Social Vulnerability, Frailty and Self-Perceived Health: Findings from The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Social vulnerability interacts with frailty and influences individuals' health status. Although frailty and social vulnerability are highly predictive of adverse outcomes, their relationship with self-perceived health(SPH) has been less investigated. METHODS: Data are from the Irish Longitudinal Study on Ageing(TILDA), a population-based longitudinal study of ageing. We included 4,222 participants aged ≥50 years (age 61.4±8.5 years;women 56%) from Wave 1 (2009-2011) followed over three longitudinal waves (2012,2014-2015,2016). Participants responded to single questions with five response options to rate their 1)physical health, 2)mental health, and 3)health compared to peers. 30-item Frailty (FI) and Social Vulnerability (SVI) indices were calculated using standardised methods. Multivariable regression analyses were performed to establish the association between FI and SVI cross-sectionally and longitudinally over 6 years. RESULTS: Cross-sectionally, SVI (mean:0.40±0.08; range:0.14-0.81) and FI (mean: 0.13±0.08; range:0.10-0.58) were modestly correlated (r=0.256), and independently associated with poor physical health (SVI: OR 1.43, 95%CI 1.15-1.78; FI: OR 3.16, 95%CI 2.54-3.93), poor mental health (SVI: OR 1.65, 95%CI 1.17-2.35; FI: OR 3.64, 95%CI 2.53-5.24), and poor health compared to peers (SVI: OR 1.41,95%CI 1.06-1.89; FI: OR 3.86, 95%CI 2.9-5.14). Longitudinally, FI and SVI were independently and positively associated with poor physical health (SVI: ß 1.08, 95%CI 0.76-1.39; FI: ß 1.97, 95%CI 1.58-2.36), poor mental health (SVI: ß 1.18, 95%CI 0.86-1.5; FI: ß 1.58, 95%CI 1.2-1.97), and poor overall health compared to peers (SVI: ß 0.78, 95%CI 0.89-1.33; FI: ß 1.74, 95%CI 0.47-1.1). CONCLUSIONS: In a large cohort of community-dwelling older adults, frailty and social vulnerability were associated with poor SPH and with risk of SPH decline over six years.

Validation of the 8-item Centre for Epidemiological Studies Depression Scale in a cohort of community-dwelling older people: data from The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: The aim of this study was to validate the 8-item Centre for Epidemiological Studies Depression Scale (CES-D-8) against the 20-item version (CES-D-20) in a large sample of community-dwelling older people. METHODS: Scales were compared for correlation and internal consistency. The ideal cut-off score for the CES-D-8 was determined by comparing scores ranging from 7 to 12 on the CES-D-8 to CES-D-20. RESULTS: 8033 participants were included. The Spearman co-efficient between the scales was 0.8980 indicating high degree of correlation. At a score of 9/24, the sensitivity and specificity of the CES-D-8 were 98 and 83%, respectively. The Cohen's κ for a score of 9 was 0.7855, indicating strong agreement and the ROC area was 0.88. CONCLUSION: When compared to the CES-D-20, the CES-D-8 is a valid and reliable measure of depressive symptoms in community-dwelling older people, and a score of 9 can be used to identify those with clinically significant symptoms.

Failure to control hypercholesterolaemia in the Irish adult population: cross-sectional analysis of the baseline wave of The Irish Longitudinal Study on Ageing (TILDA).

BACKGROUND: Hypercholesterolaemia is an important modifiable risk factor for cardiovascular disease (CVD) which requires monitoring and management at a population level. AIMS: This study aims to describe the distribution of serum cholesterol in a community living population of older adults in Ireland and to examine the awareness, treatment and control of hypercholesterolaemia according to CVD risk status. METHOD: This is a cross-sectional study in a nationally representative sample of adults aged 50-79 years (n = 5287). Hypercholesterolaemia was defined as low-density lipoprotein cholesterol (LDL-C) in excess of the recommended CVD risk category target and/or on lipid-lowering medication. RESULTS: This study reports a mean total cholesterol (TC) of 5.1 mmol/L (95% CI 5.0-5.1 mmol/L) and a mean LDL-C of 2.9 mmol/L (95% CI 2.8-2.9 mmol/L) in those aged 50-79 years. In a subgroup aged 50-64 years, 73% (95% CI 71.5-74.5%) were hypercholesterolaemic. LDL-C was controlled to the guideline target in 57% of those with CVD and 49% of those with diabetes. Lack of awareness of hypercholesterolaemia was high across the remainder of the population. CONCLUSION: Despite a substantial reduction in population mean TC from a high of 6.0 mmol/L in the 1980s to 5.1 mmol/L, this study reports a failure to control hypercholesterolaemia to recommended risk-stratified targets in the Irish adult population. Recommendations for policy include continued monitoring of those at highest risk and CVD risk assessment in those perceived to be at low risk in order to inform shared decision making in relation to lifestyle modification and medication management.

Non-Dietary Correlates and Determinants of Plasma Lutein and Zeaxanthin Concentrations in the Irish Population.

OBJECTIVE: To investigate non-dietary correlates and determinants of plasma lutein (L) and zeaxanthin (Z) concentrations in The Irish Longitudinal Study on Ageing (TILDA) sample. DESIGN: Cross-sectional study. SETTING: Community dwelling adults in the Republic of Ireland (ROI). PARTICIPANTS: 3,681 participants aged 50 years and older. MEASUREMENTS: TILDA is a nationally representative prospective cohort study of community dwelling adults aged 50 years and over in the ROI. Demographic and health variables were collected during a face-to-face interview carried out in the home (n=8175), and a substantial proportion of these (n=5035; 62%) also attended a study visit in a health assessment centre. Blood samples collected at baseline (wave 1, the subject of the current study), were analysed for plasma concentrations of L and Z by reversed-phase high performance liquid chromatography, and macular pigment (MP) optical density was also measured (using customized heterochromatic flicker photometry). RESULTS: After excluding participants with eye disease, data from 3,681 participants were available for analysis. For this group of participants, plasma L and Z were inversely and significantly associated with body mass index (BMI), and were positively and significantly associated with MP, total cholesterol, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) (p<0.001, for all). Plasma L and Z were significantly lower in males, current smokers, participants reporting less physical exercise, and participants reporting lower levels of education (p<0.05, for all). Plasma L was significantly higher in participants reporting a family history of age-related macular degeneration (AMD) (p=0.001), and in the group of ≥75 years old (p<0.05). For each of these variables, the significant associations remained after controlling for other potential confounding variables. CONCLUSION: The findings of this large study indicate that plasma concentrations of L and Z were lower in association with indicators of a poor lifestyle (high BMI, tobacco use, and less physical exercise) and in association with lower education, indicating that modifying lifestyle in a positive way is likely to be reflected in higher concentrations of plasma carotenoids, with consequential and putative health benefits.

Polymorphisms in the regulatory region of the porcine MYLPF gene are related to meat quality traits in the Large White breed.

The MYLPF gene encodes fast myosin regulatory light chain, and is a positional and functional candidate gene for meat quality. The aim of this study was to identify associations between SNPs in the promoter region of the porcine MYLPF gene and meat quality traits. A total of 22 SNPs were identified in a population of crossbred animals (n=86) and based on minor allele frequency and proximity to the transcription start site, five SNPs were genotyped in purebred; Large White (n=98), Duroc (n=99) and Pietrain (n=98) pigs. No associations were observed in the Pietrain breed, while the Duroc breed was almost monomorphic for all SNPs. In the Large White breed SNP g-1314A>G and linked SNPS g.-871T>G, g.-566T>C, g.-403C>G were associated with ultimate pH and driploss (P<0.05). This study identified associations between MYLPF and meat quality and highlights the importance of considering the genetic background within gene-assisted selection programmes.

Prevalence and correlates of diagnosed and undiagnosed type 2 diabetes mellitus and pre-diabetes in older adults: Findings from the Irish Longitudinal Study on Ageing (TILDA).

AIMS: The prevalence of type 2 diabetes and pre-diabetes has increased rapidly in recent decades and this trend will continue as the global population ages. This study investigates the prevalence of, and factors associated with, diagnosed and undiagnosed type 2 diabetes mellitus and pre-diabetes in older adults in Ireland. METHODS: Cross-sectional data from 5377 men and women aged 50 and over from Wave 1 of the Irish Longitudinal Study on Ageing (TILDA) was analysed. Diagnosed diabetes was defined using self-reported doctors' diagnosis and medications data. Glycated haemoglobin (HbA1c) analysis was used to identify undiagnosed and pre-diabetes. Age and sex-specific prevalence estimates were generated. Logistic regression was used to investigate the association between diabetes classification and the demographic, health and lifestyle characteristics of the population. RESULTS: The prevalence of diagnosed and undiagnosed type 2 diabetes was 8.6% (95% confidence interval (CI): 7.6-9.5%) and 0.9% (95% CI: 0.6-1.1%) respectively. Diabetes was more prevalent in men than women and increased with age. The prevalence of pre-diabetes was 5.5% (95% CI: 4.8-6.3%) and increased with age. Diabetes and pre-diabetes were independently associated with male sex, central obesity and a history of hypertension, while undiagnosed diabetes was associated with geographic location and medical costs cover. CONCLUSION: Despite high rates of obesity and other undiagnosed health conditions, the prevalence of undiagnosed and pre-diabetes is relatively low in community-dwelling older adults in Ireland. Addressing lifestyle factors in this population may help to further reduce the prevalence of pre-diabetes and improve outcomes for those with a previous diagnosis.

Measuring frailty using self-report and test-based health measures.

BACKGROUND: previously, frailty indices were constructed using mostly subjective health measures. The reporting error in this type of measure can have implications on the robustness of frailty findings. OBJECTIVE: to examine whether frailty assessment differs when we construct frailty indices using solely self-reported or test-based health measures. DESIGN: secondary analysis of data from The Irish LongituDinal study on Ageing (TILDA). SUBJECTS AND METHODS: 4,961 Irish residents (mean age: 61.9 ± 8.4; 54.2% women) over the age of 50 years who underwent a health assessment were included in this analysis. We constructed three frailty indices using 33 self-reported health measures (SRFI), 33 test-based health measures (TBFI) and all 66 measures combined (CFI). The 2-year follow-up outcomes examined were all-cause mortality, disability, hospitalisation and falls. RESULTS: all three indices had a right-skewed distribution, an upper limit to frailty, a non-linear increase with age, and had a dose-response relationship with adverse outcomes. Levels of frailty were lower when self-reported items were used (SRFI: 0.12 ± 0.09; TBFI: 0.17 ± 0.15; CFI: 0.14 ± 0.13). Men had slightly higher frailty index scores than women when test-based measures were used (men: 0.17 ± 0.09; women: 0.16 ± 0.10). CFI had the strongest prediction for risk of adverse outcomes (ROC: 0.64-0.81), and age was not a significant predictor when it was included in the regression model. CONCLUSIONS: except for sex differences, characteristics of frailty are similar regardless of whether self-reported or test-based measures are used exclusively to construct a frailty index. Where available, self-reported and test-based measures should be combined when trying to identify levels of frailty.

Novel variation in the FABP3 promoter and its association with fatness traits in pigs.

This study examines associations between SNPs in the promoter region of the fatty acid binding protein 3 (FABP3) gene and fatness traits in pure bred Large White (n=98), Duroc (n=99) and Pietrain (n=98) populations. In the Large White breed, SNP g.-634 C>A was associated a 27% increase in IMF (%) in the heterozygote (CA) and a 38% increase in the homozygote (CC) relative to the (AA) genotype in the M. semimembranosus (SM) muscle (P=0.02). While the associations observed in this breed were suggestive of significance in both the SM and in the M. longissimus thoracis et lumborum (LTL) (P=0.08), these associations no longer attained significance at thresholds adjusted for multiple testing. In conclusion, SNPs in the FABP3 promoter may contribute to IMF without influencing carcass fatness traits in pigs, however further confirmation of these associations in larger independent populations would be essential before their incorporation into breeding programmes.

Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2).

BACKGROUND: Both platelet function and heart disease show strong genetic components, many of which remain to be elucidated. MATERIALS AND METHODS: The roles of candidate polymorphisms in ten platelet-associated genes were compared between 1,237 Acute Coronary Syndrome (ACS) cases (with myocardial infarction and unstable angina) and 386 controls, from an Irish Caucasian population. Additionally, 361 stable angina patients were investigated. Two genes of interest were followed up in a separate Irish study of 1,484 individuals (577 with IHD and 907 unaffected). RESULTS: The GALNT4 (N-acetyl galactosaminyl transferase 4) 506I allele was significantly underrepresented in ACS (OR = 0.66, CI = 0.52-0.84; P = 0.001; P = 0.01 after correction for multiple testing), while the SULT1A1 (Sulphotransferase 1A1) 213H allele was associated with risk of ACS (OR = 1.37, CI = 1.08-1.74; P = 0.01; P = 0.1 after correction for multiple testing). Subsequent genotyping of further SNPs in GALNT4 in the family-based (IHD) group revealed that the 506I allele showed the same trend towards protecting against ACS but the haplotypic test over the four commonest haplotypes was not significant (P = 0.55). In contrast, the SULT1A1/SULT1A2 gene complex showed suggestive haplotypic association in the family-based study (P = 0.07), with the greatest increase in risk conferred by the SULT1A2 235T allele (P = 0.025). CONCLUSION: We have identified two risk genes for cardiovascular disease, one of whose (GALNT4) effects may be on either platelet or endothelial function through modifications of PSGL1 or other important glycosylated proteins. The role of sulphotransferases (SULT1A1/2) in cardiovascular disease requires further exploration. Further validation of cardiovascular risks conferred by both genes in other populations (including gene copy number variation) is warranted.

The impact on coronary artery disease of common polymorphisms known to modulate responses to pathogens.

There are two distinct models to explain how genetic variants contributing to cardiovascular disease may have arisen. Firstly, variants may result from random, initially neutral, mutations whose effects are largely revealed in post-reproductive individuals in industrialized societies. Alternatively, the introduced variants may confer an adaptive advantage in certain circumstances. Resistance to pathogens is one of the strongest selection pressures on human proteins. To determine whether this evolutionary pressure has made a large contribution to heart disease we tested whether seventeen polymorphisms in fourteen innate-immunity genes, with documented evidence of modulating response to pathogens, had an impact on heart disease. Genotyping was performed in 1,598 CAD subjects (ACS or stable angina) and 332 controls. The TLR4 399Ile allele had the greatest impact on ACS risk (uncorrected p = 0.006); however there was no evidence overall that the resistance alleles cumulatively influenced the risk of ACS compared to controls or stable angina patients (p = 0.12, and p = 0.40, respectively). We did note a significant interaction between age at onset of disease and combined resistance allele carriership when the ACS and non-thrombotic, stable angina groups were compared (p = 0.04, 16 d.f.). This suggests that innate immunity factors could have a greater impact on thrombus formation among younger CAD patients.