Statistical shape modelling of hip and lumbar spine morphology and their relationship in the MRC National Survey of Health and Development.

The anatomical shape of bones and joints is important for their proper function but quantifying this, and detecting pathological variations, is difficult to do. Numerical descriptions would also enable correlations between joint shapes to be explored. Statistical shape modelling (SSM) is a method of image analysis employing pattern recognition statistics to describe and quantify such shapes from images; it uses principal components analysis to generate modes of variation describing each image in terms of a set of numerical scores after removing global size variation. We used SSM to quantify the shapes of the hip and the lumbar spine in dual-energy x-ray absorptiometry (DXA) images from 1511 individuals in the MRC National Survey of Health and Development at ages 60-64 years. We compared shapes of both joints in men and women and hypothesised that hip and spine shape would be strongly correlated. We also investigated associations with height, weight, body mass index (BMI) and local (hip or lumber spine) bone mineral density. In the hip, all except one of the first 10 modes differed between men and women. Men had a wider femoral neck, smaller neck-shaft angle, increased presence of osteophytes and a loss of the femoral head/neck curvature compared with women. Women presented with a flattening of the femoral head and greater acetabular coverage of the femoral head. Greater weight was associated with a shorter, wider femoral neck and larger greater and lesser trochanters. Taller height was accompanied by a flattening of the curve between superior head and neck and a larger lesser trochanter. Four of the first eight modes describing lumbar spine shape differed between men and women. Women tended to have a more lordotic spine than men with relatively smaller but caudally increasing anterior-posterior (a-p) vertebral diameters. Men were more likely to have a straighter spine with larger vertebral a-p diameters relative to vertebral height than women, increasing cranially. A weak correlation was found between body weight and a-p vertebral diameter. No correlations were found between shape modes and height in men, whereas in women there was a weak positive correlation between height and evenness of spinal curvature. Linear relationships between hip and spine shapes were weak and inconsistent in both sexes, thereby offering little support for our hypothesis. In conclusion, men and women entering their seventh decade have small but statistically significant differences in the shapes of their hips and their spines. Associations with height, weight, BMI and BMD are small and correspond to subtle variations whose anatomical significance is not yet clear. Correlations between hip and spine shapes are small.

Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British Birth Cohort Study.

AIMS: Antecedent blood pressure (BP) may contribute to cardiovascular disease (CVD) independent of current BP. Blood pressure is associated with left ventricular mass index (LVMI) which independently predicts CVD. We investigated the relationship between midlife BP from age 36 to 64 and LVMI at 60-64 years. METHODS AND RESULTS: A total of 1653 participants in the British 1946 Birth Cohort underwent BP measurement and echocardiography aged 60-64. Blood pressure had previously been measured at 36, 43, and 53 years. We investigated associations between BP at each age and rate of change in systolic blood pressure (SBP) between 36-43, 43-53, and 53-60/64 years on LVMI at 60-64 years. Blood pressure from 36 years was positively associated with LVMI. Association with SBP at 53 years was independent of SBP at 60-64 years and other potential confounders (fully adjusted ß at 53 years = 0.19 g/m(2); 95% CI: 0.11, 0.27; P < 0.001). Faster rates of increase in SBP from 43 to 53 years and 53 to 60/64 years were associated with increased LVMI. Similar relationships were seen for diastolic, pulse, and mean pressure. Rate of increase in SBP between 43-53 years was associated with largest change in LVMI (ß at 43-53 years = 3.12 g/m(2); 95% CI: 1.53, 4.72; P < 0.001). People on antihypertensive medication (43 years onwards) had greater LVMI even after adjustment for current BP (ß at 43 years = 12.36 g/m(2); 95% CI: 3.19, 21.53; P = 0.008). CONCLUSION: Higher BP in midlife and rapid rise of SBP in 5th decade is associated with higher LVMI in later life, independent of current BP. People with treated hypertension have higher LVMI than untreated individuals, even accounting for their higher BP. Our findings emphasize importance of midlife BP as risk factor for future CVD.

Associations between life course longitudinal growth and hip shapes at ages 60-64 years: evidence from the MRC National Survey of Health and Development.

OBJECTIVE: We sought to examine associations between height gain across childhood and adolescence with hip shape in individuals aged 60-64 years from the Medical Research Council National Survey of Health and Development, a nationally representative British birth cohort. METHODS: Height was measured at ages 2, 4, 6, 7, 11 and 15 years, and self-reported at age 20 years. 10 modes of variation in hip shape (HM1-10), described by statistical shape models, were previously ascertained from DXA images taken at ages 60-64 years. Associations between (1) height at each age; (2) Super-Imposition by Translation And Rotation (SITAR) growth curve variables of height size, tempo and velocity; and (3) height gain during specific periods of childhood and adolescence, and HM1-10 were tested. RESULTS: Faster growth velocity was associated with a wider, flatter femoral head and neck, as described by positive scores for HM6 (regression coefficient 0.014; 95% CI 0.08 to 0.019; p<0.001) and HM7 (regression coefficient 0.07; 95% CI 0.002 to 0.013; p=0.009), and negative scores for HM10 (regression coefficient -0.006; 95% CI -0.011 to 0.00, p=0.04) and HM2 (males only, regression coefficient -0.017; 95% CI -0.026 to -0.09; p<0.001). Similar associations were observed with greater height size and later height tempo. Examination of height gains during specific periods of childhood and adolescence identified those during the adolescence period as being most consistently associated. CONCLUSION: Our analyses suggest that individual growth patterns, particularly in the adolescent period, are associated with modest variations in hip shape at 60-64 years, which are consistent with features seen in osteoarthritis.

Investigating risk factors for psychological morbidity three months after intensive care: a prospective cohort study.

INTRODUCTION: There is growing evidence of poor mental health and quality of life among survivors of intensive care. However, it is not yet clear to what extent the trauma of life-threatening illness, associated drugs and treatments, or patients' psychological reactions during intensive care contribute to poor psychosocial outcomes. Our aim was to investigate the relative contributions of a broader set of risk factors and outcomes than had previously been considered in a single study. METHODS: A prospective cohort study of 157 mixed-diagnosis highest acuity patients was conducted in a large general intensive care unit (ICU). Data on four groups of risk factors (clinical, acute psychological, socio-demographic and chronic health) were collected during ICU admissions. Post-traumatic stress disorder (PTSD), depression, anxiety and quality of life were assessed using validated questionnaires at three months (n = 100). Multivariable analysis was used. RESULTS: At follow-up, 55% of patients had psychological morbidity: 27.1% (95% CI: 18.3%, 35.9%) had probable PTSD; 46.3% (95% CI: 36.5%, 56.1%) probable depression, and 44.4% (95% CI: 34.6%, 54.2%) anxiety. The strongest clinical risk factor for PTSD was longer duration of sedation (regression coefficient = 0.69 points (95% CI: 0.12, 1.27) per day, scale = 0 to 51). There was a strong association between depression at three months and receiving benzodiazepines in the ICU (mean difference between groups = 6.73 points (95% CI: 1.42, 12.06), scale = 0 to 60). Use of inotropes or vasopressors was correlated with anxiety, and corticosteroids with better physical quality of life. CONCLUSIONS: Strikingly high rates of psychological morbidity were found in this cohort of intensive care survivors. The study's key finding was that acute psychological reactions in the ICU were the strongest modifiable risk factors for developing mental illness in the future. The observation that use of different ICU drugs correlated with different psychological outcomes merits further investigation. These findings suggest that psychological interventions, along with pharmacological modifications, could help reduce poor outcomes, including PTSD, after intensive care.

Dairy intake, blood pressure and incident hypertension in a general British population: the 1946 birth cohort.

PURPOSE: We aimed to examine the association between intake of different subgroups of dairy products and blood pressure and incident hypertension 10 years later, adjusting for confounding factors. METHODS: We studied 1,750 British men and women from the 1946 British birth cohort from 1989 to 1999 (age 43 and 53 years, respectively). Diet was assessed by 5-day food diaries using photographs in the estimation of portion size. Systolic (sbp) and diastolic (dbp) blood pressure and prevalent hypertension were assessed at age 43 and 53 years. Linear regression and logistic regression were used to examine 10-year blood pressure levels and incident hypertension by baseline dairy intake. RESULTS: There was a weak non-significant trend of a protective effect of total dairy intake on blood pressure and incident hypertension, but no evidence for a dose-response relationship (OR for incident hypertension: 0.88 (95% CI 0.68;1.14) 2nd vs. 1st tertile and 0.93 (95% CI 0.72;1.18) 3rd vs. 1st tertile). Higher intake of low-fat and fermented dairy was linked to a higher sbp but in a nonlinear manner. Adjustment for other dietary factors, health behaviours and BMI attenuated these associations. CONCLUSIONS: Total dairy intake and specific dairy subgroups were not associated with blood pressure and incident hypertension among a representative sample of British adults after adjustment for confounding factors.

Motor development in infancy and spine shape in early old age: Findings from a British birth cohort study.

Spine shape changes dramatically in early life, influenced by attainment of developmental milestones such as independent walking. Whether these associations persist across life is unknown. Therefore, we investigated associations between developmental milestones and spine shape, as determined using statistical shape models (SSMs) of lumbar spine from dual-energy X-ray absorptiometry scans in 1327 individuals (688 female) at 60 to 64 years in the MRC National Survey of Health and Development. Lumbar lordosis angle (L4 inferior endplate to T12 superior endplate) was measured using the two-line Cobb method. In analyses adjusted for sex, height, lean and fat mass, socioeconomic position, and birthweight, later walking age was associated with greater lordosis described by SSM1 (regression coefficient, 0.023; 95% CI, 0.000-0.047; P = .05) and direct angle measurement. Modest associations between walking age and less variation in anterior-posterior vertebral size caudally (SSM6) were also observed (0.021; 95% CI, -0.002 to 0.044; P = .07). Sex interactions showed that later walking was associated with larger relative vertebral anterior-posterior dimensions in men (SSM3; -0.043; 95% CI, -0.075 to 0.01; P = .01) but not women (0.018; 95% CI, -0.0007 to 0.043; P = .17). Similar associations were observed between age at independent standing and SSMs but there was little evidence of association between sitting age and spine shape. Unadjusted associations between walking age and SSMs 1 and 6 remained similar after adjustment for potential confounders and mediators. This suggests that these associations may be explained by altered mechanical loading of the spine during childhood growth, although other factors could contribute. Early life motor development, particularly walking, may have a lasting effect on the features of spine morphology with clinical significance.

Age at Onset of Walking in Infancy Is Associated With Hip Shape in Early Old Age.

Bones' shapes and structures adapt to the muscle and reaction forces they experience during everyday movements. Onset of independent walking, at approximately 12 months, represents the first postnatal exposure of the lower limbs to the large forces associated with bipedal movements; accordingly, earlier walking is associated with greater bone strength. However, associations between early life loading and joint shape have not been explored. We therefore examined associations between walking age and hip shape at age 60 to 64 years in 1423 individuals (740 women) from the MRC National Survey of Health and Development, a nationally representative British birth cohort. Walking age in months was obtained from maternal interview at age 2 years. Ten modes of variation in hip shape (HM1 to HM10), described by statistical shape models, were ascertained from DXA images. In sex-adjusted analyses, earlier walking age was associated with higher HM1 and HM7 scores; these associations were maintained after further adjustment for height, body composition, and socioeconomic position. Earlier walking was also associated with lower HM2 scores in women only, and lower HM4 scores in men only. Taken together, this suggests that earlier walkers have proportionately larger (HM4) and flatter (HM1, HM4) femoral heads, wider (HM1, HM4, HM7) and flatter (HM1, HM7) femoral necks, a smaller neck-shaft angle (HM1, HM4), anteversion (HM2, HM7), and early development of osteophytes (HM1). These results suggest that age at onset of walking in infancy is associated with variations in hip shape in older age. Early walkers have a larger femoral head and neck and smaller neck-shaft angle; these features are associated with reduced hip fracture risk, but also represent an osteoarthritic-like phenotype. Unlike results of previous studies of walking age and bone mass, associations in this study were not affected by adjustment for lean mass, suggesting that associations may relate directly to skeletal loading in early life when joint shape changes rapidly. © 2018 American Society for Bone and Mineral Research.

Associations between back pain across adulthood and spine shape in early old age in a British birth cohort.

We aimed to examine whether back pain across adulthood was associated with spine shape at age 60-64 years. Data were from 1405 participants in the MRC National Survey of Health and Development, a nationally representative British birth cohort. Back pain was ascertained during nurse interviews at ages 36, 43, 53 and 60-64 years. Cumulative exposure to back pain was then derived by counting the number of ages at which back pain was reported. Statistical shape modelling was used to characterise thoracolumbar spine shape using lateral dual-energy x-ray absorptiometry images which were ascertained at age 60-64 years. Linear regression models were used to test associations of spine shape modes (SM) with: (1) cumulative exposure to back pain; (2) back pain reports during different periods of adulthood. After adjusting for sex, higher cumulative exposure to back pain across adulthood was associated with wedge-shaped L4-5 disc (lower SM4 scores) and smaller disc spaces (higher SM8 scores) in both sexes. In addition, reporting of back pain at ages 53 and/or 60-64 years was associated with smaller L4-5 disc space (lower SM6 scores) in men but not women. These findings suggest that back pain across adulthood may be associated with specific variations in spine shapes in early old age.

Body mass index and waist circumference in early adulthood are associated with thoracolumbar spine shape at age 60-64: The Medical Research Council National Survey of Health and Development.

This study investigated associations between measures of adiposity from age 36 and spine shape at 60-64 years. Thoracolumbar spine shape was characterised using statistical shape modelling on lateral dual-energy x-ray absorptiometry images of the spine from 1529 participants of the MRC National Survey of Health and Development, acquired at age 60-64. Associations of spine shape modes with: 1) contemporaneous measures of total and central adiposity (body mass index (BMI), waist circumference (WC)) and body composition (android:gynoid fat mass ratio and lean and fat mass indices, calculated as whole body (excluding the head) lean or fat mass (kg) divided by height2 (m)2); 2) changes in total and central adiposity between age 36 and 60-64 and 3) age at onset of overweight, were tested using linear regression models. Four modes described 79% of the total variance in spine shape. In men, greater lean mass index was associated with a larger lordosis whereas greater fat mass index was associated with straighter spines. Greater current BMI was associated with a more uneven curvature in men and with larger anterior-posterior (a-p) vertebral diameters in both sexes. Greater WC and fat mass index were also associated with a-p diameter in both sexes. There was no clear evidence that gains in BMI and WC during earlier stages of adulthood were associated with spine shape but younger onset of overweight was associated with a more uneven spine and greater a-p diameter. In conclusion, sagittal spine shapes had different associations with total and central adiposity; earlier onset of overweight and prior measures of WC were particularly important.

Life course body size and lipid levels at 53 years in a British birth cohort.

OBJECTIVES: To investigate the association between growth in height and change in body mass index (BMI) during the life course on lipid levels at 53 years. METHODS: 2311 men and women from a British cohort study were included in analyses. Non-fasting total, high-density lipoprotein (HDL) and low-density lipoprotein (LDL) cholesterol levels were measured at 53 years. Height and BMI at 2, 4, 7, 11, 15 and 36 years in relation to the lipid outcomes at 53 years were assessed using multiple regression models. The effects of z scores of height and BMI at 2 years and yearly rates of change (velocities) in height and BMI between 2-7, 7-15 and 15-36 years were also considered. RESULTS: Total cholesterol level decreased by 0.119 mmol/l (95% CI -0.194 to -0.045) per SD increase in height at 2 years and by 0.073 mmol/l (95% CI -0.145 to -0.001) for every SD increase in height velocity between 15 years and adulthood. Similar, but weaker associations were seen for LDL cholesterol. The relationships between leg length and total and LDL cholesterol were stronger than the relationship with trunk length. Higher BMI at 36 and 53 years and greater BMI increases between 15-36 and 36-53 years were associated with higher total and LDL cholesterol and lower HDL cholesterol levels. The effects of growth could not be explained by birth weight or lifetime socioeconomic status. CONCLUSIONS: Early life exposures, which restrict height growth in infancy, resulting in shorter adult leg length, may influence lipid levels in adult life.

Associations between body mass index across adult life and hip shapes at age 60 to 64: Evidence from the 1946 British birth cohort.

OBJECTIVE: To examine the associations of body mass index (BMI) across adulthood with hip shapes at age 60-64years. METHODS: Up to 1633 men and women from the MRC National Survey of Health and Development with repeat measures of BMI across adulthood and posterior-anterior dual-energy X-ray absorptiometry bone mineral density images of the proximal femur recorded at age 60-64 were included in analyses. Statistical shape modelling was applied to quantify independent variations in hip mode (HM), of which the first 6 were examined in relation to: i) BMI at each age of assessment; ii) BMI gain during different phases of adulthood; iii) age first overweight. RESULTS: Higher BMI at all ages (i.e. 15 to 60-64) and greater gains in BMI were associated with higher HM2 scores in both sexes (with positive HM2 values representing a shorter femoral neck and a wider and flatter femoral head). Similarly, younger age first overweight was associated with higher HM2 scores but only in men once current BMI was accounted for. In men, higher BMI at all ages was also associated with lower HM4 scores (with negative HM4 values representing a flatter femoral head, a wider neck and smaller neck shaft angle) but no associations with BMI gain or prolonged exposure to high BMI were found. Less consistent evidence of associations was found between BMI and the other four HMs. CONCLUSION: These results suggest that BMI across adulthood may be associated with specific variations in hip shapes in early old age.

Birth weight and lipids in a national birth cohort study.

OBJECTIVE: To investigate the association between birth weight and lipid levels in a 53-year-old birth cohort from England, Scotland, and Wales. METHODS AND RESULTS: Lipid levels were obtained from nonfasting blood samples, collected at the most recent follow-up of the MRC National Survey of Health and Development, for 2559 men and women. Regression models indicated that in men, a 1-kg increase in birth weight was associated with a 0.13-mmol/L decrease (95% CI: -0.23, -0.01) in total cholesterol at age 53 years (P=0.03), compared with a 0.02-mmol/L (95% CI: -0.11, 0.15) increase in women and a 0.06-mmol/L (95% CI: -0.15, 0.02) decrease in men and women combined. Adjustment for current height and body mass index (BMI) in men reduced the size of the relationship, with height being responsible for the reduction. Adult height and height at 2 and 4 years were significantly associated with total cholesterol in men and in men and women combined. The negative association between total cholesterol and birth weight was strongest among men with high BMI at age 53 years (P=0.03 for test for interaction between birth weight and BMI). There was no significant association between birth weight and LDL or HDL cholesterol in men or women before adjustment, but there was a positive association with HDL in women. When both sexes were analyzed together, an association was seen after adjustment for current body size. No confounding of these findings with social class was observed in this study. CONCLUSIONS: Our results suggest that the small effect of birth weight on lipid levels at age 53 years has a limited public health impact. The findings suggest that childhood height growth may be more important than prenatal growth.

Cardiovascular Risk Factors from Early Life Predict Future Adult Cardiac Structural and Functional Abnormalities: A Systematic Review of the Published Literature.

BACKGROUND: Clinical practice evaluates cardiovascular risk based on current risk factor (RF) levels [Blood pressure (BP), body mass index (BMI) and glycaemic control] largely disregarding previous risk-factor history over the totality of the life course. RFs are related to contemporaneous echocardiographic measures of cardiac structure and function which in turn are independently related to cardiovascular morbidity and mortality in cross-sectional studies. However, the effect of lifetime or earlier RF history on future echocardiographic changes has never been systematically examined. METHODS: A systematic review of the published literature identified 24 studies relating either earlier BP, BMI, glycaemic control or a combination to future cardiac structure and/or function. RESULTS: The majority of studies showed that elevated BP and BMI in earlier life and greater cumulative burden of these factors resulted in worse cardiac structure up to 24 years later. Studies examining glycaemic control as RF were few, but poorer glycaemic control in young adults was associated with increased future left ventricular mass. While only 5 papers related RFs to future cardiac function, all RFs were positively associated with worse future diastolic function. CONCLUSIONS: BP, BMI and glycaemic control measures in childhood, adolescence and early adulthood and subsequent longitudinal trajectories of BP and BMI are predictive of future abnormalities in cardiac structure and function. Lifetime RF history should be used to inform clinical practice. Further research is required to enable the identification of any sensitive periods in the life course to enable prevention when it is most likely to be effective.

Overweight in childhood, adolescence and adulthood and cardiovascular risk in later life: pooled analysis of three british birth cohorts.

BACKGROUND: Overweight and obesity in adulthood are established risk factors for adverse cardiovascular outcomes, but the contribution of overweight in childhood to later cardiovascular risk is less clear. Evidence for a direct effect of childhood overweight would highlight early life as an important target for cardiovascular disease prevention. The aim of this study was to assess whether overweight and obesity in childhood and adolescence contribute to excess cardiovascular risk in adults. METHODS AND FINDINGS: Data from three British birth cohorts, born in 1946, 1958 and 1970, were pooled for analysis (n = 11,447). Individuals were categorised, based on body mass index (BMI), as being of normal weight or overweight/obese in childhood, adolescence and adulthood. Eight patterns of overweight were defined according to weight status at these three stages. Logistic regression models were fitted to assess the associations of patterns of overweight with self-reported type 2 diabetes, hypertension, and coronary heart disease (CHD) in adulthood (34-53 years). Compared to cohort members who were never overweight, those who were obese in adulthood had increased risk of all outcomes. For type 2 diabetes, the odds ratio was higher for obese adults who were also overweight or obese in childhood and adolescence (OR 12.6; 95% CI 6.6 to 24.0) than for those who were obese in adulthood only (OR 5.5; 95% CI 3.4 to 8.8). There was no such effect of child or adolescent overweight on hypertension. For CHD, there was weak evidence of increased risk among those with overweight in childhood. The main limitations of this study concern the use of self-reported outcomes and the generalisability of findings to contemporary child populations. CONCLUSIONS: Type 2 diabetes and to a lesser extent CHD risk may be affected by overweight at all stages of life, while hypertension risk is associated more strongly with weight status in adulthood.

Trajectories of overweight and body mass index in adulthood and blood pressure at age 53: the 1946 British birth cohort study.

OBJECTIVE: To assess the relationship between patterns of overweight during adulthood and systolic (SBP) and diastolic (DBP) blood pressure (BP) at age 53. METHOD: Data are from 3035 male and female participants of the 1946 British birth cohort study. Body mass index (BMI) was obtained at ages 20, 26, 36, 43 and 53 years. Censored regression models accounting for medication were used to investigate associations of BP at 53 years with overweight (BMI > 25 kg/m) at each age, age at first overweight and conditional weight gain. Sex interactions were also examined. RESULTS: Overweight at all ages except for 20 years in men was positively associated with BP at 53 years. After adjusting for current BMI, only overweight at age 43 contained additional information on BP in men. Men who were overweight at age 26 had a SBP 8.7 mmHg higher [95% confidence interval (CI) 4.4-13.0] than those first overweight at 53 years. Similar patterns but smaller associations were seen in women [P(interaction) < 0.001). All periods of adult weight gain (26-36, 36-43, 43-53 years) were associated with a higher BP. BMI tracked strongly through adulthood, the BMI at 53 years in men first overweight at 26 was 30.9 kg/m (95% CI 30.5-31.4) compared to 26.4 (95% CI 26.3-26.6) in those first overweight at age 53. CONCLUSIONS: Early adult overweight and all periods of adult weight gain irrespective of earlier BMI were associated with higher BPs. This highlights the importance for later health of preventing overweight in early adulthood.

Alpha1-antitrypsin as a risk for infant and adult respiratory outcomes in a national birth cohort.

Reduced alpha1-antitrypsin (AAT) encoded by the gene SERPINA1 is a potential risk for pulmonary disease. We investigated SERPINA1 polymorphism as a risk for infant and adult pulmonary morbidity, and adult respiratory function and its change between 43 and 53 yr. We used data on a British national representative sample (n = 5,362) studied since birth in 1946 to age 53 yr (when n = 3,035), when DNA was first obtained. SERPINA1 Z and, to a lesser extent, S carriers had an increased risk of infant lower respiratory infection compared with those who were neither S nor Z carriers (Z carriers: odds ratio = 2.32, 95% confidence interval = 1.37-3.92; S but not Z carriers odds ratio = 1.58, 95% confidence interval = 1.10-2.28) after adjustment for environmental, socioeconomic, and developmental factors, and breast-feeding. There was no difference in the adult outcomes at 53 yr according to genotype, nor was there any association of genotype with change in forced expiratory volume at 1 s between 43 and 53 yr. Lower alpha1-antitrypsin, as indicated by carrier status for the Z and S alleles, was a risk for infant lower respiratory infection, but not for adult respiratory outcomes.