Morbidities among older workers and work exit: the HEAF cohort.

BACKGROUND: Governments need people to work to older ages, but the prevalence of chronic disease and comorbidity increases with age and impacts work ability. AIMS: To investigate the effects of objective health diagnoses on exit from paid work amongst older workers. METHODS: Health and Employment After Fifty (HEAF) is a population cohort of adults aged 50-64 years recruited from English GP practices which contribute to the Clinical Practice Research Datalink (CPRD). Participants have completed questionnaires about health and work at baseline and annually for 2 years: their responses were linked with their objective health diagnoses from the CPRD and data analysed using Cox regression. RESULTS: Of 4888 HEAF participants ever in paid work, 580 (25%) men and 642 (25%) women exited employment, 277 of them mainly or partly for a health reason (health-related job loss (HRJL)). Amongst HEAF participants who remained in work (n = 3666) or who exited work but not for health reasons (n = 945), there was a similar prevalence of background health conditions. In men and women, HRJL was associated with inflammatory arthritis, sleep disorders, common mental health conditions and musculoskeletal pain. There were however gender differences: widespread pain and lower limb osteoarthritis were associated with HRJL in women but hypertension and cardiovascular disease in men. CONCLUSIONS: Improved diagnosis and management of common conditions might be expected to increase working lives. Workplace well-being interventions targeting obesity and increasing mobility might contribute to extended working lives. Employers of predominantly female, as compared with male workforces may need different strategies to retain older workers.

Relationships between markers of inflammation and bone density: findings from the Hertfordshire Cohort Study.

Among 365 Hertfordshire Cohort Study participants (aged 59-71 years at baseline), higher adiponectin and adiponectin to leptin ratios were associated with lower baseline lumbar spine and femoral neck bone mineral density (BMD). Lower IL-10 was associated with accelerated decline in lumbar spine BMD. This suggests that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis. INTRODUCTION: The aim of this study was to examine the association between indices of inflammation and BMD in a population-based cohort of older adults in the UK. METHODS: Analyses were based on a sample of 194 men and 171 women of the Hertfordshire Cohort Study (community-living, older adults). Dual energy X-ray absorptiometry (DXA) was performed at the lumbar spine and proximal femur at baseline and repeated at a median of 4.5 years (inter-quartile range 3.6 to 5.2). Inflammatory markers (CRP, TNF, IL-1ß, IL-6, IL-8, IL-10, adiponectin and leptin) were ascertained at baseline using enzyme-linked immunosorbent assay (ELISA) techniques and Bio-Plex Pro Assays. Gender-adjusted linear regression was used to examine the associations between markers of inflammation and outcomes with and without adjustment for anthropometric and lifestyle factors. RESULTS: The mean (SD) ages at baseline were 64.4 (2.5) and 66.5 (2.7) years for men and women respectively. Higher levels of adiponectin and adiponectin to leptin ratios were each associated with lower baseline lumbar spine and femoral neck BMD in gender-adjusted (p < 0.01) and fully adjusted (p < 0.05) analyses. Lower levels of IL-10 and TNF were each associated with accelerated decline in lumbar spine BMD in both gender-adjusted (p ≤ 0.05) and fully adjusted (p < 0.05) analyses. CONCLUSIONS: In a cohort of older adults, high levels of adiponectin and adiponectin to leptin ratios were both associated with lower BMD at the lumbar spine and femoral neck at baseline, and lower IL-10 was associated with accelerated decline in BMD at the lumbar spine. This adds weight to the theory that bone health can be influenced by changes in immune phenotype and alterations in adipokine homeostasis.

Correlates of Level and Loss of Grip Strength in Later Life: Findings from the English Longitudinal Study of Ageing and the Hertfordshire Cohort Study.

Characterisation of grip strength (GS) using isometric dynamometry is central to the definition of sarcopenia. Determinants of low GS include: older age, shorter stature, low physical activity, poor nutrition, socioeconomic disadvantage and multimorbidity. Less is known about risk factors for accelerated loss of GS. We investigated determinants of level and 8-year loss of GS in 3703 men and women (aged 52-82 years) in the English Longitudinal Study of Ageing (ELSA). Four hundred and forty-one men and women (aged 59-71 years) who participated in a 10-year follow-up of the Hertfordshire Cohort Study (HCS) were used for replication. Variables were harmonised between cohorts. Change in GS was characterised using mixed-effects models in ELSA and a residual change approach in HCS and analysed for men and women combined. Men in ELSA and HCS had higher average levels of GS at baseline, and accelerated rates of loss, compared with women. In ELSA, older age, shorter stature and multimorbidity were correlated with lower level, and accelerated rate of loss, of GS in both sexes (accelerated loss of 0.04 (95% CI 0.00-0.08) standard deviation scores per additional morbidity after multivariable adjustment). Socioeconomic disadvantage, low level of physical activity and poorer self-reported health were also correlated with low GS level, but not loss rate, after multivariable adjustment. Analysis in HCS yielded similar results. Our results identify multimorbidity as a modifiable determinant of loss of muscle strength in later life, and raise the possibility that developmental influences may impact on rate of involutional decline in muscle strength.

Relationships Between Markers of Inflammation and Muscle Mass, Strength and Function: Findings from the Hertfordshire Cohort Study.

We investigated the longitudinal relationships between inflammation markers and the following outcomes in a UK cohort study: appendicular lean mass (ALM); walking speed; level and change in grip strength; and sarcopenia defined by the European Working Group on Sarcopenia in Older People. Analyses were based on 336 community-dwelling older men and women (aged 59-70 years) who participated in the Hertfordshire Cohort Study (HCS). Inflammation markers were ascertained at baseline using enzyme-linked immunosorbent assay techniques and Bio-Plex Pro Assays. Grip strength was measured at baseline and follow-up [median follow-up time: 10.8 years (inter-quartile range 10.2-11.6)] and change in grip strength was ascertained using a residual change approach. At follow-up, ALM was ascertained using dual-energy X-ray absorptiometry, customary walking speed was measured and sarcopenia status was ascertained. Gender-adjusted linear and Poisson regression was used to examine the associations between inflammation markers and outcomes with and without adjustment for anthropometric and lifestyle factors. Higher C-reactive protein was associated (p < 0.04) with lower grip strength and accelerated decline in grip strength from baseline to follow-up. Higher cortisol was associated with lower ALM (p < 0.05). Higher interleukin-8 (IL-8) was associated with lower ALM (p < 0.05) and increased risk of sarcopenia [fully-adjusted relative risk per SD increase in IL-8: 1.37 (95% CI 1.10, 1.71), p = 0.005]. All associations were robust in fully-adjusted analyses. Inflammation markers were associated with measures of muscle mass, strength and function in HCS. Further work is required to replicate these associations and to delineate the underlying mechanisms.

Muscle Mass, Muscle Morphology and Bone Health Among Community-Dwelling Older Men: Findings from the Hertfordshire Sarcopenia Study (HSS).

Sarcopenia and osteoporosis are associated with poor health outcomes in older people. Relationships between muscle and bone have typically been reported at a functional or macroscopic level. The aims of this study were to describe the relationships between muscle morphology and bone health among participants of the Hertfordshire Sarcopenia Study (HSS). 105 older men, mean age 72.5 (SD 2.5) years, were recruited into the HSS. Whole body lean mass as well as appendicular lean mass, lumbar spine and femoral neck bone mineral content (BMC) and bone mineral density (BMD) were obtained through dual-energy X-ray absorptiometry scanning. Percutaneous biopsy of the vastus lateralis was performed successfully in 99 participants. Image analysis was used to determine the muscle morphology variables of slow-twitch (type I) and fast-twitch (type II) myofibre area, myofibre density, capillary and satellite cell (SC) density. There were strong relationships between whole and appendicular lean body mass in relation to femoral neck BMC and BMD (r ≥ 0.43, p < 0.001). Type II fibre area was associated with both femoral neck BMC (r = 0.27, p = 0.01) and BMD (r = 0.26, p = 0.01) with relationships robust to adjustment for age and height. In unadjusted analysis, SC density was associated with whole body area (r = 0.30, p = 0.011) and both BMC (r = 0.26, p = 0.031) and area (r = 0.29, p = 0.017) of the femoral neck. We have demonstrated associations between BMC and changes in muscle at a cellular level predominantly involving type II myofibres. Interventions targeted at improving muscle mass, function and quality may improve overall musculoskeletal health. Larger studies that include women are needed to explore these relationships further.

Heavy manual work throughout the working lifetime and muscle strength among men at retirement age.

INTRODUCTION: Reductions in heavy manual work as a consequence of mechanisation might adversely impact muscle strength at older ages. We investigated the association between grip strength at retirement age and lifetime occupational exposure to physically demanding activities. Grip strength is an important predictor of long-term health and physical function in older people. METHODS: Grip strength (maximum of three readings in each hand) was measured in men from the Hertfordshire Cohort Study at a single examination when their mean age was 65.8 (SD 2.9) years. Associations with lifetime occupational exposure (ascertained by questionnaire) to three activities (standing/walking ≥ 4 h/day; lifting ≥ 25 kg; and energetic work sufficient to induce sweating) were assessed by multivariable linear regression with adjustment for various potential confounders. RESULTS: Complete data were available from 1418 men who had worked for at least 20 years. After adjustment for age, height and weight, those with longer exposures to walking/standing and heavy lifting had lower grip strength, but the relationship disappeared after further adjustment for confounders. Working at physical intensity sufficient to induce sweating was not significantly associated with grip strength. CONCLUSIONS: We found no evidence that physically demanding occupational activities increase hand grip strength at normal retirement age. Any advantages of regular physical occupational activity may have been obscured by unmeasured socioeconomic confounders.

Skeletal muscle morphology in sarcopenia defined using the EWGSOP criteria: findings from the Hertfordshire Sarcopenia Study (HSS).

BACKGROUND: Sarcopenia is defined as the loss of muscle mass and function with age and is associated with decline in mobility, frailty, falls and mortality. There is considerable interest in understanding the underlying mechanisms. Our aim was to characterise muscle morphology changes associated with sarcopenia among community dwelling older men. METHODS: One hundred and five men aged 68-76 years were recruited to the Hertfordshire Sarcopenia Study (HSS) for detailed characterisation of muscle including measures of muscle mass, strength and function. Muscle tissue was obtained from a biopsy of the vastus lateralis for 99 men and was processed for immunohistochemical studies to determine myofibre distribution and area, capillarisation and satellite cell (SC) density. RESULTS: Six (6 %) men had sarcopenia as defined by the European Working Group on Sarcopenia in Older People (EWGSOP) criteria. These men had lower SC density (1.7 cells/mm(2) vs 3.8 cells/mm(2), p = 0.06) and lower SC/fibre ratio (0.02 vs 0.06, p = 0.06) than men without sarcopenia. Although men with sarcopenia tended to have smaller myofibres and lower capillary to fibre ratio, these relationships were not statistically significant. CONCLUSION: We have shown that there may be altered muscle morphology parameters in older men with sarcopenia. These results have the potential to help identify cell and molecular targets for therapeutic intervention. This work now requires extension to larger studies which also include women.

Exposure to heavy physical occupational activities during working life and bone mineral density at the hip at retirement age.

BACKGROUND: People in sedentary occupations are at increased risk of hip fracture. Hip fracture is significantly associated with low bone mineral density (BMD) measured at the hip. Physical activity is important in the development and maintenance of BMD, but the effects of occupational physical activity on bone health are unclear. We investigated the influence of lifetime physical activity on BMD at the hip. METHODS: This was a cross-sectional epidemiological study of the associations between total hip BMD measured by dual-energy X-ray absorptiometry at retirement age and lifetime exposure to occupational physical workload (standing/walking ≥4 h/day; lifting ≥25 kg; energetic work sufficient to induce sweating and manual work). RESULTS: Complete data on occupational exposures were available for 860 adults (488 men and 372 women) who had worked ≥20 years. Their mean age was 65 years, and many reported heavy physical workplace activities over prolonged durations. There were no statistically significant associations between total hip BMD and any of these measures of lifetime occupational physical activity in men or women. CONCLUSIONS: Lifetime cumulative occupational activity was not associated with hip BMD at retirement age. Our findings suggest that, if sedentary work conveys an increased risk of hip fracture, it is unlikely that the mechanism is through reductions in BMD at the hip and may relate to other physical effects, such as falls risk. Further studies will be needed to test this hypothesis.

Dietary total antioxidant capacity is related to glucose tolerance in older people: the Hertfordshire Cohort Study.

BACKGROUND AND AIMS: Dietary antioxidants may play a protective role in the aetiology of type 2 diabetes. However, observational studies that examine the relationship between the antioxidant capacity of the diet and glucose metabolism are limited, particularly in older people. We aimed to examine the relationships between dietary total antioxidant capacity (TAC) and markers of glucose metabolism among 1441 men and 1253 women aged 59-73 years who participated in the Hertfordshire Cohort Study, UK. METHODS AND RESULTS: Diet was assessed by food frequency questionnaire. Dietary TAC was estimated using published databases of TAC measured by four different assays: oxygen radical absorbance capacity (ORAC), ferric-reducing ability of plasma (FRAP), total radical-trapping antioxidant parameter (TRAP) and trolox equivalent antioxidant capacity (TEAC). Fasting and 120-min plasma glucose and insulin concentrations were measured during a standard 75-g oral glucose tolerance test. In men, dietary TAC estimated by all four assays was inversely associated with fasting insulin concentration and homoeostasis model assessment of insulin resistance (HOMA-IR); with the exception of ORAC, dietary TAC was also inversely related to 120-min glucose concentration. There were no associations with fasting glucose or 120-min insulin concentrations. In women, with the exception of the association between ORAC and 120-min insulin concentration, dietary TAC estimated by all assays showed consistent inverse associations with fasting and 120-min glucose and insulin concentrations and HOMA-IR. These associations were more marked among women with BMI ≥ 30 kg/m(2). CONCLUSION: These findings suggest dietary TAC may have important protective effects on glucose tolerance, especially in older obese women.

The relationship of dietary patterns with adult lung function and COPD.

Previous studies of diet and lung function have focused on associations with individual nutrients and foods, and not dietary patterns. The relationships between dietary patterns and lung function and spirometrically defined chronic obstructive pulmonary disease (COPD) were investigated in 1,551 males and 1,391 females in Hertfordshire, UK. Dietary information was obtained by food frequency questionnaire and dietary patterns were identified using principal components analysis. Using regression analysis, after controlling for confounders, a "prudent" pattern (high consumption of fruit, vegetables, oily fish and wholemeal cereals) was positively associated with forced expiratory volume in 1 s (FEV(1)) (trend p-value <0.001 in males, 0.008 in females) (difference in FEV(1) between top and bottom quintiles of pattern score, 0.18 L (95% CI 0.08-0.28 L) in males, 0.08 L (95% CI 0.00-0.16 L) in females). This pattern was also positively associated with forced vital capacity (FVC) in both sexes. Males with a higher "prudent" pattern score had a higher FEV(1)/FVC (trend p-value 0.002) and a lower prevalence of COPD (odds ratio comparing top versus bottom quintile 0.46, 95% CI 0.26-0.81; trend p-value 0.012). Associations in males were stronger in smokers than nonsmokers (interaction p-value for FEV(1)/FVC 0.002). A "prudent" dietary pattern may protect against impaired lung function and COPD, especially in male smokers.

Bone health and deterioration in quality of life among participants from the Hertfordshire cohort study.

UNLABELLED: We utilised the Hertfordshire cohort study to examine relationships between bone density at baseline and SF-36 status 4 years later. We found deterioration in the mental health domain over follow-up in osteoporotic men (but not women) compared with other groups (relative rate ratio=5.78, 95% confidence interval (CI) 1.78-19.2). INTRODUCTION: Osteoporosis is associated with decreased quality of life, although it has been difficult to evaluate the confounding effects of fracture and co-morbidity. Having previously shown that male osteoporotics have poorer health than counterparts with normal bone mineral density, even after adjustment for co-morbidity and prior fracture, we assessed quality of life in both groups 4 years apart. METHODS: Four hundred and ninety-eight men and 468 women completed questionnaires detailing lifestyle factors, co-morbidities and quality of life (SF-36) before undergoing bone density measurements at the lumbar spine and total femur. At follow-up 4 years later, 322 men and 320 women were reassessed. RESULTS: Multinomial logistic regression confirmed deterioration in mental health over follow-up in osteoporotic men compared with other groups (relative rate ratio=5.78, 95% CI 1.78-19.2). These patterns were not apparent among women. CONCLUSIONS: Men with lower bone density at baseline had poorer quality of life some 4 years later, even after adjustment for co-morbidity and fracture. This may reflect secondary osteoporosis in men (due to alcohol or hypogonadism).

Grip strength and cardiovascular drug use in older people: findings from the Hertfordshire Cohort Study.

BACKGROUND: reduced grip strength is associated with adverse health consequences, and there is interest in identifying modifiable influences. Cardiovascular drugs are commonly used by older people, but their effect on muscle strength is unclear. METHODS: we investigated associations between cardiovascular drug use and grip strength among 1,572 men and 1,415 women, aged 59-73, who participated in the Hertfordshire Cohort Study. RESULTS: Forty-five percent of participants were taking a cardiovascular drug. Furosemide was associated with average decreases in grip strength of 3.15 kg (95% confidence interval [CI] 0.90, 5.39, P < 0.01) among men and 2.35 kg (95% CI 0.93, 3.77, P < 0.01) among women after adjustment for age and height. Corresponding differences for nitrates were 1.84 kg (95% CI 0.29, 3.39, P = 0.02) among men and 3.66 kg (95% CI 1.99, 5.33, P < 0.01) among women. Calcium channel blockers and fibrates were associated with reduced grip among women. Statins were not associated with grip. The associations between grip strength and nitrate use in men and nitrate and fibrate use in women were robust to additional adjustment for co-morbidity. CONCLUSIONS: use of some cardiovascular drugs is associated with reduced grip strength in older people. These findings have potential implications for the functional ability of older people treated with these drugs.

Physical performance and physical activity in older people: are developmental influences important?

BACKGROUND: Reduced physical performance and physical activity have serious health consequences, but adult determinants do not fully explain variation in older people. OBJECTIVE: Our objective was to investigate the relationship between early growth, physical performance and physical activity in older people. METHODS: We studied 349 men and 280 women born 1931-1939 with known birth weight and weight at 1 year who were taking part in the Hertfordshire Cohort Study, UK. Physical performance was measured (3-m walk, chair rises and standing balance) and physical activity was assessed by questionnaire and converted to estimated energy expenditure. RESULTS: Poor balance was associated with lower birth weight (odds ratio [OR] for poor balance per standard deviation [SD] increase in birth weight = 0.68, p=0.01) and weight at 1 year (OR for poor balance per SD increase in weight at 1 year=0.67, p=0.03) after adjustment for age and current size in men, but not in women. There were no significant positive relationships between early size and growth and the other measures of physical performance or physical activity in men or women. CONCLUSION: Current lifestyle factors, particularly those affecting adult weight, may be more important than developmental influences on most measures of physical performance and physical activity in older people.

The SF-36: a simple, effective measure of mobility-disability for epidemiological studies.

BACKGROUND: Mobility disability is a major problem in older people. Numerous scales exist for the measurement of disability but often these do not permit comparisons between study groups. The physical functioning (PF) domain of the established and widely used Short Form-36 (SF-36) questionnaire asks about limitations on ten mobility activities. OBJECTIVES: To describe prevalence of mobility disability in an elderly population, investigate the validity of the SF-36 PF score as a measure of mobility disability, and to establish age and sex specific norms for the PF score. METHODS: We explored relationships between the SF-36 PF score and objectively measured physical performance variables among 349 men and 280 women, 59-72 years of age, who participated in the Hertfordshire Cohort Study (HCS). Normative data were derived from the Health Survey for England (HSE) 1996. RESULTS: 32% of men and 46% of women had at least some limitation in PF scale items. Poor SF-36 PF scores (lowest fifth of the gender-specific distribution) were related to: lower grip strength; longer timed-up-and-go, 3m walk, and chair rises test times in men and women; and lower quadriceps peak torque in women but not men. HSE normative data showed that median PF scores declined with increasing age in men and women. CONCLUSION: Our results are consistent with the SF-36 PF score being a valid measure of mobility disability in epidemiological studies. This approach might be a first step towards enabling simple comparisons of prevalence of mobility disability between different studies of older people. The SF-36 PF score could usefully complement existing detailed schemes for classification of disability and it now requires validation against them.

Lipid profile, obesity and bone mineral density: the Hertfordshire Cohort Study.

BACKGROUND: Body mass index (BMI) and bone mineral density (BMD) are positively correlated in several studies, but few data relate bone density, lipid profile and anthropometric measures. AIM: To investigate these relationships in a large, well-characterized cohort of men and women (The Hertfordshire Cohort Study). METHODS: Men (n = 465) and women (n = 448) 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. RESULTS: 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 in both sexes (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. DISCUSSION: In this cohort, relationships between lipid profile and BMD were robust to adjustment for one measure of central obesity (waist-hip ratio), but not total body fat. This broadly supports the idea that adiposity may confound the relationship between lipids and bone mass.

Grip strength and the metabolic syndrome: findings from the Hertfordshire Cohort Study.

INTRODUCTION: Sarcopenia, the loss of muscle mass and strength with age, is significantly associated with type 2 diabetes in older people. AIM: To determine whether there is a relationship between grip strength and features of the metabolic syndrome. DESIGN: Cross-sectional study. METHODS: Data were collected on grip strength, fasting glucose, triglycerides and HDL cholesterol, blood pressure, waist circumference and 2 h glucose after an oral glucose tolerance test, in a population-based sample of 2677 men and women aged 59-73 years. RESULTS: In men and women combined, a standard deviation (SD) decrease in grip strength was significantly associated with higher: fasting triglycerides (0.05 SD unit increase, 95%CI 0.02-0.09, p = 0.006); blood pressure (OR 1.13, 95%CI 1.04-1.24, p = 0.004); waist circumference (0.08 SD unit increase, 95%CI 0.06-0.10, p < 0.001); 2 h glucose (0.07 SD unit increase, 95%CI 0.03-0.11, p = 0.001) and HOMA resistance (0.05 SD unit increase, 95%CI 0.01-0.09, p = 0.008), after adjustment for gender, weight, age, walking speed, social class, smoking habit and alcohol intake. Lower grip strength was also significantly associated with increased odds of having the metabolic syndrome according to both the ATPIII (OR 1.18, 95%CI 1.07-1.30, p < 0.001) and IDF definitions (OR 1.11, 95%CI 1.01-1.22, p = 0.03). DISCUSSION: Our findings suggest that impaired grip strength is associated with the individual features, as well as with the overall summary definitions, of the metabolic syndrome. The potential for grip strength to be used in the clinical setting needs to be explored.

Angiotensin II type I receptor gene polymorphism: anthropometric and metabolic syndrome traits.

BACKGROUND: The renin angiotensin system is important in the regulation of vascular tone and fluid and electrolyte balance. The angiotensin converting enzyme gene (ACE) genotype has been shown to affect exercise response and glucose load response dependent on birth weight. Angiotensin II type I receptor (AGTR1) A1166C has previously been associated with the development of hypertension and coronary disease, but its metabolic effects have not been investigated. METHOD: AGTR1 A1166C was genotyped by allele specific PCR in 378 individuals from Hertfordshire, UK, who had been characterised for metabolic syndrome traits. RESULTS: Genotype counts were: AA, 183; AC, 170; CC, 25, consistent with Hardy-Weinberg equilibrium. The CC genotype was associated with significantly lower body mass index (by 1.7 units) in men (p = 0.03), and the same magnitude effect in women with significant lower weight in both genders (p = 0.01), also lower waist circumference and waist-hip ratio (p = 0.01) in men, with a trend for lower waist circumference in women also. Additionally, the CC genotype and/or C allele was associated with lower fasting glucose and insulin, and 30 and 120 min glucose in men (respectively, p = 0.08, 0.04, 0.01, 0.06). Lower means of systolic blood pressure, pulse pressure, cholesterol, and fasting triglyceride were also observed for the CC genotype in both genders though these were not statistically significant. CONCLUSIONS: The AGTR1 1166 CC genotype appears to predispose to favourable anthropometric and metabolic traits, relative to cardiovascular risk.

Fetal, infant, and childhood growth and adult blood pressure: a longitudinal study from birth to 22 years of age.

BACKGROUND: People who are small at birth tend to have higher blood pressure in later life. However, it is not clear whether it is fetal growth restriction or the accelerated postnatal growth that often follows it that leads to higher blood pressure. METHODS AND RESULTS: We studied blood pressure in 346 British men and women aged 22 years whose size had been measured at birth and for the first 10 years of life. Their childhood growth was characterized using a conditional method that, free from the effect of regression to the mean, estimated catch-up growth. People who had been small at birth but who gained weight rapidly during early childhood (1 to 5 years) had the highest adult blood pressures. Systolic pressure increased by 1.3 mm Hg (95% CI, 0.3 to 2.3) for every standard deviation score decrease in birth weight and, independently, increased by 1.6 mm Hg (95% CI, 0.6 to 2.7) for every standard deviation score increase in early childhood weight gain. Adjustment for adult body mass index attenuated the effect of early childhood weight gain but not of birth weight. Relationships were smaller for diastolic pressure. Weight gain in the first year of life did not influence adult blood pressure. CONCLUSIONS: Part of the risk of adult hypertension is set in fetal life. Accelerated weight gain in early childhood adds to this risk, which is partly mediated through the prediction of adult fatness. The primary prevention of hypertension may depend on strategies that promote fetal growth and reduce childhood obesity.

Investigating the role of the growth hormone-insulin-like growth factor (GH-IGF) axis as a determinant of male bone mineral density (BMD).

INTRODUCTION: The GH-IGF axis has profound effects on bone metabolism and may be important in the etiology of idiopathic osteoporosis. Serum IGF-I is often low in men with osteoporosis, which may be attributable to GH hypo-secretion or hepatic GH insensitivity. We studied the GH-IGF axis in depth to look for evidence to support these hypotheses. MATERIALS AND METHODS: 28 healthy 60- to 70-year-old men with low, intermediate, or normal BMD were studied. GH secretion was measured by overnight urine collection. GH reserve was assessed by exercise and glucagon stimulation tests. Hepatic IGF-I production was investigated using a GH-IGF-I generation test. Data were analyzed using Pearson's correlation coefficient, linear regression, and analysis of variance. RESULTS: Serum IGF-I was reduced in subjects with low BMD (P = 0.009). There was no difference in GH secretion or reserve between the groups. Overall, GH reserve and IGF-I were positively related but this was attenuated in the low BMD group. However, no statistically significant difference in IGF-I generation capacity between BMD groups was found. CONCLUSIONS: Men with reduced BMD have low IGF-I but normal GH secretion and reserve. Our data suggested, but could not confirm, hepatic resistance to GH as a mechanism for this association.

Polymorphism in the growth hormone gene, weight in infancy, and adult bone mass.

Epidemiological studies point to the importance of gene-environment interactions during early life as determinants of later osteoporosis and fracture. We examined associations between common single nucleotide polymorphisms in the human GH (GH1) gene and weight in infancy, adult bone mass and bone loss rates, and circulating GH profiles. Two hundred and five men and 132 women, aged 61-73 yr, in the Hertfordshire Cohort Study were included; bone mineral density was measured by dual energy x-ray absorptiometry over 4 yr. Twenty-four-hour circulating GH profiles were constructed in a subset of 71 men and women. Genomic DNA was examined for two single nucleotide polymorphisms in the GH gene (one in the promoter region and one in intron 4). Homozygotes at loci GH1 A5157G and T6331A displayed low baseline bone density and accelerated bone loss; there was also a significant (P = 0.04) interaction among weight at 1 yr, GH1 genotype, and bone loss rate. There was a graded association between alleles and circulating GH concentration among men. This study suggests that common diversity in the GH1 region predisposes to osteoporosis via effects on the level of GH expression. The interaction with infant weight suggests that early environment may influence the effect of GH1 genotype on bone loss.