Unhealthy dietary patterns are associated with poorer lung function. It is not known whether this is due to low consumption of antioxidant-rich fruit and vegetables, or is a consequence of higher intakes of harmful dietary constituents such as processed meat.
We examined the individual and combined associations of processed meat, fruit and vegetable consumption and dietary total antioxidant capacity (TAC) with lung function among 1551 men and 1391 women in the Hertfordshire Cohort Study, UK. Diet was assessed by food frequency questionnaire.
After controlling for confounders, processed meat consumption was negatively associated with forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC in men and women, while fruit and vegetable consumption and dietary TAC were positively associated with FEV1 and FVC, but not FEV1/FVC. In men the negative association between processed meat consumption and FEV1 was more marked in those who had low fruit and vegetable consumption (Pinteraction=0.035), and low dietary TAC (Pinteraction=0.025). The deficit in FEV1/FVC associated with processed meat consumption was larger in men who smoked (Pinteraction=0.022).
Higher processed meat consumption is associated with poorer lung function, especially in men who have lower fruit and vegetable consumption or dietary TAC, and among current smokers.
Dietary balance; total antioxidant capacity; fruit and vegetables; processed meat; lung function
We investigated relationships between early growth and proximal femoral geometry at age six years in a prospective population-based cohort, the Southampton Women’s Survey.
In 493 mother-offspring pairs we assessed linear size (individual measure dependent on developmental stage) using high-resolution ultrasound at 11, 19 and 34 weeks gestation (femur length) and at birth, 1, 2, 3, 4 and 6 years (crown-heel length/height). Standard deviation (SD)-scores were created and conditional regression modelling generated mutually independent growth variables. Children underwent hip DXA (Dual X-ray absorptiometry) at 6 years (Hologic Discovery, Hologic Inc., MA); hip structure analysis software yielded measures of geometry and strength.
There were strong associations between early linear growth and femoral neck section modulus (Z) at 6 years, with the strongest relationships observed for femur growth from 19-34 weeks gestation (β=0.26 cm3/SD, p<0.0001), and for height growth from birth to 1 year (β=0.25 cm3/SD, p<0.0001) and 1-2 years (β=0.33 cm3/SD, p<0.0001), with progressively weaker relationships over years 3 (β=0.23 cm3/SD, p=0.0002) and 4 (β=0.10 cm3/SD, p=0.18).
These results demonstrate that growth before age 3 years predicts proximal femoral geometry at six years old. The data suggest critical periods in which there is capacity for long term influence on the later skeletal growth trajectory.
We have demonstrated previously that higher birth weight is associated with greater peak and later-life bone mineral content and that maternal body build, diet, and lifestyle influence prenatal bone mineral accrual. To examine prenatal influences on bone health further, we related ultrasound measures of fetal growth to childhood bone size and density. We derived Z-scores for fetal femur length and abdominal circumference and conditional growth velocity from 19 to 34 weeks’ gestation from ultrasound measurements in participants in the Southampton Women’s Survey. A total of 380 of the offspring underwent dual-energy X-ray absorptiometry (DXA) at age 4 years [whole body minus head bone area (BA), bone mineral content (BMC), areal bone mineral density (aBMD), and estimated volumetric BMD (vBMD)]. Volumetric bone mineral density was estimated using BMC adjusted for BA, height, and weight. A higher velocity of 19- to 34-week fetal femur growth was strongly associated with greater childhood skeletal size (BA: r = 0.30, p < .0001) but not with volumetric density (vBMD: r = 0.03, p = .51). Conversely, a higher velocity of 19- to 34-week fetal abdominal growth was associated with greater childhood volumetric density (vBMD: r = 0.15, p = .004) but not with skeletal size (BA: r = 0.06, p = .21). Both fetal measurements were positively associated with BMC and aBMD, indices influenced by both size and density. The velocity of fetal femur length growth from 19 to 34 weeks’ gestation predicted childhood skeletal size at age 4 years, whereas the velocity of abdominal growth (a measure of liver volume and adiposity) predicted volumetric density. These results suggest a discordance between influences on skeletal size and volumetric density.
EPIDEMIOLOGY; OSTEOPOROSIS; PROGRAMMING; DEVELOPMENTAL ORIGINS
Chronic widespread pain (CWP) is a common disorder affecting ~10% of the general population and has an estimated heritability of 48-52%. In the first large-scale genome-wide association study (GWAS) meta-analysis, we aimed to identify common genetic variants associated with CWP.
We conducted a GWAS meta-analysis in 1,308 female CWP cases and 5,791 controls of European descent, and replicated the effects of the genetic variants with suggestive evidence for association in 1,480 CWP cases and 7,989 controls (P<1×10−5). Subsequently, we studied gene expression levels of the nearest genes in two chronic inflammatory pain mouse models, and examined 92 genetic variants previously described associated with pain.
The minor C-allele of rs13361160 on chromosome 5p15.2, located upstream of CCT5 and downstream of FAM173B, was found to be associated with a 30% higher risk of CWP (MAF=43%; OR=1.30, 95%CI=1.19-1.42, P=1.2×10−8). Combined with the replication, we observed a slightly attenuated OR of 1.17 (95%CI=1.10-1.24, P=4.7×10−7) with moderate heterogeneity (I2=28.4%). However, in a sensitivity analysis that only allowed studies with joint-specific pain, the combined association was genome-wide significant (OR=1.23, 95%CI=1.14-1.32, P=3.4×10−8, I2=0%). Expression levels of Cct5 and Fam173b in mice with inflammatory pain were higher in the lumbar spinal cord, not in the lumbar dorsal root ganglions, compared to mice without pain. None of the 92 genetic variants previously described were significantly associated with pain (P>7.7×10−4).
We identified a common genetic variant on chromosome 5p15.2 associated with joint-specific CWP in humans. This work suggests that CCT5 and FAM173B are promising targets in the regulation of pain.
Gene Polymorphism; Fibromyalgia/Pain Syndromes; Epidemiology
Previous studies suggest a link between depression, anxiety and cardiovascular disease (CVD). The aim of the study was to determine the relationship between depressive and anxiety symptoms and CVD in a population based cohort.
1,578 men and 1,417 women from the Hertfordshire Cohort Study were assessed for CVD at baseline and after 5.9±1.4 years. Depressive and anxiety symptoms were measured using the HADS Scale.
Baseline HAD-D score, but not HAD-A, was significantly associated with baseline plasma triglycerides, glucose and insulin resistance (men only) and HDL cholesterol (women only).
After adjustment for CVD risk factors, higher baseline HAD-D scores were associated with increased odds ratios for CVD (men: 1.162 [95% CI 1.096 - 1.231]; women: 1.107 [1.038 – 1.181]). Higher HAD-A scores associated with increased CVD in men only.
High HAD-D scores predicted incident CVD (adjusted OR 1.130 [1.034 - 1.235]), all-cause mortality (adjusted HR 1.081, [1.012 – 1.154]) and cardiovascular mortality (adjusted HR 1.109 [1.002 - 1.229]) in men but not in women.
The use of a self-report measure of depressive and anxiety symptoms, ‘healthy’ responder bias and the low number of cardiovascular events are all limitations.
Depressive and anxiety symptoms are commoner in people with CVD. These symptoms are independent predictors of CVD in men. Although HAD-D score was significantly associated with several cardiovascular risk factors, this did not fully explain the association between HAD-D and CVD.
Depression; anxiety; cardiovascular disease; epidemiology; population studies
Use of psychotropic drugs has been linked with an increased risk of fracture in older people, but there are indications that the conditions for which these drugs were prescribed may themselves influence fracture risk.
To investigate the relation between symptoms of anxiety and depression and risk of fracture in older people.
Prospective cohort study.
1087 men and 1050 women aged 59-73 years completed the Hospital Anxiety and Depression Scale (HADS). Data on incident fracture during an average follow-up period of 5.6 years was collected through interview and a postal questionnaire.
Compared to men with no or few symptoms of anxiety (score ≤7 on the HADS anxiety subscale), men with probable anxiety (score ≥11) had an increased risk of fracture: after adjustment for age and potential confounding factors, the odds ratio (OR) (95% confidence interval) was 4.03 (1.55, 10.5). Men with possible anxiety (score 8-10) did not have an increased risk of fracture: multivariate-adjusted OR was 1.04 (0.36, 3.03). There were no associations between levels of anxiety and fracture risk in women. Few men or women had probable depression at baseline (score ≥11 on the HADS depression subscale). Among men with possible depression (score 8-10) there was an increased risk of fracture that was of borderline significance: multivariate-adjusted OR 3.57 (0.99, 12.9). There was no association between possible depression and fracture risk in women.
High levels of anxiety in older men may increase their risk of fracture. Future research needs to replicate this finding in other populations and investigate the underlying mechanisms.
anxiety; depression; fracture
Osteoarthritis (OA), the most common form of arthritis, is a major contributor to functional impairment and loss of independence in older persons. The European Project on OSteoArthritis (EPOSA) is a collaborative study involving six European cohort studies on ageing. This project focuses on the personal and societal burden and its determinants of osteoarthritis. This paper describes the design of the project, and presents some descriptive analyses on selected variables across countries.
EPOSA is an observational study including pre-harmonized data from European cohort studies (Germany, Italy, the Netherlands, Spain, Sweden and the United Kingdom) on older community-dwelling persons aged 65 to 85 years. In total, 2942 persons were included in the baseline study with a mean age of 74.2 years (SD 5.1), just over half were women (51,9%). The baseline assessment was conducted by a face-to-face interview followed by a clinical examination. Measures included physical, cognitive, psychological and social functioning, lifestyle behaviour, physical environment, wellbeing and care utilisation. The clinical examination included anthropometry, muscle strength, physical performance and OA exam. A follow-up assessment was performed 12–18 months after baseline.
The EPOSA study is the first population-based study including a clinical examination of OA, using pre-harmonized data across European countries. The EPOSA study provides a unique opportunity to study the determinants and consequences of OA in general populations of older persons, including both care-seeking and non care-seeking persons.
Bone mineral density (BMD) is the most important predictor of fracture risk. We performed the largest meta-analysis to date on lumbar spine and femoral neck BMD, including 17 genome-wide association studies and 32,961 individuals of European and East Asian ancestry. We tested the top-associated BMD markers for replication in 50,933 independent subjects and for risk of low-trauma fracture in 31,016 cases and 102,444 controls. We identified 56 loci (32 novel)associated with BMD atgenome-wide significant level (P<5×10−8). Several of these factors cluster within the RANK-RANKL-OPG, mesenchymal-stem-cell differentiation, endochondral ossification and the Wnt signalling pathways. However, we also discovered loci containing genes not known to play a role in bone biology. Fourteen BMD loci were also associated with fracture risk (P<5×10−4, Bonferroni corrected), of which six reached P<5×10−8 including: 18p11.21 (C18orf19), 7q21.3 (SLC25A13), 11q13.2 (LRP5), 4q22.1 (MEPE), 2p16.2 (SPTBN1) and 10q21.1 (DKK1). These findings shed light on the genetic architecture and pathophysiological mechanisms underlying BMD variation and fracture susceptibility.
Osteoporosis is a major health problem, especially in elderly populations, and is associated with fragility fractures at the hip, spine, and wrist. Hip fracture contributes to both morbidity and mortality in the elderly. The demographics of world populations are set to change, with more elderly living in developing countries, and it has been estimated that by 2050 half of hip fractures will occur in Asia. This review conducted using the PubMed database describes the incidence of hip fracture in different regions of the world and discusses the possible causes of this wide geographic variation. The analysis of data from different studies show a wide geographic variation across the world, with higher hip fracture incidence reported from industrialized countries as compared to developing countries. The highest hip fracture rates are seen in North Europe and the US and lowest in Latin America and Africa. Asian countries such as Kuwait, Iran, China, and Hong Kong show intermediate hip fracture rates. There is also a north–south gradient seen in European studies, and more fractures are seen in the north of the US than in the south. The factors responsible of this variation are population demographics (with more elderly living in countries with higher incidence rates) and the influence of ethnicity, latitude, and environmental factors. The understanding of this changing geographic variation will help policy makers to develop strategies to reduce the burden of hip fractures in developing countries such as India, which will face the brunt of this problem over the coming decades.
Epidemiology; geographic variation; hip fracture; incidence rate; osteoporosis
Common variants at only two loci, FTO and MC4R, have been reproducibly associated with body mass index (BMI) in humans. To identify additional loci, we conducted meta-analysis of 15 genome-wide association studies for BMI (n > 32,000) and followed up top signals in 14 additional cohorts (n > 59,000). We strongly confirm FTO and MC4R and identify six additional loci (P < 5 × 10−8): TMEM18, KCTD15, GNPDA2, SH2B1, MTCH2 and NEGR1 (where a 45-kb deletion polymorphism is a candidate causal variant). Several of the likely causal genes are highly expressed or known to act in the central nervous system (CNS), emphasizing, as in rare monogenic forms of obesity, the role of the CNS in predisposition to obesity.
A number of studies have shown strong graded positive relationships between size at birth and grip strength and estimates of muscle mass in older people. However no studies to date have included direct measures of muscle size.
We studied 313 men and 318 women born in Hertfordshire UK between 1931 and 1939 who were still resident there and had historical records of growth in early life. Information on lifestyle was collected and participants underwent peripheral quantitative computed tomography to directly measure forearm and calf muscle size.
Birth weight was positively related to forearm muscle area in the men (r = 0.24 p < 0.0001) and women (r = 0.17 p =0.003). There were similar but weaker associations between birth weight and calf muscle area in the men (r=0.13, p=0.03) and in the women (r=0.17, p=0.004). These relationships were all attenuated by adjustment for adult size.
We present first evidence that directly measured muscle size in older men and women is associated with size at birth. This may reflect tracking of muscle size and is important because it suggests that benefit may be gained from taking a life course approach both to understanding the aetiology of sarcopenia and to developing effective interventions.
To examine relationships between diet and grip strength in older men and women, and to determine whether these relationships are modified by prenatal growth.
Cross-sectional and retrospective cohort study
Two thousand, nine hundred and eighty three men and women aged 59 to 73 years who were born and still live in Hertfordshire, UK
Weight at birth recorded in Health Visitor ledgers. Current food and nutrient intake assessed using an administered food frequency questionnaire, grip strength was measured with a hand-held dynamometer.
Grip strength was positively associated with height and weight at birth, and inversely related to age (all P<0.001). Of the dietary factors considered in relation to grip strength, the most important was fatty fish consumption. An increase in grip strength of 0.43kg (95% CI 0.13 to 0.74) in men (P=0.005), and 0.48kg (95% CI 0.24 to 0.72) in women (P<0.001), was observed for each additional portion of fatty fish consumed per week. These relationships were independent of adult height, age and birth weight, each of which had additive effects on grip strength. There was no evidence of interactive effects of weight at birth and adult diet on grip strength.
These data suggest that fatty fish consumption can have an important influence on muscle function in older men and women. This raises the possibility that the anti-inflammatory actions of n-3 fatty acids may play a role in the prevention of sarcopenia.
diet; sarcopenia; grip strength
Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data are available relating bone density, lipid profile and anthropometric measures. We addressed these relationships in a large well-characterised cohort of men and women (The Hertfordshire Cohort Study, UK).
Four hundred and sixty five men and 448 women from Hertfordshire, UK were recruited. Information was available on demographic and lifestyle factors, anthropometric measurements, body fat percentage, fasting triglycerides, cholesterol (total, HDL, LDL), apolipoprotein (a) and apolipoprotein (b); bone mineral density (BMD) was recorded at the lumbar spine and total femur.
BMD at the lumbar spine (males r=0.15, p=0.001; females r=0.14 p=0.003) and total femoral region (males r=0.18, p=0.0001; females r==0.16, p=0.0008) was related to serum triglyceride level, even after adjustment for waist hip ratio, age, social class and lifestyle factors, but not if body fat percentage was substituted for waist-hip ratio in the regression model. Fasting HDL cholesterol level was related to lumbar spine BMD in women (r=−0.15, p=0.001) and total femoral BMD (males r=−0.15, p=0.002; females r=−0.23, p<0.0001); these relationships were also attenuated by adjustment for body fat percentage but not waist hip ratio. No relationships were seen between total or LDL cholesterol with BMD.
We have demonstrated relationships between lipid profile and BMD that are robust to adjustment for one measure of central obesity (waist-hip ratio) but not total body fat.
lipid; bone; cohort; anthropometry; obesity
Infant growth is a determinant of adult bone mass, and poor childhood growth is a risk factor for adult hip fracture. Peripheral quantitative computed tomography (pQCT) allows non-invasive assessment of bone strength. We utilised this technology to examine relationships between growth in early life and bone strength.
We studied 313 men and 318 women born in Hertfordshire between 1931-39 who were still resident there in adult life, for whom detailed early life records were available. Lifestyle factors were evaluated by questionnaire, anthropometric measurements made, and peripheral QCT examination of the radius and tibia performed (Stratec 4500).
Birthweight and conditional weight at one year were strongly related to radial and tibial length in both sexes (p<0.001), and to measures of bone strength [fracture load X, fracture load Y, polar strength strain index (SSI)] at both the radius and tibia. These relationships were robust to adjustment for age, body mass index (BMI), social class, cigarette and alcohol consumption, physical activity, dietary calcium intake, HRT use and menopausal status in women. Among men, BMI was strongly positively associated with radial (r=0.46, p=0.001) and tibial (r=0.24, p=0.006) trabecular bone mineral density (BMD). Current smoking was associated with lower cortical (radius: p=0.0002; tibia: p=0.08) and trabecular BMD (radius: p=0.08; tibia: p=0.04) in males. Similar trends of BMD with these anthropometric and lifestyle variables were seen in women but they were non-significant. Current HRT use was associated with greater female cortical (radius: p=0.0002; tibia: p=0.001) and trabecular (radius: p=0.008; tibia: p=0.04) BMD. Current HRT use was also associated with greater radial strength (polar SSI: p=0.006; fracture load x: p=0.005; fracture load y: p=0.02) in women. Women who had sustained any fracture since the age of 45 years had lower radial total (p=0.0001), cortical (p<0.005) and trabecular (p=0.0002) BMD, poorer forearm bone strength [polar SSI (p=0.006), fracture load X & Y (p=0.02)], and lower tibial total (p<0.001), cortical (p=0.008) and trabecular (p=0.0001) BMD.
We have shown that growth in early life is associated with bone size and strength in a UK population aged 65-73 years. Lifestyle factors were associated with volumetric bone density in this population.
Bone; Strength; Density; Programming; Epidemiology
Recent studies have shown that people with poor early growth have an increased risk of sarcopenia. Sarcopenia is an important risk factor for falls but it is not known whether poor early growth is related to falls. We investigated this in the Hertfordshire Cohort Study where 2148 participants completed a falls history. Grip strength was used as a marker of sarcopenia. Birth weight, weight at one year and conditional infant growth were analysed in relation to falls history. The prevalence of any fall in the last year was 14.3% for men and 22.5% for women. Falls in the last year were inversely related to adult grip strength, height and walking speed in men and women as well as to lower conditional infant growth in men (OR 1.27 [95% CI 1.04, 1.56] per SD decrease in conditional infant growth, p=0.02). This association was attenuated after adjustment for grip strength. Our findings support an association between poor early growth and falls in older men which appears to be mediated partly through sarcopenia. The lack of relationship with birth weight suggests that postnatal rather than prenatal influences on muscle growth and development may be important for risk of falls in later life.
Falls accidental; muscle skeletal; muscle development; frail older adults; geriatrics; epidemiology; cohort studies
To assess if a coding variant in the gene encoding transient receptor potential cation channel, subfamily V, member 1 (TRPV1) is associated with genetic risk of painful knee osteoarthritis (OA).
The Ile585Val TRPV1 variant encoded by rs8065080 was genotyped in 3270 cases of symptomatic knee OA, 1098 cases of asymptomatic knee OA and 3852 controls from seven cohorts from the UK, the USA and Australia. The genetic association between the low-pain genotype Ile–Ile and risk of symptomatic and asymptomatic knee OA was assessed.
The TRPV1 585 Ile–Ile genotype, reported to be associated with lower thermal pain sensitivity, was associated with a lower risk of symptomatic knee OA in a comparison of symptomatic cases with healthy controls, with an odds ratio (OR) of 0.75 (95% CI 0.64 to 0.88; p=0.00039 by meta-analysis) after adjustment for age, sex and body mass index. No difference was seen between asymptomatic OA cases and controls (OR=1.02, 95% CI 0.82 to 1.27 p=0.86) but the Ile–Ile genotype was associated with lower risk of symptomatic versus asymptomatic knee OA adjusting for covariates and radiographic severity (OR=0.73, 95% CI 0.57 to 0.94 p=0.0136). TRPV1 expression in articular cartilage was increased by inflammatory cytokines (tumour necrosis factor α and interleukin 1). However, there were no differences in TRPV1 expression in healthy and arthritic synovial tissue.
A genotype involved in lower peripheral pain sensitivity is significantly associated with a decreased risk of painful knee OA. This indicates a role for the pro-nociceptive gene TRPV1 in genetic susceptibility to symptomatic knee OA, which may also be influenced by a role for this molecule in cartilage function.
Previous studies of skeletal remains have suggested that both enthesophytes and osteophytes are manifestations of an underlying bone-forming tendency. A greater prevalence of osteophytes has been observed among individuals with high bone mass (HBM) compared with controls. This study was undertaken to examine the possible interrelationships between bone mass, enthesophytes, and osteophytes in a population of individuals with extreme HBM.
Cases of HBM (defined according to bone mineral density [BMD] Z scores on dual x-ray absorptiometry) from the UK-based HBM study were compared with a control group comprising unaffected family members and general population controls from the Chingford and Hertfordshire cohort studies. Pelvic radiographs from cases and controls were pooled and evaluated, in a blinded manner, by a single observer, who performed semiquantitative grading of the radiographs for the presence and severity of osteophytes and enthesophytes (score range 0–3 for each). Logistic regression analysis was used to identify significant associations, with a priori adjustment for age, sex, and body mass index.
In this study, 226 radiographs from HBM cases and 437 radiographs from control subjects were included. Enthesophytes (grade ≥1) and moderate enthesophytes (grade ≥2) were more prevalent in HBM cases compared with controls (adjusted odds ratio [OR] 3.00 [95% confidence interval (95% CI) 1.96–4.58], P < 0.001 for any enthesophyte; adjusted OR 4.33 [95% CI 2.67–7.02], P < 0.001 for moderate enthesophytes). In the combined population of cases and controls, the enthesophyte grade was positively associated with BMD at both the total hip and lumbar spine (adjusted P for trend < 0.001). In addition, a positive association between osteophytes and enthesophytes was observed; for each unit increase in enthesophyte grade, the odds of any osteophyte being present were increased >2-fold (P < 0.001).
Strong interrelationships were observed between osteophytes, enthesophytes, and HBM, which may be helpful in defining a distinct subset of patients with osteoarthritis characterized by excess bone formation.