Anthropometric protocols for the construction of new international fetal and newborn growth standards: the INTERGROWTH-21st Project.

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes, in detail, the selection of anthropometric personnel, equipment, and measurement and calibration protocols used to construct the new standards. Implementing these protocols at each study site ensures that the anthropometric data are of the highest quality to construct the international standards.

Anthropometric standardisation and quality control protocols for the construction of new, international, fetal and newborn growth standards: the INTERGROWTH-21st Project.

The primary aim of the INTERGROWTH-21(st) Project is to construct new, prescriptive standards describing optimal fetal and preterm postnatal growth. The anthropometric measurements include the head circumference, recumbent length and weight of the infants, and the stature and weight of the parents. In such a large, international, multicentre project, it is critical that all study sites follow standardised protocols to ensure maximal validity of the growth and nutrition indicators used. This paper describes in detail the anthropometric training, standardisation and quality control procedures used to collect data for these new standards. The initial standardisation session was in Nairobi, Kenya, using newborns, which was followed by similar sessions in the eight participating study sites in Brazil, China, India, Italy, Kenya, Oman, UK and USA. The intraobserver and inter-observer technical error of measurement values for head circumference range from 0.3 to 0.4 cm, and for recumbent length from 0.3 to 0.5 cm. These standardisation protocols implemented at each study site worldwide ensure that the anthropometric data collected are of the highest quality to construct international growth standards.

Frailty consensus: a call to action.

Frailty is a clinical state in which there is an increase in an individual's vulnerability for developing increased dependency and/or mortality when exposed to a stressor. Frailty can occur as the result of a range of diseases and medical conditions. A consensus group consisting of delegates from 6 major international, European, and US societies created 4 major consensus points on a specific form of frailty: physical frailty. 1. Physical frailty is an important medical syndrome. The group defined physical frailty as "a medical syndrome with multiple causes and contributors that is characterized by diminished strength, endurance, and reduced physiologic function that increases an individual's vulnerability for developing increased dependency and/or death." 2. Physical frailty can potentially be prevented or treated with specific modalities, such as exercise, protein-calorie supplementation, vitamin D, and reduction of polypharmacy. 3. Simple, rapid screening tests have been developed and validated, such as the simple FRAIL scale, to allow physicians to objectively recognize frail persons. 4. For the purposes of optimally managing individuals with physical frailty, all persons older than 70 years and all individuals with significant weight loss (>5%) due to chronic disease should be screened for frailty.

Longitudinal changes in calcaneal quantitative ultrasound measures during childhood.

UNLABELLED: This longitudinal study examined how calcaneal quantitative ultrasound (QUS) measures change during childhood while taking into account skeletal maturation, body mass index (BMI), and physical activity. The study reported sex differences in QUS growth curves and an inverse relationship between BMI and speed of sound (SOS) measures. INTRODUCTION: The aim of this study was to examine how calcaneal QUS parameters change over time during childhood and to determine what factors influence these changes. METHODS: The study sample consisted of a total of 192 Caucasian children participating in the Fels Longitudinal Study. A total of 548 calcaneal broadband ultrasound attenuation (BUA) and SOS observations were obtained between the ages of 7.6 and 18 years. The best fitting growth curves were determined using statistical methods for linear mixed effect models. RESULTS: There are significant sex differences in the pattern of change in QUS parameters (p < 0.05). The relationship between QUS measures and skeletal age is best described by a cubic growth curve in boys and a linear pattern among girls. Boys experience their most rapid growth in BUA and SOS in early and late adolescence, while girls experience constant growth throughout childhood. Adiposity levels were significantly associated with the changes in SOS among boys (p < 0.001) and girls (p < 0.01), indicating that children with higher BMI are likely to have lower SOS over time compared to children with lower BMI. For girls, physical activity levels showed positive associations with changes in QUS measures (p < 0.05). CONCLUSION: This study documents significant sex differences in the pattern of change in QUS measures over childhood and adolescence. Our study also shows significant influences of adiposity and physical activity on the pattern of change in QUS measures during childhood.

Left ventricular mass, abdominal circumference and age: the Fels longitudinal study.

PURPOSE: To determine the relationship of abdominal circumference with increased left ventricular mass (LVM) from young adulthood into old age. METHODS: Cross-sectional echocardiographic images were taken from 182 men and 220 women in the Fels Longitudinal Study 20 to 75 years of age to determine left ventricular mass. Left ventricular mass was divided by stature raised to the power of 2.7 (LVM/ht2.7) in order to minimize the impact of heart size variation from body size without overcompensating for the adverse effect of obesity. Abdominal circumference was measured and BMI calculated from stature and weight and categories of overweight, obesity and abdominal obesity were determined using published cut points. Regression models were used to describe the relationships of age, abdominal circumference, BMI and self-reported physical activity to LVM/ht2.7. RESULTS: Age, abdominal circumference and BMI were each positively and significantly related to an increased LVM/ht2.7 in men and women (p < 0.05). In the men, multivariate models indicated that abdominal circumference and BMI were both significantly related to an increased LVM/ht2.7, but the inclusion of BMI in these models for the women reduced the association of abdominal circumference and physical activity below significant levels. In the men, there was also a quadratic association of abdominal circumference with LVM/ht2.7 that was significant along with BMI and physical activity. Sex-specific logistic regressions with BMI and abdominal circumference obesity categories did not change or improve the initial findings in men or women. CONCLUSIONS: In women, increases in abdominal fatness as reflected in abdominal circumference at any age are linearly related to an increase in LVM/ht2.7, but the relationship of overall fatness as reflected in BMI with LVM/ht2.7 is stronger. In men, both abdominal fatness and overall fatness at any age are linearly related to an increase LVM/ht2.7. However, the significant curvilinear association of abdominal circumference and a linear association of BMI and physical activity with LVM/ht2.7 indicate the possible positive covariate relationship of overall muscle mass with LVM/ht2.7. This reflects the physiological changes with age and demonstrate, in part, the complexity of the interpretations of the inter associations of body composition, the cardiovascular system and the aging process, but the impact among the elderly and the known inadequacy of BMI at these ages remains an area for continued clinical study.

Sleep disturbance in relation to health-related quality of life in adults: the Fels Longitudinal Study.

OBJECTIVE: Sleep disturbances are prevalent problems in the general population. Symptoms of insomnia can impact various physical and mental conditions. Furthermore, sleep disturbances may worsen the quality of life independently of co-occurring medical conditions. In this study, we examined the relationships between self-reported sleep disturbance symptoms and health-related quality of life measures in the Fels Longitudinal Study. DESIGN: Cross-sectional study. PARTICIPANTS: A total of 397 adults (175 men and 222 women) aged 40 years and older were included in the present study. MEASUREMENTS: Three self-reported sleep disturbance measures (difficulty falling asleep, nocturnal awakenings and maintaining sleep, and daytime tiredness) were collected between 2003 and 2006. Health-related quality of life measures were assessed using the Medical Outcomes Survey Short Form (SF)-36. Socio-demographic status (marital status, employment status, and education) and current medical conditions were collected from participants during study visits. RESULTS: Individuals who reported frequent sleep disturbances showed significantly worse quality of life on all SF-36 subscales examined. The odds ratio (OR) ranged from 1.71 to 18.32 based on symptoms of insomnia across seven SF-36 domains in analyses adjusted for significant covariates influencing quality of life. Participants with severe sleep disturbances (both sleep problems and daytime impairment) showed generally higher odds of reporting poor SF-36 scores (adjusted ORs; 5.88 - 17.09) compared to participants with no problems. CONCLUSION: Sleep disturbance is comprehensively and independently associated with poor health-related quality of life in middle-aged and older adults.

Rapid infant weight gain and advanced skeletal maturation in childhood.

OBJECTIVE: To test the hypothesis that rapid infant weight gain is associated with advanced skeletal maturity in children from the United States and South Africa. STUDY DESIGN: Longitudinal data from 467 appropriate-for-gestational-age infants in the Fels Longitudinal Growth Study (Dayton, Ohio) and 196 appropriate-for-gestational-age infants in the Birth to Twenty birth cohort study (Johannesburg, South Africa) were used. Multiple linear regression models tested the association between internal SD score change in weight from 0 to 2 years and relative skeletal age at 9 years, adjusting for body mass index, stature, and other covariates. RESULTS: In both studies, faster infant weight gain was associated with more advanced skeletal maturity (approximately 0.2 years or 2.4 months per SD score) at age 9 years (P <.0001-.005), even when adjusting for the positive associations of both birth weight and body mass index at age 9 years. This effect appeared to be accounted for by the greater childhood stature of subjects with more rapid infant weight gain. CONCLUSIONS: Relatively rapid infant weight-gain is associated with advanced skeletal development in late childhood, perhaps via effects on stature.

Visceral adiposity and its anatomical distribution as predictors of the metabolic syndrome and cardiometabolic risk factor levels.

BACKGROUND: Despite the recognition that central obesity plays a critical role in chronic disease, few large-scale imaging studies have documented human variation in abdominal adipose tissue patterning. OBJECTIVE: We aimed to compare the associations between abdominal subcutaneous adipose tissue (ASAT) and visceral abdominal tissue (VAT), which were measured at different locations across the abdomen, and the presence of the metabolic syndrome (MS; National Cholesterol Education Program Adult Treatment Panel III definition) and individual cardiometabolic risk factors. DESIGN: This study included 713 non-Hispanic whites aged 18-86 y, in whom VAT and ASAT were assessed by using multiple-image magnetic resonance imaging. The anatomical position of the magnetic resonance image containing the maximum VAT area for each subject was used as a measure of VAT patterning. Multivariate linear and logistic regression analyses were used to examine the relation of VAT, ASAT, and VAT patterning to cardiometabolic risk. RESULTS: VAT mass was a stronger predictor of the MS than was ASAT mass, but ASAT mass (and other measures of subcutaneous adiposity) had signification interactions with VAT mass, whereby elevated ASAT reduced the probability of MS among men with high VAT (P = 0.0008). There was variation across image locations in the association of VAT area with the MS in men, and magnetic resonance images located 4-8 cm above L4-L5 provided the strongest correlations between VAT area and cardiometabolic risk factors. Subjects whose maximum VAT area was higher in the abdomen had higher LDL-cholesterol concentrations (R(2) = 0.07, P < 0.0001), independent of age and adiposity. CONCLUSION: Further studies are needed to confirm the effects of VAT patterning on cardiometabolic risk.

Sarcopenia: its assessment, etiology, pathogenesis, consequences and future perspectives.

Sarcopenia is a loss of muscle protein mass and loss of muscle function. It occurs with increasing age, being a major component in the development of frailty. Current knowledge on its assessment, etiology, pathogenesis, consequences and future perspectives are reported in the present review. On-going and future clinical trials on sarcopenia may radically change our preventive and therapeutic approaches of mobility disability in older people.

Sex differences in young adulthood metabolic syndrome and physical activity: the Fels longitudinal study.

OBJECTIVE: To evaluate the effects of habitual physical activity (PA) on the metabolic syndrome (MS) in young adult men and women. RESEARCH METHODS AND PROCEDURES: Cross-sectional PA data were utilized from 249 women and 237 men, aged 18-40 years in the Fels Longitudinal Study. MS components--abdominal circumference (AC), triglycerides (TG), HDL, blood pressure (BP), and fasting glucose (FG)--were dichotomized according to the National Cholesterol Education Program's Adult Treatment Panel III revised criteria. Leisure, sport, work, and total PA scores were calculated using the Baecke Questionnaire of Habitual Physical Activity. Multiple logistic regression modeling assessed the effects of PA, age, smoking, and BMI on MS status. RESULTS: 26.9% of men and 19.3% of women had MS. For men, MS risk was reduced with increases in both total PA [OR = 0.65 (95% CI: 0.47, 0.90)] and sport PA [OR = 0.40 (95% CI: 0.23, 0.70)]. AC, TG, and HDL values also improved with total and sport PA. Among women, the risk for MS was marginally reduced by total PA [OR = 0.72 (95% CI: 0.50, 1.02)] and HDL levels were increased by both total PA [OR = 0.79 (95% CI: 0.63, 0.98)] and sport PA [OR = 0.54 (95% CI: 0.35, 0.84)]. DISCUSSION: Increased total and sport PA reduces risk for the MS in young men, though not as clearly in young women.

Anatomical patterning of visceral adipose tissue: race, sex, and age variation.

OBJECTIVE: We tested sex, race, and age differences in the patterning of visceral adipose tissue (VAT) and subcutaneous adipose tissue. RESEARCH METHODS AND PROCEDURES: Contiguous 1-cm-thick magnetic resonance (MR) images of the abdomen were collected from 820 African-American and white adults. Repeated-measures ANOVA was used to examine the effects of image location, sex, race, and age (>or=50 vs. <50 years) on adipose tissue areas. Maximum VAT area was identified for each subject from the raw data. RESULTS: Compared to women, men had greater total VAT volume (p < 0.0001), and their maximum VAT area occurred higher in the abdomen (p < 0.0001). Among white men, maximim VAT area most frequently occurred 5 to 10 cm above L4-L5, whereas in the other groups, maximim VAT area most frequently occurred 1 to 4 cm above L4-L5 (p < 0.0001). African-American men had greater total VAT volume than African-American women (p < 0.01), but this sex difference was only significant using single images cranial to L4-L5 + 2 cm. Age-related increases in VAT tended to be greatest 5 to 10 cm above L4-L5 in men and near L4-L5 in women. DISCUSSION: A single MR image 5 to 10 cm above L4-L5 may allow more accurate conclusions than the L4-L5 image regarding group differences in visceral adiposity.

Validity of a new automated software program for visceral adipose tissue estimation.

INTRODUCTION: Given the considerable time and research cost of analyzing biomedical images to quantify adipose tissue volumes, automated image analysis methods are highly desirable. Hippo Fat is a new software program designed to automatically quantify adipose tissue areas from magnetic resonance images without user inputs. Hippo Fat has yet to be independently validated against commonly used image analysis software programs. OBJECTIVE: Our aim was to compare estimates of VAT (visceral adipose tissue) and SAT (subcutaneous adipose tissue) using the new Hippo Fat software against those from a widely used, validated, computer-assisted manual method (slice-O-matic version 4.2, Tomovision, Montreal, CA, USA) to assess its potential utility for large-scale studies. METHODS: A Siemens Magnetom Vision 1.5-T whole-body scanner and a T1-weighted fast-spin echo pulse sequence were used to collect multiple, contiguous axial images of the abdomen from a sample of 40 healthy adults (20 men) aged 18-77 years of age, with mean body mass index of 29 kg/m(2) (range=19-43 kg/m(2)). RESULTS: Hippo Fat provided estimates of VAT and SAT that were highly correlated with estimates using slice-O-matic (R (2)>0.9). Average VAT was 9.4% lower and average SAT was 3.7% higher using Hippo Fat compared to slice-O-matic; the overestimation of SAT tended to be greater among individuals with greater adiposity. Individual-level differences for VAT were also substantial; Hippo Fattrade mark gave estimates of VAT ranging from 1184 cm(3) less to 566 cm(3) more than estimates for the same person using slice-O-matic. CONCLUSION: Hippo Fat provides a rapid method of quantifying total VAT, although the method does not provide estimates that are interchangeable with slice-O-matic at either the group (mean) or individual level.

Overview of the MNA--Its history and challenges.

The Mini Nutritional Assessment (MNA) is a simple tool, useful in clinical practice to measure nutritional status in elderly persons. From its validation in 1994, the MNA has been used in hundreds of studies and translated into more then 20 languages. It is a well-validated tool, with high sensitivity, specificity, and reliability. An MNA score > or = 24 identifies patients with a good nutritional status. Scores between 17 and 23.5 identify patients at risk for malnutrition. These patients have not yet started to lose weight and do not show low plasma albumin levels but have lower protein-calorie intakes than recommended. For them, a multidisciplinary geriatric intervention is needed, which takes into account all aspects that might interfere with proper alimentation and, when necessary, proposes therapeutic interventions for diet or supplementation. If the MNA score is less than 17, the patient has protein-calorie malnutrition. It is important at this stage to quantify the severity of the malnutrition (by measuring biochemical parameters like plasma albumin or prealbumin levels, establishing a 3- day record of food intake, and measuring anthropometric features like weight, BMI, arm circumference and skin folds). Nutritional intervention is clearly needed and should be based on achievable objectives established after a detailed comprehensive geriatric assessment. The MNA has been shown to be useful for nutritional intervention follow-up as well. The MNA can help clinicians design an intervention by noting where the patient loses points when performing the MNA. Moreover, when a nutritional intervention is successful, the MNA score increases. The MNA is recommended by many national and international clinical and scientific organizations. It can be used by a variety of professionals, including physicians, dietitians, nurses or research assistants. A short screening version (MNA-SF) has been developed, which, if positive, indicates the need to complete the full MNA. It takes less than 4 minutes to administer the MNA-SF and between 10 and 15 minutes for the full MNA.

Is the MNA valid in different populations and across practice settings?

OBJECTIVE: The MNA is a successful screening tool in geriatric medicine, but this success is in Europe or countries with Western health care practice settings. The MNA is not directly applicable in many ethnic groups or countries or those with non-Western cultural and dietary habits or health care systems. There is an increased prevalence of type 2 diabetes, the metabolic syndrome and obesity among the elderly; however, the MNA does not include questions or measures related to these or other important health conditions affected by nutritional status. This paper addresses the relevance of anthropometry and the impact of different clinical practice settings on the MNA and discusses the development of the Chinese Nutritional Screen (CNS) in China. CONCLUSIONS: If the MNA is to continue to be successful among groups of elderly around the world, then the MNA, CNS or similar instruments should be as country or culturally and ethnically specific as possible. The development of the CNS maintained the underlying assumptions and concept of the MNA but modified them for a country with diverse food and cultural habits and health care settings.

Growth and health in children with moderate-to-severe cerebral palsy.

BACKGROUND: Children with cerebral palsy frequently grow poorly. The purpose of this study was to describe observed growth patterns and their relationship to health and social participation in a representative sample of children with moderate-severe cerebral palsy. METHODS: In a 6-site, multicentered, region-based cross-sectional study, multiple sources were used to identify children with moderate or severe cerebral palsy. There were 273 children enrolled, 58% male, 71% white, with Gross Motor Function Classification System levels III (22%), IV (25%), or V (53%). Anthropometric measures included: weight, knee height, upper arm length, midupper arm muscle area, triceps skinfold, and subscapular skinfold. Intraobserver and interobserver reliability was established. Health care use (days in bed, days in hospital, and visits to doctor or emergency department) and social participation (days missed of school or of usual activities for child and family) over the preceding 4 weeks were measured by questionnaire. Growth curves were developed and z scores calculated for each of the 6 measures. Cluster analysis methodology was then used to create 3 distinct groups of subjects based on average z scores across the 6 measures chosen to provide an overview of growth. RESULTS: Gender-specific growth curves with 10th, 25th, 50th, 75th, and 90th percentiles for each of the 6 measurements were created. Cluster analyses identified 3 clusters of subjects based on their average z scores for these measures. The subjects with the best growth had fewest days of health care use and fewest days of social participation missed, and the subjects with the worst growth had the most days of health care use and most days of participation missed. CONCLUSIONS: Growth patterns in children with cerebral palsy were associated with their overall health and social participation. The role of these cerebral palsy-specific growth curves in clinical decision-making will require further study.

Do changes in body mass index percentile reflect changes in body composition in children? Data from the Fels Longitudinal Study.

OBJECTIVE: Our aim was to examine the degree to which changes in BMI percentile reflect changes in body fat and lean body mass during childhood and how age and gender affect these relationships. METHODS: This analysis used serial data on 494 white boys and girls who were aged 8 to 18 years and participating in the Fels Longitudinal Study (total 2319 observations). Total body fat (TBF), total body fat-free mass (FFM), and percentage of body fat (%BF) were determined by hydrodensitometry, and then BMI was partitioned into its fat and fat-free components: fat mass index (FMI) and FFM index (FFMI). We calculated predicted changes (Delta) in FMI, FFMI, and %BF for each 10-unit increase in BMI percentile using mixed-effects models. RESULTS: FFMI had a linear relationship with BMI percentile, whereas FMI and %BF tended to increase dramatically only at higher BMI percentiles. Gender and age had significant effects on the relationship between BMI percentile and FFMI, FMI, and %BF. Predicted Delta%BF for boys 13 to 18 years of age was negative, suggesting loss of relative fatness for each 10-unit increase in BMI percentile. CONCLUSIONS: In this longitudinal study of white children, FFMI consistently increased with BMI percentile, whereas FMI and %BF had more complicated relationships with BMI percentile depending on gender, age, and whether BMI percentile was high or low. Our results suggest that BMI percentile changes may not accurately reflect changes in adiposity in children over time, particularly among male adolescents and children of lower BMI.

Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study.

INTRODUCTION: Areal bone mineral density (BMD) and calcaneal quantitative ultrasound (QUS) measures are correlated, and both traits predict osteoporotic fracture risk independently. However, few studies have examined whether common genetic effects (i.e., pleiotropy) exist between these traits in extended families. In this study, we estimated the additive genetic correlation and random environmental correlation between BMD measured at various skeletal sites and calcaneal QUS measures. METHODS: Our sample included 537 adults (251 men and 286 women) from 110 families participating in the Fels Longitudinal Study. Total hip, femoral neck, lumbar spine, and total body BMD were measured using dual energy X-ray absorptiometry. Three measures of calcaneal structure--broadband ultrasound attenuation (BUA), speed of sound (SOS), and quantitative ultrasound index (QUI)--were collected from the non-dominant heel using the Sahara sonometer. Applying a variance components-based maximum likelihood method, we estimated the heritability of each trait and estimated the genetic and environmental correlations between the different BMD and QUS measures. RESULTS: Heritability estimates were significant for all measures of BMD and QUS ranging from 0.55 to 0.78. Significant non-zero genetic correlations were found between the different BMD and QUS measures. All genetic correlations were also significantly different from 1. Genetic correlations between total hip BMD and each of the QUS measures were 0.63 with BUA, 0.50 with SOS, and 0.56 with QUI. For femoral neck BMD, genetic correlations were similar to those between total hip BMD and QUS measures. Genetic correlations between BMD of the lumbar spine and QUS measures ranged from 0.34 to 0.38, and those between total body BMD and QUS measures, from 0.51 to 0.54. In contrast, all random environmental correlations were not significantly different from zero. CONCLUSION: This study demonstrates that BMD and calcaneal QUS measures among healthy men and women are significantly heritable and are, in part, jointly influenced by a common set of underlying genes. Additionally, this study also provides evidence for a unique set of genes that independently influences each individual trait.

Radiographic joint space of the knee in healthy young adults.

The primary objective of this study was to characterize normal variation in radiographic joint space of the knee in a large sample of healthy young adults and to identify factors that contribute to this variation. We measured radiographic knee joint space in 279 skeletally mature subjects, age between 16 and 22 years, who participated in the Fels Longitudinal Study. Minimum joint space was measured in the medial and lateral knee compartments. Independent sample t tests and correlation analyses were performed to examine sex differences and associations between joint space, joint size, and body size [weight, stature, body mass index (BMI)]. Results show that young men have thicker articular cartilage than young women in both the medial and lateral compartments of the knee. Significant positive correlations were found between joint space and body size measures in the total sample. When the sexes were considered independently, however, correlations between joint space and body size were significant in men only. Regression analyses of the combined-sex sample identified sex, BMI, and joint width as significant explanatory factors of medial joint space, together accounting for 26% of the observed variance. In contrast, sex was the sole significant explanatory factor of lateral joint space, explaining 19% of the observed variance. Results of this study show that during early adulthood, when articular cartilage is healthy and at its peak thickness, men have thicker knee cartilage than women. At this young age body size accounts for a modest proportion of the variation observed in knee cartilage thickness.

Lipids, lipoproteins, lifestyle, adiposity and fat-free mass during middle age: the Fels Longitudinal Study.

INTRODUCTION: Although lipid profiles tend to worsen with age, it is not fully known if such age-related changes are influenced primarily by body composition and lifestyle or by other aspects of aging. OBJECTIVE: We investigated the extent to which the fat and fat-free components of body mass index (BMI) and lifestyle factors influence patterns of change in lipids independent of age. DESIGN: Serial data were analyzed using sex-specific longitudinal models. These models use serial data from individuals to assume a general pattern of change over time, while allowing baseline age and the rate of change to vary among individuals. SUBJECTS: Serial data were obtained from 940 examinations of 269 healthy white participants (126 men, 143 women), aged 40-60 years, in the Fels Longitudinal Study. MEASUREMENTS: Measurements included age, the fat (FMI) and fat-free mass (FFMI) components of BMI, high-density lipoprotein (HDL-C), low-density lipoprotein (LDL-C), triglycerides (TG), total cholesterol (TC), fasting glucose and insulin, physical activity, alcohol use and smoking, and women's menopausal status and estrogen use. RESULTS: In both sexes, increased FMI was significantly associated with increased LDL-C, TG and TC, and decreased HDL-C. Increased FFMI was significantly related to decreased HDL-C and increased TG. Independent age effects remained significant only for LDL-C and TC in men and TC in women. Increased insulin was significantly related to increased TG in women. Moderate alcohol consumption was associated with higher HDL-C in men. Physical activity lowered male LDL-C and TC levels, and increased female HDL-C levels. Menopause was associated with increases in LDL-C. Premenopausal women not using estrogen had significantly lower HDL-C, TG, and TC than postmenopausal women taking estrogen. CONCLUSIONS: (1) Age is an important independent predictor for LDL-C and TC in men, and TC in women, but it is not as influential as body composition and lifestyle on HDL-C and TG in men and women, and LDL-C in women. (2) Increasing FMI is the major contributor to elevated TC, LDL-C and TG levels, and decreased HDL-C levels in men and women. (3) FFMI significantly influences HDL and TG levels in both sexes. (4) Maintaining a lower BMI via a reduced fat component may be more beneficial in lowering CVD risks than other factors.