Substantial advances have been made in identifying common genetic variants influencing cardiometabolic traits and disease outcomes through genome wide association studies. Nevertheless, gaps in knowledge remain and new questions have arisen regarding the population relevance, mechanisms, and applications for healthcare. Using a new high-resolution custom single nucleotide polymorphism (SNP) array (Metabochip) incorporating dense coverage of genomic regions linked to cardiometabolic disease, the University College-London School-Edinburgh-Bristol (UCLEB) consortium of highly-phenotyped population-based prospective studies, aims to: (1) fine map functionally relevant SNPs; (2) precisely estimate individual absolute and population attributable risks based on individual SNPs and their combination; (3) investigate mechanisms leading to altered risk factor profiles and CVD events; and (4) use Mendelian randomisation to undertake studies of the causal role in CVD of a range of cardiovascular biomarkers to inform public health policy and help develop new preventative therapies.
Common etiology of vascular diseases and later-life depression may provide important synergies for prevention. We examined whether standard clinical risk profiles developed for vascular diseases also predict depressive symptoms in older adults.
Data were drawn from the Whitehall II cohort study with baseline examination in 1991/93, follow-up screenings in 1997/99, 2003/04 and 2008/09, and additional disease ascertainment from hospital data and registry linkage, on 5318 participants (mean age 54.8 years, 31% women) without depressive symptoms at baseline. Vascular risk was assessed with the Framingham Cardiovascular, Coronary Heart Disease and Stroke Risk Scores. New depressive symptoms at each follow-up screening were identified by General Health Questionnaire caseness, a Center for Epidemiologic Studies Depression Scale (CES-D) score ≥ 16, and use of antidepressant medication.
Diagnosed vascular disease (that is, coronary heart disease or stroke) was associated with an increased risk for depressive symptoms, age- and sex-adjusted odds ratios from 1.5 (95% confidence interval 1.0–2.2) to 2.0 (1.4–3.0) depending on the indicator of depressive symptoms. Among participants without manifest vascular disease at baseline, the Stroke Risk Score was associated with CES-D depressive symptoms before age 65 [age- and sex-adjusted odds ratio per 10% absolute change in the score =3.1 (1.5–6.5)], but none of the risk scores predicted new-onset depressive symptoms in those aged ≥ 65 (odds ratios from 0.8 to 1.2).
These data suggest that public health measures to improve vascular risk status will influence the incidence of later-life depressive symptoms via reduced rates of manifest vascular disease.
Depressive symptoms; vascular depression; late-onset depression; cardiovascular risk factors; risk prediction; aging
Meta-analysis of case-control genome wide association studies (GWAS) for early onset and morbid obesity identified four variants in/near the PRL, PTER, MAF and NPC1 genes.
We aimed to validate association of these variants with obesity-related traits in population-based samples.
Genotypes and anthropometric traits were available in up to 31 083 adults from the Fenland, EPIC-Norfolk, Whitehall II, Ely and Hertfordshire studies and in 2 042 children and adolescents from the European Youth Heart Study. In each study, we tested associations of rs4712652 (near-PRL), rs10508503 (near-PTER), rs1424233 (near-MAF) and rs1805081 (NPC1), or proxy variants (r2>0.8), with the odds of being overweight and obese, as well as with BMI, percentage body fat (%BF) and waist circumference (WC). Associations were adjusted for sex, age and age2 in adults and for sex, age, age-group, country and maturity in children and adolescents. Summary statistics were combined using fixed effects meta-analysis methods.
We had 80% power to detect ORs of 1.046 to 1.092 for overweight and 1.067 to 1.136 for obesity. Variants near PRL, PTER and MAF were not associated with the odds of being overweight or obese, or with BMI, %BF or WC after meta-analysis (P > 0.15). The NPC1 variant rs1805081 showed some evidence of association with %BF (beta=0.013 SD/allele, P =0.040), but not with any of the remaining obesity-related traits (P >0.3).
Overall, these variants, which were identified in a GWAS for early onset and morbid obesity, do not seem to influence obesity-related traits in the general population.
Obesity-susceptibility loci; genome-wide association; morbid; early-onset; anthropometric traits; children and adolescents; population-based
The glucokinase regulatory protein encoded by GCKR plays an important role in glucose metabolism and a single nucleotide polymorphism (SNP) rs1260326 (P446L) in the gene has been associated with several age-related biomarkers, including triglycerides, glucose, insulin and apolipoproteins. However, associations between SNPs in the gene and other ageing phenotypes such as cognitive and physical capability have not been reported.
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women from five UK cohorts aged between 44 and 90+ years were genotyped for rs1260326. Meta-analysis was used to pool within-study genotypic associations between the SNP and several age-related phenotypes, including body mass index (BMI), blood lipid levels, lung function, and cognitive and physical capability.
We confirm the associations between the minor allele of the SNP and higher triglycerides and lower glucose levels. We also observed a triglyceride-independent association between the minor allele and lower BMI (pooled beta on z-score = −0.04, p-value = 0.0001, n = 16,251). Furthermore, there was some evidence for gene-environment interactions, including physical activity attenuating the effects on triglycerides. However, no associations were observed with measures of cognitive and physical capability.
Findings from middle-aged to older adults confirm associations between rs1260326 GCKR and triglycerides and glucose, suggest possible gene-environment interactions, but do not provide evidence that its relevance extends to cognitive and physical capability.
Although research productivity in the field of frailty has risen exponentially in recent years, there remains a lack of consensus regarding the measurement of this syndrome. This overview offers three services: first, we provide a comprehensive catalogue of current frailty measures; second, we evaluate their reliability and validity; third, we report on their popularity of use.
In order to identify relevant publications, we searched MEDLINE (from its inception in 1948 to May 2011); scrutinized the reference sections of the retrieved articles; and consulted our own files. An indicator of the frequency of use of each frailty instrument was based on the number of times it had been utilized by investigators other than the originators.
Of the initially retrieved 2,166 papers, 27 original articles described separate frailty scales. The number (range: 1 to 38) and type of items (range of domains: physical functioning, disability, disease, sensory impairment, cognition, nutrition, mood, and social support) included in the frailty instruments varied widely. Reliability and validity had been examined in only 26% (7/27) of the instruments. The predictive validity of these scales for mortality varied: for instance, hazard ratios/odds ratios (95% confidence interval) for mortality risk for frail relative to non-frail people ranged from 1.21 (0.78; 1.87) to 6.03 (3.00; 12.08) for the Phenotype of Frailty and 1.57 (1.41; 1.74) to 10.53 (7.06; 15.70) for the Frailty Index. Among the 150 papers which we found to have used at least one of the 27 frailty instruments, 69% (n = 104) reported on the Phenotype of Frailty, 12% (n = 18) on the Frailty Index, and 19% (n = 28) on one of the remaining 25 instruments.
Although there are numerous frailty scales currently in use, reliability and validity have rarely been examined. The most evaluated and frequently used measure is the Phenotype of Frailty.
Frailty; Frail elderly; Measure; Overview; Reliability; Validity
Smoking is a possible risk factor for dementia although its impact may have been underestimated in elderly populations due to the shorter lifespan of smokers.
To examine the association between smoking history and cognitive decline in the transition from midlife to old age.
Design, Setting, and Participants
Data are from 5099 men and 2137 women in the Whitehall II study, mean age 56 years (range=44–69 years) at the first cognitive assessment (1997–1999), repeated over 2002–2004 and 2007–2009.
Main Outcome Measures
The cognitive test battery was composed of tests of memory, vocabulary, executive function (composed of one reasoning and two fluency tests), and a global cognitive score summarising performance across all five tests. Smoking status was assessed over the entire study period. Linear mixed models were used to assess the association between smoking history and 10-year cognitive decline, expressed as z-scores.
In men, 10-year cognitive decline in all tests except vocabulary among never smokers ranged from a quarter to a third of the baseline standard deviation. Faster cognitive decline was observed among current smokers compared to never smokers in men [mean difference in 10-year decline in global cognition=−0.09 (95%CI:−0.15;−0.03) and executive function=−0.11 (−0.17;−0.05)]. Recent ex-smokers had greater decline in executive function (−0.08 (−0.14;−0.02)) while the decline in long-term ex-smokers was similar to that among never smokers. In analyses that additionally took drop-out and death into account, these differences were 1.2 to 1.5 times larger. In women, cognitive decline did not vary as a function of smoking status.
Compared to never smokers, middle-aged male smokers experienced faster cognitive decline in global cognition and executive function. In ex-smokers with at least 10-year cessation there were no adverse effects on cognitive decline.
Adult; Aged; Cognition Disorders; etiology; physiopathology; Cohort Studies; Female; Great Britain; Humans; Male; Middle Aged; Neuropsychological Tests; Smoking; adverse effects; Time Factors
Epidemiological studies have repeatedly investigated the association between depression and metabolic syndrome (MetS). However, the results have been inconsistent. This meta-analysis aimed to summarize the current evidence from cross-sectional and prospective cohort studies that evaluated this association.
RESEARCH DESIGN AND METHODS
MEDLINE, EMBASE, and PsycINFO databases were searched for articles published up to January 2012. Cross-sectional and cohort studies that reported an association between the two conditions in adults were included. Data on prevalence, incidence, unadjusted or adjusted odds ratio (OR), and 95% CI were extracted or provided by the authors. The pooled OR was calculated separately for cross-sectional and cohort studies using random-effects models. The I2 statistic was used to assess heterogeneity.
The search yielded 29 cross-sectional studies (n = 155,333): 27 studies reported unadjusted OR with a pooled estimate of 1.42 (95% CI 1.28–1.57; I2 = 55.1%); 11 studies reported adjusted OR with depression as the outcome (1.27 [1.07–1.57]; I2 = 60.9%), and 12 studies reported adjusted OR with MetS as the outcome (1.34 [1.18–1.51]; I2 = 0%). Eleven cohort studies were found (2 studies reported both directions): 9 studies (n = 26,936 with 2,316 new-onset depression case subjects) reported adjusted OR with depression as the outcome (1.49 [1.19–1.87]; I2 = 56.8%), 4 studies (n = 3,834 with 350 MetS case subjects) reported adjusted OR with MetS as the outcome (1.52 [1.20–1.91]; I2 = 0%).
Our results indicate a bidirectional association between depression and MetS. These results support early detection and management of depression among patients with MetS and vice versa.
The impact of diet on specific age-related diseases has been studied extensively, but few investigations have adopted a more holistic approach to determine the association of diet with overall health at older ages. We examined whether diet, assessed in midlife, using dietary patterns and adherence to the Alternative Healthy Eating Index (AHEI), is associated with aging phenotypes, identified after a mean 16-year follow-up.
Data were drawn from the Whitehall II cohort study of 5350 adults (age 51.3 ± 5.3 years, 29.4% women). Diet was assessed at baseline (1991-1993). Mortality, chronic diseases, and functioning were ascertained from hospital data, register linkage, and screenings every 5 years and were used to create 5 outcomes at follow-up: ideal aging (free of chronic conditions and high performance in physical, mental, and cognitive functioning tests; 4%), nonfatal cardiovascular event (7.3%), cardiovascular death (2.8%), noncardiovascular death (12.7%), and normal aging (73.2%).
Low adherence to the AHEI was associated with an increased risk of cardiovascular and noncardiovascular death. In addition, participants with a “Western-type” diet (characterized by high intakes of fried and sweet food, processed food and red meat, refined grains, and high-fat dairy products) had lower odds of ideal aging (odds ratio for top vs bottom tertile: 0.58; 95% confidence interval, 0.36-0.94; P = .02), independently of other health behaviors.
By considering healthy aging as a composite of cardiovascular, metabolic, musculoskeletal, respiratory, mental, and cognitive function, the present study offers a new perspective on the impact of diet on aging phenotypes.
Aging; Cognitive functioning; Dietary patterns; Diet quality indices; Mortality; Nutritional epidemiology; Overall diet; Physical functioning
Although it has been hypothesized that the depression-obesity relation is bidirectional, few studies have addressed this hypothesis in a prospective setting. We aimed to examine the bidirectional relationship in middle-aged and elderly women.
A total of 65,955 women aged 54–79 years in the Nurses’ Health Study were prospective followed from 1996 to 2006 with updated information on body weight, depression status and various covariates every two years. Depression was defined as self-report of physician-diagnosed depression and/or antidepressant use. Obesity was defined as a body mass index ≥30.0 kg/m2. The first three waves (1996–2000) were used as the baseline period, and the last three waves (2002–2006) were used as the follow-up period.
After adjusting for baseline age, physical activity, comorbidities, body mass index (BMI) and other covariates, depression at the baseline period was associated with an increased risk of obesity at the follow-up period in all women (multivariate-adjusted odds ratio [OR], 1.38; 95% CI, 1.24–1.53) and baseline non-obese women (OR, 1.51; 95% CI, 1.36–1.67). In the opposite direction, after adjusting for baseline age, physical activity, comorbidities, depression status and other covariates, obese women at baseline had a moderately increased risk of depression at the follow-up period compared with normal weight women (OR, 1.11; 95% CI, 1.03–1.18); and this association was similar for new onset of depression (OR for obese vs. normal weight women, 1.10; 95% CI, 1.02–1.20).
Our results suggest a bidirectional association between depression and obesity in middle-aged and elderly women. Future studies are needed to confirm our findings in different populations, and investigate the potential mechanisms underlying this association. Our results underscore the importance of early detection and proper behavioral modifications to lower the burden of both conditions.
obesity; depression; prospective cohort study
Several investigations have observed positive associations between good nutritional status, as indicated by micronutrients, and cognitive measures; however, these associations may not be causal. Genetic polymorphisms that affect nutritional biomarkers may be useful for providing evidence for associations between micronutrients and cognitive measures. As part of the Healthy Ageing across the Life Course (HALCyon) program, men and women aged between 44 and 90 y from 6 UK cohorts were genotyped for polymorphisms associated with circulating concentrations of iron [rs4820268 transmembrane protease, serine 6 (TMPRSS6) and rs1800562 hemochromatosis (HFE)], vitamin B-12 [(rs492602 fucosyltransferase 2 (FUT2)], vitamin D ([rs2282679 group-specific component (GC)] and β-carotene ([rs6564851 beta-carotene 15,15'-monooxygenase 1 (BCMO1)]. Meta-analysis was used to pool within-study effects of the associations between these polymorphisms and the following measures of cognitive capability: word recall, phonemic fluency, semantic fluency, and search speed. Among the several statistical tests conducted, we found little evidence for associations. We found the minor allele of rs1800562 was associated with poorer word recall scores [pooled β on Z-score for carriers vs. noncarriers: −0.05 (95% CI: −0.09, −0.004); P = 0.03, n = 14,105] and poorer word recall scores for the vitamin D–raising allele of rs2282679 [pooled β per T allele: −0.03 (95% CI: −0.05, −0.003); P = 0.03, n = 16,527]. However, there was no evidence for other associations. Our findings provide little evidence to support associations between these genotypes and cognitive capability in older adults. Further investigations are required to elucidate whether the previous positive associations from observational studies between circulating measures of these micronutrients and cognitive performance are due to confounding and reverse causality.
There is some evidence to suggest that obesity is a risk factor for the development of depression, although this is not a universal finding. This discordance might be ascribed to the existence of a ‘healthy obese phenotype’– that is, obesity in the absence of the associated burden of cardio-metabolic risk factors. We examined whether the association of obesity with depressive symptoms is dependent on the individual’s metabolic health. Participants were 3851 men and women (aged 63.0 ± 8.9 yrs, 45.1% men) from the English Longitudinal Study of Ageing, a prospective study of community dwelling older adults. Obesity was defined as body mass index ≥ 30 kg/m2. Based on blood pressure, HDL-cholesterol, triglycerides, glycated haemoglobin, and C-reactive protein, participants were classified as ‘metabolically healthy’ (0 or 1 metabolic abnormality) or ‘unhealthy’ (≥ 2 metabolic abnormalities). Depressive symptoms were assessed at baseline and at 2 years follow up using the 8-item Centre of Epidemiological Studies Depression (CES-D) scale. Obesity prevalence was 27.5%, but 34.3% of this group was categorized as metabolically healthy at baseline. Relative to non-obese healthy participants, after adjustment for baseline CES-D score and other covariates, the metabolically unhealthy obese participants had elevated risk of depressive symptoms at follow-up (odds ratio [OR] = 1.50, 95% CI, 1.05–2.15), although the metabolically healthy obese did not (OR = 1.38, 95% CI, 0.88–2.17). The association between obesity and risk of depressive symptoms appears to be partly dependent on metabolic health, although further work is required to confirm these findings.
Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized.
Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA).
rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08–0.18 mm, P = 8.2 × 10−8). A proxy SNP (rs4916251, R2 = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case–control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03–1.17, p = 2.8 × 10−3, I2 = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling.
Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development.
► In the IMPROVE study (n > 3000) variants at 1q24.3 were strongly associated with larger carotid diameters. ► The lead variant was associated with Abdominal Aortic Aneurysm (AAA) in meta-analysis of 5 studies (n > 50,000). ► Variants at 1q24.3 appear to be associated with vascular remodelling and risk of AAA.
Abdominal aortic aneurysm; Genome-wide association studies; Vascular remodelling; Carotid artery
Background: It has been suggested that dietary patterns are associated with future risk of depressive symptoms. However, there is a paucity of prospective data that have examined the temporality of this relation.
Objective: We examined whether adherence to a healthy diet, as defined by using the Alternative Healthy Eating Index (AHEI), was prospectively associated with depressive symptoms assessed over a 5-y period.
Design: Analyses were based on 4215 participants in the Whitehall II Study. AHEI scores were computed in 1991–1993 and 2003–2004. Recurrent depressive symptoms were defined as having a Center for Epidemiologic Studies Depression Scale score ≥16 or self-reported use of antidepressants in 2003–2004 and 2008–2009.
Results: After adjustment for potential confounders, the AHEI score was inversely associated with recurrent depressive symptoms in a dose-response fashion in women (P-trend < 0.001; for 1 SD in AHEI score; OR: 0.59; 95% CI: 0.47, 0.75) but not in men. Women who maintained high AHEI scores or improved their scores during the 10-y measurement period had 65% (OR: 0.35%; 95% CI: 0.19%, 0.64%) and 68% (OR: 0.32%; 95% CI: 0.13%, 0.78%) lower odds of subsequent recurrent depressive symptoms than did women who maintained low AHEI scores. Among AHEI components, vegetable, fruit, trans fat, and the ratio of polyunsaturated fat to saturated fat components were associated with recurrent depressive symptoms in women.
Conclusion: In the current study, there was a suggestion that poor diet is a risk factor for future depression in women.
The association between functioning of the hypothalamic pituitary adrenal (HPA) axis and physical performance at older ages remains poorly understood. We carried out meta-analyses to test the hypothesis that dysregulation of the HPA axis, as indexed by patterns of diurnal cortisol release, is associated with worse physical performance. Data from six adult cohorts (ages 50–92 years) were included in a two stage meta-analysis of individual participant data. We analysed each study separately using linear and logistic regression models and then used meta-analytic methods to pool the results. Physical performance outcome measures were walking speed, balance time, chair rise time and grip strength. Exposure measures were morning (serum and salivary) and evening (salivary) cortisol. Total sample sizes in meta-analyses ranged from n = 2146 for associations between morning Cortisol Awakening Response and balance to n = 8448 for associations between morning cortisol and walking speed. A larger diurnal drop was associated with faster walking speed (standardised coefficient per SD increase 0.052, 95% confidence interval (CI) 0.029, 0.076, p < 0.001; age and gender adjusted) and a quicker chair rise time (standardised coefficient per SD increase −0.075, 95% CI −0.116, −0.034, p < 0.001; age and gender adjusted). There was little evidence of associations with balance or grip strength. Greater diurnal decline of the HPA axis is associated with better physical performance in later life. This may reflect a causal effect of the HPA axis on performance or that other ageing-related factors are associated with both reduced HPA reactivity and performance.
HPA axis; Physical capability; Healthy ageing
Increases in life expectancy make it important to remain healthy for as long as possible. Our objective was to examine the extent to which healthy behaviours in midlife, separately and in combination, predict successful aging.
We used a prospective cohort design involving 5100 men and women aged 42–63 years. Participants were free of cancer, coronary artery disease and stroke when their health behaviours were assessed in 1991–1994 as part of the Whitehall II study. We defined healthy behaviours as never smoking, moderate alcohol consumption, physical activity (≥ 2.5 h/wk moderate physical activity or ≥ 1 h/wk vigorous physical activity), and eating fruits and vegetables daily. We defined successful aging, measured over a median 16.3-year follow-up, as good cognitive, physical, respiratory and cardiovascular functioning, in addition to the absence of disability, mental health problems and chronic disease (coronary artery disease, stroke, cancer and diabetes).
At the end of follow-up, 549 participants had died and 953 qualified as aging successfully. Compared with participants who engaged in no healthy behaviours, participants engaging in all 4 healthy behaviours had 3.3 times greater odds of successful aging (95% confidence interval [CI] 2.1–5.1). The association with successful aging was linear, with the odds ratio (OR) per increment of healthy behaviour being 1.3 (95% CI 1.2–1.4; population-attributable risk for 1–4 v. 0 healthy behaviours 47%). When missing data were considered in the analysis, the results were similar to those of our main analysis.
Although individual healthy behaviours are moderately associated with successful aging, their combined impact is substantial. We did not investigate the mechanisms underlying these associations, but we saw clear evidence of the importance of healthy behaviours for successful aging.
The goal of cardiovascular disease (CVD) research using linked bespoke studies and electronic health records (CALIBER) is to provide evidence to inform health care and public health policy for CVDs across different stages of translation, from discovery, through evaluation in trials to implementation, where linkages to electronic health records provide new scientific opportunities. The initial approach of the CALIBER programme is characterized as follows: (i) Linkages of multiple electronic heath record sources: examples include linkages between the longitudinal primary care data from the Clinical Practice Research Datalink, the national registry of acute coronary syndromes (Myocardial Ischaemia National Audit Project), hospitalization and procedure data from Hospital Episode Statistics and cause-specific mortality and social deprivation data from the Office of National Statistics. Current cohort analyses involve a million people in initially healthy populations and disease registries with ∼105 patients. (ii) Linkages of bespoke investigator-led cohort studies (e.g. UK Biobank) to registry data (e.g. Myocardial Ischaemia National Audit Project), providing new means of ascertaining, validating and phenotyping disease. (iii) A common data model in which routine electronic health record data are made research ready, and sharable, by defining and curating with meta-data >300 variables (categorical, continuous, event) on risk factors, CVDs and non-cardiovascular comorbidities. (iv) Transparency: all CALIBER studies have an analytic protocol registered in the public domain, and data are available (safe haven model) for use subject to approvals. For more information, e-mail email@example.com
electronic heath records; linkages; cardiovascular
There are few longitudinal data on physical activity patterns from mid-life into older age. The authors examined associations of self-reported physical activity, adiposity and socio-demographic factors in mid-life with objectively assessed measures of activity in older age.
Participants were 394 healthy men and women drawn from the Whitehall II population-based cohort study. At the baseline assessment in 1997 (mean age 54 years), physical activity was assessed through self-report and quantified as metabolic equivalent of task hours/week. At the follow-up in 2010 (mean age 66 years), physical activity was objectively measured using accelerometers worn during waking hours for seven consecutive days (average daily wear time 891±68 min/day).
Self-reported physical activity at baseline was associated with objectively assessed activity at follow-up in various activity categories, including light-, moderate- and vigorous-intensity activity (all ps<0.04). Participants in the highest compared with lowest quartile of self-reported activity level at baseline recorded on average 64.1 (95% CI 26.2 to 102.1) counts per minute more accelerometer-assessed activity at follow-up and 9.0 (2.0–16.0) min/day more moderate-to-vigorous daily activity, after adjusting for baseline covariates. Lower education, obesity and self-perceived health status were also related to physical activity at follow-up. Only age and education were associated with objectively measured sedentary time at follow-up.
Physical activity behaviour in middle age was associated with objectively measured physical activity in later life after 13 years of follow-up, suggesting that the habits in adulthood are partly tracked into older age.
Actigraph; ageing; education; epidemiology; obesity; physical activity; health behaviour; psychological stress; prevention; coronary heart disease
Negative psychological states such as stress and depression are associated with increased risk of coronary heart disease (CHD), but it is unclear whether some positive states are protective. We investigated satisfaction with specific life domains as predictors of incident CHD.
Methods and results
Coronary risk factors and satisfaction within seven life domains (e.g. job and family) were assessed in 7956 initially healthy members of the Whitehall II cohort. Incident CHD (angina, non-fatal myocardial infarction, or death from CHD) was ascertained from medical screening, hospital data, and registry linkage over five person-years of follow-up. Satisfaction averaged across domains was associated with reduced CHD risk (HR: 0.87; 95% CI: 0.78–0.98), controlling for demographic characteristics, health behaviours, blood pressure, and metabolic functioning. Associations with CHD risk were evident for satisfaction in four life domains—one's job, family, sex life, and self, but not one's love relationship, leisure activities, or standard of living. When examining CHD outcomes separately, average domain satisfaction was associated with angina but not myocardial infarction or coronary death.
Satisfaction in most life domains was associated with reduced CHD risk, with definite angina being mostly responsible for this association. These findings suggest that satisfaction with life may promote heart health. Further research should examine whether interventions to enhance life satisfaction in specific domains reduce CHD risk and whether life satisfaction is primarily associated with atherosclerosis rather than thrombotic factors associated with plaque rupture.
Coronary heart disease; Angina; Life satisfaction; Domain satisfaction; Well-being
A potential role for cardiovascular disease (CVD) risk factors in the aetiology of suicide has not been comprehensively examined. In addition to being small in scale and poorly characterized, existing studies very rarely sample Asian populations in whom risk factor–suicide relationships may plausibly differ to Caucasian groups. We examined the association between a series of CVD risk factors and future mortality from suicide.
Methods and results
The Korean Cancer Prevention Study is a prospective cohort study comprising 1 234 927 individuals (445 022 women) aged 30–95 years with extensive measurement of established CVD risk factors at baseline and subsequent mortality surveillance. Fourteen years of follow-up gave rise to 472 deaths (389 in men and 83 in women) from suicide. After adjustment for a range of covariates, in men, smoking hazard ratio; 95% CI: (current vs. never: 1.69; 1.27, 2.24), alcohol intake (1–24 g/day vs. none: 1.29; 1.00, 1.66), blood cholesterol (≥240 vs. <200 mg/dL: 0.54; 0.36, 0.80), body mass index (underweight vs. normal weight: 2.08; 1.26, 3.45), stature [quartile 1(lowest) vs. 4: 1.68; 1.23, 2.30], socioeconomic status [quartile 1(lowest) vs. 4: 1.65; 1.21, 2.24], and martial status (unmarried vs. other: 1.60; 0.83, 3.06) were related to suicide mortality risk. These associations were generally apparent in women, although of lower magnitude. Exercise and blood pressure were not associated with completed suicide.
In this cohort of Korean men and women, a series of CVD risk factors were associated with an elevated risk of future suicide mortality.
Cardiovascular disease; Risk factors; Epidemiology; Suicide
Little is known about psychological risk factors in cerebrovascular disease. We examined the association between psychological distress and risk of death due to cerebrovascular disease.
We obtained data from 68 652 adult participants of the Health Survey for England (mean age 54.9 [standard deviation 13.9] yr, 45.0% male sex) with no known history of cardiovascular diseases at baseline. We used the 12-item General Health Questionnaire (GHQ-12) to assess the presence of psychological distress. We followed participants for eight years for cause-specific death using linkage to national registers.
There were 2367 deaths due to cardiovascular disease during follow-up. Relative to participants with no symptoms of psychological distress (GHQ-12 score 0) at baseline, people with psychological distress (GHQ-12 score ≥ 4, 14.7% of participants) had an increased risk of death from cerebrovascular disease (adjusted hazard ratio [HR] 1.66, 95% confidence interval [CI] 1.32–2.08) and ischemic heart disease (adjusted HR 1.59, 95% CI 1.34–1.88). There was also evidence of a dose–response effect with increasing GHQ-12 score (p for trend < 0.001 in all analyses). Associations were only marginally attenuated after we adjusted for possible confounders, including socioeconomic status, smoking and use of antihypertensive medications.
Psychological distress was associated with increased risk of death due to cerebrovascular disease in a large population-representative cohort. These data suggest that the cardiovascular effects of psychological distress are not limited to coronary artery disease.
Polymorphisms in several distinct genomic regions, including the F7 gene, were recently associated with factor VII (FVII) levels in European Americans (EAs). The genetic determinants of FVII in African Americans (AAs) are unknown. We used a 50 000 single nucleotide polymorphism (SNP) gene-centric array having dense coverage of over 2 000 candidate genes for cardiovascular disease (CVD) pathways in a community-based sample of 16 324 EA and 3898 AA participants from the Candidate Gene Association Resource (CARe) consortium. Our aim was the discovery of new genomic loci and more detailed characterization of existing loci associated with FVII levels. In EAs, we identified three new loci associated with FVII, of which APOA5 on chromosome 11q23 and HNF4A on chromosome 20q12–13 were replicated in a sample of 4289 participants from the Whitehall II study. We confirmed four previously reported FVII-associated loci (GCKR, MS4A6A, F7 and PROCR) in CARe EA samples. In AAs, the F7 and PROCR regions were significantly associated with FVII. Several of the FVII-associated regions are known to be associated with lipids and other cardiovascular-related traits. At the F7 locus, there was evidence of at least five independently associated SNPs in EAs and three independent signals in AAs. Though the variance in FVII explained by the existing loci is substantial (20% in EA and 10% in AA), larger sample sizes and investigation of lower frequency variants may be required to identify additional FVII-associated loci in EAs and AAs and further clarify the relationship between FVII and other CVD risk factors.
Lung function predicts mortality; whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in 1 s, height FEV1), walking speed (2.44 m), cognitive function (memory and reasoning) and self-reported physical and mental functioning (SF-36) were available on 4,443 individuals, aged 50–74 years. In models adjusted for age, 1 standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta = 0.16, 95% CI: 0.13, 0.19), memory (beta = 0.09, 95% CI: 0.06, 0.12), reasoning (beta = 0.16, 95% CI: 0.13, 0.19) and self-reported physical functioning (beta = 0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), body mass index (BMI) and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good ‘summary’ measure of overall functioning in early old age.
Ageing; Lung function; Cognitive function; Physical function
Lung function predicts mortality, whether it is associated with functional status in the general population remains unclear. This study examined the association of lung function with multiple measures of functioning in early old age. Data are drawn from the Whitehall II study; data on lung function (forced expiratory volume in one second, height FEV1), walking speed (over 2.44 m), cognitive function (memory and reasoning), and self-reported physical and mental functioning (SF-36) were available on 4443 individuals, aged 50–74 years. In models adjusted for age, one standard deviation (SD) higher height-adjusted FEV1 was associated with greater walking speed (beta=0.16, 95% CI: 0.13, 0.19), memory (beta=0.09, 95% CI: 0.06, 0.12), reasoning (beta=0.16, 95% CI: 0.13, 0.19), and self-reported physical functioning (beta=0.13, 95% CI: 0.10, 0.16). Socio-demographic measures, health behaviours (smoking, alcohol, physical activity, fruit/vegetable consumption), BMI and chronic conditions explained two-thirds of the association with walking speed and self-assessed physical functioning and over 80% of the association with cognitive function. Our results suggest that lung function is a good “summary” measure of overall functioning in early old age.
Aged; Aging; physiology; psychology; Cognition; physiology; Female; Health Status; Humans; Lung; physiology; Male; Middle Aged; Spirometry; Walking; physiology; ageing; lung function; cognitive function; physical function
Higher Lp-PLA2 activity is associated with increased risk of coronary heart disease (CHD), making Lp-PLA2 a potential therapeutic target. PLA2G7 variants associated with Lp-PLA2 activity could evaluate whether this relationship is causal.
Methods and Results
A meta-analysis including a total of 12 studies (5 prospective, 4 case-control, 1 case-only and 2 cross-sectional, n=26,118) was undertaken to examine the association of: (i) LpPLA2 activity vs. cardiovascular biomarkers and risk factors and CHD events (two prospective studies; n=4884); ii) PLA2G7 SNPs and Lp-PLA2 activity (3 prospective, 2 case-control, 2 cross-sectional studies; up to n=6094); and iii) PLA2G7 SNPs and angiographic coronary artery disease (2 case-control, 1 case-only study; n=4971 cases) and CHD events (5 prospective, 2 case-control studies; n=5523). Lp-PLA2 activity correlated with several CHD risk markers. Hazard ratio for CHD events top vs. bottom quartile of Lp-PLA2 activity was 1.61 (95%CI: 1.31, 1.99) and 1.17 (95%CI: 0.91, 1.51) after adjustment for baseline traits. Of seven SNPs, rs1051931 (A379V) showed the strongest association with Lp-PLA2 activity, VV subjects having 7.2% higher activity than AAs. Genotype was not associated with risk markers, angiographic coronary disease (OR 1.03 (95%CI 0.80, 1.32), or CHD events (OR 0.98 (95%CI 0.82, 1.17).
Unlike Lp-PLA2 activity, PLA2G7 variants associated with modest effects on Lp-PLA2 activity were not associated with cardiovascular risk markers, coronary atheroma or CHD. Larger association studies, identification of SNPs with larger effects, or randomised trials of specific Lp-PLA2 inhibitors are needed to confirm/refute a contributory role for Lp-PLA2 in CHD.
genetics; epidemiology; risk factors; Mendelian randomization
Several age-related traits are associated with shorter telomeres, the structures that cap the end of linear chromosomes. A common polymorphism near the telomere maintenance gene TERT has been associated with several cancers, but relationships with other ageing traits such as physical capability have not been reported.
As part of the Healthy Ageing across the Life Course (HALCyon) collaborative research programme, men and women aged between 44 and 90 years from 9 UK cohorts were genotyped for the single nucleotide polymorphism (SNP) rs401681. We then investigated relationships between the SNP and 30 age-related phenotypes, including cognitive and physical capability, blood lipid levels and lung function, pooling within-study genotypic effects in meta-analyses.
No significant associations were found between the SNP and any of the cognitive performance tests (e.g. pooled beta per T allele for word recall z-score=0.02, 95% CI: -0.01- 0.04, p-value=0.12, n=18,737), physical performance tests (e.g. pooled beta for grip strength=-0.02, 95% CI:-0.045- 0.006, p-value=0.14, n=11,711), blood pressure, lung function or blood test measures. Similarly, no differences in observations were found when considering follow-up measures of cognitive or physical performance after adjusting for its measure at an earlier assessment.
The lack of associations between SNP rs401681 and a wide range of age-related phenotypes investigated in this large multi-cohort study suggests that whilst this SNP may be associated with cancer, it is not an important contributor to other markers of ageing.
Aging; ageing; middle-aged; telomere; cognition; physical