA and HCC. We followed 510,217 Korean adults who underwent health checkups during 2002–2003 until 2013 via linkage to national hospital discharge records. Hazard ratios (HRs) were calculated after adjustment for confounders. During the mean follow-up of 10.5 years, 1388 and 2920 individuals were diagnosed with CCA and HCC, respectively. Choledocholithiasis (HR = 13.7; 95% confidence interval (CI) = 7.58–24.88) was the strongest risk factor for CCA, followed by cholelithiasis (HR = 2.94) and hepatitis B virus (HBV) infection (HR = 2.71). Two of the strongest risk factors for HCC—liver cirrhosis (HR = 1.29; 95% CI = 0.48–3.45) and hepatitis C virus infection (HR = 1.89; 95% CI = 0.49–7.63)—were not significantly associated with the risk of CCA. HBV infection and diabetes increased the risk of both HCC and CCA, but the HRs were lower for CCA than for HCC (Pheterogeneity < 0.001 for HBV; Pheterogeneity = 0.001 for diabetes). The magnitudes of the effects of age, sex, obesity, alcohol consumption, and smoking on the development of both cancers were different (Pheterogeneity < 0.05 for each variable). In conclusion, choledocholithiasis, cholelithiasis, HBV, older age, male sex, diabetes, smoking, alcohol drinking, and obesity were found to be potential risk factors of CCA. Liver cirrhosis did not increase the risk of CCA. The magnitudes of the potential effects of common risk factors were generally different between CCA and HCC.

Mechanisms of Racial and Ethnic Differences in Cognitive Aging

Racial and ethnic disparities in age-related cognitive function and dementia risk in the US are well recognized. However, the psychosocial drivers of these disparities and underlying mechanisms are less well studied. This symposium will highlight novel research regarding our current understanding of racial/ethnic differences in brain and cognitive aging and the underlying mechanisms of the disparities. Frist, two papers will describe results regarding racial/ethnic differences in cognitive function and brain aging markers. Few studies have assessed racial/ethnic differences in cognitive function across age groups. Indira Turney will utilize data from a multigenerational study to explore how age impacts racial/ethnic differences in cognitive function. Underlying brain mechanisms of racial/ethnic differences in cognitive outcomes are also not well defined. Sara Godina will present a systematic review of racial/ethnic differences in structural markers of brain aging and neuropathology. Second, three papers will explore how various risk factors may explain the racial/ethnic disparities in cognitive outcomes. Melissa Lamar will demonstrate the differential associations of various blood pressure indicators with cognitive change among black older adults. B. Gwen Windham will present data from two studies that illustrate differential effects of common risk factors by race and region, highlighting inherent difficulties in race-place disparity research. Finally, Laura Zahodne will present results on how psychosocial factors, beyond socioeconomic status, contribute to racial/ethnic disparities in cognitive function. Jen Manly will lead a discussion on the implications of these results for the future of dementia prevention efforts for an increasingly diverse older US population.

Evidence That Environmental and Familial Risks for Psychosis Additively Impact a Multidimensional Subthreshold Psychosis Syndrome.

The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration). Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio. Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other. Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

Causal effects of cardiovascular risk factors on onset of major age-related diseases: A time-to-event Mendelian randomization study

BackgroundsElucidating the causal effects of common intermediate risk factors on the onset of age-related diseases is indispensable for developing prevention and intervention procedures. MethodsWe conducted two-stage time-to-event Mendelian randomization meta-analyses combining five large-scale longitudinal cohorts to investigate dynamic causal effects of cardiovascular disease risk factors including body mass index (BMI), systolic blood pressure (SBP), and lipids on the age-at-onset of age-related diseases. We constructed weighted polygenic scores based on genetic markers from previously reported genome-wide association studies as instrumental variables to estimate the causal effects. To avoid false positive due to potential pleiotropic effects of the genetic markers, we performed a leave-one-out sensitivity analysis and an MR-Egger sensitivity analysis that we expanded in the survival context. ResultsOur results show that elevated BMI increases the absolute risk of type 2 diabetes (T2D) (p=7.68e−04), heart failure (p=9.03e−03), and cardiovascular diseases (CVD) (p=1.69e−03) and the causal effects start at different ages. A significant association between BMI and the risk of stroke is observed; however, the sensitivity analyses suggest that the association is attributed to the potential pleiotropic effects of rs2867125 and rs1558902. Raised SBP levels are significantly associated with the development of atrial fibrillation (p=6.42e−03). Low-density lipoprotein cholesterol (LDL-C) levels are inversely associated with the age-at-onset of T2D (p=1.05e−02). In addition, LDL-C and triglycerides are inversely associated with the risks of cancer and T2D, respectively. Nevertheless, the sensitivity analyses suggest that these associations are probably due to pleiotropic effects of several single-nucleotide polymorphisms including rs4970834 and rs1260326. ConclusionsOur results highlight the involvement of BMI in the development of multiple age-related diseases. Some observed causal associations can attribute to pleiotropic effects of some genetic variations. These findings have important implications in unraveling causal effects of common risk factors on age-related diseases and guiding effective intervention strategies to reduce the incidence of these diseases.

The effects of common risk factors on stock returns: A detrended cross-correlation analysis

In this paper, we investigate the cross-correlations between Fama and French three factors and the return of American industries on the basis of cross-correlation statistic test and multifractal detrended cross-correlation analysis (MF-DCCA). Qualitatively, we find that the return series of Fama and French three factors and American industries were overall significantly cross-correlated based on the analysis of a statistic. Quantitatively, we find that the cross-correlations between three factors and the return of American industries were strongly multifractal, and applying MF-DCCA we also investigate the cross-correlation of industry returns and residuals. We find that there exists multifractality of industry returns and residuals. The result of correlation coefficients we can verify that there exist other factors which influence the industry returns except Fama three factors.

Geographic Variation of the Incidence Rate of Lower Limb Amputation in Australia from 2007-12

In Australia, little is known about how the incidence rate (IR) of lower limb amputation (LLA) varies across the country. While studies in other economically developed countries have shown considerable geographic variation in the IR-LLA, mostly these have not considered whether the effect of common risk factors are the same across regions. Mapping variation of the IR-LLA, and the effect of common risk factors, is an important first step to focus research into areas of greatest need and support the development of regional specific hypotheses for in-depth examination. The aim of this study was to describe the geographic variation in the IR-LLA across Australia and understand whether the effect of common risk factors was the same across regions. Using hospital episode data from the Australian National Hospital Morbidity database and Australian Bureau of Statistics, the all-cause crude and age-standardised IR-LLA in males and females were calculated for the nation and each state and territory. Generalised Linear Models were developed to understand which factors influenced geographic variation in the crude IR-LLA. While the crude and age-standardised IR-LLA in males and females were similar in most states and territories, they were higher in the Northern Territory. The effect of older age, being male and the presence of type 2 diabetes was associated with an increase of IR-LLA in most states and territories. In the Northern Territory, the younger age at amputation confounded the effect of sex and type 2 diabetes. There are likely to be many factors not included in this investigation, such as Indigenous status, that may explain part of the variation in the IR-LLA not captured in our models. Further research is needed to identify regional- and population- specific factors that could be modified to reduce the IR-LLA in all states and territories of Australia.

The Impact of Sleep Disturbance on the Association Between Stressful Life Events and Depressive Symptoms.

Sleep problems are common across the adult life span and may exacerbate depressive symptoms and the effect of common risk factors for depressive symptoms such as life stress. We examine sleep disturbance as a moderator of the association between stressful life events and depressive symptoms across five waves (25 years) of the nationally representative, longitudinal American Changing Lives Study. The sample includes 3,597 adults aged 25 years or older who were surveyed up to five times over 25 years. Multilevel models were run to examine between- and within-person variability in sleep disturbance and life event stress as predictors of depressive symptoms, and an interaction to test sleep disturbance as a moderator is included in a second step. Life events and sleep disturbance were associated with elevated depressive symptoms at the between- and within-person levels. A significant sleep disturbance by interaction of life events was found, indicating that when individuals experienced an above average number of life events and slept more restlessly than usual, they had a higher risk for depressive symptoms than individuals who experienced above average stress but slept well. Sleeping restfully may allow individuals the rejuvenation needed to manage stress adaptively and reduce depressive symptom burden.

Risk factors for non‐melanoma skin cancer in patients with essential thrombocythemia and polycythemia vera

Population-based studies have reported an increased incidence of skin cancer in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We have examined the risk factors for non-melanoma skin cancer (NMSC) in patients diagnosed with ET or PV during 1973-2012. A case-control study was performed to compare the clinical and treatment-related data of 51 ET/PV patients who had NMSC with that of 401 patients who did not. We also evaluated whether polymorphisms in 12 genes involved in DNA integrity predisposed to NMSC. By multivariate logistic regression analysis, risk factors for NMSC were older age (OR: 1.7, 95% CI: 1.3-2.1, P < 0.001), male sex (OR: 2.1, 95% CI: 1.1-3.8, P = 0.023), higher cumulated hydroxycarbamide dose (OR: 1.3, 95% CI: 1.1-1.7, P = 0.017), and busulphan exposure (OR: 3.2, 95% CI: 1.05-10.0, P = 0.041). On the time-to-event prognostic model, factors independently associated with increased cumulative incidence of NMSC were age (5% increased risk per year; P < 0.001), male sex (91% increased risk; P = 0.022), and hydroxycarbamide exposure (22% increased risk; P = 0.065). No susceptibility gene variant was identified. These findings suggest that the risk to develop NMSC in ET/PV patients results from the combined effect of common risk factors (age, male sex) together with cytoreductive treatment.

Sexual Risk Behavior in Young Adulthood: Broadening the Scope Beyond Early Sexual Initiation

A robust link between early sexual initiation and sexual risk-taking behavior is reported in previous studies. The relationship may not be causal, however, as the effect of common risk factors is often not considered. The current study examined whether early initiation was a key predictor of risky sexual behavior in the 20s and 30s, over and above co-occurring individual and environmental factors. Data were drawn from the Seattle Social Development Project, a longitudinal panel of 808 youth. Early predictors (ages 10 to 15) and sexual risk taking (ages 21 to 24 and 30 to 33) were assessed prospectively. Early sexual initiation (before age 15) was entered into a series of probit regressions that also included family, neighborhood, peer, and individual risk factors. Although a positive bivariate relation between early sexual initiation and sexual risk taking was observed at both ages, the link did not persist when co-occurring risk factors were included. Behavioral disinhibition and antisocial peer influences emerged as the strongest predictors of sexual risk over and above early sexual initiation. These results suggest that early sexual initiation must be considered in the context of common antecedents; public health policy aimed at delaying sexual intercourse alone is unlikely to substantially reduce sexual risk behavior in young adulthood.

Mental health service utilization in children adopted from US foster care, US private agencies and foreign countries: Data from the 2007 National Survey of Adoption Parents (NSAP)

Abstract Aims In this analysis, we (1) described the rate of mental health service utilization for children from domestic foster care adoption, domestic private adoption, and international adoption and (2) analyzed the effect of common risk factors on mental health service utilization. Data As part of the 2007 National Survey on Adoptive Parents (NSAP), parents with children 5–17 years old (N = 1722) were asked if their children had received mental health services and how helpful these services were. Parents also provided data on the children's demographics and likelihood of pre-adoption adversity (e.g., abuse). Results For boys, mental health services were utilized by 52.4% of domestic foster care adoptees, 41.0% domestic private adoptees, and 40.0% of international adoptees. For girls, the corresponding rates were 36.3%, 24.8%, and 30.9% respectively. Parents reported that the services were very helpful for about half of the children. Logistic regression analyses showed that adoptees from domestic foster care were more likely than international adoptees to have received mental health services, but there was no difference between domestic private adoptees and international adoptees. Older age at placement, older age at assessment, having special health care needs, and being male all increased the odds for having received mental health services.

Cross-lagged links among gambling, substance use, and delinquency from midadolescence to young adulthood: Additive and moderating effects of common risk factors.

The authors examined cross-lagged links among gambling, substance use, theft, and violence from midadolescence to young adulthood and whether behavioral disinhibition, deviant peers, and parental supervision as common risk factors explain or moderate those links. In 2 community samples, male Caucasians were assessed for gambling participation and problems with the South Oaks Gambling Screen-Revised for Adolescents (K. C. Winters, R. Stinchfield, & J. Fulkerson, 1993) at age 16 years and the South Oaks Gambling Screen (H. R. Lesieur & S. B. Blume, 1987) at age 23. Other problem behaviors were also assessed both times. Risk factors were measured at age 16. Adolescent substance use was related to subsequent theft and violence but not gambling. Gambling problems were linked to subsequent gambling participation. For adolescents with deviant peers, gambling problems were linked to subsequent theft; this was not the case for adolescents without deviant peers. Only for individuals high on disinhibition did stability of gambling problems resemble moderate stabilities of other problem behaviors. Each risk factor was related to each problem behavior (exception: parenting unrelated to gambling). These risk factors partly explained the cross-lagged links among behaviors and thus may be useful targets of prevention. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

Suicidal risk factors and completed suicide: meta-analyses based on psychological autopsy studies

The purpose of the present review is to evaluate the effects of common risk factors for suicide by meta-analyses using data extracted from studies based on the psychological autopsy method. We focused on five common risk factors of suicide: substance-related disorders, mood disorders, adverse marital status, adverse employment status, and self-harm behaviors. A total of 24 articles were identified from MEDLINE in which the crude odds ratio (OR) could be calculated for the above five risk factors through 30 April 2007, using such search keywords as "suicide," "psychological autopsy," and "case-control study." Overall, both substance-related disorders [OR = 5.24; 95% confidence interval (CI) = 3.30-8.31] and mood disorders [OR = 13.42; 95% CI = 8.05-22.37] were strongly associated with suicidal risk. Suicidal attempt and deliberate self-harm, which can directly lead to completed suicide, have been shown to be very strongly associated with suicidal risk [OR = 16.33; 95% CI = 7.51-35.52]. Effects of social factors such as adverse marital and employment status were relatively small. As substance-related disorders and mood disorders were strongly associated with an increased risk of completed suicide, the comorbidity of these two disorders should be paid a maximum attention. The effective prevention of suicide depends on whether we can successfully incorporate these personal factors as well as social factors into an adequate multi-factorial model.

β2-adrenergic receptor and UCP3 variants modulate the relationship between age and type 2 diabetes mellitus

BackgroundIt is widely accepted that Type 2 Diabetes Mellitus (T2DM) and other complex diseases are the product of complex interplay between genetic susceptibility and environmental causes. To cope with such a complexity, all the statistical and conceptual strategies available should be used. The working hypothesis of this study was that two well-known T2DM risk factors could have diverse effect in individuals carrying different genotypes. In particular, our effort was to investigate if a well-defined group of genes, involved in peripheral energy expenditure, could modify the impact of two environmental factors like age and obesity on the risk to develop diabetes. To achieve this aim we exploited a multianalytical approach also using dimensionality reduction strategy and conservative significance correction strategies.MethodsWe collected clinical data and characterised five genetic variants and 2 environmental factors of 342 ambulatory T2DM patients and 305 unrelated non-diabetic controls. To take in account the role of one of the major co-morbidity conditions we stratified the whole sample according to the presence of obesity, over and above the 30 Kg/m2 BMI threshold.ResultsBy monofactorial analyses the ADRB2-27 Glu27 homozygotes had a lower frequency of diabetes when compared with Gln27 carriers (Odds Ratio (OR) 0.56, 95% Confidence Interval (CI) 0.36 – 0.91). This difference was even more marked in the obese subsample.Multifactor Dimensionality Reduction method in the non-obese subsample showed an interaction among age, ADRB2-16 and UCP3 polymorphisms. In individuals that were UCP3 T-carriers and ADRB2-16 Arg-carriers the OR increased from 1 in the youngest to 10.84 (95% CI 4.54–25.85) in the oldest. On the contrary, in the ADRB2-16 GlyGly and UCP3 CC double homozygote subjects, the OR for the disease was 1.10 (95% CI 0.53–2.27) in the youngest and 1.61 (95% CI 0.55–4.71) in the oldest.ConclusionAlthough our results should be confirmed by further studies, our data suggests that, when properly evaluated, it is possible to identify genetic factors that could influence the effect of common risk factors.

Income change at retirement, neighbourhood-based social support, and ischaemic heart disease: Results from the prospective cohort study “Men born in 1914”

Retirement from active life often leads to decreased finances and reduced social contact, which may increase ischaemic heart disease (IHD) risk in individuals. We examined whether income evolution during the decade before retirement has an impact on subsequent IHD, and explored the mediating effect of common risk factors and social support from different sources (marriage/cohabitation, support from friends/relatives, and neighbourhood-based social support). We analyzed data from the 1982–1983 prospective cohort study, “Men born in 1914” ( n=498, follow-up period=10 years) conducted in Malmö, Sweden, merged with yearly income data for 14 years preceding baseline. Low income 10 years before retirement predicted both higher prevalence of IHD risk factors at retirement, and weaker neighbourhood-based social support. Income 10 years before retirement was a strong predictor of IHD incidence and mortality after retirement, but a significant downward income mobility at retirement did not increase IHD risk. After adjustment, low neighbourhood-based social support increased the risk of IHD incidence and mortality, and mediated 7–8% of the income effect. In conclusion, income 10 years before retirement, but not the subsequent income evolution, was a strong predictor of IHD post-retirement. This socioeconomic gradient was partly mediated by the protective effect of neighbourhood-based social support, which may be particularly important among the elderly in compensating for social disruptions related to retirement.