Lifestyle factors and BMI attenuate relationships between biomarkers of inflammation and depressive symptoms and well-being: A cross-sectional study.

Background: Mental disorders are a growing public health concern and evidence has linked chronic low-grade inflammation with depression and well-being. Research also suggests that certain modifiable lifestyle factors such as smoking, alcohol use, physical activity, diet quality and BMI are related to psychological health. These may modulate the relationship between low-grade inflammation and mental health conditions. In this study we examined inflammatory biomarker associations with two psychological health scores and investigated whether relationships are influenced by lifestyle factors and BMI. Methods: This was a cross-sectional study of 1824 middle-to older-aged men and women randomly selected from a large primary care centre. Depressive symptoms and well-being were assessed using the 20-item Centre for Epidemiologic Studies Depression (CES-D) Scale and the World Health Organization-Five (WHO-5) Well-Being Index. Linear regression analyses were performed to examine depression and well-being score relationships with six inflammatory biomarkers, and a composite inflammatory biomarker score, adjusting for demographic characteristics, health conditions, lifestyle factors and BMI. Results: Depression and well-being score associations with complement component 3 (CES-D only) c-reactive protein, interleukin 6, leptin, white blood cell counts, neutrophils and the inflammatory biomarker score were observed. These relationships survived adjustment for demographic variables and health conditions but were attenuated in models which included lifestyle factors and BMI. In final models, only leptin (ß = 0.566, p = 0.018) and inflammatory score (ß = 0.137, p = 0.004) associations with the CES-D score remained. Conclusions: These findings suggest that the relationship between systemic low-grade inflammation and depressive symptoms and well-being may be largely explained by lifestyle factors and adiposity, highlighting the potential importance of promoting a healthy lifestyle in the treatment of depressive disorders.

Relationships between childhood adversity and inflammatory biomarkers in adulthood: A cross-sectional analysis of a middle-to older-aged population.

Background: Exposure to adverse childhood experiences (ACEs) has been linked with increased cardiometabolic risk in adulthood. Low-grade systemic inflammation may underlie this association. Thus far, however, there has been limited investigation of later life inflammatory biomarkers in the context of childhood adversity. Objectives: To assess ACE history, and ACE subcategory, relationships with a broad range of inflammatory biomarkers in middle-to older-aged adults to test the hypothesis that ACE exposure is associated with an unfavourable inflammatory profile in adulthood and determine whether associations vary by ACE subtype and sex. Methods: This study used data from a random sample of 1,839 men and women aged 46-74 years. Participant exposure to ACEs (overall and subtypes including abuse, neglect and household dysfunction) was determined using a validated 10-item ACE questionnaire. Inflammatory biomarkers (pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, white blood cell counts and their constituents, coagulation factors and glycoprotein acetyl) were measured from participant blood samples. Linear regression analyses examined relationships between ACE history (overall and each subcategory) and inflammatory biomarkers in adulthood, controlling for potential confounders. Sex-stratified and mediation analyses were also conducted. Results: In age and sex-adjusted models, ACE history was significantly associated with higher c-reactive protein (p = 0.027), resistin (p = 0.024), white blood cell count (WBC) (p = 0.034), monocyte (p = 0.044), eosinophil (p = 0.031) and plasminogen activator inhibitor-1 (p = 0.047) concentrations, and lower adiponectin (p = 0.025) levels. Results from stratified analyses indicated sex differences and ACE subtype specific associations, with household dysfunction identified as the main driver of positive ACE associations with WBCs and constituents (all p < 0.05). Mediation analyses suggested that BMI and smoking mediate relationships between ACE exposures and increased inflammation. Conclusions: This study provides evidence that ACE exposure may be associated with more pro-inflammatory and pro-thrombotic profiles in adulthood. Associations differed according to ACE subtype, and sex differences exist, which may influence cardiometabolic risk.

Anthropometric measures, predicted visceral adipose tissue and biomarkers of chronic inflammation.

BACKGROUND: Evidence has linked low-grade systemic inflammation and visceral adipose tissue (VAT) with development of chronic conditions. Cytokines and select proteins released by VAT may promote a low-grade inflammatory response. A number of equations have been developed to estimate VAT levels. In this study, we compared predicted VAT equation relationships with biomarkers of inflammation. METHODS: This was a cross-sectional study of 2038 men and women aged 46-73 years. Correlation and linear regression analyses were performed to examine inflammatory biomarker relationships with four commonly assessed anthropometric measures and 10 predicted VAT equations. RESULTS: Compared with anthropometric measures, predicted VAT equations were found to explain a greater proportion of variance in CRP (R2 = .075, p = .001), IL-6 (R2 = .060, p = .001), TNF-α (R2 = .017, p = .005), resistin (R2 = .011, p = .012), monocyte (R2 = .027, p = .001), eosinophil (R2 = .012, p = .01) and basophil (R2 = .015, p = .002) levels in males, and a greater variance in concentrations of C3 (R2 = .175, p = .001), IL-6 (R2 = .090, p = .001), TNF-α (R2 = .036, p = .001), adiponectin (R2 = .121, p = .001), the adiponectin-to-leptin ratio (R2 = .444, p = .001), resistin (R2 = .025, p = .001), white blood cell count (R2 = .057, p = .001), neutrophils (R2 = .061, p = .001) and lymphocytes (R2 = .020, p = .001) in females. CONCLUSION: Equations for assessing VAT levels might be useful to characterise metabolic health. Further studies that examine predicted VAT relationships with disease and mortality outcomes are warranted.

Plant-based dietary indices and biomarkers of chronic low-grade inflammation: a cross-sectional analysis of adults in Ireland.

PURPOSE: There is increasing interest in the health benefits of plant-based diets (PBDs). Evidence reports favourable associations with inflammatory profiles and reduced cardiovascular disease risk. However, limited studies have examined relationships between PBD indices (PDIs) and inflammatory biomarkers. We explored overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with inflammatory biomarker profiles. METHODS: This cross-sectional analysis included 1986 middle- to older-aged adults from the Mitchelstown Cohort. PDI scores were calculated using validated food frequency questionnaires. PDI score associations with inflammatory biomarkers were assessed via linear regression analysis, with adjustment for potential confounders. RESULTS: Comparison of quintiles (Q5 vs Q1) revealed lower concentrations of C-reactive protein (CRP), interleukin 6 (IL-6), white blood cells (WBCs), neutrophils and monocytes, and the leptin-to-adiponectin ratio (PDI and hPDI P < 0.05); lower leptin (PDI, P < 0.05), and complement component 3 (C3), tumour necrosis factor alpha (TNF-α), plasminogen activator inhibitor 1, lymphocytes and eosinophils (hPDI, P < 0.05); and higher concentrations of adiponectin (PDI and hPDI, P < 0.05). Conversely, higher concentrations of C3, CRP, IL-6, TNF-α, resistin, WBCs, neutrophils, lymphocytes, monocytes and eosinophils, and the neutrophil-to-lymphocyte ratio, and lower adiponectin concentrations were observed comparing uPDI quintiles (P < 0.05). In fully adjusted regression models, higher hPDI scores were associated with lower concentrations of C3, TNF-α, WBCs, neutrophils and monocytes (all P < 0.01). Higher uPDI scores were associated with higher C3 and TNF-α concentrations (all P < 0.01). CONCLUSION: This study provides evidence that a more healthful PBD is associated with a more favourable inflammatory profile and that a more unhealthful PBD is associated with the reverse.

Factors associated with public awareness of the relationship between alcohol use and breast cancer risk.

BACKGROUND: Public awareness of the carcinogenic effects of alcohol is low, particularly the association between alcohol use and the risk of developing breast cancer. Breast cancer is the third most common cancer in Ireland and alcohol use remains high. This study examined factors related to awareness of the association between alcohol use and breast cancer risk. METHODS: Using data from Wave 2 of the national Healthy Ireland Survey, a representative sample of 7,498 Irish adults aged 15 + years, descriptive and logistic regression analyses were conducted to investigate relationships between demographic characteristics, type of drinker and awareness of breast cancer risk. RESULTS: A low level of awareness of the risk of alcohol use (drinking more than the recommended low-risk limit) associated with breast cancer was found, with just 21% of respondents correctly identifying the relationship. Multivariable regression analyses found that factors most strongly associated with awareness were sex (female), middle age (45-54 years) and higher educational levels. CONCLUSION: As breast cancer is a prevalent disease among women in Ireland, it is essential that the public, in particular women who drink, are made aware of this association. Public health messages that highlight the health risks associated with alcohol use, and which target individuals with lower educational levels, are warranted.

Associations between the Nutrient Profiling System Underlying the Nutri-Score Nutrition Label and Biomarkers of Chronic Low-Grade Inflammation: A Cross-Sectional Analysis of a Middle- to Older-Aged Population.

Low-grade systemic inflammation is associated with a range of conditions. Diet may modulate inflammation and public health strategies are needed to guide consumers' dietary choices and help prevent diet-related disease. The Food Standards Agency nutrient profiling system (FSAm-NPS) constitutes the basis of the five-colour front-of-pack Nutri-Score labelling system. No study to date has examined FSAm-NPS dietary index associations with biomarkers of inflammation. Therefore, our objective was to test relationships between the FSAm-NPS and a range of inflammatory biomarkers in a cross-sectional sample of 2006 men and women aged 46-73 years. Individual participant FSAm-NPS scores were derived from food frequency questionnaires. Pro-inflammatory cytokine, adipocytokine, acute-phase response protein, coagulation factor and white blood cell count concentrations were determined. Correlation and linear regression analyses were used to examine FSAm-NPS relationships with biomarker levels. In crude and adjusted analyses, higher FSAm-NPS scores, reflecting poorer nutritional quality, were consistently and positively associated with biomarkers. In fully adjusted models, significant associations with concentrations of complement component 3, c-reactive protein, interleukin 6, tumour necrosis factor alpha, resistin, white blood cell count, neutrophils, eosinophils and the neutrophil-to-lymphocyte ratio persisted. These results suggest that dietary quality, determined by Nutri-Score rating, is associated with inflammatory biomarkers related to health.

Dietary score associations with markers of chronic low-grade inflammation: a cross-sectional comparative analysis of a middle- to older-aged population.

PURPOSE: To assess relationships between the Dietary Approaches to Stop Hypertension (DASH), Mediterranean Diet (MD), Dietary Inflammatory Index (DII®) and Energy-adjusted DII (E-DII™) scores and pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. METHODS: This was a cross-sectional study of 1862 men and women aged 46-73 years, randomly selected from a large primary care centre in Ireland. DASH, MD, DII and E-DII scores were derived from validated food frequency questionnaires. Correlation and multivariate-adjusted linear regression analyses with correction for multiple testing were performed to examine dietary score relationships with biomarker concentrations. RESULTS: In fully adjusted models, higher diet quality or a less pro-inflammatory diet was associated with lower concentrations of c-reactive protein, neutrophils (all dietary scores), complement component 3 [C3], interleukin 6 [IL-6], tumour necrosis factor-alpha [TNF-α], white blood cell count [WBC], the neutrophil-to-lymphocyte ratio [NLR] (DASH, DII and E-DII), monocytes (DASH and DII) and resistin (DII and E-DII). After accounting for multiple testing, relationships with C3 (DASH: ß = - 2.079, p = .011 and DII: ß = 2.521, p = .036), IL-6 (DASH: ß = - 0.063, p = .011), TNF-α (DASH: ß = - 0.027, p = .034), WBC (DASH: ß = - 0.028, p = .001 and DII: ß = 0.029, p = .02), neutrophils (DASH: ß = - 0.041, p = .001; DII: ß = 0.043, p = .007; E-DII: ß = 0.029, p = .009) and the NLR (DASH: ß = - 0.035, p = .011) persisted. CONCLUSIONS: Better diet quality, determined by the DASH score, may be more closely associated with inflammatory biomarkers related to health in middle- to older-aged adults than the MD, DII and E-DII scores.

Associations between a protective lifestyle behaviour score and biomarkers of chronic low-grade inflammation: a cross-sectional analysis in middle-to-older aged adults.

BACKGROUND/OBJECTIVES: Certain lifestyle behaviours may have a protective effect against low-grade systemic inflammation, which is linked to chronic disease. Our objective was to examine associations between a five-component protective lifestyle behaviour (PLB) score and a range of pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cells. SUBJECTS/METHODS: This was a cross-sectional study of 2045 middle-to-older aged men and women. Low-risk behaviours included never smoking, moderate alcohol intake, moderate-to-vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5-24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with biomarkers. RESULTS: Analysis of individual low-risk behaviours revealed varied associations depending on the biomarker, with normal BMI showing the most consistent associations. Examination of the PLB score showed that compared to subjects with 4-5 protective behaviours, those with 0-1 protective behaviours had 1.4-3.8 increased odds of having a less favourable inflammatory profile. Following adjustment for BMI, significant trend relationships were observed between the number of protective behaviours and complement component 3 (P < 0.001), c-reactive protein (P < 0.001), interleukin 6 (P < 0.001), tumour necrosis factor alpha (P < 0.001) and white blood cell count (P < 0.001) concentrations. CONCLUSIONS: These results suggest a cumulative protective effect of healthy lifestyle behaviours against systemic inflammation in middle-to-older aged adults which is independent of having a healthy body weight.

Relationships between patterns of cannabis use, abuse and dependence and recent stimulant use: Evidence from two national surveys in Ireland.

BACKGROUND AND OBJECTIVES: Epidemiological studies show that the use of cannabis is related to the use of other illicit drugs, including stimulants such as cocaine and ecstasy. However, few studies have examined how patterns of cannabis use relate to the use of stimulants. In this research we determined relationships between patterns of cannabis use and recent stimulant use, drawing on data from two large nationally representative surveys. We also explored how frequency of cannabis use relates to stimulant use and whether subjects with a cannabis use disorder (CUD)-defined as cannabis abuse or dependence-are more likely to be recent users of cocaine or ecstasy. MATERIALS AND METHODS: We analysed data from Ireland's 2010/11 and 2014/15 National Drug Prevalence Surveys,which recruited 5,134 and 7,005 individuals respectively, aged 15 years and over, living in private households. We included only those people who reported some past cannabis use. Multivariable logistic regression analysis was used to examine associations between patterns of cannabis use and recent stimulant use. RESULTS: Among survey participants who had used cannabis in the last month, 17.9% reported recent cocaine use, while almost one-quarter (23.6%) reported recent ecstasy use. There was a significant linear relationship between patterns of cannabis use and recent use of cocaine, ecstasy or any stimulant, with last month cannabis users displaying greater odds (OR = 12.03, 95% CI: 8.15-17.78) of having recent stimulant use compared to last year (OR = 4.48, 95% CI: 2.91-6.91) and former (reference) cannabis users. Greater frequency of cannabis use in the last 30 days was also significantly related to the use of stimulants. In addition, results demonstrated an association between CUD and recent use of cocaine or ecstasy (OR = 2.28, 95% CI: 1.55-3.35). CONCLUSIONS: Findings from this study suggest a relationship between patterns and frequency of cannabis use and recent use of stimulants and an association between CUD and stimulant use. As the use of cannabis with stimulants may increase the risk of negative health consequences, education in community and medical settings about polydrug use and its increased risks may be warranted.

Relationships between age at first substance use and persistence of cannabis use and cannabis use disorder.

BACKGROUND: From a secondary prevention perspective, it is useful to know who is at greatest risk of progressing from substance initiation to riskier patterns of future use. Therefore, the aim of this study was to determine relationships between age at first use of alcohol, tobacco and cannabis and patterns of cannabis use, frequency of use and whether age of substance use onset is related to having a cannabis use disorder (CUD). METHODS: We analysed data from Ireland's 2010/11 and 2014/15 National Drug Prevalence Surveys, which recruited 5134 and 7005 individuals respectively, aged 15 years and over, living in private households. We included only those people who reported lifetime cannabis use. Multinomial, linear and binary logistic regression analyses were used to determine relationships between age of substance use onset and patterns of cannabis use, frequency of use and having a CUD. RESULTS: When compared to former users, the odds of being a current cannabis user were found to be reduced by 11% (OR = 0.89; 95% CI: 0.83, 0.95) and 4% (OR = 0.96; 95% CI: 0.92, 1.00) for each year of delayed alcohol and cannabis use onset, respectively. Among current users, significant inverse linear relationships were noted, with increasing age of first use of tobacco (ß = - 0.547; P < .001) and cannabis (ß = - 0.634; P < .001) being associated with a decreased frequency of cannabis use within the last 30 days. The odds of having a CUD were found to be reduced by 14% (OR = 0.86; 95% CI: 0.78, 0.94) and 11% (OR = 0.89; 95% CI: 0.82, 0.98) for each year of delayed tobacco and cannabis use onset respectively in analyses which examined survey participants aged 15-34 years. CONCLUSIONS: Among people who report past cannabis use, it is those with a more precocious pattern of early use of substances, including alcohol, and especially tobacco and cannabis, who are more likely to report ongoing, heavy and problematic cannabis use. Secondary prevention initiatives should prioritise people with a pattern of very early onset substance use.

Correlates of patterns of cannabis use, abuse and dependence: evidence from two national surveys in Ireland.

BACKGROUND: Knowledge of factors relating to patterns of cannabis use is important for informing drug policy. This study determined factors associated with recent and current cannabis use. In addition, we explored factors related to having a cannabis use disorder (CUD)-defined using the Diagnostic and Statistical Manual of Psychiatric Disorders-among current users. METHODS: We analyzed data from Ireland's 2010-11 and 2014-15 National Drug Prevalence Surveys, which recruited 5134 and 7005 individuals respectively, aged 15 years or more, living in private households. Multinomial logistic regression was used to identify factors associated with recent (last year) and current (last month) cannabis use compared to experiential use. Binary logistic regression was used to determine factors related to CUD among current users. RESULTS: The weighted prevalence of experiential cannabis use was 18.3%, with 3.0% and 3.3% of participants indicating recent or current use, respectively; 41.3% of current users indicated having a CUD. Factors associated with both recent or current cannabis use included younger age, not being married or cohabiting, having no dependent children and current use of tobacco or alcohol. Male gender, younger age and lower educational levels were significantly related to CUD among current users. CONCLUSIONS: Males, adolescents/young adults and individuals with lower educational levels are more likely to be current users of cannabis and are at a greater risk of having a CUD. Health professionals should be aware of these factors to improve detection and prevention of CUD.

Dietary Quality Determined by the Healthy Eating Index-2015 and Biomarkers of Chronic Low-Grade Inflammation: A Cross-Sectional Analysis in Middle-to-Older Aged Adults.

Low-grade systemic inflammation is associated with a range of chronic diseases. Diet may modulate inflammation and represents a promising therapeutic target to reduce metabolic dysfunction. To date, no study has examined Healthy Eating Index-2015 (HEI-2015) diet score associations with biomarkers of inflammation. Thus, our objective was to assess relationships between the HEI-2015 score and a range of inflammatory biomarkers in a cross-sectional sample of 1989 men and women aged 46-73 years, to test the hypothesis that better dietary quality would be associated with more favourable circulating levels of inflammatory biomarkers. Pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cell counts were determined. Correlation and linear regression analyses were used to test HEI-2015 diet score relationships with biomarker concentrations. Higher dietary quality as determined by the HEI-2015 was associated with lower c-reactive protein (CRP) and interleukin 6 concentrations, white blood cell (WBC) counts and its constituents, adjusting for sex and age. Associations with CRP concentrations and WBC counts persisted in the fully adjusted models. No associations with complement component 3, tumour necrosis factor alpha, adiponectin, leptin, resistin or plasminogen activator inhibitor-1 levels were identified. Our data suggest that dietary quality, determined by the HEI-2015 score, in middle-to-older aged adults is associated with inflammatory biomarkers related to cardiometabolic health.

Protective lifestyle behaviours and lipoprotein particle subclass profiles in a middle-to older-aged population.

BACKGROUND AND AIMS: Lipoprotein particle size is associated with increased atherosclerosis and cardiovascular disease risk. Certain lifestyle behaviours may be cardioprotective. We examined lipoprotein particle size and concentration relationships with a protective lifestyle behaviour (PLB) score. METHODS: This was a cross-sectional analysis of 2045 middle-to older-aged adults. Lipoprotein particle subclass size and concentrations were determined using nuclear magnetic resonance spectroscopy. Five protective behaviours included never smoking, moderate alcohol intake, moderate to vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5-24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with lipoprotein subclasses. RESULTS: Individual behaviour associations varied according to lipoprotein subclass, with normal BMI showing the greatest number of significant relationships. Logistic regression analyses revealed that subjects with the fewest number of protective behaviours had 1.4-2.8 increased odds of having less favourable lipoprotein profiles defined as above or below median level lipoprotein particle subclass size or concentration. Following additional adjustment for BMI, significant trend relationships were observed between the PLB score and large and medium very low-density lipoprotein (p = 0.001 and p < 0.001), total and smaller low-density lipoprotein (LDL) concentrations (p = 0.008 and p < 0.001), LDL size (p = 0.003) and a lipoprotein insulin resistance score (p = 0.003). CONCLUSIONS: Results show a cumulative protective effect of healthy lifestyle behaviours against an unfavourable potentially pro-atherogenic lipoprotein profile in middle-to older-aged adults, highlighting the importance of lifestyle promotion in healthy ageing.